CN102753887A - Systems, devices, and methods including a dark-field reflected-illumination apparatus - Google Patents

Abstract

Systems, devices, and methods are described for providing a monitor or treatment device configured to, for example, detect hemozoin, as well as to monitor or treat a malarial infection.

Description

The system, device and the method that comprise details in a play not acted out on stage, but told through dialogues indirect illumination equipment

The cross reference of related application

All themes of any and all previous generation (parent) of related application and related application, last two generations (grandparent), last three generations's (great-grandparent) etc. application are to combine by reference in this article at this, as long as these themes do not exist inconsistent therewith.

Related application

Purpose for the non-legal requirements of USPTO; The application constitute Michael C sea lattice (MICHAEL C.HEGG), horse repair P Huo Ning (MATTHEW P.HORNING), about fourth T Kai Er (JORDIN T.KARE), in gloomy P Mai Woerde (NATHAN P.MYHRVOLD), Clarens T spy Green (CLARENCE T.TEGREENE), Benjamin K Weir inferior (BENJAMIN K.WILSON), little Luo Weier L Wood (LOWELLL.WOOD; JR.) title of submitting on February 10th, 2010 as the inventor is 12/658 of " comprising system, device and method (SYSTEMS; DEVICES; AND METHODS INCLUDING MULTI-HARMONIC OPTICALDETECTION OF HEMOZOIN NANOPARTICLES) to the multiple-harmonic optical detection of hemozoin nano particle "; The part continuation application of No. 619 U.S. Patent applications; This U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute Michael C sea lattice, horse repair P Huo Ning, about fourth T Kai Er, in the title submitted on February 10th, 2010 as the inventor of gloomy P Mai Woerde, the special Green of Clarens T, inferior, the little Luo Weier L of Benjamin K Weir Wood be " comprising system, device and method (SYSTEMS; DEVICES; AND METHODS INCLUDING ENHANCEDDARK FIELD DETECTION OF HEMOZOIN NANOPARTICLES) " to the enhancement mode dark field detection of hemozoin nano particle 12/658; The part continuation application of No. 580 U.S. Patent applications; This U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute Michael C sea lattice, horse repair P Huo Ning, about fourth T Kai Er, in gloomy P Mai Woerde, the special Green of Clarens T, inferior, the little Luo Weier L of Benjamin K Weir Wood as the title that the inventor submitted on February 10th, 2010 be " comprising system, device and method (SYSTEMS; DEVICES; AND METHODS INCLUDING PARAMAGNETICOSCILLATION; ROTATION AND TRANSLATION OF HEMOZOINASYMMETRIC NANOPARTICLES IN RESPONSE TOMULTI-HARMONIC OPTICAL DETECTION OF THE PRESENCE OFHEMOZOIN) " in response to paramagnetism vibration, rotation and the translation of the asymmetric nano particle of hemozoin that the multiple-harmonic optical detection of the existence of hemozoin is carried out 12/658; The part continuation application of No. 617 U.S. Patent applications; This U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute Michael C sea lattice, horse repair P Huo Ning, about fourth T Kai Er, in gloomy P Mai Woerde, the special Green of Clarens T, inferior, the little Luo Weier L of Benjamin K Weir Wood as the title that the inventor submitted on February 10th, 2010 be " comprising system, device and the method (SYSTEMS; DEVICES; AND METHODS INCLUDING PARAMAGNETICOSCILLATION; ROTATION AND TRANSLATION OF HEMOZOINASYMMETRIC NANOPARTICLES IN RESPONSE TOMULTI-HARMONIC OPTICAL DETECTION OF THE PRESENCE OFHEMOZOIN) of carrying out paramagnetism vibration, rotation and the translation of the asymmetric nano particle of hemozoin " in response to the multiple-harmonic optical detection of the existence of hemozoin 12/658; The part continuation application of No. 638 U.S. Patent applications; This U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute Michael C sea lattice, horse repair P Huo Ning, about fourth T Kai Er, in the title submitted on February 10th, 2010 as the inventor of gloomy P Mai Woerde, the special Green of Clarens T, inferior, the little Luo Weier L of Benjamin K Weir Wood for " comprise in response to the dark field detection of the existence of hemozoin or Lay system, device and method (SYSTEMS; DEVICES; AND METHODS INCLUDINGPARAMAGNETIC OSCILLATION; ROTATION; AND TRANSLATION OFHEMOZOIN ASYMMETRIC NANOPARTICLES IN RESPONSE TODARK-FIELD OR RHEINBERG DETECTION OF THE PRESENCE OFHEMOZOIN) " because of paramagnetism vibration, rotation and the translation of Burger detection the carrying out asymmetric nano particle of hemozoin 12/658; The part continuation application of No. 589 U.S. Patent applications; This U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute Michael C sea lattice, horse repair P Huo Ning, about fourth T Kai Er, in the title submitted on February 10th, 2010 as the inventor of gloomy P Mai Woerde, the special Green of Clarens T, inferior, the little Luo Weier L of Benjamin K Weir Wood for " being used for causing system, device and the method (SYSTEMS; DEVICES; AND METHODS FORINDUCING ULTRAVIOLET ENERGY GENERATION VIA HEMOZOINNANOPARTICLES IN A BIOLOGICAL TISSUE) of ultraviolet energy generation " via the hemozoin nano particle of biological tissue 12/658; The part continuation application of No. 607 U.S. Patent applications; This U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute horse repair R Bel moral (MATTHEW R.BEHREND), Michael C sea lattice, horse repair the inferior title of submitting on October 25th, 2010 as the inventor of P Huo Ning, Benjamin K Weir for " system, device and the method (SYSTEMS; DEVICES; AND METHODSINCLUDING A DARK-FIELD REFLECTED-ILLUMINATIONAPPARATUS) that comprise details in a play not acted out on stage, but told through dialogues indirect illumination equipment " 12/925; The part continuation application of No. 653 U.S. Patent applications, this U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

Purpose for the non-legal requirements of USPTO; The application constitute horse repair R Bel moral, Michael C sea lattice, horse repair the inferior title of submitting on October 25th, 2010 as the inventor of P Huo Ning, Benjamin K Weir for " being used for system, device and method (SYSTEMS; DEVICES; AND METHODS FOR DETECTION OF MALARIA) that malaria detects " 12/925; The part continuation application of No. 650 U.S. Patent applications, this U.S. Patent application is current to be in co-pendingly jointly, or its current common application co-pending can obtain the application of applying date rights and interests.

USPTO has announced a statement, and its effect is that the computer program of USPTO requires the patent applicant not only will mention sequence number, and will point out whether application is continue case or part continuation application." rights and interests (Benefit of Prior-Filed Aplication) of the previous application of submitting to " that Shi Difen G elder brother peaceful (Stephen G.Kunin) delivered in USPTO official gazette on March 18th, 2003 can Http:// www.uspto.gov/web/offices/corn/sol/og/2003/weekl1/patben e.htmObtain.Applicant of the present invention individual (hereinafter referred to as " applicant ") provides specifically mentioning the application that requires priority according to decree at preceding text.The applicant understands, and this decree is clear and definite on its concrete reference language, and do not need sequence number or for example any characterization such as " case continues " or " part continuation application " come the priority of requirement to U.S. Patent application.However; The applicant recognizes; The computer program of USPTO has some data input requirement; Therefore the applicant is appointed as the part continuation application like a plurality of higher levels' applications of the application of preceding text statement with the application, but points out clearly, these specify should not be interpreted as by any way about the application except theme of its female generation application, whether contain any new theme any kind note and/or admit.

General introduction

In one aspect, especially to a kind of equipment, this equipment comprises a dark ground illuminator in the present invention.In one embodiment, this dark ground illuminator comprises a plurality of sensors, a plurality of device and agent structure that defines at least one aperture of inquiring after.In one embodiment, but a plurality of independently sensors in these a plurality of sensors are connected to this with mode of operation that a plurality of to inquire after in the device one or more right to form one or more sensors-inquire after device.For instance, in one embodiment, form a sensor-inquire after device and the sensor of a part is positioned as only captures freely to form the electromagnetic energy through scattering of inquiring after a sample that device inquire after of this sensor-inquire after device a part.In one embodiment; Form a sensor-inquire after device one or more sensors of a part (for example are positioned an optical path;, a light path); This optical path has been avoided not the electromagnetic energy from the sample scattering substantially, and this sample is to inquire after in the device one or more and inquire after this of a part is a plurality of by forming these sensors-inquire after device.

In one embodiment, these sensors-inquire after device depends on the electromagnetic energy scattered information of angle or depends on the electromagnetic energy scattered information of wavelength at least one from a sample acquiring of being inquired after by dark ground illuminator being configured to.In one embodiment, these a plurality of each of inquiring after in the device comprise a waveguide sub-assembly, and this waveguide sub-assembly has the one or more electromagnetic energy waveguides that are configured to be connected at least one electromagnetic energy emitter.For instance, in one embodiment, an electromagnetic energy waveguide guides from the electromagnetic energy of electromagnetic energy emitter radiation along an optical path, and this electromagnetic energy is directed on the focal zone of a sample.In one embodiment, these a plurality of waveguide sub-assemblies focus on electromagnetic energy at least one focal zone in this at least one aperture at the one or more incidence angles place with respect to an optical axis of an optical package.

In one aspect, especially to a kind of dark ground illuminator, this dark ground illuminator comprises a plurality of device and a plurality of sensors inquired after in this disclosure, and these inquire after the part of an agent structure of device and this dark ground illuminator of sensor formation.In one embodiment, these a plurality of each of inquiring after in the device comprise a waveguide sub-assembly, and this waveguide sub-assembly has the one or more electromagnetic energy waveguides that are configured to be connected at least one electromagnetic energy emitter.In one embodiment, these a plurality of waveguide sub-assemblies are oriented electromagnetic energy are focused at least one focal zone of a sample.In one embodiment, these a plurality of sensors be configured to capture come a sample that free this dark ground illuminator inquires after, through the electromagnetic energy of scattering.In one embodiment, these a plurality of sensors are configured to depend on the electromagnetic energy scattered information of angle or depend on the electromagnetic energy scattered information of wavelength at least one from a sample acquiring of being inquired after by dark ground illuminator.

In one aspect, especially to a kind of malaria checkout equipment, this malaria checkout equipment comprises: an optical package, this optical package have a sample side, a detector side and an optical axis that passes wherein in this disclosure; And a dark ground illuminator, this dark ground illuminator approaches the sample side of this optical package.In one embodiment, this dark ground illuminator comprises: a plurality of waveguide sub-assemblies; A sensor cluster, this sensor cluster comprise a sample that is configured to from being inquired after by this dark ground illuminator and receive the one or more sensors through the electromagnetic energy of scattering; And the agent structure with at least one aperture, this at least one aperture is aimed at along an axis that is parallel to an optical axis substantially.

In one aspect, especially to a kind of dark ground illuminator system, this system comprises one and inquires after stimulation circuit and a testing circuit in this disclosure.In one embodiment, this is inquired after stimulation circuit and is configured to electromagnetic energy stimulated and is directed on one or more volume of focus of a sample.In one embodiment, this testing circuit be configured to obtain at one or more incidence angles place free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.In one embodiment, testing circuit be configured to obtain at place, one or more azimuths with respect to an optical axis free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.In one embodiment, testing circuit is configured to obtain and comes free this to inquire after an electromagnetic energy scattered information sample, that depend on wavelength that stimulation circuit is inquired after.In one embodiment; This testing circuit comprises one or more detectors, these detectors be configured to obtain at place, one or more visual fields and at one or more depths of focus place free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.

Aforementioned general introduction only is illustrative, and and is not intended to by any way as restriction.Except above-described illustrative aspect, embodiment and characteristic, will understand other aspect, embodiment and characteristic through referenced in schematic and following detailed description.

Brief Description Of Drawings

Figure 1A is the perspective view according to the system of an embodiment.

Figure 1B is the plan view from above according to the part of monitor of an embodiment or treating apparatus, and this device comprises the energy radiation assembly that at least one electromagnetic energy of sending patterning stimulates.

Fig. 2 A is the perspective view that is used to regulate the active system of plasmodium parasitism according to an embodiment.

Fig. 2 B is the perspective view that is used to monitor/regulate the active system of plasmodium parasitism according to an embodiment.

Fig. 3 A is the perspective view according to the hemozoin monitoring device of an embodiment.

Fig. 3 B is the perspective view according to the medical diagnosis device of an embodiment.

Fig. 3 C is the perspective view according to the medical diagnosis device of an embodiment.

Fig. 3 D is the perspective view according to the original position hemozoin monitoring device of an embodiment.

Fig. 3 E is the perspective view according to the anti-malarial therapeutic system of an embodiment.

Fig. 4 A is the perspective view according to an equipment of an embodiment.

Fig. 4 B is the perspective view according to an equipment of an embodiment.

Fig. 5 is the flow chart according to a kind of method of an embodiment.

Fig. 6 is the flow chart according to a kind of method of an embodiment.

Fig. 7 is the flow chart according to a kind of method of an embodiment.

Fig. 8 is the flow chart according to a kind of method of an embodiment.

Fig. 9 is the flow chart according to a kind of method of an embodiment.

Figure 10 is the flow chart according to a kind of method of an embodiment.

Figure 11 is the flow chart according to a kind of method of an embodiment.

Figure 12 is the flow chart according to a kind of method of an embodiment.

Figure 13 is the flow chart according to a kind of method of an embodiment.

Figure 14 is the flow chart according to a kind of method of an embodiment.

Figure 15 is the flow chart according to a kind of method of an embodiment.

Figure 16 is the flow chart according to a kind of method of an embodiment.

Figure 17 is the flow chart according to a kind of method of an embodiment.

Figure 18 A and 18B are depicted as the flow chart according to a kind of method of an embodiment.

Figure 19 is the flow chart according to a kind of method of an embodiment.

Figure 20 is the perspective view according to monitor of an embodiment or treating apparatus configuration.

Figure 21 A and 21B be depicted as according to an embodiment, respective representative, from the plan view from above of the z of hemozoin film scanning and transversal scanning method.

Figure 22 produces the drawing of (THG) intensity to lateral separation according to embodiment (a 1) hemozoin and (2) quartzy third harmonic.

The third harmonic that Figure 23 A and 23B are depicted as according to a plurality of illustrated embodiments produces the drawing of (THG) power to exciting power.

Figure 24 is according to the drawing of the photomultiplier of an embodiment (PMT) electric current to the power mark.

Figure 25 is the voxel image according to the hemozoin crystal in the infected erythrocyte of an embodiment.

Figure 26 illustrates the intensity peak corresponding to the hemozoin crystal in the infected cell according to an embodiment, to the erythrocytic two-dimensional space scanning of infected and uninfection.

Figure 27 is according to the drawing of the photomultiplier of an embodiment (PMT) electric current to the time.

Figure 28 produces (THG) drawing to signal power according to the third harmonic of an embodiment.

Figure 29 produces (THG) drawing to the time according to the third harmonic of an embodiment.

Figure 30 is according to the drawing to source wavelength of the detected wavelength of an embodiment.

Figure 31 A is according to the monitor of an embodiment or the perspective view of treating apparatus.

Figure 31 B is according to the monitor of the use external detection (epi-detection) of an embodiment or the perspective view of treating apparatus.

Figure 32 A according to an embodiment, monitor using that third harmonic produces that (THG) detect or the perspective view of treating apparatus.

Figure 32 B is according to the monitor of the use dark field detection of an embodiment or the perspective view of treating apparatus.

Figure 33 is according to the monitor of the use dark field detection of an embodiment or the exploded view of treating apparatus.

Figure 34 A is the exploded view according to the dark ground illuminator of an embodiment.

Figure 34 B is the perspective view according to the dark ground illuminator of an embodiment.

Figure 35 is according to the monitor of the use dark field detection of an embodiment or the cross-sectional view of treating apparatus.

Figure 36 is the perspective view according to the system of an embodiment.

Figure 37 A and 37B are depicted as the flow chart according to a kind of method of an embodiment.

Figure 38 is the sketch map according to the system of an embodiment.

Describe in detail

With reference to accompanying drawing, accompanying drawing forms the part of this paper in following detailed description.In the drawings, similar sign indicates similar assembly usually, only if context is stipulated in addition.Illustrative embodiment described in detailed description, diagram and claims and being not intended to limits.Under the situation of spirit that does not break away from the theme that this paper appears or scope, can utilize other embodiment, and can make other change.

One aspect of the present invention comprises and is used for (for example detecting; Assessment, calculate, estimate, confirm, metering, identification, measurement, monitoring, quantification, parsing, sensing or similar approach) system, device and the method for the factor label that for example exists in the biological specimen (for example, in vivo or blood in vitro, bone, muscle, skin, adipose tissue, body fluid, tendon, organ, chamber or analog).Factor label can comprise indicates the for example label of the existence of infectious agent.A limiting examples comprises monitors system, device and the method that the doubtful biology that is being infected by the malaria original endoparasite is tried on one's own initiative.Limiting examples comprises and comprises details in a play not acted out on stage, but told through dialogues or Lay system, device and the method because of Burger (Rheinberg) detection technique and method.

Malaria remains one of most important infectious disease in the world.The World Health Organization makes estimation, and only about half of in the world population is lived in the area of certain risk that meets with malaria.For example, referring to " world's malaria report 2008 " (WHO: Geneva 9 (2008)) of the World Health Organization.Malaria is the insect-borne infectious disease that the protist by Plasmodium causes.In the middle of the plasmodium kind that can infect the mankind, instance comprises plasmodium falciparum, Plasmodium knowlesi, malariae, egg type plasmodium and Plasmodium vivax.The estimation of 2006 World Health Organization shows, annual 247,000,000 malaria case takes place approximately, wherein 230,000,000th, and plasmodium falciparum causes.For example, referring to " world's malaria report 2008 " (WHO: Geneva 10 (2008)) of the World Health Organization.

Primary malaria original endoparasite produces hemozoin (birefringence heme crystal) as the media of malaria in the time of in being in the red blood cell that is loaded with hemochrome.For example, (PLoS ONE 4 (12) (2009): e8446.doi:10.1371/journal.pone.0008446) may to draw people's such as (Lamikanra) article " hemozoin (malaria pigment) directly promotes the Apoptosis (Hemozoin (Malarial Pigment) Directly Promotes Apoptosis of Erythroid Precursors) of red blood cell precursor " referring to Lay rice.Hemozoin is synthetic between the degradative phase of hemochrome, and is found in the digestibility food vacuole of malaria original endoparasite in the red blood cell as the biomarker of malaria.

One aspect of the present invention comprises and comprises system, device and the method for the hemozoin nano particle being carried out the multiple-harmonic optical detection.A limiting examples comprises and comprises system, device and the method for the hemozoin nano particle being carried out the enhancement mode dark field detection.One aspect of the present invention comprises system, device, method and the composition that is used for detecting on one's own initiative and handling malaria infection.A limiting examples comprises system, device and the method that is used for the red blood cell that receives malaria infection is carried out thermal shock.A limiting examples comprises, and comprises in response to system, device and the method for carrying out paramagnetism concussion, rotation and translation to the multiple-harmonic optical detection of the existence of hemozoin and to the asymmetric nano particle of hemozoin.A limiting examples comprises and comprises system, device and the method for carrying out the ultraviolet energy generation via the hemozoin nano particle in the biological tissue.

Figure 1A is depicted as system 100, wherein can implement one or more methods or technology for example to detect or to handle malaria infection on one's own initiative.In one embodiment, system 100 especially comprises one or more monitors or treating apparatus 102.The limiting examples of monitor or treating apparatus 102 comprises hemozoin monitoring device, spectrometer, anti-malaria treatment device, malaria retinal diagnosis device, through skin diagnostic device 102a, ophthalmoscope 102b (for example, adopting nonlinear optical element, details in a play not acted out on stage, but told through dialogues or Lay to detect the ophthalmoscope of configuration, technology and method because of Burger), parasitemia detector, malaria checkout equipment 102c or similar device.

In one embodiment, system 100 especially comprises energy radiation assembly 104, and this energy radiation assembly 104 is configured to stimulate with electromagnetic energy inquires after one or more volume of focus.The limiting examples of energy radiation assembly 104 comprises electromagnetic radiation emitter, circuit, electric conductor, cavity resonator, dynamo-electric assembly, electro-optical package, laser instrument, quantum dot, laser diode, light emitting diode (for example, Organic Light Emitting Diode, polymer LED, polymer phosphorescence light emitting diode, tiny cavity light-emitting diode, efficient LED or similar diode), flashing lamp, incandescent emitter, continuous wave bulb or analog.In one embodiment, energy radiation assembly 104 comprises at least one two-photon excitation assembly.In one embodiment, energy radiation assembly 104 comprises one or more laser instruments, laser diode and light emitting diode.In one embodiment, energy radiation assembly 104 comprises one or more quantum dots, Organic Light Emitting Diode, tiny cavity light-emitting diode and polymer LED.In one embodiment, energy radiation assembly 104 comprises at least one in exciplex laser, diode pumping formula solid-state laser or the semiconductor laser.In one embodiment, energy radiation assembly 104 comprises one or more tunable ultrafast laser.In one embodiment, energy radiation assembly 104 comprises one or more femtosecond lasers.In one embodiment, energy radiation assembly 104 comprises one or more Ti: sapphire laser.In one embodiment; Energy radiation assembly 104 usefulness stimulate through the electromagnetic energy of spatial patterned (spatially-patterned) inquires after at least one volume of focus, and this electromagnetic energy stimulates and has one first district and second district that is different from this first district at least.In one embodiment; Energy radiation assembly 104 usefulness stimulate through the electromagnetic energy of spatial patterned inquires after at least one volume of focus; This electromagnetic energy stimulation has one first district and one second district at least, and at least one in the illumination intensity in this second district, energy radiation pattern, peak value radiation wavelength, pulse-on duration, pulse-off duration or the pulse frequency is different from this first district.In one embodiment, energy radiation assembly 104 usefulness stimulate through the multiplexed electromagnetic energy of the pulse of spatial patterned and inquire after at least one volume of focus.In one embodiment, energy radiation assembly 104 produces and has for example two or more peak value radiation electromagnetic energy stimulation wavelength, multiplexed.

In one embodiment, electromagnetic energy radiation assembly 104 is configured to towards biological specimen (for example, the capillary or the analog of tissue, skin below) guiding (for example, via one or more waveguides) electromagnetic radiation.Infect if this biological specimen receives the malaria original endoparasite, the hemozoin in these malaria original endoparasites will pass skin and penetrate a kind of distinctive optic response to playback so.

In one embodiment, the wavelength of the electromagnetic stimulation that is produced by energy radiation assembly 104 through adjustment can be controlled the light wavelength that manifests from hemozoin (that is, can control the wavelength of the nonlinear optical response that hemozoin manifests).In one embodiment, the one or more peak value radioactive wave progress row that radiated the electromagnetic stimulation of assembly 104 generations by energy are selected, in the wave-length coverage of infringement inhereditary material, radiated so that cause the nonlinear optical response of hemozoin.

In one embodiment, energy radiation assembly 104 is sent through the multiplexed electromagnetic energy of the pulse of spatial patterned to stimulate, and this electromagnetic energy stimulation has the peak power from about 400 m. gigawatt (GW)s to about 8 TW terawatts.In one embodiment, energy radiation assembly 104 produces through the multiplexed electromagnetic energy of the pulse of spatial patterned to stimulate, and this electromagnetic energy stimulation has the peak value irradiation level less than about 200 m. gigawatt (GW)s/cm^2.In one embodiment, energy radiation assembly 104 produces through the multiplexed electromagnetic energy of the pulse of spatial patterned to stimulate, and this electromagnetic energy stimulation has from about 1 milliwatt to about 1 watt mean power.In one embodiment, energy radiation assembly 104 produces through the multiplexed electromagnetic energy of the pulse of spatial patterned to stimulate, and this electromagnetic energy stimulates the one or more peak value radiation wavelength that have from about 690 nanometers to about 2000 nanometers.In one embodiment, energy radiation assembly 104 produces through the multiplexed electromagnetic energy of the pulse of spatial patterned to stimulate, and this electromagnetic energy stimulation has from about 300 nanometers to about 10 microns resolution ratio [0.61* (peak value radiation wavelength/numerical aperture)].The energy radiation assembly 104 that forms the part of monitor or treating apparatus 102 can be taked various ways, configuration and geometrical pattern; Comprise for example (but being not limited to) one dimension, two dimension or cubical array, comprise concentric geometry pattern, comprise rectangle, square, circle, triangle, polygon, any rule or erose pattern or analog or its arbitrary combination.In these energy radiation assemblies 104 one or more can have the peak value radiation wavelength in x ray, ultraviolet ray, visible light, infrared ray, near infrared ray, terahertz, microwave or radio spectrum.In one embodiment, energy radiation assembly 104 comprises a patterned energy radioactive source.In one embodiment, energy radiation assembly 104 comprises a patterned light emitting source.

In one embodiment, energy radiation assembly 104 usefulness stimulate through the multiplexed electromagnetic energy of the pulse of spatial patterned and side by side or sequentially inquire after a plurality of volume of focus.In one embodiment, energy radiation assembly 104 usefulness stimulate through many depths of focus electromagnetic energy of spatial patterned and side by side or sequentially inquire after a plurality of volume of focus.

In one embodiment, energy radiation assembly 104 is sent an electromagnetic energy to stimulate, and this electromagnetic energy stimulation has long and second peak value radiation wavelength that is different from this first peak value radioactive wave length of at least one first peak value radioactive wave.In one embodiment, energy radiation assembly 104 comprises at least one first energy emitter and at least one second energy emitter, and this at least one second energy emitter has the peak value radiation wavelength that is different from this at least one first energy emitter.In one embodiment; Energy radiation assembly 104 side by side or is sequentially sent one first pulse electromagnetic energy stimulation and one second pulse electromagnetic energy stimulates, and at least one in pulse duration, pulse frequency, pulse strength, pulse ratio or the pulse recurrence rate that this second pulse energy stimulates is different from this first pulse electromagnetic energy to stimulate.In one embodiment; Energy radiation assembly 104 side by side or is sequentially sent one first pulse electromagnetic energy stimulation and one second pulse electromagnetic energy stimulates, and this second pulse electromagnetic energy stimulation has the depth of focus that is different from this first pulse electromagnetic energy stimulation.In one embodiment; Energy radiation assembly 104 side by side or is sequentially sent one first pulse electromagnetic energy stimulation and one second pulse electromagnetic energy stimulates, and this second pulse electromagnetic energy stimulation has the resolution ratio that is different from this first pulse electromagnetic energy stimulation.In one embodiment, at least a portion of energy radiation assembly 104 is configured to be used for being attached to the biological surface that biology is tried with removably.

In one embodiment, energy radiation assembly 104 is configured to send the electromagnetic energy stimulation through space-focusing.

In one embodiment; Energy radiation assembly 104 comprises a lens arra; This lens arra is configured to send a plurality of isolated energy to stimulate, and these energy stimulations have at least one first district and at least one second district, and this second district has the depth of focus that is different from this first district.In one embodiment, this second district has the peak value radiation wavelength that is different from this first district.In one embodiment, this second district has the peak value irradiation level that is different from this first district.In one embodiment, at least one in the intensity in this second district, frequency, pulse strength, pulse duration, pulse ratio and the pulse recurrence rate is different from intensity, frequency, pulse strength, pulse duration, pulse ratio and the pulse recurrence rate in this first district.In one embodiment, energy radiation assembly 104 comprises one or more quadratures polarizer of (or intersection).In one embodiment, sensor cluster 440 comprises one or more quadratures polarizer of (or intersection).

In one embodiment; Energy radiation assembly 104 comprises a plurality of alternative electromagnetic energy waveguides that activate, and the multiplexed electromagnetic energy of the pulse through spatial patterned that these electromagnetic energy waveguides will be radiated stimulates the one or more districts that are directed to this at least one volume of focus.In one embodiment, energy radiation assembly 104 comprises a details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly, is delivered at least one blood vessel in order to a multimode details in a play not acted out on stage, but told through dialogues is inquired after stimulate.

Referring to Figure 1B, in one embodiment, energy radiation assembly 104 provides lighting pattern 600, and this lighting pattern 600 comprises at least one first district 202 and one second district 204.In one embodiment, the illumination intensity (I in second district 204 of lighting pattern 600 _n), energy radiation pattern, peak value radiation wavelength (λ _n), pulse-on duration (D _(ON)), pulse-off duration (D _(OFF)) or pulse frequency (v _n) at least one be different from first district 202.Energy radiation assembly 104 can be configured to the electromagnetic energy through spatial patterned is stimulated at least a portion that offers the tissue that approaches monitor or treating apparatus 102, and this electromagnetic energy stimulates the peak value radiation wavelength that has at least one or its combination that is in x ray, ultraviolet ray, visible light, infrared ray, near infrared ray, terahertz, microwave or the radio spectrum.In one embodiment, energy radiation assembly 104 provides the optical energy through spatial patterned to stimulate.In one embodiment, monitor or treating apparatus 102 especially comprise the emission source of the light of a patterning.In one embodiment, the emission source of the light of this patterning is provided to one or more districts that biology is tried with an energy stimulation through spatial patterned.

Continuation is referring to Figure 1A; In one embodiment; System 100 especially comprises circuit 108, and this circuit 108 is configured to detect (for example, assessment, calculate, estimate, confirm, metering, measurement, monitoring, quantification, parsing, sensing or similar approach), and nonlinear optical response (for example; Non-linear multiple-harmonic response, the non-linear multiple-harmonic response energy that is associated with the hemozoin nano particle that stimulates by electromagnetic energy at least one volume of focus of being inquired after, or analog).In one embodiment; Circuit comprises one or more assemblies; But these assemblies (for example are coupled to each other with mode of operation; Connect, can connect with communication mode with electromagnetic mode, magnetic means, ultrasonic power, optical mode, inductance mode, electric means, capacitive way, or similar fashion).In one embodiment, circuit comprises the assembly of one or more long range positionings.In one embodiment, but the assembly of long range positioning can connect with mode of operation via radio communication.In one embodiment, but the assembly of long range positioning can connect with mode of operation via one or more receivers, transmitter, transceiver or analog.

In one embodiment; Circuit especially comprises one or more calculation elements 402; For example processor (for example; Microprocessor) 404, CPU (CPU) 406, digital signal processor (DSP) 408, special IC (ASIC) 410, field programmable gate array (FPGA) 412 or analog or its any combination, and can comprise discrete numeral or analog circuit element or electronic component or its combination.In one embodiment, circuit especially comprises one or more field programmable gate arrays 412, and these field programmable gate arrays 412 have a plurality of programmable logic components.In one embodiment, circuit especially comprises one or more special ICs, and these special ICs have a plurality of predefined logic modules.In one embodiment, but at least one calculation element 402 is connected to one or more energy radiation assemblies 104 with mode of operation.In one embodiment, circuit comprises side by side or sequentially operates one or more calculation elements 402 of a plurality of energy radiation assemblies 104.In one embodiment; One or more calculation elements 402 are configured at least one waveform characteristic (for example, intensity, frequency, pulse strength, pulse duration, pulse ratio, pulse recurrence rate or similar characteristics) that is associated of sending of automatically control and one or more energy stimulations.For instance, the characteristic of impulse wave can stimulate the time score that in a pulse period, exists for energy.This mark is called dutycycle, and is through pulse turn-on time was calculated divided by the total time (for example, adding the turn-off time turn-on time) of a pulse period.In one embodiment, pulse generator 403 is configured to the electricity consumption submode and produces a plurality of pulse periods and non-pulse (or inertia) cycle.In one embodiment; Circuit comprises a calculation element 402; But this calculation element 402 is connected to energy radiation assembly 104 with mode of operation, and this calculation element is configured to control and at least one parameter that is associated of sending that stimulates through the multiplexed electromagnetic energy of the pulse of spatial patterned.

In one embodiment, calculation element 402 is configured to control sending system, isolatedly sending in pattern, spatial modulation, time modulation, value, space pattern configuration or the spatial distribution at least one of being associated with sending of stimulating of multiplexed electromagnetic energy through spatial patterned.In one embodiment; Calculation element 402 comprises one or more processors 404, these processors 404 be configured to control with stimulate through the multiplexed electromagnetic energy of the pulse of spatial patterned send the space illumination modulation, space illumination intensity or the space illumination that are associated send in the pattern one or more related one or more parameters.In one embodiment; Calculation element 402 comprises one or more processors 404, these processors 404 be configured to control the pulse frequency, pulse strength, pulse ratio or the pulse recurrence rate that are associated with sending of stimulating through the multiplexed electromagnetic energy of the pulse of spatial patterned related one or more parameters.In one embodiment; Calculation element 402 comprises one or more processors 404, these processors 404 be configured to control with stimulate through the multiplexed electromagnetic energy of the pulse of spatial patterned send the depth of focus that is associated distribute related one or more parameters.In one embodiment; Calculation element 402 comprises one or more processors 404, but these processors are connected to energy radiation assembly and are configured to control the spatial distribution that stimulates through the multiplexed electromagnetic energy of the pulse of spatial patterned with mode of operation.In one embodiment; System 100 comprises at least one processor 404, this processor 404 can operate so that store with in a biological tissue with at least one information that is associated in vibration, translation and the rotation of the hemozoin nano particle of magnetic means induction.In one embodiment; System 100 comprises at least one processor 404, and this processor 404 can be operated so that store with the information that relatively is associated with the reference hemozoin response message on non-linear multiple-harmonic response message and the one or more computer-readable storage mediums.

In one embodiment; Calculation element 402 comprises one or more processors 404, the control signal that these processors 404 are used for producing and following item is associated: control at least one of the dutycycle, burst frequencies and the pulse recurrence rate that are associated with the magnetic field that is applied to biological specimen on one's own initiative.In one embodiment, calculation element 402 comprises one or more processors 404, and these processors are used to produce the control signal that is associated with the ACTIVE CONTROL field orientation.In one embodiment, calculation element 402 comprises one or more processors 404, and these processors are used to produce the control signal that is associated with the ACTIVE CONTROL magnetic field intensity.In one embodiment, calculation element 402 comprises one or more processors 404, and these processors are used to produce the control signal that distributes and be associated with the ACTIVE CONTROL magnetic field space.In one embodiment, calculation element 402 comprises one or more processors 404, and these processors are used to produce the control signal that is associated with ACTIVE CONTROL magnetic field time pattern.In one embodiment, calculation element 402 comprises one or more processors 404, and these processors are used to produce the control signal that is associated with the ACTIVE CONTROL magnetic field on-time.In one embodiment, calculation element 402 comprises one or more processors 404, and these processors are used to produce the control signal that the polarization in the magnetic field that is produced with ACTIVE CONTROL is associated.

In one embodiment, but calculation element 402 be configured in response to detected non-linear multiple-harmonic Response Distribution curve and one or more magnetic field producer that activates ACTIVE CONTROL with reference to the comparison of hemozoin nonlinear response distribution curve.In one embodiment, calculation element 402 be configured in response to sensor detect with biological specimen in the non-linear multiple-harmonic Response Distribution curve that is associated of hemozoin nano particle and change in magnetic field on-time, magnetic field intensity, field frequency or the magnetic field at least one.In one embodiment, calculation element 402 be configured in response to sensor detect with biological specimen in the non-linear multiple-harmonic Response Distribution curve that is associated of hemozoin nano particle and change the magnetic field space distribution patterns.In one embodiment, calculation element 402 be configured in response to sensor detect with biological specimen in the non-linear multiple-harmonic Response Distribution curve that is associated of hemozoin nano particle and change magnetic field time pattern.

In one embodiment; Circuit especially comprises one or more memories 414 of store instruction for example or data; For example; Volatile memory (for example, random-access memory (ram) 416, dynamic random access memory (DRAM) or analog), nonvolatile memory (for example, read-only storage (ROM) 418, Electrically Erasable Read Only Memory (EEPROM), compact disk read-only storage (CD-ROM) or analog), long-time memory or analog.The other limiting examples of one or more memories 414 comprises Erasable Programmable Read Only Memory EPROM (EPROM), flash memory or analog.These one or more memories 414 can be connected to for example one or more calculation elements 402 through one or more instruction bus, data/address bus or power bus.

In one embodiment, circuit especially comprises one or more databases 422.In one embodiment, database 422 comprises with reference to hemozoin spectral response information, with reference in hemozoin nonlinear optical response information, the parameter of confirming with the exploration mode that is associated with at least one measuring of in vivo or in vitro confirming at least one.In one embodiment, database 422 comprises at least one in absorption coefficient data, extinction coefficient data, scattering coefficient data or type likelihood data.In one embodiment, database 422 comprises reference data that infectious agent marker data for example etc. stored or in type likelihood data at least one.In one embodiment, database 422 comprises references object information.In one embodiment, database 422 comprises the red blood cell plot information, receives the red blood cell plot information of malaria infection or in the hemozoin plot information at least one.

In one embodiment, database 422 comprises the information that the morbid state that tried with a biology is associated.In one embodiment, database 422 comprises measurement data.In one embodiment; Database 422 comprises cryptography scheme information, regulatory compliance scheme information (for example, FDA regulatory compliance scheme information or similar information), regulations operational version information, proof scheme information, mandated program information, sends the system scheme information, activates at least one in scheme information, encipherment scheme information, decrypt scheme information, processing scheme information or the similar information.In one embodiment, database 422 comprises at least one in electromagnetic energy stimulation control delivery information, the control information of electromagnetic energy emitter, power control information or the similar information.

In one embodiment, system 100 be configured to at least one characteristic of being tried to be associated with a biology the database 422 of a related input and institute's stored reference value compare, and be based in part on this comparison and produce response.In one embodiment, system 100 be configured to at least one characteristic that is associated with the existence of hemozoin the database 422 of a related input and institute's stored reference value compare, and be based in part on this comparison and produce response.

In one embodiment, system 100 especially comprises circuit 108, and this circuit 108 is configured to detect through stimulating with electromagnetic energy inquires after the non-linear multiple-harmonic spectral response that a doubtful biological specimen with hemozoin obtains.

The behavior of electric field, magnetic field, charge density and current density can for example be described through Maxwell equation.For example, referring to Sa Lihe people's such as (Saleh) the 152nd to 170 page of works " photonic propulsion basic principle (Fundamentals of Photonics) " (second edition, 2007).Nonlinear optical phenomena especially comprises those interactions of electromagnetic radiation and material; Wherein the response of material (for example; Polarization, power absorption or similar effect) not with the variable of describing electromagnetic radiation (for example; Irradiation level, electric-field intensity, can stream, fundamental wavelength, fundamental frequency or like variable) proportional linearly (that is, the amount of response not bi-directional scaling) linearly.In one embodiment, energy radiation assembly 104 is delivered to one or more doubtful volume of focus that contain hemozoin with the electromagnetic energy stimulation.Characteristic and the duration of depending on electromagnetic energy, the interaction of the hemozoin in electromagnetic stimulation and the one or more volume of focus causes producing nonlinear optical response, and this radiation through for example scattering detects.

Nonlinear optical phenomena especially comprises second harmonic and produces (the double frequency with the fundamental wavelength that is radiated by electromagnetic energy source; The generation of the light of 1/2nd wavelength); Third harmonic produces (has the treble frequency by the fundamental wavelength of electromagnetic energy source radiation; The generation of the light of 1/3rd wavelength); The 4th harmonic wave produces; Difference frequency produces; Higher harmonics produces; Optical parametric amplifies; Optical parametric produces; The optical parametric vibration; Optical rectification; Autonomous parameter is changed downwards; Summation frequency produces or similar phenomenon.The other limiting examples of nonlinear optical phenomena comprises Brillouin (Brillouin) scattering, multiphoton ionization, optics Ke Er (Kerr) effect, two-photon absorption or similar phenomenon.

The interactional polarization density relationship of describing electromagnetic radiation and material can be similar to through the summation of following linear segment and non-linear partial (to fully weak field; Suppose and do not have permanent dipole moment) (for example; Referring to people's such as Sa Lihe works " photonic propulsion basic principle (Fundamentals of Photonics) " the 873rd to 935 page (second edition, 2007)):

$P_i\left(E\right)=({\mathrm{\ϵ}}_0{\mathrm{\χ}}_{\mathrm{Ij}}^{\left(1\right)}{E}_j+2{\mathrm{\χ}}_{\mathrm{Ijk}}^{\left(2\right)}{E}_j{E}_k+{4\mathrm{\χ}}_{\mathrm{Ijkl}}^{\left(3\right)}{E}_j{E}_k{E}_l...).$ (equation 1)

Wherein,

describes linear single order optical phenomena, comprises to absorb and refraction;

describes the second nonlinear phenomenon; Comprise electric light rectification, Pockels (Pockels) electrooptic effect and second harmonic and produce (for example, doubling frequency); And

describes the third-order non-linear phenomenon; Comprise optical rectification, the mixing of four ripples, the refractive index that depends on intensity, secondary Kerr effect, self-focusing and third harmonic generation (for example, frequency becomes three times) that electric field causes.

In one embodiment, the circuit 108 that is configured to detect non-linear multiple-harmonic response energy comprises a sensor cluster 440, and this sensor cluster comprises one or more sensors 442.In one embodiment; Sensor cluster 440 is configured to detect and the non-linear multiple-harmonic Response Distribution curve that is stimulated a plurality of hemozoin nano particles of inquiring after to be associated by electromagnetic energy, and is configured to detected non-linear multiple-harmonic Response Distribution curve and one or more is compared with reference to hemozoin nonlinear response distribution curve.In one embodiment, comprise with at least one in vivo or is in vitro confirmed with reference to hemozoin Response Distribution curve and measure the one or more parameters of confirming with the exploration mode that are associated.In one embodiment, these one or more parameters of confirming with the exploration mode comprise at least one in threshold level or the target component.In one embodiment, these one or more parameters of confirming with the exploration mode comprise threshold information.

In one embodiment; Sensor cluster 440 comprises an optical energy sensor cluster, and this optical energy sensor cluster is configured to detect and exists under the situation in magnetic field from inquired after the optical energy of a plurality of hemozoin nano particle scattering that stimulation inquires after by the multimode details in a play not acted out on stage, but told through dialogues.

In one embodiment; Sensor cluster 440 comprises an electromagnetic energy sensor cluster, and this electromagnetic energy sensor cluster is configured to dispose via dark field detection and detects the response energy that under the situation that exists first electromagnetic energy to stimulate, is associated with the hemozoin nano particle of being inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation.In one embodiment, system 100 especially comprises circuit 110, and this circuit is configured to produce the multimode details in a play not acted out on stage, but told through dialogues and inquires after and stimulate or the multimode Lay is inquired after in the stimulation at least one because of Burger.

In fact, dark field detection configuration comprises an optical axis blocking-up center electromagnetic energy ray (for example, through darkground stop or opaque article) on the objective lens component 114, and these rays normally pass and around a sample.Stop that center electromagnetic energy ray makes to have only those to arrive detector with the oblique ray that rises than wide-angle (that is, only by the light of the biological specimen scattering in the volume of focus).In one embodiment; The dark field detection configuration comprises the compound microscope sub-assembly; This compound microscope sub-assembly comprises a concentrator systems; This concentrator systems makes the electromagnetic energy ray that on all azimuths, manifests from a focal zone can form the hollow illumination cone of a reversing, and the summit of this cone is positioned at the center of sample plane.The dark-ground illumination detection technique can be further through adding polarizer (for example, polarizer of quadrature (or intersection) or the like) to luminaire and detector comes enhancing contrast ratio and selectivity.Cross polarization is limited to the scattering events that makes illumination eliminate polarization with detection, thereby has significantly reduced false positive signal and the undesired signal from health tissues.This in vivo with in vitro imaging and spectroscope detection system, device and method all be relevant.

In one embodiment; Sensor cluster 440 comprises an electromagnetic energy sensor cluster, and this electromagnetic energy sensor cluster is configured to detect the response energy that under the situation that exists first electromagnetic energy to stimulate, is associated with the hemozoin nano particle of being inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation via Lay because of Burger detects configuration.In fact, Lay is similar to the dark field detection configuration because of Burger detects configuration, but is not to use darkground stop, opaque article or the like along an optical axis; Lay comprises a Lay with at least two kinds of different colours because of the Burger filter because of Burger detects configuration.In one embodiment, the darkground stop central area at place usually is a kind of color (for example, green), and external rings (endless belt) is a kind of contrast color (for example a, redness).The light of unmodified (not being radiated at the light on the sample) is filled background with the even light of color with center circle, and modified light (be radiated on the sample and through the light of refraction, scattering or the like) will have the color of outside endless belt.

In one embodiment, this electromagnetic energy sensor cluster comprises at least one Lay because of the Burger filter.In one embodiment, this electromagnetic energy sensor cluster is configured to detect the scattared energy that is associated with the hemozoin nano particle of being inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation under the situation that first electromagnetic energy stimulates or second electromagnetic energy stimulates existing.In one embodiment, this electromagnetic energy sensor cluster comprises at least one spectrometer.In one embodiment, this electromagnetic energy sensor cluster is configured to detect the spectral response that is associated with the hemozoin nano particle of being inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation under the situation that first electromagnetic energy stimulates or second electromagnetic energy stimulates existing.

In one embodiment, this electromagnetic energy sensor cluster is configured to detect the scattared energy that is associated with the hemozoin nano particle of being inquired after by multimode details in a play not acted out on stage, but told through dialogues stimulation under the situation that first electromagnetic energy stimulates or second electromagnetic energy stimulates existing.

In one embodiment; System 100 especially comprises a sensor cluster 440; This sensor cluster comprises at least one sensor 442, this sensor be configured to detect with at least one volume of focus that stimulates a biological tissue of being inquired after by electromagnetic energy in the non-linear multiple-harmonic response energy that is associated of hemozoin nano particle.In one embodiment; System 100 especially comprises a calculation element 402; But this calculation element radiates assembly 104 with at least one sensor and this energy that mode of operation is connected to sensor cluster 440, and this calculation element 402 is configured to a control signal is provided to an energy radiation assembly.

In one embodiment; System 100 especially comprises an energy radiation assembly 104; The electromagnetic energy stimulation that this energy radiation assembly 104 is configured to send an effective dose is to extract the nonlinear optical response of a plurality of hemozoin nano particles in biological tissue, and characteristic that this nonlinear response of drawing has and duration are enough to regulate the biologically active of the malaria infectious agent in this biological tissue.In one embodiment, this nonlinear response of drawing comprises the one or more peak value radiation wavelength from about 175 nanometers to about 650 nanometers.In one embodiment, this nonlinear response of drawing comprises the one or more peak value radiation wavelength from about 250 nanometers to about 270 nanometers.In one embodiment, this nonlinear response of drawing comprises the peak value radiation wavelength with about 260 nanometers.

In one embodiment, this nonlinear response of the drawing characteristic and the duration that have are enough to cause an apoptosis that comprises the malaria original endoparasite of hemozoin nano particle.Many eukaryotics comprise some unicellular organisms, are experiencing the apoptosis of one or more forms.Apoptosis can through stimulate (for example, pair cell can not the infringement of reparation property, infection, hunger, be exposed to ionising radiation, heat or toxic chemical) or cause through removing repressor.The initial orders cell death possibly represented the favourable adaptation of carrying out through organism in response to particular stimulation, and can in organic life cycle, bring advantage.Under the situation of for example malaria original endoparasite; The apoptosis of one of parasite colony son group can be the means that are used to prevent the early stage death of infected host; Thereby for parasite provide time enough to develop and be delivered to another carrier or the host (for example; Referring to the works that is attached to Pang Te and Bake (Deponte&Becker) among this paper by reference " parasitology trend (Trends Parasitol.) 20:165-169,2004) ".By contrast, downright bad (necrosis) is defined as the not controlled cell death that extreme physics or chemical damage because of pair cell bring.Downright bad can and be exposed to high toxicity reagent because of cell lysis, the high temperature of mechanical damage, anoxic, complement-mediated and cause.The reaction that in the host, causes inflammation of downright bad more possibility owing to the catastrophic failure of pair cell.

Various types of apoptosis have been described, comprise (but being not limited to) Apoptosis, autophagy, expand die, dependence born of the same parents are dissolved and type transfer and to die.Features of apoptosis is a series of biochemical events that cause the change of cellular morphology and finally cause cell death.The change that the characteristic of the cellular morphology that is associated with Apoptosis changes the formation that comprises (but being not limited to) nuclear foaming and segmentation, apoptotic bodies, cell membrane (for example; Membrane asymmetry and the loss of adhering to), cellular contraction and change circle, the change of cytoplasm density, nucleus segmentation, chromatin concentrate, chromosomal DNA segmentation, oxidation stress, protein (for example, cytochrome c) from mitochondria be discharged into the cytosol, protein is by the activity of division of protease (especially Pepsin) selectivity and protease self.By contrast, autophagy is a catabolic process, relates to the degraded that the component of cell self is carried out through the lysozyme means, is characterised in that the formation of big vacuole, and these vacuoles digested organelle with particular order before nucleus destroys.Expanding dies is to causing depleted of energy, organelle to expand and the response of the conditioned of the serious DNA infringement that cell membrane destroys.It is the dead approach of short inflammatory cell that is caused by bacterium in the cell in the phagocyte that dependence born of the same parents are dissolved, and is different from apoptotic anti-inflammatory approach.The class apoptosis is similar to necrosis on morphology, wherein form cytoplasm vacuole and mitochondria and expand, but need new RNA and protein to synthesize, and this is consistent with procedural biochemical event.For example, referring to the Duranty, Walter and the works " bioinformatics and biological study (Bioinform.Biol.Insights) 2:101-117,2008 " of Ke Zeer (Durand&Coetzer) that are attached to by reference among this paper.

Being similar to apoptotic apoptosis observes in the malaria original endoparasite.For instance; Bai Shi is plasmodial to show the multiple mark that is similar to apoptotic apoptosis through the ookinete of cultivating; The loss, nuclear chromatin that comprises mitochondrial membrane potential concentrates, DNA segmentation, phosphatidylserine to the outer surface displacement of cell membrane and the activity that is similar to Pepsin (for example; Referring to the works " parasite and host (Parasit.Vectors) (2:32,2009) " that is attached to I the nurse crust people such as (Arambage) among this paper by reference.Though the genome of malaria original endoparasite seems the homologue that lacks mammalian protease enzyme; But other protease that comprises first Pepsin and calpain possibly be used for as cause the malaria original endoparasite apoptosis media (for example; Referring to the works that is attached to the Wu people such as (Wu) among this paper by reference " genome research (Genome Res.) (13:601-616; 2003) ", look into spy people's such as (Chat) works " molecule biochemical parasitology (Mol.Biochem.Parasitol) (153:41-47,2007) ").

The apoptosis that is similar to autophagy is observed in plasmodium.For instance; Processing with blood level plasmodium falciparum of S-nitroso-N-acetyl group penicillamine (SNAP), staurosporin and chloroquine has suppressed parasitemia; And cause have the cellular component vacuolization the form that is similar to autophagy (for example; Referring to the works " experimental parasitology (Exp.Parasitol) (118:478-486,2008) " that is attached to the Tuo Dinuo people such as (Totino) among this paper by reference).

Apoptosis can cause through thermal shock or rapid being exposed to than the high temperature of organic normal physiological scope.Hyperthermia therapy between 40 ° of C and the 60 ° of C can cause unordered cell metabolism and film function, and causes cell death in many cases.In general, under the temperature that is lower than 60 ° of C, hyperthermia more maybe the initiator cell death and can not cause necrosis substantially.Under the temperature that is higher than about 60 ° of C, the downright bad possibility of condensing of trigger cell and tissue increases.The less relatively temperature that is higher than the normal function temperature of cell increases (for example, 3 ° of C) and can cause apoptosis.For instance, from the temperature of 40 ° of C to 47 ° of C can usually the cell of 37 ° of C performance functions with the reproducible mode trigger cell death that depends on time and temperature.The temperature of mammalian cell for example is elevated to 43 ° of C can causes the change that cell protein expresses and the increase of apoptosis.For example; Referring to Suo Muwolu people's such as (Somwaru) works " andrology periodical (J.Androl.) (25:506-513; 2004) ", Stankovic people's such as (Stankiewicz) works " biochemistry periodical (J.Biol.Chem.) (280:38729-38739; 2005) ", the works " cell science periodical (J.Cell Sci.) (111:2305-2313; 1998) " that rope adds people such as (Soaja), Si Teluokeluomo people's such as (Setroikromo) works " cellular stress and chaperone (Cell Stress Chaperones) (12:320-330; 2007) ", Dubinsky people's such as (Dubinsky) works " AJR (190:191-199; 2008) ", works " international thermotherapy periodical (the Int.J.Hyperthermia) (19:252-266 of lining slope gram (Lepock); 2003) ", the works of Luo Diluodi (Roti Roti) " international thermotherapy periodical (Int.J.Hyperthermia) 24:3-15; 2008 ", Fuchs people such as (Fuchs) " is using laser medicine (Applied Laser Medicine) (Han Si-Peter Berlin (Hans-Peter Berlien) editor; Jie Hade J Muller (Gerhard J.Muller), and Co., Ltd of New York Springer Verlag publishing house (Springer-Verlag New York, LLC); 2003 " works in the 187-198 page or leaf " status (The Laser's Position in Medicine) of laser in medical science ", above document all is attached among this paper by reference.

The malaria original endoparasite also suffers apoptosis in response to the hyperthermia therapy easily.For instance; The list of the plasmodium falciparum of being established exsomatizes and exsomatizes and can't under the cultivation temperature of 40 ° of C, grow from the wild list that malaria patients obtain; Wherein schizont represents chromatin concentrated (pyknosis) and Hyposegmentation (referring to the works that is attached to the section's watt Butterworth base (Kwiatkowski) among this paper by reference " experimental medicine periodical (J.Exp.Med.) (169:357-361,1989) ".Propose, at high temperature the remarkable inhibition to the plasmodium falciparum growth is the back half the destruction owing to asexual red blood cell circulation, and the schizont that is wherein developing stands thermal shock especially easily.Under 40 ° of C, the processing of red blood cell level plasmodium falciparum (is for example also seemed the cytoplasm vacuolization that causes parasitic food vacuole and destruction; Works " parasitology periodical (J.Parasitol.) (94:473-480,2008) " referring to baud people such as (Porter).The temperature that plasmodium falciparum is exposed to 41 ° of C is lasted to reach two minutes less and can cause when after 48 hours, measuring and (is for example reduced 20%, 70% and 100% respectively relatively at the interim parasite number of ring stage, trophozoite phase and schizont; Referring to the works " FEBS (312:91-94,1992) " that is attached to the assorted approximately people such as (Joshi) among this paper by reference).Under 41 ° of C, the heating of red blood cell level plasmodium falciparum being lasted 2,8 and 16 hours makes parasitic survival reduce by 23%, 66% and 100% (referring to the works " infection immunity (Infection Immunity) (75:2012-2025,2007) " that is attached to the Ou Kelei people such as (Oakley) among this paper by reference) respectively.Survival under these thermal shock conditions reduce the appearance that also is attended by parasitic " crisis form " and positive original position end deoxyribonucleic acid transferase mediated dUTP nick end labeling breach end-labelling (TUNEL) movable with increase time correlation, this is the sign of apoptosis.The response of thermal shock also is attended by the change of plasmodium gene and protein expression, and this shows that being exposed to high temperature (for example, 41 ° of C) has caused the organized number of the delivering a letter approach that when promoting apoptosis, relates to and be used as the response to high temperature.For instance, mRNA and the protein corresponding to plasmodium falciparum thermal shock protein 70 (PfHSP-70) raises 7.42 times and 3.7 times respectively in response to the thermal shock of 41 ° of C.Many other parasite protein matter are in response to hyperthermia and regulate up or down; Comprise other stress protein matter, DNA reparation/replication protein, histone, RNA and handle protein, secretion and transport protein matter and various serine/threonine protein matter kinases (referring to the works that is attached to the people such as Ou Kelei among this paper by reference " infection immunity (75:2012-2025,2007) ").

In some instances, the apoptosis in the plasmodium can cause through being exposed to one or more medicines.For instance, the anti-malaria medicaments chloroquine concentrates in plasmodium food vacuole, at this place's chloroquine the hemozoin molecule is carried out end-blocking to prevent the further biological crystallization of heme, and this crystallization meeting causes the accumulation of the heme in the parasite.With the chloroquine of heme complexing be highly toxic for the malaria original endoparasite, and destroy the film function, thereby cause the cell bacteriolyze and finally cause parasite cell autodigestion.For example, referring to the works " science (Science) (214:667-669,1981) " that is attached to the Ao Ji people such as (Orjih) among this paper by reference.In another example; Can detected infected erythrocytic decreased number 2 to 3 times with the atropic quinoline to the processing of red blood cell level plasmodium falciparum; Wherein be attended by the loss of parasite mitochondrial membrane potential; This is the sign (referring to the works " infected by microbes (Microbes Infect.) (8:1560-1568,2006) " that is attached to the Nai Jieluge people such as (Nyajeruga) among this paper by reference) of apoptosis.With parasite form " crisis form " and the dna degradation of S-nitroso-N-acetyl group penicillamine (SNAP) to the processing exception throw of red blood cell level plasmodium falciparum, this also is the sign of apoptosis.Suppress growth of malaria parasites and cause the change that plasmodium death possibly be attended by malaria original endoparasite proteosome through various anti-malaria medicaments.For instance; The incremental adjustments of the processing of plasmodium falciparum being brought 41 and 38 parasite protein matter respectively with qinghaosu and chloroquine (for example; Referring to the works " PLoS ONE, (3:e4098,2008) " that is attached to the Puli's holder people such as (Prieto) among this paper by reference).In one embodiment, the system of describing among this paper, device or method can sequentially or side by side be used with anti-malaria medicaments, for example to cause the apoptosis in the plasmodium falciparum.

In one embodiment; The characteristic of the nonlinear response of being drawn and duration be enough to cause with the apoptosis of cell, host cell, malaria infectious agent or analog (for example; Apoptosis, be the cell death or the analogue of media with the cell internal program) the initiation cell stress, the eucaryotic cell structure that are associated change the activation or the analogue of (for example, chromatin concentrates, cellular contraction, DNA segmentation or the like), Pepsin gene.

The characteristic of the nonlinear response of being drawn in one embodiment, and duration are enough to produce antimicrobial energy.In one embodiment, the non-linear harmonic wave of the ultraviolet radiation brought of the hemozoin in biological tissue (for example, in vivo hemozoin) produces and can be used for antimicrobial energy radiation plasmodium.The electromagnetic energy of incident stimulate can be focus on and pulsed so that intensity is increased to be enough to the level that realizes that effective harmonic wave produces.In one embodiment, duty ratio of time can be in enough low level, makes the linear energy deposition of incident light can not damage other tissue.Processing can be in vivo (for example, through skin, intraocular, through optical fiber or the like) or in vitro the blood flow of external device (ED) (for example, through) take place.In one embodiment, electromagnetic energy stimulates the light that comprises narrow bandwidth, produces efficient in order to increase spectral luminance factor and therefore to increase harmonic wave.In one embodiment, send electromagnetic energy to increase total output via a plurality of pulses.In one embodiment, use the superimposed pulses of phase matched to make up a plurality of beam/pulses in target site.

In one embodiment, characteristic that the nonlinear response of being drawn has and duration are enough to produce a sterilization energy to stimulate, and this sterilization energy stimulates the one or more peak value radiation wavelength that have in ultraviolet ray range.Characteristic that the nonlinear response of being drawn in one embodiment, has and duration are enough to cause the apoptosis of the host cell that is loaded with the malaria infectious agent.

In one embodiment, comprise one or more electromagnetic sensors 442 in order to the circuit 108 that detects non-linear multiple-harmonic response energy.The limiting examples of electromagnetic sensor 442 comprises the calutron that the electromagnetic energy that receives or absorb is had detectable response.Electromagnetic sensor (for example can comprise antenna; Lead/loop antenna, horn antenna, reflector antenna, chip aerial, phased-array antenna or similar antenna), solid-state photo detector (for example; Photodiode, charge coupled device and photo-resistor), the vacuum photoelectric detector (for example; Photoelectric tube and photoelectric multiplier), the chemical light photodetector (for example; Photographic emulsion), low temperature photoelectric detector (for example, bolometer), luminescence generated by light detector (for example, phosphor powder or fluorescent dye/label), MEMS (MEMS) detector are (for example; Micro-cantilever array with electromagnetic response material or element), maybe can operate to detect and/or any other device of conversion electromagnetic energy.

In one embodiment, comprise one or more sensors 442 in order to the circuit 108 that detects non-linear multiple-harmonic response energy, in order to detect the nonlinear response distribution curve that stimulates one or more hemozoin nano particles of inquiring after by electromagnetic energy.The limiting examples of sensor 442 comprises electric charge coupling arrangement, cmos device, photodiode image sensor apparatus or Whispering-gallery-mode microcavity device.

In one embodiment, comprise in time integral optical module, linear session integration assembly, nonlinear optical component or the time auto-correlation assembly at least one in order to the circuit 108 that detects non-linear multiple-harmonic response energy.In one embodiment, comprise one or more one dimensions, two dimension or three-dimensional photodiode array in order to the circuit 108 that detects non-linear multiple-harmonic response energy.In one embodiment, comprise one or more sensors 442, be used to detect the nonlinear response distribution curve of the one or more hemozoin nano particles at least one volume of focus in order to the circuit 108 that detects non-linear multiple-harmonic response energy.In one embodiment, comprise at least one charge coupled device, be used to detect the nonlinear response distribution curve of a plurality of hemozoin nano particles at least one volume of focus in order to the circuit 108 that detects non-linear multiple-harmonic response energy.In one embodiment; Circuit 108 in order to detect non-linear multiple-harmonic response energy comprises at least one spectrometer, and this spectrometer is configured to detect the non-linear spectral Response Distribution curve of a plurality of hemozoin nano particles at least one volume of focus.In one embodiment; Circuit 108 in order to detect non-linear multiple-harmonic response energy comprises at least one ultraviolet ray-visible light (UV-VIS) PDAD, is used to detect the nonlinear response distribution curve of a plurality of hemozoin nano particles at least one volume of focus.In one embodiment; Circuit 108 in order to detect non-linear multiple-harmonic response energy comprises at least one high sensitivity ultraviolet ray-visible light (UV-VIS) PDAD, is used to detect the nonlinear response distribution curve of a plurality of hemozoin nano particles at least one volume of focus.In one embodiment, comprise in order to the circuit 108 that detects non-linear multiple-harmonic response energy and be configured to detect circuit with the multiple-harmonic photo response (nonlinear optical response that for example, electromagnetic energy is stimulated) of radiating through the skin mode.

In one embodiment; Comprising in order to the circuit 108 that detects non-linear multiple-harmonic response energy can be at the wavelength of a correspondence polynary group (multiplet) or one polynary group sensor 442 of wavelength band place operation; That is, can be at the first sensor of first wavelength/wavelength band place operation, second sensor that can operate at second wavelength/wavelength band place or the like.In one embodiment, the focal plane arrays (FPA) (for example, Baeyer (Bayer) or Foveon sensor) that comprises polynary group of sensor 442 or sensor in order to the circuit 108 that detects non-linear multiple-harmonic response energy.

In one embodiment; Circuit 108 in order to detect non-linear multiple-harmonic response energy comprises a sensor cluster 440, in order to detect with a plurality of volume of focus of inquiring after by the stimulation of pulse electromagnetic energy in a biological tissue in the non-linear multiple-harmonic Response Distribution curve that is associated of a plurality of hemozoin nano particles.In one embodiment; Circuit 108 in order to detect non-linear multiple-harmonic response energy comprises at least one sensor 442; Be used for detecting with the second harmonic response, third harmonic response or the 4th harmonic response that stimulate (for example, the pulse electromagnetic energy stimulates, stimulates, stimulates, stimulates, stimulates or analog through the electromagnetic energy of time patterning through the multiplexed electromagnetic energy of the pulse of spatial patterned through multiplexed electromagnetic energy through the electromagnetic energy of spatial patterned) to draw by electromagnetic energy at least one non-linear multiple-harmonic response energy that is associated.

In one embodiment; Circuit 108 in order to detect non-linear multiple-harmonic response energy comprises an optical package 112 and at least one sensor 442, is used for collecting and detecting by stimulate at least one of second harmonic response, third harmonic response or the 4th harmonic response of drawing through the multiplexed electromagnetic energy of the pulse of spatial patterned via collected outside (epi-collection) pattern.Optical package 112 can be taked multiple shape and configuration.In one embodiment; Optical package 112 (for example comprises one or more lens, optical element; Optical splitter and lens), diffraction element (for example; Fresnel (Fresnel) lens), filter, polarizer or analog, in order to guiding from the electromagnetic radiation of a source (for example, energy radiation assembly 104, nonlinear optical response or analog) and being shaped.In one embodiment, dark-ground illumination detection technique can further add luminaire to through the polarizer with quadrature (or intersection) and detector comes enhancing contrast ratio and selectivity.Cross polarization is limited to the scattering events that makes illumination eliminate polarization with detection, thereby has significantly reduced false positive signal and the undesired signal from health tissues.This in vivo with in vitro imaging and spectroscope detection system, device and method all be relevant.

The limiting examples of lens comprises cylindrical graded index (GRIN) lens, doublet lens or triple lens; These lens are to collecting from the electromagnetic radiation of a source (for example, energy radiation assembly 104, nonlinear optical response or analog) and being shaped.Comprise at electromagnetic radiation source under the situation of a plurality of optical fiber that one or more lens are presented, these lens randomly join these optical fiber to or are integral formula with these optical fiber.

In one embodiment, optical package 112 comprises one or more in polarization sensitive material, chromatic aberration correction or other optical technology, with shape, phase place, polarization or other characteristic that is used to control electromagnetic radiation.In one embodiment, optical package 112 comprises one or more polarizers, colour filter, emergent pupil expander, chromatic aberration correcting element, eye tracer element and background shade, and these elements can be incorporated into wherein to application-specific in due course.In one embodiment, optical package 112 comprises at least one Lay because of the Burger filter.In one embodiment, optical package 112 comprises an objective lens component 114, and this objective lens component has the numerical aperture of from about 0.5 to about 1.4 alternative control.In one embodiment; The circuit 108 that is configured to detect non-linear multiple-harmonic response energy comprises a calculation element 402, is used for controlling on one's own initiative the numerical aperture of the objective lens component 114 of the numerical aperture with alternative control of from about 0.5 to about 1.4.In one embodiment, system 100 comprises the objective lens component 114 with numerical aperture of from about 0.5 to about 1.4.

In one embodiment, optical package 112 is collected configuration with details in a play not acted out on stage, but told through dialogues and is received the part through the radiation of scattering.In one embodiment, optical package 112 is collected configuration with Lay because of Burger and is received the part through the radiation of scattering.In one embodiment, optical package 112 disposes a part that receives through the radiation of scattering with collected outside.In one embodiment, comprise in order to the circuit 108 that detects non-linear multiple-harmonic response energy and be configured to detect in position and the circuit that responds energy by the non-linear multiple-harmonic that stimulates a plurality of hemozoin nano particles at least one volume of focus of inquiring after to be associated through the multiplexed electromagnetic energy of the pulse of spatial patterned.

In one embodiment, system 100 especially comprises circuit 116, and this circuit 116 compares in order to information that will be associated with detected non-linear multiple-harmonic response message and the reference information that is configured as data structure 424.In one embodiment, system 100 especially comprises circuit 116, and this circuit is configured to information that is associated with detected non-linear multiple-harmonic response message and the reference hemozoin response message that is configured as data structure 424 are compared.In one embodiment, data structure 424 comprises one or more explorations (heuristics).In one embodiment, these one or more explorations comprise one be used for confirming at least one physical parameter of being associated with a kind of biofluid the exploration of related rate of change.In one embodiment, these one or more explorations comprise an exploration that is used for the existence of definite hemozoin nano particle.In one embodiment, these one or more explorations comprise an exploration that is used for the existence of definite infectious agent.In one embodiment, these one or more explorations comprise an exploration that is used at least one dimension in a definite infected tissue district.In one embodiment, these one or more explorations comprise an exploration that is used for definite position of infecting.In one embodiment, these one or more explorations comprise an exploration that is used for definite rate of change that is associated with an interior biochemical marker of these one or more volume of focus.

In one embodiment, these one or more explorations comprise an exploration that is used for confirming biochemical marker aggregation rate (for example, hemozoin aggregation rate, hemozoin polymer aggregational speed or similar aggregation rate).In one embodiment, these one or more explorations comprise an exploration that is used for the type of definite biochemical marker.In one embodiment, these one or more explorations comprise at least one a exploration that is used for producing the red blood cell plot information, receives red blood cell plot information or the hemozoin plot information of malaria infection.

In one embodiment, these one or more explorations comprise an exploration that is used to produce at least one initial parameter.In one embodiment, these one or more explorations comprise an exploration that is used for forming from one or more initial parameters an initial parameter set.In one embodiment, these one or more explorations comprise an exploration that is used to produce at least one initial parameter and forms an initial parameter set from this at least one initial parameter.In one embodiment, these one or more explorations comprise at least one pattern classification and recurrence scheme.

In one embodiment, at least one data structure 424 comprise at least one parameter of being associated with hemozoin nonlinear optical phenomena spectral information related information.For instance; In one embodiment, data structure 424 comprise with hemozoin second harmonic response spectrum information, hemozoin third harmonic response spectrum information or hemozoin the 4th harmonic response spectral information at least one at least one parameter that is associated related information.In one embodiment, data structure 424 comprises references object information.In one embodiment, data structure 424 comprises the red blood cell plot information, receives the red blood cell plot information of malaria infection or in the hemozoin plot information at least one.

In one embodiment; System 100 especially comprises one or more computer-readable media driver 426, interface socket, USB (USB) port, memory cards slot or analog; And one or more I/O assemblies 428; For example graphical user interface 430, display, keyboard 432, keypad, trace ball, control stick, touch-screen, mouse, switch, dial or analog, and any other peripheral unit.In one embodiment; System 100 comprises one or more user's I/O assemblies 428; But these user's I/O assemblies with mode of operation be connected at least one calculation element 402 with control (electricity, dynamo-electric, software is implemented, firmware is implemented or other control, or its combination) with this one or more energy radiate energy that assemblies 104 are associated send related at least one parameter.In one embodiment, system 100 especially comprises one or more modules, and these modules randomly can be operated being used for and communicated by letter with the one or more I/O assemblies 428 that are configured to trunk subscriber output and/or input.In one embodiment, a module comprises electricity, dynamo-electric, that software is implemented, firmware one or more instances that implement or other control device.This device comprises the one or more instances with lower device: memory 414, calculation element 402, port, valve 132, antenna, power supply or other supply; Logic module or other signalling module; Scale or other this type of active or passive detection assembly; Or PZT (piezoelectric transducer), shape memory member, MEMS (MEMS) element or other actuator.

Computer-readable media driver 426 or memory bank can be configured to acknowledge(ment) signal carrying media (for example, computer-readable storage medium, computer-readable recording medium or analog).The program of any one of the method that in one embodiment, is used for making system 100 to carry out being disclosed can be stored in for example computer-readable recording medium (CRMM) 434, signal bearing media or analog.The limiting examples of signal bearing media comprises recordable-type media; For example tape, floppy disc, hard disk drive, compact disk (CD), digital video disk (DVD), Blu-ray Disc, digital magnetic tape, computer storage or analog; And transmission type media; For example numeral and/or analogue communication medium are (for example; Fiber optic cables, waveguide, wire communication link, wireless communication link (for example, transmitter, receiver, transceiver, TL, RL or the like) or the like).The other limiting examples of signal bearing media comprises (but being not limited to) DVD-ROM; DVD-RAM; DVD+RW; DVD-RW; DVD-R; DVD+R; CD-ROM; Super-audio CD; CD-R; CD+R; CD+RW; CD-RW; Video compact disc; Super video compact disc; Flash memory; Tape; Magneto-optic disk; Minidisk (MINIDISC); Non-volatile memory card; EEPROM; CD; Optical storage; RAM; ROM; System storage; The webserver or analog.

In one embodiment; System 100 comprises and (for example is one or more logic devices; Programmable logic device, compound programmable logic device, field programmable gate array, special IC or analog) the signal bearing media of form, these logic devices comprise the data structure 424 that for example comprises one or more look-up tables.In one embodiment, system 100 especially comprises the signal bearing media of the reference hemozoin nonlinear response information with data structure of being configured to 424.In one embodiment, data structure 424 comprises at least one in malaria infection indication information, hemozoin spectral information, hemozoin spectral response information, morbid state indication information or the diseased tissue indication information.

System 100 can especially comprise one or more receiver 1206, transceiver 1208, transmitter 1210 or analog.In one embodiment, at least one in this one or more receiver 1206, transceiver 1208 or the transmitter 1210 is connected to a calculation element 402 with wireless mode, and this calculation element 402 is communicated by letter with the control module of system 100 via radio communication.In one embodiment, at least one receiver 1206 or transceiver 1208 are configured to obtain the information that is associated with one group of target, biomarker or analog and detect being used for.In one embodiment, at least one receiver 1206 or transceiver 1208 are configured to obtain the information that is associated with one group of physiological property and detect being used for.In one embodiment, at least one receiver 1206 or transceiver 1208 are configured to obtain the information that is associated with one or more physiological properties and detect being used for.In one embodiment, at least one receiver 1206 or transceiver 1208 are configured to obtain the information that is associated with one or more hemozoin characteristics and detect being used for.

In one embodiment, system 100 comprises at least one transceiver 1208, and this transceiver 1208 is configured in response to this comparison and with a plurality of time interval reporting state informations.In one embodiment, system 100 comprises at least one transceiver 1208, and this transceiver 1208 is configured to ask with reference to hemozoin nonlinear response information in response to this comparison.

In one embodiment, system 100 comprises a transmitter, and this transmitter is configured to send with detected non-linear multiple-harmonic and responds energy with the comparison information that relatively is associated with reference to hemozoin Response Distribution curve.In one embodiment, at least one in receiver 1206 or the transceiver 1208 is configured to obtain the information about the target detection set of one or more characteristics of being tried to be associated with biology.In one embodiment, system 100 comprises at least one in transmitter 1210, receiver 1206 or the transceiver 1208, this at least one be configured to obtain by a nonlinear optical response information biological specimen radiation, that cause because of magnetization.In one embodiment, system 100 comprises side by side or emission sequentially or receive at least one transceiver 1208 of information.

In one embodiment, system 100 especially comprises circuit 116, and this circuit 116 is configured to the information of same that is associated with detected non-linear multiple-harmonic response energy is compared with reference to hemozoin Response Distribution curve.In one embodiment; Be used for and comprise one or more computer-readable storage mediums with the information of same that detected non-linear multiple-harmonic response energy is associated with reference to the circuit 116 that hemozoin Response Distribution curve compares; This computer-readable storage medium has the reference hemozoin Response Distribution curve of configuration as data structure 424, and this comprises in hemozoin second harmonic response spectrum information, hemozoin third harmonic response spectrum information or hemozoin the 4th harmonic response spectral information at least one with reference to plasmodium Response Distribution curve.In one embodiment, the reference nonlinear response information that comprises indication hemozoin nano particle aggregation rate with reference to hemozoin Response Distribution curve.In one embodiment, the reference nonlinear response information that comprises the existence of indicating the hemochrome metabolin that comprises the heme polymer with reference to hemozoin Response Distribution curve.In one embodiment, comprise with reference to the non-linear neurological susceptibility information of hemozoin nano particle with reference to hemozoin Response Distribution curve.

In one embodiment; Be configured to detected non-linear multiple-harmonic response energy is comprised one or more computer-readable storage mediums with the circuit 116 that compares with reference to hemozoin Response Distribution curve; This computer-readable storage medium has the reference hemozoin Response Distribution curve of configuration as data structure 424, and this comprises in the non-linear neurological susceptibility information of hemozoin nonlinear response information, hemozoin spectral information or hemozoin at least one with reference to hemozoin Response Distribution curve.

In one embodiment; Be configured to detected non-linear multiple-harmonic response energy is comprised one or more computer-readable storage mediums with the circuit 116 that compares with reference to hemozoin Response Distribution curve; This computer-readable storage medium comprises the executable instruction that is stored thereon, and these executable instructions are indication calculation element 402 when on a computer, carrying out: (a) call and the one or more parameters that are associated with reference to hemozoin nonlinear response information from storage device; And (b) comparison of the same one or more parameters called of the detected non-linear multiple-harmonic Response Distribution curve of execution.In one embodiment; These one or more computer-readable storage mediums further comprise the executable instruction that is stored thereon, the existence of these executable instructions indication calculation element 402 definite malaria when on a computer, carrying out in response to this comparison, do not exist or seriousness in one or more.

In one embodiment; Be configured to detected non-linear multiple-harmonic response energy is comprised a transmitter with the circuit 116 that compares with reference to hemozoin Response Distribution curve, this transmitter is configured to send and the same comparison information that relatively is associated with reference to hemozoin Response Distribution curve of detected non-linear multiple-harmonic response energy in position.In one embodiment; Be configured to detected non-linear multiple-harmonic response energy is comprised a transceiver 1208 with the circuit 116 that compares with reference to hemozoin Response Distribution curve, this transceiver is configured to receive to emission hemozoin reference information, the request of at least one in detected non-linear multiple-harmonic response energy and the comparison information in position.

In one embodiment, be configured to detected non-linear multiple-harmonic response energy is comprised the transceiver 1208 that is configured to receive the hemozoin filtering information with the circuit 116 that compares with reference to hemozoin Response Distribution curve.In one embodiment, be configured to detected non-linear multiple-harmonic response energy and the circuit 116 that compares with reference to hemozoin Response Distribution curve comprised and be configured to receive the transceiver 1208 that stimulates delivery parameter information through the multiplexed electromagnetic energy of the pulse of spatial patterned.In one embodiment, be configured to detected non-linear multiple-harmonic response energy is comprised the transceiver 1208 that is configured to come by rule or irregular time intervals reporting state information with the circuit 116 that compares with reference to hemozoin Response Distribution curve.In one embodiment, be configured to detected non-linear multiple-harmonic response energy and the circuit 116 that compares with reference to hemozoin Response Distribution curve comprise be configured to be stored as to and the circuit of azygous non-linear multiple-harmonic response data.In one embodiment; Be configured to detected non-linear multiple-harmonic response energy is comprised at least one processor with the circuit 116 that compares with reference to hemozoin Response Distribution curve, this processor can be operated so that will be stored on one or more computer-readable storage mediums with the information that relatively is associated that non-linear multiple-harmonic response energy is carried out with reference to hemozoin Response Distribution curve together.

In one embodiment, system 100 especially comprises circuit 120, and this circuit is configured to wirelessly transmit and the comparison information that relatively is associated that detected non-linear multiple-harmonic response energy is carried out with reference to hemozoin Response Distribution curve together.In one embodiment; System 100 especially comprises circuit 122, and this circuit is configured to optionally tuning in the Wavelength distribution of Wavelength distribution that the multiplexed electromagnetic energy of the pulse of spatial patterned stimulates or collected non-linear in position multiple-harmonic response at least one.

In one embodiment, system 100 especially comprises circuit 124, and this circuit is configured to produce response based on detected non-linear multiple-harmonic response energy and with reference to the one or more comparisons between the hemozoin Response Distribution curve at least in part.In one embodiment; This response (for example comprises visual representation, audio representation; The audio volume control of alarm, a tissue area is represented or analog), sense of touch is represented or sense of touch (is for example represented; Sense of touch figure, sense of touch demonstration, sense of touch curve map, haptic interaction formula are described, haptic model (for example; The multidimensional model in an infected tissue district or analog), tactile patterns (for example, refreshable braille (Braille) display), sense of touch audio frequency show, sense of touch-audio curve figure or analog) at least one.In one embodiment, this response comprises at least one vision, audio frequency, sense of touch or the sense of touch that produces in biological specimen spectral information, tissue spectrum information, fatty spectral information, muscle spectral information, bone spectral information, blood constituent spectral information, hemozoin spectral information or the similar information at least one in representing.In one embodiment, this response comprise produce below among both at least one: biological specimen receives the probability of malaria infection, or receives the level of confidence of the definite probability correlation couplet of institute of malaria infection with biological specimen.

In one embodiment, this response comprises in representing at least one of the vision, audio frequency, sense of touch or the sense of touch that produce at least one physics that tried to be associated with a biology or biochemical characteristic.In one embodiment, at least one during this response vision, audio frequency, sense of touch or sense of touch of comprising at least one physics that generation is associated with parasitic infection, morbid state or analog or biochemical characteristic represented.

In one embodiment, this response comprises initial one or more processing scheme.In one embodiment, this response that comprises initial one or more processing schemes comprises initial at least one disposal system.In one embodiment, this response comprises and sends energy and stimulate.In one embodiment, this response comprises and sends a kind of activating agent.In one embodiment, this response comprises side by side or sequentially sends an energy stimulates and a kind of activating agent.In one embodiment, this response comprise response signal, control signal, to the change of processing parameter or in the analog at least one.

In one embodiment, this response comprises the change of the characteristic that an electromagnetic energy is stimulated.For instance, in one embodiment, this response comprises at least one the change in peak power, peak value irradiation level, focal spot size, pulse width, peak value radiation wavelength or the analog.In one embodiment, this response comprises at least one the change in electromagnetic energy stimulus intensity, electromagnetic energy frequency of stimulation, electromagnetic energy boost pulse frequency, electromagnetic energy boost pulse ratio, electromagnetic energy boost pulse intensity, electromagnetic energy boost pulse duration, electromagnetic energy boost pulse repetitive rate or the analog.

In one embodiment, the circuit 124 that is configured to produce based on one or more comparisons at least in part response comprises one or more receiver 1206, transmitter 1210, transceiver 1208 or analog.In one embodiment; The circuit 124 that is configured to produce based on one or more comparisons at least in part response comprises at least one in transmitter 1210 or the transceiver 1208, this at least one be configured to send and detected non-linear multiple-harmonic response energy with the comparison information that relatively is associated with reference to hemozoin Response Distribution curve.In one embodiment; The circuit 124 that is configured to produce based on one or more comparisons at least in part response comprises at least one in receiver 1206 or the transceiver 1208, this at least one be configured to obtain with reference to hemozoin Response Distribution calibration curve information.

In one embodiment, system 100 especially comprises the circuit 126 that is configured to feasible generation magnetic field.For instance, in one embodiment, circuit 126 comprises and is configured to apply the one or more conductive traces that produce magnetic field under the situation of current potential in existence.In one embodiment, the circuit 126 that is configured to produce magnetic field comprises a radiofrequency launcher that is configured to produce radiofrequency signal.In one embodiment; The circuit 126 that is configured to produce magnetic field comprises a radiofrequency launcher that is configured to produce radiofrequency signal, and the characteristic of this radiofrequency signal and duration are enough to aim at a plurality of hemozoin nano particles with magnetic means in vivo.In one embodiment, the circuit 126 that is configured to produce magnetic field comprises in order to produce one or more coils of one or more radio-frequency pulses.

In one embodiment, system 100 especially comprises in order to produce the circuit 128 of magnetic stimulation.In one embodiment, circuit 128 comprises a radiofrequency launcher that is configured to produce radiofrequency signal.In one embodiment, circuit 128 comprises and is configured to apply the one or more conductive traces that produce magnetic field under the situation of current potential in existence.In one embodiment, circuit 128 comprises the one or more coils that are configured to produce one or more radio-frequency pulses.In one embodiment, circuit 128 comprises a plurality of radio-frequency coils.In one embodiment, circuit 128 comprises a plurality of coils that are configured to produce time-varying magnetic field.

The characteristic of the electromagnetic stimulation that is produced in one embodiment, and duration are enough to cause that the hemozoin nano particle in the biological specimen sends the hyperthermia therapy that magnetic causes in vivo.Because the hemozoin nano particle is paramagnetic, so in one embodiment, applies magnetic field gradient and can apply power the hemozoin in the malaria original endoparasite.In one embodiment, with time-varying magnetic field be applied to hemozoin can cause the hemozoin particle fast, moving of vibration a little, and then with hemozoin and therefore parasite is heated; Heat is enough to influence negatively or kill parasite, can not influence the normal function of the cell of uninfection simultaneously in fact.

In one embodiment; System 100 especially comprises circuit 130, and this circuit 130 is configured to detect and exists under the situation in magnetic field and stimulate or inquire after the scattered information that at least one a plurality of hemozoin nano particles inquired after in the stimulation are associated through multiplexed Lay because of Burger by inquiring after through multiplexed details in a play not acted out on stage, but told through dialogues.

In one embodiment; System 100 especially comprises circuit 128; This circuit 128 is configured to produce a magnetic stimulation, and the characteristic of this magnetic stimulation and duration are enough to cause that the hemozoin nano particle in the biological specimen sends the hyperthermia therapy that magnetic causes in vivo.

In one embodiment, system 100 especially comprises and is configured to the circuit 132 that controlling magnetic field dynamically stimulates.In one embodiment; The circuit 132 that is configured to dynamically controlling magnetic field stimulation comprises one or more processors 404; But these processors are connected to the circuit 128 that is configured to generate an electromagnetic field and stimulates with mode of operation, and are configured to manage and the send one or more parameters that are associated of pulsed magnetic sexual stimulus to a district that a biology is tried.In one embodiment; The circuit 132 that being configured to controlling magnetic field dynamically stimulates comprises one or more processors 404, these processors be configured to regulate with generate an electromagnetic field stimulate be associated send the system parameter, the isolated pattern parameter or temporal sent is sent in the pattern parameter at least one.

In one embodiment, system 100 especially comprises and is configured to detected scattered information and the circuit 134 that compares with reference to hemozoin details in a play not acted out on stage, but told through dialogues scattering data.In one embodiment; The circuit 134 that is configured to more non-linear multiple-harmonic response energy distribution curve comprises one or more computer-readable storage mediums, and these computer-readable storage mediums have the reference hemozoin nonlinear response information of configuration as data structure 424.In one embodiment, this comprises through modeled with reference to comparison information with reference to hemozoin nonlinear response information.In one embodiment; The circuit 134 that is configured to more non-linear multiple-harmonic response energy distribution curve comprises one or more computer-readable storage mediums, and these computer-readable storage mediums have the reference hemozoin nonlinear response information of configuration as data structure 424.In one embodiment, this with reference to hemozoin nonlinear response packets of information be contained in situ detection to the non-linear neurological susceptibility information of nonlinear response information, hemozoin spectral information or hemozoin at least one.

In one embodiment; System 100 especially comprises circuit 136, and this circuit 136 is configured to (a) stimulated non-linear multiple-harmonic response energy distribution curve that at least one volume of focus of inquiring after is associated and (b) compare with reference to hemozoin nonlinear response information with using through the pulse electromagnetic energy of spatial patterned.

In one embodiment; System 100 especially comprises circuit 138; This circuit 138 is configured to cause in vibration, translation or the rotation of the hemozoin nano particle in the biological specimen at least one with magnetic means, and the characteristic of at least one in vibration, translation and the rotation of this initiation of the hemozoin nano particle in this biological specimen and duration are enough to influence the integrality of the organelle of malaria original endoparasite.In one embodiment; Be configured to comprise a flexible circuit with at least one the circuit 138 that magnetic means causes in vibration, translation or the rotation of the hemozoin nano particle in the biological tissue, this flexible circuit has one or more conductive trace that is configured under existence applies the situation of current potential, produce magnetic field.In one embodiment; Be configured to comprise a printed circuit with at least one the circuit 138 that magnetic means causes in vibration, translation or the rotation of the hemozoin nano particle in the biological tissue, this printed circuit has one or more conductive trace that is configured under existence applies the situation of electric current, produce magnetic field.In one embodiment, be configured to cause at least one circuit 138 in vibration, translation or the rotation of the hemozoin nano particle in the biological tissue and comprise in receiver 1206, transmitter 1210 or the transceiver 1208 at least one with magnetic means.In one embodiment, be configured to comprise at least one electromagnet with at least one the circuit 138 that magnetic means causes in vibration, translation or the rotation of the hemozoin nano particle in the biological tissue.In one embodiment, be configured to comprise at least one permanent magnet with at least one the circuit 138 that magnetic means causes in vibration, translation or the rotation of the hemozoin nano particle in the biological tissue.

In one embodiment, system 100 especially comprises circuit 140, and this circuit is configured to transmit the comparison information that is associated with more non-linear multiple-harmonic response energy distribution curve.

In one embodiment, system 100 especially comprises circuit 142, and this circuit is configured to transmit with the vibration, the translation that cause the hemozoin nano particle with magnetic means and at least one process information that is associated in rotating.

In one embodiment, system 100 especially comprises circuit 144, and this circuit is configured in dark field detection configuration or Lay detect in the configuration at least one because of Burger, detect the scattared energy from a biological tissue.In one embodiment, the circuit 144 that is configured to detect scattared energy comprises at least one sensor 442, and this sensor is configured in the dark field detection configuration, receive the part of scattared energy.In one embodiment, the circuit 144 that is configured to detect scattared energy comprises at least one sensor 442, and this sensor is configured to detect a part that receives scattared energy in the configuration because of Burger at Lay.In one embodiment, the circuit 144 that is configured to detect scattared energy comprises a lens arra sub-assembly, and this lens arra sub-assembly is configured to receive at least a portion of the scattared energy that is tried from this biology.In one embodiment, the circuit 144 that is configured to detect scattared energy comprises a Lay because of Burger dyeing illuminating assembly, and this sub-assembly is configured to receive at least a portion of the scattared energy that is tried from this biology.In one embodiment, the circuit 144 that is configured to detect scattared energy comprises at least one Lay because of the Burger filter.

In one embodiment; System 100 especially comprises circuit 146, and this circuit 146 is configured to disturb the hemozoin nano particle in the biological tissue in response to detected scattared energy information and with reference to the comparison between the hemozoin nano particle scattared energy information with magnetic means.In one embodiment; Be configured to disturb the circuit 146 of the hemozoin nano particle in the biological tissue to comprise a coil assembly with magnetic means, this coil assembly is configured at least one with vibration, the translation of the hemozoin nano particle in biological tissue of magnetic means initiation or in rotating.In one embodiment; Be configured to disturb the circuit 146 of the hemozoin nano particle in the biological tissue to comprise one or more conductive trace with magnetic means, these conductive traces are configured to cause at least one in vibration, translation or the rotation of a hemozoin nano particle in the biological tissue.In one embodiment; Be configured to disturb the circuit 146 of the hemozoin nano particle in the biological tissue to comprise one or more processors 404 with magnetic means; These processors produce a control signal when being activated, this control signal causes detected scattared energy and with reference to the comparison between the hemozoin nano particle scattared energy information.

In one embodiment; System 100 especially comprises circuit 148, and this circuit 148 is configured in dark field detection configuration the electromagnetic energy of an effective dose is stimulated in the one or more districts that shine a biological tissue to produce scattared energy from this biological tissue.In one embodiment; The circuit 148 that being configured to shine the electromagnetic energy of this effective dose stimulates comprises a lens arra sub-assembly, and this lens arra sub-assembly is configured to one or more incident electromagnetic energies are stimulated and focuses on that this biology is tried and from this biology receipts scattared energy of being tried.

In one embodiment; System 100 especially comprises circuit 150, this circuit be configured to detect with at least one volume of focus that stimulates a biological tissue of inquiring after by electromagnetic energy in the non-linear multiple-harmonic response energy that is associated of hemozoin nano particle.In one embodiment; The circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises at least one charge coupled device, this charge coupled device be configured to detect respond with the second harmonic response, the third harmonic that stimulate the hemozoin nano particle at least one volume of focus of inquiring after to be associated by electromagnetic energy or the 4th harmonic response at least one.In one embodiment; The circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises at least one ultraviolet ray-visible light PDAD, and this detector is used for detecting and responds with the second harmonic response, the third harmonic that are stimulated the hemozoin nano particle at least one volume of focus of inquiring after to be associated by electromagnetic energy or at least one of the 4th harmonic response.In one embodiment, the circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises and is configured to detect the circuit with the multiple-harmonic photo response of radiating through the skin mode.

In one embodiment; The circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises one or more sensors 442, and these sensors are used to detect the nonlinear response distribution curve of the one or more hemozoin nano particles in this at least one volume of focus.In one embodiment; The circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises one or more sensors 442, and this sensor is used to detect the spectral response of the one or more hemozoin nano particles in this at least one volume of focus.In one embodiment, the circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises and is configured to detect in position and the circuit that is responded energy by the non-linear multiple-harmonic that stimulates the hemozoin nano particle at least one volume of focus of inquiring after to be associated through the multiplexed electromagnetic energy of the pulse of spatial patterned.In one embodiment; The circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises an optical package 112 and at least one sensor 442, is used for collecting and detecting by stimulate at least one of second harmonic response, third harmonic response or the 4th harmonic response of drawing through the multiplexed electromagnetic energy of the pulse of spatial patterned via the collected outside pattern.In one embodiment; The circuit 150 that is configured to detect non-linear multiple-harmonic response energy comprises an optical package 112 and at least one sensor 442, is used for collecting and detecting by stimulate at least one of second harmonic response, third harmonic response or the 4th harmonic response of drawing through the multiplexed electromagnetic energy of the pulse of spatial patterned because of Burger detects configuration via Lay.

In one embodiment; System 100 especially comprises circuit 152, and the pulse electromagnetic energy stimulation that this circuit is configured to produce an effective dose is to extract the nonlinear response of the hemozoin nano particle in this biological tissue at least one volume of focus of a biological tissue.The characteristic of the nonlinear response of being drawn in one embodiment, and duration are enough to regulate the biologically active of malaria infectious agent.

The absorption of electromagnetic radiation, transmission, scattering or the like are different between various biological tissues, biological specimen, equipment, other material or analog.For instance, to organize for skin to the scope of about 1300 nanometers be a minimum scope of photonic absorption and scattering (produce effective optical power on skin transmit a best district) to about 800 nanometers.Therefore, in one embodiment, the peak value radiation wavelength of the electromagnetic stimulation that is produced by energy radiation assembly 104 is selected as and makes sending and maximizing from the detection of concern sample the concern sample.For instance, for improve an electromagnetic stimulation through skin transmission and to the subsequent detection of the nonlinear optical response that produced, the peak value radiation wavelength of electromagnetic stimulation is chosen in about 1000 nanometers in the scope of about 1300 nanometers.This will cause (producing to second harmonic to about 650 nanometers in about 500 nanometers from the nonlinear optical response of hemozoin; Half of wavelength), about 333 nanometers (produce to third harmonic to about 433 nanometers; Wavelength 1/3rd) or the like scope in.One or more peak values radiation wavelength of the electromagnetic stimulation that is produced by energy radiation assembly 104 in one embodiment, are selected as the nonlinear optical response that causes hemozoin and in the wave-length coverage of infringement inhereditary material, launch.For at Medical Devices for example, medical facilities, in vivo the effective optical power on goods or the analog transmits, other scope possibly be better.

In one embodiment; The circuit 152 that being configured to produce the pulse electromagnetic energy of this effective dose stimulates comprises at least one first energy emitter and at least one second energy emitter is used for multiplexed nonlinear response chemical examination; This first energy emitter has the peak value radiation wavelength of about 690 nanometers to about 2100 nanometers, and this second energy emitter has the peak value radiation wavelength of about 1000 nanometers to about 2000 nanometers.In one embodiment; The circuit 152 that being configured to produce the pulse electromagnetic energy of this effective dose stimulates comprises energy radiation assembly 104, and this energy radiation assembly is configured to use stimulate through the multiplexed electromagnetic energy of the pulse of spatial patterned inquires after at least one volume of focus.

In one embodiment, the circuit 152 that is configured to produce the pulse electromagnetic energy of this effective dose and stimulates comprises one or more laser instruments, laser diode and light emitting diode.In one embodiment, the circuit 152 that is configured to produce the pulse electromagnetic energy of this effective dose and stimulates comprises one or more quantum dots, Organic Light Emitting Diode, tiny cavity light-emitting diode and polymer LED.In one embodiment, the circuit 152 that is configured to produce the pulse electromagnetic energy of this effective dose and stimulates comprises one or more femtosecond lasers.In one embodiment, the circuit 152 that is configured to produce the pulse electromagnetic energy of this effective dose and stimulates comprises the radioactive source of the energy of a patterning.In one embodiment; The circuit 152 that being configured to produce the pulse electromagnetic energy of this effective dose stimulates comprises and is configured to send the lens arra that an isolated energy stimulates; This lens arra has one first district and one second district at least, and this second district has the depth of focus that is different from this first district.

In one embodiment, system 100 especially comprises circuit 154, and this circuit 154 is configured to produce through multiplexed pulse electromagnetic energy to stimulate, and this electromagnetic energy stimulation has the peak power from about 400 m. gigawatt (GW)s to about 8 TW terawatts.

In one embodiment, system 100 especially comprises circuit 156, and this circuit 156 is configured to be directed on a plurality of volume of focus of a biology in being tried stimulating through multiplexed pulse electromagnetic energy.

In one embodiment; System 100 especially comprises circuit 158, and this circuit is configured to detect and the multiple-harmonic response that is associated by a plurality of hemozoin nano particles in the biological tissue that stimulates through multiplexed pulse electromagnetic energy in a plurality of volume of focus of inquiring after one or more.In one embodiment; The circuit 158 that is configured to detect the multiple-harmonic response comprises at least one outside direction sensor, is used for detecting in position and is responded by a plurality of hemozoin nano particles multiple-harmonic that be associated, that radiated that stimulates a biological tissue of inquiring after through multiplexed pulse electromagnetic energy.

In one embodiment, system 100 especially comprises a magnetic field component 160, and this magnetic field component 160 is configured to produce a magnetic field, and the characteristic in this magnetic field and duration are enough to aim at a plurality of hemozoin nano particles in vivo with magnetic means.In one embodiment, magnetic field component 160 comprises a radiofrequency launcher that is configured to produce radiofrequency signal.In one embodiment, magnetic field component 160 comprises the one or more coils that are configured to produce one or more radio-frequency pulses.In one embodiment, medical diagnosis device is configured to be used for being attached to the biological surface that a biology is tried with removably.

In one embodiment; System 100 especially comprises a physical connection element, and this physical connection element is configured in details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly, magnetic field component and the optical energy sensor cluster at least one is attached to the biological surface that a biology is tried with removably.

In one embodiment; But system 100 especially comprises the magnetic field producer 162 of an ACTIVE CONTROL; This magnetic field producer is configured to send the magnetic stimulation of a variation, and the dosage in this magnetic field is enough to cause the hemozoin nano particle in the biological specimen to produce heat.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL comprises the circuit that is configured to produce and send the electromagnetic energy stimulation, and characteristic that this electromagnetic energy stimulates and duration are enough to make stimulates the hemozoin nano particle in the biological specimen of inquiring after to produce heat energy by electromagnetic energy.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL comprises an electric coil sub-assembly; This electric coil sub-assembly produces a magnetic field by energy supply the time, the characteristic in this magnetic field and duration are used in the biological specimen that comprises the hemozoin nano particle, causing one or more of Blang's (Brownian) process and Neil (Neelian) process.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL comprises a magnetic field that is used to apply the magnetic field of variation produces coil assembly.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL comprises a volumes coil arrangement, and this volume coils arrangement comprises a plurality of coils that are used to produce a Circular Polarisation magnetic field.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL comprises one or more electromagnets.

In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL comprises one or more alternating current magnets.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL comprises the one or more coils that are configured to produce a magnetic field, and the characteristic in this magnetic field and duration are enough to make the temperature in the district that comprises the hemozoin nano particle in the plasmodium to increase about 3 ° of C to about 22 ° of C.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL comprises the one or more coils that are configured to produce a magnetic field, and the temperature that the characteristic in this magnetic field and duration are enough to make in the malaria original endoparasite that exists in the biological specimen to contain the district of hemozoin increases about 3 ° of C to about 10oC.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL comprises the one or more coils that are configured to produce a magnetic field, and the characteristic in this magnetic field and duration are enough to make the temperature in the district that comprises the hemozoin nano particle in the malaria original endoparasite to increase about 3 ° of C to about 4 ° of C.

In one embodiment, but the magnetic field producer of ACTIVE CONTROL 162 produces a magnetic field, and the characteristic in this magnetic field and duration are enough to make the temperature increase in the district that comprises the hemozoin nano particle of malaria original endoparasite.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL produces a magnetic field, and the intensity in this magnetic field or duration are enough to make the decay of activity of malaria infectious agent.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL provides a magnetic field, and the intensity in this magnetic field or duration are enough to regulate the heme polymerase activity of malaria infectious agent.

In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL provides a magnetic field, and the characteristic in this magnetic field and duration are enough to improve the plasmodium influence, and can not destroy the erythrocytic integrality of having wrapped up the malaria original endoparasite substantially.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL provides a magnetic field; The characteristic in this magnetic field and duration are enough to make the temperature in the district of the malaria original endoparasite in the biological specimen to increase, and this temperature increase is enough to cause the apoptosis that causes because of heat in this malaria original endoparasite.

In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL provides a magnetic field, and the characteristic in this magnetic field and duration are enough to cause the apoptosis of the host cell that is loaded with the malaria infectious agent.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL provides a magnetic field; The characteristic in this magnetic field and duration are enough to make the temperature in the district of the malaria original endoparasite in the biological specimen to increase, and this temperature increase is enough to reduce the parasitemia level.In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL produces an AC magnetic field; The characteristic of this AC magnetic field and duration are enough to cause the temperature in the district that comprises the hemozoin nano particle in the malaria original endoparasite to increase; And improve the influence of malaria original endoparasite, and can not destroy substantially and wrap up plasmodial erythrocytic integrality.

In one embodiment; But the magnetic field producer 162 of ACTIVE CONTROL comprises one or more conductive coils; These conductive coils are configured to produce a time-varying magnetic field in response to the electric current that is applied, and the characteristic of this time-varying magnetic field and duration are enough to cause the hemozoin nano particle in the biological specimen to produce heat owing in Blang's process and the Neil process one or more.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL produces a magnetic field, and the characteristic in this magnetic field and duration are enough to cause the pyrolytic damage to the organelle film in the malaria original endoparasite in the biological specimen.In one embodiment, but the magnetic field producer 162 of ACTIVE CONTROL comprises at least one radiofrequency launcher, and these radiofrequency launchers comprise one or more radio-frequency coils that the radio frequency that is configured to produce localization stimulates.

In one embodiment; One first electromagnetic energy stimulates and one second electromagnetic energy stimulates but the magnetic field producer 162 of ACTIVE CONTROL side by side or sequentially produces at least; Characteristic that this first electromagnetic energy stimulates and duration are enough to aim at the hemozoin nano particle in the biological tissue with magnetic means, and characteristic that this second electromagnetic energy stimulates and duration are enough at least one with vibration, the translation of the hemozoin nano particle in this biological tissue of magnetic means initiation or in rotating.In one embodiment, at least one in the vibration of the hemozoin nano particle in the caused biological tissue, translation and the rotation is enough to influence the integrality of the organelle of malaria infectious agent.In one embodiment, at least one in the vibration of the hemozoin nano particle in the caused biological tissue, translation and the rotation is enough to influence the integrality of plasmodial digestibility food vacuole.In one embodiment, at least one in the vibration of the hemozoin nano particle in the caused biological tissue, translation and the rotation is enough to destroy heme polymerization process in vivo.

In one embodiment, system 100 especially comprises a calculation element 402, but but this calculation element is connected to the magnetic field producer of this ACTIVE CONTROL with mode of operation.In one embodiment, calculation element 402 comprises one or more processors 404, is used at least one of controlling magnetic field on-time, magnetic field intensity, field frequency or field waveform.

In one embodiment, system 100 especially comprises details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly, and this details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly is configured to stimulate at least one volume of focus of inquiring after biological tissue with the multimode details in a play not acted out on stage, but told through dialogues.

In one embodiment, system 100 especially comprises one or more power supplys 700.In one embodiment, power supply 700 can be connected to one or more energy radiation assemblies 104 with electromagnetic mode, magnetic means, ultrasonic power, optical mode, inductance mode, electric mode or capacitive way.In one embodiment, power supply 700 is carried by monitor or treating apparatus 102.In one embodiment, power supply 700 comprises at least one rechargeable power supply 702.In one embodiment, power supply 700 is configured to wireless mode from a remote power supply received power.

In one embodiment, monitor or treating apparatus 102 comprise one or more electric organs 704 that received examination (for example, people) energy supply by biology.In one embodiment, this biology electric organ 704 of being tried energy supply is configured to the motion collecting energy from for example one or more joints.In one embodiment; The electric organ 704 that biology is tried energy supply is configured to use in thermoelectric generator 706, piezoelectric generating unit 708, dynamo-electric electric organ 710 (for example, MEMS (MEMS) electric organ or analog), biomethanics energy acquisition electric organ 712 or the analog at least one to gather by biology and is test-manufactured living energy.

In one embodiment, the biology electric organ 704 that tried energy supply is configured to gather by biology and is test-manufactured living heat energy.In one embodiment, thermoelectric generator 706 is configured to gather the heat of being tried to dissipate by biology.In one embodiment, the biology electric organ 704 that tried energy supply is configured to gather any physical motion that is tried by biology or moves the energy that (for example, walking) produces.For instance, in one embodiment, the electric organ 704 that biology is tried energy supply is configured to gather the energy that is tried the mobile generation in an interior joint by biology.The energy of the mobile generation of the fluid (for example, biofluid) in one embodiment, the biology electric organ 704 that tried energy supply is configured to gather and is tried by biology.

In the middle of power supply 700, instance comprises (but being not limited to) one or more button cells, chemical storage batteries, fuel cell, secondary cell, lithium ion battery, little electric paster, nickel metal hydride battery, silver-zinc battery, capacitor, ultracapacitor, thin-film secondary battery, ultra-capacitor (ultra-capacitors), zinc-air battery or analog.The other limiting examples of power supply 700 (for example comprises one or more electric organs; Electric electric organ, heat energy to electric energy electric organ, mechanical energy to electric energy electric organ, micron electric organ, nanometer generating device or analog), for example thermoelectric generator, piezoelectric generating unit, dynamo-electric electric organ, biomethanics energy acquisition electric organ or analog.In one embodiment, monitor or treating apparatus 102 comprise one or more electric organs, and these electric organs are configured to from for example gathering mechanical energy ultrasonic wave, mechanical oscillation, blood flow or the analog.In one embodiment, monitor or treating apparatus 102 comprise one or more power receivers 732, and these power receivers 732 are configured to ex vivo or sv power supply received power.In one embodiment, in vivo power supply comprises thermoelectric generator, piezoelectric generating unit, electromechanics and can arrive in power generation device or the biomethanics energy acquisition electric organ at least one.

In one embodiment; Power supply 700 comprises at least one in thermoelectric generator, piezoelectric generating unit, dynamo-electric electric organ or the biomethanics energy acquisition electric organ, and in button cell, chemical storage batteries, fuel cell, secondary cell, lithium ion battery, little electric paster, nickel metal hydride battery, silver-zinc battery, capacitor, ultracapacitor, thin-film secondary battery, ultra-capacitor or the zinc-air battery at least one.In one embodiment, power supply 700 comprises at least one rechargeable power supply.

In one embodiment, monitor or treating apparatus 102 comprise a power supply 700, and this power supply 700 comprises at least one in thermoelectric generator, piezoelectric generating unit, dynamo-electric electric organ or the biomethanics energy acquisition electric organ.In one embodiment, power supply 700 is configured to manage the dutycycle that is associated with the electromagnetic energy stimulation of radiating an effective dose from one or more energy radiation assemblies 104.In one embodiment, power supply 700 is configured to manage the dutycycle that is associated with the sterilization energy stimulation of radiating an effective dose from one or more energy radiation assemblies 104.

In one embodiment, power supply 700 is configured to manage with the vibration, the translation that cause the hemozoin nano particle in the biological tissue with magnetic means or at least one dutycycle that is associated in rotating.In one embodiment; Power supply 700 is configured to manage and compares the dutycycle that is associated, and this relatively is with stimulating non-linear multiple-harmonic response energy distribution curve that at least one volume of focus of inquiring after is associated and compare with reference to hemozoin nonlinear response information with using through the pulse electromagnetic energy of spatial patterned.In one embodiment, system 100 especially comprises an energy accumulating device.In one embodiment, this energy accumulating device comprises at least one in battery, capacitor or the mechanical energy holder.

Fig. 2 A is depicted as and is used to regulate the parasitic active system 100 of plasmodium.Be used to regulate the parasitic active system 100 of plasmodium and especially comprise circuit 128; This circuit is configured to produce a magnetic stimulation, the characteristic of this magnetic stimulation and duration be enough to cause in the biological specimen the hemozoin nano particle in position in, send the hyperthermia therapy that causes with magnetic means in vivo, in vitro or similarly.Be included in position in vivo or in vitro.In one embodiment, being used to regulate the parasitic active system 100 of plasmodium comprises and is configured to the circuit 208 that controlling magnetic field dynamically stimulates.In one embodiment; The circuit 208 that is configured to dynamically controlling magnetic field stimulation comprises one or more processors 404; But these processors are connected to the circuit 202 that is configured to generate an electromagnetic field and stimulates with mode of operation, and are configured to manage and the send one or more parameters that are associated of a pulsed magnetic sexual stimulus to a district that a biology is tried.In one embodiment; The circuit 208 that being configured to controlling magnetic field dynamically stimulates comprises one or more processors 404, these processors be configured to regulate with generate an electromagnetic field stimulate be associated send the system parameter, the isolated pattern parameter or temporal sent is sent in the pattern parameter at least one.

Fig. 2 B is depicted as and is used for the parasitic active system 100 of optical mode monitoring/adjusting plasmodium.In one embodiment, system 100 comprises the scanning/optical projection system 210 and the detection subsystem 212 of operation under the control that is at least one calculation element 402.System 100 can implement with various ways, and for example (but being not limited to) for example 6,445, the system of describing in one or more among No. 362 United States Patent (USP)s, U.S.2006/0284790 and/or the U.S.2005/0020926 based on optical scanner.

In one approach, scanning/optical projection system 210 stimulates 214 guiding through optical splitter 216 and through optical lens sub-assembly 218 one or more electromagnetic energies towards the eyes 220 that a biology is tried.For instance; System 100 stimulates 214 to be directed on one or more volume of focus that a biology tried producing the radiation that is tried scattering from this biology the electromagnetic energy of an effective dose, and uses dark field detection to dispose at least a portion of the radiation 225 that detects this scattering.

In an illustrative embodiment; System 100 adopts one or more energy radiation assemblies 104; For example laser diode or optical fiber connect laser instrument, have the peak value radiation wavelength from about 690 nanometers to about 2100 nanometers, are used at least one of illumination radiation 214.Monitoring/regulating system 210 with illumination radiation 214 scanning through for example grating pattern or Li Shayu (Lissajous) pattern.

Optical lens sub-assembly 218 will be coupled in the eyes through the pupil of illumination radiation 214 through eyes of scanning, and at this pupil place, illuminating bundle 214 shines retina 222.In certain methods, optical lens sub-assembly 218 can provide a beam 224, and this beam 224 converges in the field of being paid close attention to, for example the surface of retina 222 or near.In other method, can make beam collimation substantially.Optical splitter 216 can be any one in the multiple optical texture, and these optical textures can be along at least a portion of ground transmission of one or more Path selection property and/or redirecting light.In an illustrative embodiment, optical splitter can come optionally to transmit and/or at least a portion of redirecting light in response to one or more optical wavelength.To describe like this paper, and use the difference illumination arrangement to collect some light from the light that the field of being paid close attention to is returned.Optical splitter 216 can be configured to the light that is in an input wavelength optionally is transferred to eyes, optionally is redirected the light that is in a scattering wavelength and/or this input wavelength simultaneously.It should be noted that optical splitter also can be redirected all or part of of the light that returned in response to polarisation of light or other characteristic.

Fig. 3 A is depicted as hemozoin monitoring device 300, wherein can implement one or more methods or technology.Hemozoin monitoring device 300 especially comprises a sensor cluster 440; This sensor cluster be configured to detect with a plurality of volume of focus that stimulate (for example, the pulse electromagnetic energy stimulates, stimulates, stimulates, stimulates, stimulates or analog through the electromagnetic energy of time patterning through the multiplexed electromagnetic energy of the pulse of spatial patterned through multiplexed electromagnetic energy through the electromagnetic energy of spatial patterned) to inquire after by electromagnetic energy in a biological tissue in the non-linear multiple-harmonic Response Distribution curve that is associated of hemozoin nano particle.In one embodiment, sensor cluster 440 is configured to use one or more difference illumination arrangement (for example, dark-ground illumination, Lay are because of Burger illumination or similar illumination) to detect non-linear multiple-harmonic Response Distribution curve.In one embodiment, sensor cluster 440 is configured to use dark field detection configuration or Lay to detect non-linear multiple-harmonic Response Distribution curve because of Burger detects in the configuration at least one.In one embodiment, sensor cluster 440 is configured to randomly to use dark field detection configuration or Lay to detect the spectrum evident characteristics of hemozoin because of Burger detects in the configuration at least one.

Hemozoin monitoring device 300 can especially comprise one or more computer-readable storage mediums; These computer-readable storage mediums comprise the executable instruction that is stored thereon; These executable instructions indication calculation element 402 when on a computer, carrying out calls and the one or more parameters that are associated with reference to hemozoin nonlinear response information from storage device, and carries out detected non-linear multiple-harmonic Response Distribution curve and the comparison of one or more parameters of being called.In one embodiment, hemozoin monitoring device 300 comprises a transceiver 1208, and this transceiver 1208 side by side or is sequentially launched or reception information.

Fig. 3 B is depicted as medical diagnosis device 310, wherein can implement one or more methods or technology.Medical diagnosis device 310 especially comprises circuit 312, and this circuit is configured to produce through multiplexed pulse electromagnetic energy to stimulate, and this electromagnetic energy stimulation has the peak power from about 400 m. gigawatt (GW)s to about 8 TW terawatts.In one embodiment, medical diagnosis device 310 comprises circuit 156, and this circuit is configured to be directed on a plurality of volume of focus of a biology in being tried stimulating through multiplexed pulse electromagnetic energy.In one embodiment; Medical diagnosis device 310 comprises circuit 158, and this circuit is configured to detect and the multiple-harmonic response that is associated by a plurality of hemozoin nano particles in the biological tissue that stimulates through multiplexed pulse electromagnetic energy in a plurality of volume of focus of inquiring after one or more.

Fig. 3 C is depicted as medical diagnosis device 320, wherein can implement one or more methods or technology.Medical diagnosis device 320 especially comprises a details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly 104a.In one embodiment, details in a play not acted out on stage, but told through dialogues electromagnetic energy radiation assembly 104a is configured to that stimulation is inquired after in the multimode details in a play not acted out on stage, but told through dialogues and is delivered at least one blood vessel.Medical diagnosis device 320 can especially comprise a magnetic field component 322.In one embodiment, these magnetic field component 322 generation magnetic fields, the characteristic in this magnetic field and duration are enough to aim at a plurality of hemozoin nano particles in vivo with magnetic means.Medical diagnosis device 320 especially comprises an optical energy sensor cluster 440a.In one embodiment, this optical energy sensor cluster 440a is configured to detect free multimode details in a play not acted out on stage, but told through dialogues to inquire after the diffuse optical energy of a plurality of hemozoin nano particles that stimulation inquires after existing under the situation in magnetic field.

Fig. 3 D is depicted as original position hemozoin monitoring device 330, wherein can implement one or more methods or technology.But original position hemozoin monitoring device 330 especially comprises the excitation component 104b of an ACTIVE CONTROL; But the excitation component of being somebody's turn to do ACTIVE CONTROL is configured to a pulse electromagnetic energy stimulation through spatial patterned is delivered to one or more volume of focus, and is configured to extract the non-linear multiple-harmonic response message of the hemozoin nano particle in a biological tissue in these a plurality of volume of focus.In one embodiment; Original position hemozoin monitoring device 330 comprises a control device 332, but but this control device be connected to the excitation component 104b of this ACTIVE CONTROL with mode of operation and be configured to regulate the numerical aperture that is associated with sending of stimulating through the pulse electromagnetic energy of spatial patterned, the isolated pattern parameter or temporal sent is sent in the pattern parameter at least one.In one embodiment, but excitation component 104b that should ACTIVE CONTROL is configured to regulate at least one in the parameter that is associated with peak power, peak value irradiation level, focal spot size or pulse width.

Fig. 3 E is depicted as anti-malarial therapeutic system 340, wherein can implement one or more methods or technology.In one embodiment; Anti-malarial therapeutic system 340 especially comprises a sensor cluster 440; This sensor cluster comprises at least one sensor 442, this sensor be configured to detect with at least one volume of focus that stimulates a biological tissue of inquiring after by electromagnetic energy in the non-linear multiple-harmonic response energy that is associated of hemozoin nano particle.In one embodiment; Anti-malarial therapeutic system 340 comprises an energy radiation assembly 104; The electromagnetic energy stimulation that this energy radiation assembly is configured to send an effective dose is to extract the nonlinear optical response of the hemozoin nano particle in this biological tissue, and the characteristic of the nonlinear response of being drawn and duration are enough to regulate the biologically active of the malaria infectious agent in this biological tissue.In one embodiment; Anti-malarial therapeutic system 340 comprises a calculation element 402; But this calculation element radiates assembly 104 with at least one sensor 442 and the energy that mode of operation is connected to sensor cluster 440, and this calculation element 402 is configured to a control signal is offered energy radiation assembly.

Fig. 4 A is depicted as an equipment 460, wherein can implement one or more methods or technology.But but but equipment 460 especially comprises the magnetic field producer 462 of an ACTIVE CONTROL and a calculation element being connected to the magnetic field producer 462 of this ACTIVE CONTROL with mode of operation.In one embodiment, but magnetic field producer 462 that should ACTIVE CONTROL is configured to send the magnetic stimulation of a variation, and the dosage of this magnetic stimulation is enough to cause the hemozoin nano particle in the biological specimen to produce heat.In one embodiment; But but calculation element 402 is connected to the magnetic field producer 462 of this ACTIVE CONTROL with mode of operation; And comprise one or more processors 404, be used at least one of controlling magnetic field on-time, magnetic field intensity, field frequency or field waveform.

Fig. 4 B is depicted as an equipment 470, wherein can implement one or more methods or technology.In one embodiment; Equipment 460 comprises a magnetic field producer 472; This magnetic field producer 472 side by side or sequentially produces at least one first electromagnetic energy stimulation and one second electromagnetic energy stimulates; Characteristic that this first electromagnetic energy stimulates and duration are enough to aim at the hemozoin nano particle in the biological tissue with magnetic means, and characteristic that this second electromagnetic energy stimulates and duration are enough at least one with vibration, the translation of the hemozoin nano particle in this biological tissue of magnetic means initiation or in rotating.

Instance for the method 500 that is used to detect the situation that is associated with the red blood cell that infected by plasmodium shown in Figure 5.At 510 places, method 500 comprises via circuit will stimulate non-linear multiple-harmonic Response Distribution curve that at least one volume of focus of inquiring after is associated and compare with reference to hemozoin nonlinear response information with using through the pulse electromagnetic energy of spatial patterned.At 512 places, use non-linear multiple-harmonic Response Distribution curve that circuit will be associated with at least one volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after to comprise with comparing with reference to hemozoin nonlinear response information: produce non-linear multiple-harmonic Response Distribution curve with through the comparison of configuration as the reference hemozoin nonlinear response information of physical data structure 424.At 514 places, use non-linear multiple-harmonic Response Distribution curve that circuit will be associated with at least one volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after to comprise with comparing with reference to hemozoin nonlinear response information: with in the second harmonic response of being drawn, the third harmonic response of being drawn and the 4th harmonic response of being drawn one or more with compare with reference to hemozoin nonlinear response information.At 516 places, use non-linear multiple-harmonic Response Distribution curve that circuit will be associated with at least one volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after to comprise with comparing with reference to hemozoin nonlinear response information: with in situ detection to second harmonic response, in situ detection to third harmonic response and in situ detection to the 4th harmonic response at least one with compare with reference to hemozoin nonlinear response information.At 518 places, use non-linear multiple-harmonic Response Distribution curve that circuit will be associated with at least one volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after to comprise with comparing: will detected non-linear photon response and compare with reference to hemozoin nonlinear response information with reference to hemozoin nonlinear response information.

At 520 places, method 500 can further comprise based on this detected non-linear multiple-harmonic response energy with relatively produce response with reference to hemozoin nonlinear response information.At 522 places, produce this response and comprise to provide with using and stimulate in representing at least one of vision, audio frequency, sense of touch or the sense of touch of the non-linear multiple-harmonic Response Distribution curve that at least one volume of focus of inquiring after is associated through the pulse electromagnetic energy of spatial patterned.At 524 places, produce this response comprise based on this detected non-linear multiple-harmonic response energy with reference to hemozoin nonlinear response information relatively come to confirm the existence of malaria situation, do not exist or seriousness in one or more.At 526 places, produce this response comprise based on this detected non-linear multiple-harmonic response energy with relatively come to confirm the malaria infection score with reference to hemozoin nonlinear response information.

Shown in Figure 6 is the instance of method 600.At 610 places, method 600 comprises the pulse electromagnetic energy of using through spatial patterned to stimulate and inquires after doubtful at least one volume of focus that contains hemozoin.At 620 places, method 600 can further comprise uses circuit to compare with the information that is associated with reference to the hemozoin nonlinear response with the information of same that the doubtful non-linear multiple-harmonic response that contains at least one volume of focus of hemozoin is associated.At 630 places, method 600 can further comprise uses circuit to confirm whether the information that is associated with the doubtful non-linear multiple-harmonic response that contains at least one volume of focus of hemozoin is similar substantially with the information that is associated with reference to the hemozoin nonlinear response together.At 640 places, at least one result that method 600 can further comprise this comparison is sent to the user.

Shown in Figure 7 is an instance of method 700.At 710 places; Method 700 comprises through stimulating with the pulse electromagnetic energy inquires after the non-linear multiple-harmonic response that volume of focus extracts the hemozoin nano particle in the biological tissue in this volume of focus, and this pulse electromagnetic energy stimulation has from about 300 nanometers to about 10 microns resolution ratio [0.61* (peak value radiation wavelength/numerical aperture)].At 712 places; Draw the response of non-linear multiple-harmonic and comprise a multiplexed electromagnetic energy of pulse stimulated and be delivered to a plurality of volume of focus, characteristic that the multiplexed electromagnetic energy of this pulse stimulates and duration are enough to extract the non-linear multiple-harmonic response of the hemozoin nano particle that in this at least one volume of focus, exists.At 720 places, method 700 can further comprise uses circuit that non-linear multiple-harmonic response is compared with the reference hemozoin nonlinear response information that is configured as physical data structure 424.At 722 places, use circuit to compare and comprise: detected second harmonic response is compared with the reference hemozoin second harmonic response message that is configured as physical data structure 424 with non-linear multiple-harmonic response and with reference to hemozoin nonlinear response information.At 724 places, use circuit to compare and comprise: detected third harmonic response is compared with the reference hemozoin third harmonic response message that is configured as physical data structure 424 with non-linear multiple-harmonic response and with reference to hemozoin nonlinear response information.At 726 places, use circuit to compare and comprise: detected the 4th harmonic response and reference hemozoin the 4th harmonic response information that is configured as physical data structure 424 are compared with non-linear multiple-harmonic response and with reference to hemozoin nonlinear response information.

At 730 places, method 700 can further comprise based on the response of non-linear multiple-harmonic with relatively produce response with reference to hemozoin nonlinear response information.

Shown in Figure 8 is the instance of method 800.At 810 places; Method 800 comprises to be used information of same that circuit will be associated with the doubtful non-linear multiple-harmonic response that contains at least one volume of focus of hemozoin and responds the information that is associated with reference to the non-linear multiple-harmonic of hemozoin and compare, and this at least one volume of focus is to use pulse electromagnetic energy through spatial patterned to stimulate to inquire after.

Shown in Figure 9 is the instance of in-situ method 900.At 910 places, method 900 comprises via one or more sensors 442 and detects the non-linear multiple-harmonic response message that is associated with a plurality of volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after.At 920 places, method 900 can comprise confirm to be associated with a plurality of volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after, whether detected non-linear multiple-harmonic response message satisfied with a biological tissue in the threshold value index that is associated of not the existing of hemozoin nano particle, existence or seriousness.At 930 places, method 900 can further comprise in response to confirm to be associated with a plurality of volume of focus of using pulse electromagnetic energy through spatial patterned to stimulate to inquire after, whether detected non-linear multiple-harmonic response message satisfied with a biological tissue in the threshold value index that is associated of the existence of hemozoin nano particle produce response.

Shown in Figure 10 is the instance of method 1000.At 1010 places; Method 1000 comprises to stimulate with the multiplexed electromagnetic energy of pulse carries out optionally energy supply to a plurality of volume of focus of a biology in being tried, and the multiple-harmonic that characteristic that the multiplexed electromagnetic energy of this pulse stimulates and duration are enough to extract one or more the interior hemozoin nano particle that parasite had in free this a plurality of volume of focus responds.At 1012 places; A plurality of volume of focus are carried out optionally energy supply comprise and send pulse electromagnetic energy and stimulate, characteristic that this pulse electromagnetic energy stimulates and duration are enough to extract one or more in second harmonic response, third harmonic response or the 4th harmonic response of a free hemozoin nano particle that parasite had.At 1020 places, method 1000 comprises the comparison that produces between the multiple-harmonic of a being drawn response and the hemozoin multiple-harmonic characteristic information.

Shown in Figure 11 is the instance of method 1100.At 1110 places, method 1100 comprises and side by side produces a multimode details in a play not acted out on stage, but told through dialogues and inquire after and stimulate and a magnetic stimulation.At 1120 places, method 1100 is included under the situation that has magnetic field and detects and respond by inquire after the scattering that a plurality of hemozoin nano particles that stimulation inquires after are associated through multiplexed details in a play not acted out on stage, but told through dialogues.At 1130 places, method 1100 can further comprise the direction that changes magnetic stimulation.At 1140 places, method 1100 can further be included in and detect under the situation in the magnetic field that exist to change and respond by inquire after the scattering that a plurality of hemozoin nano particles that stimulation inquires after are associated through multiplexed details in a play not acted out on stage, but told through dialogues.At 1150 places, method 1100 can further comprise the intensity that changes magnetic stimulation.

At 1160 places, method 1100 can further be included in and detect under the situation in the magnetic field that exist to change and respond by inquire after the scattering that a plurality of hemozoin nano particles that stimulation inquires after are associated through multiplexed details in a play not acted out on stage, but told through dialogues.At 1162 places, the polarization that detection scattering response comprises the scattered information that manifests detects.At 1164 places, detect the scattering respond packet be contained in detect under the situation that has magnetic field with by inquire after in diffraction light, reverberation or the refract light that a plurality of hemozoin nano particles that stimulation inquires after are associated at least one through multiplexed details in a play not acted out on stage, but told through dialogues.

Shown in Figure 12 is the instance of method 1200.At 1210 places; Method 1200 comprises and side by side produces a multimode details in a play not acted out on stage, but told through dialogues and inquire after and stimulate and a magnetic stimulation; Characteristic and duration that stimulation is inquired after in this multimode details in a play not acted out on stage, but told through dialogues are enough to extract the details in a play not acted out on stage, but told through dialogues scattering response of the hemozoin nano particle in a biological tissue, and the characteristic of this magnetic stimulation and duration are enough to aim at the hemozoin nano particle in the biological tissue with magnetic means.

At 1220 places, method 1200 be included under the situation that has magnetic stimulation detect with by inquire after the electromagnetic radiation that a biology that stimulation the inquires after a plurality of target areas in being tried are associated through multiplexed details in a play not acted out on stage, but told through dialogues through scattering.

Shown in Figure 13 for plasmodium being carried out the instance of the method 1300 of thermal shock.At 1310 places, method 1300 comprises and a time-varying magnetic field energy is delivered to biology is tried, and this time-varying magnetic field energy is enough to make that the hemozoin nano particle in this plasmodium produces heat energy.

Shown in Figure 14 for to the doubtful instance that receives the method 1400 that a biology that the malaria original endoparasite infects tried to handle.At 1410 places, method 1400 comprises through changing the magnetic field applied fully so that make hemozoin nano particle in the plasmodium produce heat energy and has a plasmodial biology and send targetedly in being tried that magnetic heats doubtful.At 1412 places; Send targetedly the magnetic heating and comprise via one or more magnetic energy radiation assemblies an alternation external magnetic field to be stimulated and be provided to doubtful one or more districts with malaria infection that a biology is tried, characteristic that this alternation external magnetic field stimulates and duration are enough to cause the apoptosis that causes because of heat of malaria original endoparasite.At 1414 places, send and become the external magnetic field when this magnetic heating targetedly comprises one and be delivered to doubtful one or more districts that this biology is tried with hemozoin.At 1416 places, send this magnetic heating targetedly and be delivered to doubtful one or more districts that this biology is tried in external magnetic field that become, that spatially focus on when comprising with hemozoin with one.At 1418 places; Send this magnetic heating targetedly and comprise the pulsed magnetic field of sending an effective dose and stimulate with the Blang's relaxation that causes a hemozoin nano particle in the biological tissue and in the Neil relaxation one or more, this effective dose is enough to make the temperature in the district in the malaria original endoparasite to increase about 3 ° of C to about 22 ° of C.At 1420 places; Send this magnetic heating targetedly and comprise the pulsed magnetic field of sending an effective dose and stimulate with the Blang's relaxation that causes a hemozoin nano particle in the biological tissue and in the Neil relaxation one or more, this effective dose is enough to make the temperature in the district in the malaria original endoparasite to increase about 3 ° of C to about 10 ° of C.At 1422 places; Send this magnetic heating targetedly and comprise the pulsed magnetic sexual stimulus of sending an effective dose with the Blang's relaxation that causes a hemozoin nano particle in the biological tissue and in the Neil relaxation one or more, this effective dose is enough to make the temperature in the district in the malaria original endoparasite to increase about 3 ° of C to about 4 ° of C.At 1424 places, send this magnetic heating targetedly and comprise the magnetic energy of a focusing to be stimulated and be delivered to doubtful biology and tried with hemozoin via a radiofrequency launcher.At 1426 places, send this magnetic heating targetedly comprise change with dutycycle, magnetic field intensity, field frequency or field waveform that the external magnetic field that is applied is associated at least one.

Instance for method 1500 that the Blang's process or the Neil process of a hemozoin nano particle strengthened shown in Figure 15.At 1510 places, method 1500 comprises uses circuit will (a) to compare with reference to hemozoin nonlinear response information with the non-linear multiple-harmonic Response Distribution calibration curve information same (b) of using at least one volume of focus of inquiring after through the pulse electromagnetic energy stimulation of spatial patterned to be associated.At 1520 places, the magnetic field that method 1500 comprises a variation is applied to this at least one volume of focus, and the magnetic field energy of this variation is enough to make that at least one in vibration, translation or the rotation appears in the hemozoin nano particle.

The instance of the method for handling for plasmodium is parasitized 1600 shown in Figure 16.At 1610 places, method 1600 comprises uses circuit will (a) to compare with reference to hemozoin nonlinear response information with the non-linear multiple-harmonic Response Distribution calibration curve information same (b) of using at least one volume of focus of inquiring after through the pulse electromagnetic energy stimulation of spatial patterned to be associated.At 1620 places, method 1600 comprises at least one with vibration, the translation of the hemozoin nano particle in this at least one volume of focus of magnetic means initiation or in rotating.At 1622 places; Cause in vibration, translation and the rotation of the hemozoin nano particle in this at least one volume of focus at least one comprises with magnetic means: one or more conductive coils are carried out energy supply; Continue to be enough to produce the time of a time-varying magnetic field, the characteristic of this time-varying magnetic field and duration are enough to make that at least one in vibration, translation and the rotation appears in the hemozoin nano particle.At 1624 places; Cause in vibration, translation and the rotation of the hemozoin nano particle in this at least one volume of focus at least one comprises with magnetic means: being based in part on the non-linear multiple-harmonic Response Distribution curve that is associated with this at least one volume of focus stimulates with the pulsed magnetic field of relatively sending an effective dose with reference to hemozoin nonlinear response information, with the integrality of the organelle that influences a malaria infectious agent.At 1626 places; Cause in vibration, translation and the rotation of the hemozoin nano particle in the biological tissue at least one comprises with magnetic means: the electric current that applies that a radio-frequency coil sub-assembly is provided an effective dose; The characteristic that applies electric current of this effective dose and duration are enough to produce a magnetic field, and the characteristic in this magnetic field and duration are enough to make the hemozoin nano particle in the biological tissue one or more in vibration, translation and the rotation to occur.At 1628 places, cause in vibration, translation and the rotation of the hemozoin nano particle in the biological tissue at least one with magnetic means and comprise: the pulsed magnetic field of sending an effective dose stimulates so that one or more in vibration, translation and the rotation appears in the hemozoin nano particle in biological tissue.At 1630 places; Cause in vibration, translation and the rotation of the hemozoin nano particle in the biological tissue at least one comprises with magnetic means: the electromagnetic energy of sending an effective dose stimulates, so that in vibration, translation and the rotation one or more appears in the hemozoin nano particle in biological tissue.

Shown in Figure 17 is the instance of method 1700.At 1710 places, method 1700 comprise generation (a) under having the situation of magnetic stimulation with inquire after the biological tissue that stimulation inquires after by details in a play not acted out on stage, but told through dialogues in the detected scatter distributions calibration curve information that is associated of a plurality of target areas with (b) with reference to the comparison between the hemozoin details in a play not acted out on stage, but told through dialogues scattered information.At 1712 places, produce this relatively comprise use circuit will exist under the situation of magnetic stimulation with that a biology that stimulation the inquires after a plurality of target areas in being tried are associated by inquiring after through multiplexed details in a play not acted out on stage, but told through dialogues, detected scatter distributions curve is same compares with reference to hemozoin details in a play not acted out on stage, but told through dialogues scattered information.At 1714 places, produce this and relatively comprise and use circuit to use that Lay obtains because of the Burger illumination arrangement, detected scatter distributions curve under the situation of magnetic stimulation and to compare because of Burger illumination spectrum information existing with reference to the hemozoin Lay.

At 1720 places, method 1700 comprises and is based in part on this comparison and disturbs the hemozoin nano particle in this biological tissue with magnetic means.At 1722 places; Disturb hemozoin nano particle in the biological tissue to comprise with magnetic means and apply a magnetic stimulation, the characteristic of this magnetic stimulation and duration are enough to make the hemozoin nano particle in the biological tissue to influence the integrality of the digestibility food vacuole of malarial parasite.At 1724 places; Disturbing hemozoin nano particle in the biological tissue to comprise to apply an alternating magnetic field with magnetic means stimulates, and characteristic that this alternating magnetic field stimulates and duration are enough to make the hemozoin nano particle in the biological tissue to destroy the film of the digestibility food vacuole of malarial parasite.At 1726 places, disturbing hemozoin nano particle in the biological tissue to comprise to apply a time-varying magnetic field with magnetic means stimulates, and characteristic that this time-varying magnetic field stimulates and duration are enough to make the parasitemia level to reduce.

Shown in Figure 180 for being used to regulate the instance of the active method 1800 of plasmodium parasitism.At 1810 places; Method 1800 comprises through stimulating with the pulse electromagnetic energy inquires after the non-linear multiple-harmonic response that a plurality of volume of focus extract the hemozoin nano particle in a biological tissue; This pulse electromagnetic energy stimulation has less than the peak value irradiation level of about 200 m. gigawatt (GW)s/cm^2 and has at least one peak value radiation wavelength from about 690 nanometers to about 2100 nanometers, the biologically active that characteristic that this pulse electromagnetic energy stimulates and duration are enough to regulate the malaria infectious agent.At 1812 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength from about 1000 nanometers to about 1300 nanometers.At 1814 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength from about 1000 nanometers to about 1080 nanometers.At 1816 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength from about 1012 nanometers to about 1060 nanometers.At 1818 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength of about 1040 nanometers.At 1820 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength from about 700 nanometers to about 870 nanometers.At 1822 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength from about 750 nanometers to about 810 nanometers.At 1824 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength from about 760 nanometers to about 780 nanometers.At 1826 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has the peak value radiation wavelength of about 780 nanometers.At 1828 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more; The characteristic of this electromagnetic energy and duration make the part of the hemozoin nano particle in the biological tissue produce non-linear multiple-harmonic response, and this non-linear multiple-harmonic response has the wavelength from about 233 nanometers to about 434 nanometers.At 1830 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more; The characteristic of this electromagnetic energy and duration make the part of the hemozoin nano particle in the biological tissue produce non-linear multiple-harmonic response, and this non-linear multiple-harmonic response has the wavelength from about 175 nanometers to about 325 nanometers.

At 1832 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more; The characteristic of this electromagnetic energy and duration make the part of the hemozoin nano particle in the biological tissue produce non-linear multiple-harmonic response, and this non-linear multiple-harmonic response has the wavelength from about 175 nanometers to about 290 nanometers.At 1834 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises through stimulating with the pulse electromagnetic energy inquires after a hemozoin nano particle in the biological tissue and draws in second harmonic response, third harmonic response or the 4th harmonic response one or more, this second harmonic response of being drawn, third harmonic responds and the 4th harmonic response in one or more characteristic and duration apoptosis of being enough to cause an infectious agent.At 1836 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises through stimulating with the pulse electromagnetic energy inquires after a hemozoin nano particle in the biological tissue and draws in second harmonic response, third harmonic response or the 4th harmonic response one or more, this second harmonic response of being drawn, third harmonic responds and the 4th harmonic response in one or more characteristic and duration Apoptosis of being enough to cause a host cell that has infectious agent.At 1838 places; The non-linear multiple-harmonic that extracts the hemozoin nano particle in a biological tissue responds to comprise and applies an electromagnetic energy stimulation, and intensity that this electromagnetic energy stimulates and duration are enough to cause that the hemozoin nano particle in the biological tissue in the biological specimen produces antimicrobial energy.At 1840 places; The non-linear multiple-harmonic that extracts the hemozoin nano particle in a biological tissue responds to comprise and applies an electromagnetic energy stimulation; Intensity that this electromagnetic energy stimulates and duration are enough to cause a non-linear multiple-harmonic response, the propagation that the characteristic of this non-linear multiple-harmonic response and duration are enough to suppress the malaria infectious agent.At 1842 places; The non-linear multiple-harmonic response that extracts hemozoin nano particle in a biological tissue comprises the hemozoin nano particle in the biological tissue in these a plurality of volume of focus of electricity consumption magnetic energy irradiation one or more, and this electromagnetic energy has from about 300 nanometers to about 10 microns resolution ratio [0.61* (peak value radiation wavelength/numerical aperture)].

Shown in Figure 19 is the instance of anti-malarial methods of treatment 1900.At 1910 places; Method 1900 comprises and applies an electromagnetic energy in response to confirming in biological specimen, to have the hemozoin nano particle and stimulate, intensity that this electromagnetic energy stimulates and duration be enough to cause the hemozoin nano particle in the biological specimen produce one in vivo antimicrobial energy stimulate.At 1912 places, applying electromagnetic energy stimulates to comprise and sends an electromagnetic energy and stimulate, and this electromagnetic energy stimulates and has less than about 200 m. gigawatt (GW)s/cm^2 to the peak value irradiation level less than about 200 m. gigawatt (GW)s/cm^2.At 1914 places; Applying electromagnetic energy stimulates to comprise and sends a pulse duration, and this pulse duration has femtosecond pulse frequency, the radiation wavelength of the peak value from about 690 nanometers to about 2100 nanometers and from about 300 nanometers to about 10 microns resolution ratio [0.61* (the peak value radiation wavelength/numerical aperture)] of about 8 megahertzes.At 1916 places, apply the electromagnetic energy stimulation and comprise the electromagnetic energy stimulation that produces the peak value radiation wavelength that has from 1200 nanometers to about 1300 nanometers.At 1918 places, apply the electromagnetic energy stimulation and comprise the electromagnetic energy stimulation that produces the peak value radiation wavelength that has from 700 nanometers to about 1000 nanometers.

At least a portion of device described herein and/or process can be integrated in the data treatment system.Data handling system comprises one or more in the following substantially: the calculating individuality of processor 404, for example operating system, driver, graphical user interface and the application program of the memory of system unit shell, video display device, for example volatibility or nonvolatile memory, for example microprocessor or digital signal processor, one or more interactive devices are (for example; Touch pad, touch-screen, antenna or the like); And/or comprise backfeed loop and control motor the control system (for example, be used for detection position and/or speed feedback, be used for moving and/or the control motor of adjustment assembly and/or quantity).Data handling system can utilize suitable commercially available assembly to implement, for example being seen those assemblies in data computation/communication and/or network calculations/communication system usually.

Shown in instance 1, nonlinear optical response information, spectral information or the similar information that is associated with for example hemozoin nano particle can in vivo or in vitro technology or method be confirmed through one or more.

Instance 1: the in vivo analysis of hemozoin nano particle

A kind of method that is used to detect the non-linear multiple-harmonic response energy properties of the material with hemozoin nano particle is described.Analyze in order to carry out this, synthetic hemozoin crystal crushing is become fine powder, and be that five parts of isopropyl alcohols are suspended in the isopropyl alcohol than a hemozoin crystal with volume ratio.A drop of hemozoin/isopropanol suspension is positioned on the quartzy cover plate (0.25mm is thick), and lets the isopropyl alcohol evaporation to produce the hemozoin film.Further under 70 ° of C, the hemozoin film is heated one minute to eliminate any remaining concentrate.Hemozoin perfection of crystal and distribution this hemozoin film of assessment under 20 times to 100 times magnifying power.In the hemozoin film size of observed crystal be from below 1 micron to about 10 to 20 microns.

Using the experimental configuration of summarizing among Figure 20 that the hemozoin film is exposed to the pulse electromagnetic energy stimulates to extract the nonlinear optical response from the hemozoin nano particle.This experimental configuration is used a Ti in order to the wavelength of scanning from 690 to 1040nm: a sapphire laser and an optical parametric oscillator (OPO) provide and are in 690nm and stimulate to the pulse electromagnetic energy the total size of 1600nm.The quartzy cover plate that will contain the hemozoin film is attached to a nanoscale positioning table, with allow along optical axis (z scanning) and transversely surperficial (transversal scanning) come scanned samples.Sample is positioned between an achromatic objective (0.58 numerical aperture) and the achromatic condenser.A prism and filter system are radiated wavelength as spatial light filter with the peak value of containing from 175nm to 650nm.Use spectrometer or photomultiplier to detect non-linear multiple-harmonic response energy from the hemozoin particle.The various assemblies of experimental configuration are connected to a control unit interface (for example, computer), and this control unit interface comprises Ti: sapphire laser, OPO, detector and nanoscale positioning table.

In the one group of experiment that is being designed to measure the third harmonic response, scan the hemozoin film along the optical axis (z scanning) and the volume of focus of passing excitation energy with 810nm.In this example, use 100 times of object lens with 0.9 numerical aperture.Third harmonic is responded energy and exciting light collimates, make it pass UG-11 stained glass filter (transmission 250 to 350nm and 700 to 800nm wavelength) and 265nm groove (notch) filter, and send to photomultiplier.Directly measure anode current with electrometer, convert this electric current into a voltage linearly from photomultiplier, and via the data collecting card record on computers.Figure 21 A is depicted as the representative z scanning of using the method to carry out from the hemozoin film.Also illustrate the contrast of quartz substrate is measured.The width at the peak under two kinds of situation is all less than 5 μ m, with the beam size consistent (based on 100 times of object lens and 0.9 numerical aperture) less than 800nm.Depend on the size of hemozoin crystal and the amount that is filled with the volume of focus of hemozoin, the value change at hemozoin peak reaches 20%.Through at first carrying out the z scanning analysis, also use above-described parameter to carry out transversal scanning (Figure 21 B) to find maximum third harmonic response and to carry out transversal scanning in this z position.Shown in Figure 22 is with respect to the instance in the third harmonic response of the transversal scanning (1) on whole hemozoin film of the transversal scanning on the whole quartz substrate (2).

Square (the Aspot of third harmonic response efficiency and spot size ²) and square (τ of pulse width ²) be inversely proportional to, and therefore to monitor these two variablees and these two variablees are minimized be important.The diffractive technology of the use standard knife-edge volume of focus that the pulse electromagnetic energy stimulates that distributes, so as along optical axis in some positions measurement beam receive waist.Use autocorrelator to come the pulse width of measurement beam.Proved that through drawing laser excitation power P (ω) [mW] contrast third harmonic responding power P (3 ω) [arbitrary unit] as illustrated in fig. 23 stimulation is output as three rank dependences to power from the pulse electromagnetic energy.The double-log drawing of these data produces slope and is approximately 3 straight line.

Theme described herein is explained sometimes is the different assemblies that contain of other different assemblies or the different assemblies that connect with other different assemblies.Should be appreciated that these frameworks of describing only are instances, and in fact, can implement to realize many other frameworks of same functionality; On the concept nature meaning, be used for realizing that any assembly arrangement of same functionality " is associated " all effectively, thereby realize required functional.Therefore, can be regarded as each other " being associated " through combination with any two assemblies of realizing particular functionality among this paper, thus realize required functional, and no matter framework or intermediate module how.Equally; It is required functional to realize that any two assemblies that so are associated also can be regarded as each other " but with mode of operation connect " or " but connecting with mode of operation ", and any two assemblies that can so be associated also can be regarded as each other " but can connect with mode of operation " required functional to realize.But can comprise (but being not limited to) with the instantiation that mode of operation connects and to carry out mutual assembly in cooperation physically and/or physically; And/or can be with wireless mode mutual and/or carry out mutual assembly, and/or logically carry out mutual and/or can logically mutual assembly with wireless mode.

Figure 23 A and 23B are depicted as 3 rank power dependent of the hemozoin of on (Figure 23 A) lineal scale and (Figure 23 A) double-log scale, drawing.The 3 rank dependences that are hemozoin to incident power shown in Figure 24.Figure 25 is the voxel image of the hemozoin crystal 2 502 in infected erythrocyte 2504.Shown in Figure 26 is the erythrocytic two-dimensional space scanning of infected and uninfection, illustrates the intensity peak corresponding to the hemozoin crystal in the infected cell.Shown in Figure 27 for producing (THG) signal from the third harmonic of the hemozoin nano particle that suspends in water.Shown in Figure 28 is that absolute third harmonic from hemozoin produces (THG) power, illustrates 3 rank dependences.Shown in Figure 29 is that hemozoin-water third harmonic produces (THG) intensity.The two-dimensional graphics that produces (THG) signal for the third harmonic that becomes along with source and detected wavelength shown in Figure 30.Figure 31 A is depicted as the malaria checkout equipment 102c according to an embodiment.Figure 31 B is to use the monitor of external detection setting or the instance of treating apparatus.Figure 32 A is depicted as and uses third harmonic to produce the monitor of (THG) detection setting or the instance of treating apparatus.Figure 32 B is depicted as according to the monitor of the use dark field detection of an embodiment or the instance of treating apparatus.

Shown in Figure 33 is malaria checkout equipment 102c, wherein can implement one or more methods or technology, for example detects or handle malaria infection on one's own initiative.In one embodiment, malaria checkout equipment 102c comprises a details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300, an optical package 112 and a sensor cluster 440.In one embodiment, this malaria checkout equipment comprises: an optical package 112, this optical package 112 have a sample side, a detector side and pass an optical axis wherein; And a dark ground illuminator 3302, this dark ground illuminator approaches the sample side of optical package 112.

In one embodiment, dark ground illuminator 3302 comprises: an agent structure 3402, this agent structure have a plurality of waveguide sub-assemblies 3406; And a sensor cluster 440, this sensor cluster comprises one or more sensors 442, these sensors be configured to receive come a sample that free dark ground illuminator 3302 inquires after, through the electromagnetic energy of scattering.In one embodiment; These a plurality of waveguide sub-assemblies 3406 comprise one first electromagnetic energy emitter and one second electromagnetic energy emitter at least, and at least one in the illumination intensity of this second electromagnetic energy emitter, peak value radiation wavelength or the pulse frequency is different from this first electromagnetic energy emitter.In one embodiment, sensor cluster 440 comprises a sensor array, is used to obtain the electromagnetic energy scattered information that depends on angle.In one embodiment, sensor cluster 440 comprises a sensor array, is used to obtain the electromagnetic energy scattered information that depends on wavelength.

Referring to Figure 33,34A and 34B, in one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises dark ground illuminator 3302, and this dark ground illuminator especially has an agent structure 3402 and an a plurality of waveguide sub-assembly 3406 with aperture 3404.In one embodiment, dark ground illuminator 3302 is configured at the one or more incidence angles place with respect to an optical axis of optical package 112 electromagnetic energy is delivered at least one focal zone through a plurality of waveguide sub-assemblies 3406.For instance, in one embodiment, one or more incidence angles place that these a plurality of waveguide sub-assemblies 3406 are oriented in respect to an optical axis of optical package 112 focuses on electromagnetic energy at least one focal zone.In one embodiment, dark ground illuminator 3302 is configured to around an axis rotation that is parallel to this optical axis substantially.In one embodiment, dark ground illuminator 3302 is configured at two or more places, azimuths with respect to an optical axis of optical package 112 a plurality of electromagnetic energy beams are delivered on the focal zone.In one embodiment, dark ground illuminator 3302 is configured to electromagnetic energy is delivered on two or more positions, focal zone at two or more incidence angle places.

In one embodiment, these a plurality of waveguide sub-assemblies 3406 comprise the one or more electromagnetic energy waveguides 3408 that are configured to be connected at least one electromagnetic energy emitter 3410.For instance, in one embodiment, one or more in these a plurality of waveguide sub-assemblies 3406 comprises at least one sleeve component 3412 that is configured to receive one or more electromagnetic energy waveguides 3408.In one embodiment, one or more in these a plurality of waveguide sub-assemblies 3406 comprises at least one sleeve component 3412 that is configured to receive one or more lens 3414, polarizer 3416 and electromagnetic energy emitter 3410.

In one embodiment, these a plurality of waveguide sub-assemblies 3406 axially distribute around aperture 3404.In one embodiment, these a plurality of waveguide sub-assemblies 3406 are arranged around aperture 3404 with the pattern of one or more radial symmetric.In one embodiment, these a plurality of waveguide sub-assemblies 3406 are arranged around aperture 3404 with one or more rotational symmetric patterns.In one embodiment, these a plurality of waveguide sub-assemblies 3406 are to arrange around aperture 3404 about the symmetrical one or more concentric pattern of a radial axis that are parallel to this optical axis substantially.In one embodiment, these a plurality of waveguide sub-assemblies 3406 are to arrange around aperture 3404 about the rotational symmetric one or more concentric pattern of an axis that are parallel to this optical axis substantially.In one embodiment, one or more in these a plurality of waveguide sub-assemblies 3406 is configured in aperture 3404, electromagnetic energy collimated.

In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one polarizer 3416.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one linear polarization.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one circular polarisers.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one adjustable polarizer.

In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one lens 3414.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one lens 3414, and these lens 3414 are configured to the electromagnetic energy by these at least one electromagnetic energy emitter 3410 radiation is collimated.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one lens 3414, and these lens are configured to focus on the electromagnetic energy by these at least one electromagnetic energy emitter 3410 radiation.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one microlens array.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one planoconvex spotlight.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one non-spherical lens.

In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one multi-focus lens.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one zoom lens.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one liquid lens.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one tunable liquid lens.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises at least one liquid mirror.In one embodiment, at least one in these a plurality of waveguide sub-assemblies 3406 comprises the liquid mirror of at least one Electrowetting control.

In one embodiment, electromagnetic energy emitter 3410 comprises one or more energy radiation assemblies 104.In one embodiment, electromagnetic energy emitter 3410 comprises at least one in laser instrument, laser diode or the light emitting diode.In one embodiment, electromagnetic energy emitter 3410 comprises at least one in quantum dot, Organic Light Emitting Diode, tiny cavity light-emitting diode or the polymer LED.In one embodiment, electromagnetic energy emitter 3410 comprises at least one femtosecond laser.

In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises the device that is used for details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is attached to removably optical package 112.For instance, in one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises slip ring 3326, Lock Part 3328 and adapter 3330, is used for optical package 112 is connected to dark ground illuminator 3302.In one embodiment; Be used for details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is comprised a draw bail that is positioned on the details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 with the device that removably is attached to optical package 112, this draw bail is connected to the corresponding draw bail on the optical package 112.For instance; In one embodiment; Be used for details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is comprised a coupling member with the device that removably is attached to optical package 112; This coupling member has a surface of defining an internal path, this internal path the size and be sized to frictional fit on the outer surface of optical package 112.In one embodiment; Be used for the device that details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is attached to optical package 112 with removably is comprised at least one of bayonet socket draw bail, frictional fit draw bail, snap draw bail or thread joined structure; These structures have one or more minor structures, and these minor structures are adapted to be bayonet socket draw bail, frictional fit draw bail, snap draw bail or the thread joined structure of the correspondence that is connected on the sub-assembly 112.In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 is configured to through bayonet socket connection, frictional fit connection, snap connects or thread connection is attached to optical package 112 with removably.In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises a draw bail, and this draw bail is configured to details in a play not acted out on stage, but told through dialogues indirect illumination equipment to optical package 112.In one embodiment, this draw bail is configured to through bayonet socket connection, frictional fit connection, snap connects or thread connection is attached to optical package 112 with this details in a play not acted out on stage, but told through dialogues indirect illumination equipment with removably.

Referring to Figure 33; In one embodiment; Optical package 112 especially comprises one or more optical package agent structures 3310; These optical package agent structures are connected to detector 440 (for example, photoelectric detector, electromagnetic energy sensor, charge coupled device, video camera or analog) via one or more adapters 3312 an end.In one embodiment, optical package 112 comprises at least one planoconvex spotlight 3314 and at least one lens retaining member 3316.In one embodiment, optical package 112 comprises at least one polarizer 3318 and at least one polarizer retaining member 3320.In one embodiment, optical package 112 comprises at least one retaining member 3322, and this retaining member 3322 is configured to a lens assembly is anchored in the optical package agent structure 3310.In one embodiment, optical package 112 comprises at least one objective lens component 3324.

In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises and is used for adjusting the device 3304 of dark ground illuminator with respect to the distance of optical package 112 along an axis of an optical axis that is parallel to optical package 112 substantially.In one embodiment, be used to adjust dark ground illuminator and comprise a rotatable adjustment structure 3332, the size of this structure and be sized to and connect a screwed part 3334 with respect to the device 3304 of the distance of optical package 112.In one embodiment, be used to adjust dark ground illuminator and comprise a dark ground illuminator clamp structure 3333 with respect to the device 3304 of the distance of optical package 112, this member can be operated rotation or the displacement with constraint dark ground illuminator 3302.

Referring to Figure 34 B, in one embodiment, dark ground illuminator 3302 comprises a plurality of sensors 442 and a plurality of device of inquiring after.In one embodiment, these a plurality of sensors 442 be configured to capture come a sample that free dark ground illuminator 3302 inquires after, through the electromagnetic energy of scattering.In one embodiment; These a plurality of each of inquiring after in the device all comprise a waveguide sub-assembly 3406; This waveguide sub-assembly comprises the one or more electromagnetic energy waveguides 3408 that are configured to be connected at least one electromagnetic energy emitter 3410, and these are a plurality of inquires after one or more incidence angles place that device is oriented in respect to an optical axis of an optical package electromagnetic energy is focused at least one focal zone in this at least one aperture 3404.

In one embodiment; These are a plurality of inquire after device side by side or sequentially with at least one first inquire after stimulate and one second inquire after to stimulate and be directed on the focal zone, this second is inquired after in illumination intensity, peak value radiation wavelength or the pulse frequency of stimulation at least one and is different from this and first inquires after stimulation.In one embodiment, these are a plurality of inquire after device side by side or sequentially to one first of major general inquire after stimulate and one second inquire after to stimulate and be directed on the focal zone, this second inquire after stimulate have be different from this first inquire after stimulation an incidence angle.In one embodiment, these are a plurality of inquire after device side by side or sequentially to one first of major general inquire after stimulate and one second inquire after to stimulate and be directed on the focal zone, this second is inquired after to stimulate to have and is different from this and first inquires after the peak value radiation wavelength of stimulation.In one embodiment; These are a plurality of inquire after device side by side or sequentially to one first of major general inquire after stimulate and one second inquire after to stimulate and be directed on the focal zone, this second is inquired after stimulation and is different from this with respect to the azimuth of an optical axis of an optical package and first inquires after stimulation.In one embodiment, these a plurality of devices of inquiring after side by side or sequentially will be inquired after at two or more incidence angle places to stimulate and be provided on two or more positions, focal zone.

In one embodiment,, a plurality of independently sensors in these a plurality of sensors 442 a plurality ofly inquire after in the device one or more but being connected to this with mode of operation, and right to form one or more sensors-inquire after device.For instance; In one embodiment; Forming a sensor-inquire after device is arranged the sensor of a part and is positioned in the optical path; This optical path allow these sensors capture freely to form this sensor-inquire after device to a part inquire after a sample that device inquires after, through the electromagnetic energy of scattering, the while is avoided the electromagnetic energy without scattering (for example, directly being reflected) substantially.In one embodiment, form a sensor-inquire after device to the sensor of a part be positioned as only capture freely to form this sensor-inquire after device to a part inquire after a sample that device inquires after, through the electromagnetic energy of scattering.In one embodiment, the sensor that forms a sensor-the inquire after right part of device be positioned as miss the light that directly is reflected and only capture freely to form this sensor-inquire after device to a part inquire after a sample that device inquires after, through the electromagnetic energy of scattering.

In one embodiment, these sensors-inquire after device depends on the electromagnetic energy scattered information of angle or depends on the electromagnetic energy scattered information of wavelength at least one from a sample acquiring of being inquired after by dark ground illuminator 3302 being configured to.For instance, in one embodiment, these are a plurality of inquires after device and at the one or more incidence angles place with respect to an optical axis of an optical package electromagnetic energy side by side or is sequentially focused at least one focal zone of a sample.In one embodiment, this one or more sensors-inquire after device to obtaining the electromagnetic energy scattered information that depends on wavelength.In one embodiment, dark ground illuminator 3302 comprises a plurality of device and a plurality of sensors 442 inquired after, and these inquire after device and sensor forms a part that defines the agent structure 3402 of at least one aperture 3404.

In one embodiment, these a plurality of each of inquiring after in the device comprise a waveguide sub-assembly 3406, and this waveguide sub-assembly 3406 has the one or more electromagnetic energy waveguides that are configured to be connected at least one electromagnetic energy emitter 3410.In one embodiment, one or more incidence angles place of being oriented in respect to an optical axis of an optical package of these a plurality of waveguide sub-assemblies focuses on electromagnetic energy at least one focal zone in this at least one aperture 3404.In one embodiment, dark ground illuminator 3302 comprises a plurality of sensors 442, these sensors be configured to capture come a sample that free this dark ground illuminator 3302 inquires after, through the electromagnetic energy of scattering.

Referring to Figure 35; In one embodiment; Be used to adjust dark ground illuminator and comprise a calculation element 402, slidably adjust in the structure at least one but this calculation element is connected to a rotatable adjustment structure, threaded adjustment structure or one with mode of operation with respect to the device 3304 of the distance of optical package 112.In one embodiment, calculation element 402 is configured to via this rotatable adjustment structure, threaded adjustment structure or slidably adjusts in the structure at least one and actuate the displacement of dark ground illuminator with respect to optical package 112 along an axis of an optical axis that is parallel to optical package 112 substantially.

In one embodiment; Be used to adjust dark ground illuminator and comprise at least one outside threaded loop configuration with respect to the device 3304 of the distance of optical package 112; The threaded loop configuration in this outside is configured to the loop configuration with an inner threaded of engage thread engagement, and the loop configuration of this inner threaded makes dark ground illuminator 3302 be shifted with respect to optical package 112 along an axis of an optical axis that is parallel to optical package 112 substantially when being actuated with respect to the threaded loop configuration rotation in this outside the time.

In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises the device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies 3406 radiation.In one embodiment; The device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises at least one calculation element 402, but this calculation element is connected in an electromechanical assembly, opto-mechanical assembly, electro-optical package or the acousto-optic assembly at least one with mode of operation.In one embodiment, the device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises at least one calculation element 402, but this calculation element is connected to an electro-optic lens system with mode of operation.

In one embodiment; The device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises at least one calculation element 402, but this calculation element is connected to one or more tunable optical modules with mode of operation.In one embodiment; The device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises a calculation element 402; But this calculation element is connected at least one optical waveguide with mode of operation, and this optical waveguide is configured to change the incidence angle by one or more electromagnetic energy sent in these a plurality of waveguide sub-assemblies 3406.In one embodiment, the device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises a calculation element 402, but this calculation element is connected at least one tunable liquid lens with mode of operation.In one embodiment, the device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises a calculation element 402, but this calculation element is connected at least one optics microprism with mode of operation.In one embodiment, the device 3502 that is used to adjust by the incidence angle of the electromagnetic energy of these a plurality of electromagnetic energy waveguide sub-assemblies radiation comprises a calculation element 402, but this calculation element is connected to one or more microlens arrays with mode of operation.

In one embodiment, details in a play not acted out on stage, but told through dialogues indirect illumination equipment 3300 comprises the device of the incidence angle that is used to adjust the electromagnetic energy of being sent by dark ground illuminator 3302.In one embodiment; The device 3502 that is used to adjust the incidence angle of the electromagnetic energy of being sent by dark ground illuminator 3302 comprises a calculation element 402, but this calculation element is connected in a mechanical optical assembly, electro-optical package or the acousto-optic assembly at least one with mode of operation.In one embodiment; The device 3502 that is used to adjust the incidence angle of the electromagnetic energy of being sent by dark ground illuminator 3302 comprises a calculation element 402; But this calculation element is connected at least one optical waveguide with mode of operation, and this optical waveguide is configured to change the incidence angle by one or more electromagnetic energy sent in these a plurality of waveguide sub-assemblies 3406.In one embodiment, the device 3502 that is used to adjust the incidence angle of the electromagnetic energy of being sent by dark ground illuminator 3302 comprises a calculation element 402, but this calculation element is connected at least one tunable liquid lens with mode of operation.In one embodiment, the device 3502 that is used to adjust the incidence angle of the electromagnetic energy of being sent by dark ground illuminator 3302 comprises a calculation element 402, but this calculation element is connected at least one optics microprism with mode of operation.In one embodiment, the device 3502 that is used to adjust the incidence angle of the electromagnetic energy of being sent by dark ground illuminator 3302 comprises a calculation element 402, but this calculation element is connected to one or more microlens arrays with mode of operation.

In one embodiment, malaria checkout equipment 102c is configured to the red blood cell that receives malaria infection is detected and counts.In one embodiment, malaria checkout equipment 102c adopts spectrum to learn to improve the sensitiveness and the specificity of diagnosis in diagnosis.

In one embodiment, malaria checkout equipment 102c comprises: an optical package 112, this optical package 112 have a sample side, a detector side and pass an optical axis wherein; A dark ground illuminator 3302, this dark ground illuminator 3302 approaches the sample side of optical package 112; And be used for adjusting the device 3304 of dark ground illuminator with respect to the distance of optical package 112 along an axis of an optical axis that is parallel to optical package 112 substantially.In one embodiment, malaria checkout equipment 102c comprises a detector 440, and this detector 440 is configured to take and the one or more microphotos sample that comes free dark ground illuminator to inquire after, that be associated through the electromagnetic energy of scattering.In one embodiment, malaria checkout equipment 102c comprises an objective table sub-assembly that is configured to the fastening sample that is used to analyze.In one embodiment, dark ground illuminator 3302 comprises a plurality of waveguide sub-assemblies 3406, and the agent structure 3402 with aperture 3404, and this aperture 3404 is aimed at along an axis that is parallel to an optical axis substantially.In one embodiment, optical package 112 be configured to receive come a sample that free dark ground illuminator 3302 inquires after, through the electromagnetic energy of scattering.In one embodiment, malaria checkout equipment 102c comprises the sample stage sub-assembly that is configured to admit during operation a biological specimen chamber.In one embodiment, this sample stage sub-assembly is configured to along x, biological specimen of y or z direction location.In one embodiment, this sample stage sub-assembly comprises a stepping motor, but this stepping motor is connected to a calculation element 402 with mode of operation and is configured to locate the biological specimen chamber based on the tiling scheme.

Referring to Figure 35, in one embodiment, system 100 especially comprises a testing circuit 3602, and this testing circuit is configured to obtain at place, one or more visual field one or more microphotos of a biological specimen.In one embodiment, this testing circuit 3602 comprises one or more detectors 440, and these one or more detectors are configured to obtain at place, one or more visual field and at one or more depths of focus place one or more microphotos of a biological specimen.

In one embodiment, system 100 comprises a resolution ratio and revises circuit 3604, and this resolution ratio is revised circuit and is configured to revise the pixel counts of at least one microphoto and produces at least one first modified microphoto.In one embodiment, this resolution ratio modification circuit 3604 comprises the one or more calculation elements 402 that are configured to revise the microphoto pixel resolution.In one embodiment; This resolution ratio is revised circuit 3604 and is comprised at least one calculation element 402 and one or more data structure 424; These one or more data structures 424 can be operated producing and to store a threshold value fiducial value, and produce and store one based on this threshold value fiducial value and be used for nuclear (kernel) that a plurality of pixels that form a microphoto are filtered.

In one embodiment; System 100 comprises one and filters nuclear generation circuit 3606; This filtration nuclear produces circuit and is configured to produce one and is used for coming nuclear that a plurality of pixels that form this first modified microphoto are filtered based on a filtering feature, and produces at least one first conspicuousness image of this at least one modified microphoto of expression.

In one embodiment; System 100 comprises an object identification circuit 3608; This object identification circuit is configured to be identified in a plurality of pixel group that this first conspicuousness image middle finger is shown in one or more objects of forming images in this at least one microphoto; And produce the one or more continuous part of a curve map, this curve is shown in this at least one microphoto a plurality of pixel group of the object of these one or more imagings of indication.In one embodiment; Object identification circuit 3608 comprises a circuit, and this circuit is configured to discern at least one the pixel group in the indication the following in this first conspicuousness image: the hemozoin nano particle in this at least one microphoto, receive the red blood cell of malaria infection or the red blood cell of uninfection.In one embodiment, object identification circuit 3608 is configured to confirm that this biological specimen receives the probability of malaria infection, and level of confidence definite and that this biological specimen is joined by the determined probability correlation of malaria infection.

In one embodiment; System 100 comprises a circuit 3610; This circuit is configured to the one or more continuous part of this curve map that is produced and the references object information that is stored in one or more data structures 424 are compared, and relatively produces a response based on this of the one or more continuous part of this curve map that is produced and this references object information.In one embodiment; This circuit 3610 that is configured to the one or more continuous part of this curve map that comparison produces comprises one or more data structures 424; Store references object information in these one or more data structures, this references object information comprises the red blood cell plot information, receive the red blood cell plot information of malaria infection or in the hemozoin plot information at least one.In one embodiment; This circuit 3610 that is configured to the one or more continuous part of this curve map that comparison produces comprises a circuit 3612; This circuit is configured to produce a response; This response comprises at least one in the following: the red blood cell that receives malaria infection that exists in object identifying information, morbid state, parasitemia level, red-cell count, this at least one microphoto and total erythrocytic ratio, or with the probability and the level of confidence information of an object associated of being discerned.

In one embodiment; System 100 comprises a spatial frequency and produces circuit 3614; This spatial frequency produces the spatial frequency spectrum that circuit 3614 is configured at least one first pixel sub group of definite this at least one microphoto; With this spatial frequency spectrum of this first pixel sub group with compare with reference to spatial frequency spectrum information, and relatively produce a response with reference to spatial frequency spectrum information based on this spatial frequency spectrum of this first pixel sub group and this.In one embodiment; Spatial frequency produces circuit 3614 and comprises one or more data structures 424, and these data structures have with reference to red blood cell spatial frequency spectrum information, with reference to the red blood cell spatial frequency spectrum information that receives malaria infection or with reference in the hemozoin spatial frequency spectrum information at least one.In one embodiment, spatial frequency produces circuit 3614 and further is configured to use at least one spatial frequency spectrum with this at least the first pixel sub group of trooping in scheme or the study scheme to be divided into one or more information groups.In one embodiment, this spatial frequency produces circuit 3614 and further is configured to use at least one this spatial frequency spectrum with this at least the first pixel sub group in the following to be divided into one or more information groups: Fuzzy C mean value troop scheme, graph theory scheme, layering troop scheme, K mean value troop scheme, position sensing hash scheme (Locality-Sensitive Hashing protocol), mixed Gaussian scheme, the modeling scheme based on the scheme of trooping of model, the weighting of trooping, expectation maximization scheme, principal component analysis scheme or splitting scheme.

In one embodiment, the dark ground illuminator system comprises one and inquires after stimulation circuit 3616 and a testing circuit 3602.In one embodiment, inquiring after stimulation circuit 3616 is configured to the electromagnetic energy stimulation is directed on one or more volume of focus of a sample.In one embodiment; Inquire after stimulation circuit 3616 and comprise one first electromagnetic energy emitter 3410 and one second electromagnetic energy emitter 3410 at least, this second electromagnetic energy emitter 3410 has the peak value radiation wavelength that is different from this first electromagnetic energy emitter 3410.

In one embodiment, testing circuit 3602 be configured to obtain at one or more incidence angles place free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.In one embodiment, testing circuit 3602 be configured to obtain at place, one or more azimuths with respect to an optical axis free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.In one embodiment; This testing circuit 3602 comprises one or more detectors, and these detectors are configured to obtain at place, one or more visual fields and at one or more depths of focus place free this to inquire after the electromagnetic energy through scattering of the sample that stimulation circuit inquires after.In one embodiment, testing circuit is configured to obtain and comes free this to inquire after an electromagnetic energy scattered information sample, that depend on wavelength that stimulation circuit is inquired after.

Shown in Figure 37 is the instance of method 3700.At 3710 places, method 3700 comprises the one or more microphotos that use a testing circuit to obtain at place, one or more visual field a biological specimen.At 3712 places, the one or more microphotos that obtain biological specimen comprise based on the tiling scheme and take at least one first microphoto and one second microphoto.At 3714 places, the one or more microphotos that obtain biological specimen are included in one or more microphotos that one or more depths of focus place obtains biological specimen.

At 3720 places, method 3700 comprise revise in these one or more microphotos at least one resolution ratio and produce at least one first modified microphoto.At 3722 places, revise microphoto resolution ratio and comprise the operation of microphoto being carried out the adjustment size.At 3724 places, revise microphoto resolution ratio and comprise microphoto execution pixel merging (binning) scheme.At 3726 places, to revise microphoto resolution ratio and comprise prioritization scheme of execution, this prioritization scheme is adjusted the size of the one or more pixels in this microphoto based on an object detection scheme.

At 3730 places, method 3700 comprises through this first modified microphoto being filtered the microphoto that produces one first warp filtration based on a filtering scheme at least.At 3732 places, generation first comprises through the microphoto that filters carries out convolution to produce the microphoto that a warp filters with a filtration nuclear and one or more pixel parameters that are associated with this first modified microphoto.At 3734 places, whether generation first satisfies a threshold value through the intensity that the microphoto that filters comprises one or more pixels of confirming this at least the first modified microphoto.At 3736 places, produce this and first comprise through the microphoto that filters at least a portion of this microphoto is filtered to examine and carried out convolution with one.At 3738 places, produce this and first comprise through the microphoto that filters and to filter nuclear with one and carry out convolution, and confirm to be directed against a plurality of continuous part of a curve map of a plurality of pixels based on the result of this convolution with this one or more pixel parameters.At 3740 places, produce this and first comprise through the microphoto that filters and to filter nuclear with one and carry out convolution, and produce and this first probable value image of being associated through the microphoto of filtration with one or more pixel parameters.

At 3742 places, produce this and first comprise through the microphoto that filters and to use in troop scheme or the study scheme at least one that this at least one microphoto is divided into one or more pixel sub groups.At 3744 places, produce this and first comprise through the microphoto that filters and to use in the following at least one that this at least one microphoto is divided into one or more pixel sub groups: Fuzzy C mean value troop scheme, graph theory scheme, layering troop scheme, K mean value troop scheme, position sensing hash scheme, mixed Gaussian scheme, modeling scheme, expectation maximization scheme, principal component analysis scheme or splitting scheme based on the scheme of trooping of model, the weighting of trooping.

At 3750 places, method 3700 comprises through the object of discerning this this biological specimen in the microphoto that filters confirms a kind of morbid state.At 3752 places, confirm that this morbid state comprises probable value and threshold value index are compared with the object in the identification microphoto.At 3754 places, confirm that this morbid state comprises based on a plurality of parts that link to each other of a probable value image with a curve map that relatively comes to confirm the contents of object in this first modified microphoto of expression of threshold value index.At 3756 places, confirm that this morbid state comprises the probability that definite biological specimen receives malaria infection.At 3758 places, confirm that this morbid state comprises the level of confidence of confirming to receive with this biological specimen the definite probability correlation couplet of an institute of malaria infection.At 3760 places, confirm this morbid state comprise Dole's Ma Ge-Mendelsohn (Dulmage-Mendelsohn) decomposing scheme is applied to microphoto at least a portion to discern a plurality of continuous parts.

At 3770 places, method 3700 is included in one or more microphotos that one or more depths of focus place obtains a biological specimen.At 3780 places, method 3700 comprises the one or more microphotos that make this biological specimen that is obtained and stores in the physical data structure 424.

Instance 2: detect the malaria in the biological specimen

Image acquisition

Referring to Figure 38, in one embodiment, malaria checkout equipment 102c takes microphoto from many visual fields to a biological specimen (for example, blood sample).In one embodiment; When obtaining microphoto, transmit microphoto as a stream one or more calculation elements 402 from a sensor cluster 440, up to being tiled in one of microphoto on this biological specimen till defining pattern and having accomplished by scan table.Store each microphoto filing and the processing of a storage device (for example, data structure 424) to be used for medical diagnosis on disease into, sample stage moves to next imageable target on the biological specimen with sample simultaneously.

Automation detects

In one embodiment; The automation of infected cell is detected and counting is that combination through a plurality of statistical methods realizes, these statistical methods confidential interval (mark that has parasitic blood cell) on the infected probability of body and the parasitemia one by one quantize.

Find remarkable object

In one embodiment, through the resolution ratio that big or small operation at first adjusts this microphoto is adjusted in pixel merging or application another kind, so that the size of each pixel in the optimization microphoto is to be used for object detection.In one embodiment, receive malaria infection to as if through measuring its bright degree detects: infected cell shows as brighter than the cell of uninfection.In one embodiment, the t testing filters is applied to adjust the microphoto after the size, so that measure the pixel probability (null hypothesis) brighter unlike background.Specify a threshold value (for example, 0.01) to null hypothesis, make any pixel that will have all can be regarded as one than the remarkable object that more becomes clear of background pixel less than the p value of null hypothesis threshold value.In one embodiment, filter nuclear background pixel is defined as certain the big or small district that has around tested pixel.This nuclear is carried out convolution on whole microphoto, and this filter can be presented as the non-linear filtration device, to the linear filter of nonlinear images intermediate, or the linear filter of microphoto.In one embodiment, be linear filter with the t test implementation, to increase computational speed to the nonlinear images intermediate.

In one embodiment, can pixel and the whole microphoto that distributes as a setting be compared.Yet filter the advantage that exists uniqueness with the nuclear with certain mark of microphoto size: laterally brightness is adaptive is intrinsic as far as small nut.Conspicuousness test about this nuclear is insensitive for the variation of the illumination intensity on the whole visual field, and has ignored many objects bigger than desirable target.

Object identification

In one embodiment, can be significant the red blood cell of a plurality of pixels in microphoto, and these pixels need be identified as single object.In one embodiment, a plurality of continuous part of the curve map through confirming remarkable pixel comes identifying object (for example, receiving the cell or the like of malaria infection).For instance, Dole Ma Ge-Mendelsohn decomposition of adjacency matrix is confirmed to discern unique remarkable pixel group.In one embodiment, the part that each that found links to each other all possibly be a cell (having the p value of being returned by the t test) that receives malaria infection.

To specific spectrum screening

In order to improve the specificity of diagnosis, in one embodiment, make false positive results minimum through spectrum (for example, the spatial frequency) analysis of carrying out to microphoto.For instance; In one embodiment; For each remarkable object, from the microphoto of original (unjustified size), select to have a plurality of windows of the big or small pixel region of difference, and definite FFT is to produce the spectrum signature of each object.In one embodiment, object spectrum and the template from previous spectrum storehouse through the object analyzed of being stored are compared.In one embodiment, the infected cell that this storehouse comprises many samples of known infected cell, automatically detects, and a large amount of tester, for example dust, scratch, fingerprint, healthy blood, defocus, defective illumination or the like.Use statistical test with the spectrum of each object with compare from the reference spectrum in this storehouse one or more so that calculate the identical probability of spectrum signature.In one embodiment, use the threshold value (two spectrums have identical distribution) of null hypothesis and screen object, and selection those objects consistent with the characteristic of infected cell.In an embodiment of spectrum screening, in various coordinate systems, integrate 2D FFT, with at x, y, radially and the power spectrum that obtains object on the angle direction.These power spectrum are actually the probability density function of the Energy distribution on whole spatial frequency in the microphoto.Use Andrei Kolmogorov-Vladimir Smirnov (Komolgorov-Smirnov) and test the null hypothesis of each power spectrum that compares with the reference spectrum in calculating and the storehouse.In another embodiment, carry out template matches through the crosscorrelation of the 2D reference spectrum in 2D object spectrum and the storehouse.Again, use the conspicuousness test and be matched with probability from a spectrum in the storehouse with the measuring object spectrum.

Diagnosis

In one embodiment, after object identification and spectrum screening,, only the object of satisfied threshold probability as infected cell is counted together with the p value that is associated of each object.In one embodiment, together with the diagnosis that is calculated, the in fact infected probability of this individuality comes together to produce infected/uninfection.In one embodiment, produce response and comprise the number of reporting infected cell as the infected cell and the ratio of total cell, wherein the confidential interval to this ratio is 95%.

Spectroscopy in the ATL is practised

In one embodiment, a process identification circuit has comprised the storehouse that under controlled condition, has a plurality of objects of known identities.In one embodiment, handle the microphoto of infected cell, and spectrum is saved in the storehouse to confirm the identity of remarkable object.In one embodiment, handle the microphoto of uninfection sample, thereby and be saved in the storehouse and can not count diagnosis report by the positive findings that these are wrong to be used for refusing wrong positive findings.In one embodiment, will be stored in from the spectrum information of treated microphoto in the data structure storehouse with the p value that is associated.Belong to by the probability of template matches process according to an object spectrum, calculate the variance and the mean value of storehouse spectrum with a plurality of weights its storehouse classification that assigns to (for example, dust particle or the like).

Multi dimensional object identification

In one embodiment, through using a objective table, and add the z axle and be used for focusing on, can obtain more spatial informations about an object 3 enterprising line scannings of dimension.For instance, can a very smooth object be different from more spherical object through moving the focal plane and taking another microphoto with same radius.An extra embodiment of process identification is in sample, to take two or two above microphotos from identical visual field in different focal planes.In one embodiment, carry out the deconvolution that microphoto piles up under the situation of some scattering function of 3 dimension shapes of reconstruct object knowing or do not know to be used for.Equally, used template matches, but be more to use in the various dimensions now a storehouse.In one embodiment, be used for a dimension of optical wavelength, can the method that be associated with monochromatic microphoto be applied to color photomicrography through interpolation.Can use compound mode in Spatial Dimension and optical wavelength dimension, to carry out analysis of spectrum subsequently.

In one embodiment, among this paper maybe with one or more assemblies be called " being configured to ", " can be configured to ", " can operate/operate with ", " through adaptive/can be adaptive ", " can ", " can meet/accord with " or the like.Assembly and/or the assembly of inactive state and/or the assembly of stand-by state of active state can be contained substantially in these terms (for example, " being configured to "), only if requirement made in addition in context.

Aforementioned detailed description is through using block diagram, flow chart and/or instance to state the various embodiments of device and/or process.So far; These block diagrams, flow chart and/or instance contain one or more functions and/or operation; The reader will recognize, the hardware that each function in these block diagrams, flow chart and/or the instance and/or operation can be through broad range, software, firmware or almost its any combination come independently and/or jointly implement.In addition, using " beginning ", " end " or " stopping " frame in the block diagram is not in order to indicate the beginning of any function among the figure or the restriction of end.Can these flow charts or figure be incorporated in other the flow chart or figure, in these other flow chart or figure, before or after the function shown in the application's the figure, carry out extra function.In one embodiment, the several portions of theme described herein can be implemented via special IC (ASIC), field programmable gate array (FPGA), digital signal processor (DSP) or other integrated form.Yet; Whole or the part of some aspects of the embodiment that this paper discloses (for example can be embodied as one or more computer programs of on one or more computers, moving comparably in integrated circuit; In one or more programs of moving on one or more computer systems), on one or more processors 404 operation one or more programs (for example; One or more programs of on one or more microprocessors, moving), almost any combination of firmware or above each item; And according to this disclosure content, design circuit and/or write the code that is used for software and/or firmware will be the those skilled in the art understand fully.In addition, the mechanism of theme described herein can be distributed as program product in a variety of forms, and regardless of the particular type of the signal bearing media that is used in fact carrying out this distribution, the illustrative embodiment of theme described herein all is suitable for.The limiting examples of signal bearing media comprises the following: but the medium of record type, for example floppy disc, hard disk drive, compact disk (CD), digital video disks (DVD), digital magnetic tape, computer storage or the like; And the medium of transport-type, for example numeral and/or analogue communication medium (for example, fiber optic cables, waveguide, wire communication link, wireless communication link (for example, transmitter, receiver, transceiver, TL, RL or the like) or the like).

Though illustrated and described the particular aspects of theme of the present invention described herein; But the reader will understand; Teachings based on this paper; Under the situation that does not break away from theme described herein and relative broad range thereof, can make a change and revise, and therefore, appended claims will belong to the true spirit of theme described herein and all these changes and modification in the scope in its encompasses.Substantially; Among this paper and especially (for example at appended claims; The main body of appended claims) term that uses in is set substantially as " open " term (for example to be; Term " comprises " and should be interpreted as " comprise but be not limited to ", and term " has " should be interpreted as " having at least ", and term " comprises " should be interpreted as " including but not limited to " or the like).In addition,, will in claim, state this scope clearly so, and under the situation that does not have this statement thing, not have this scope if the claim that is intended to be introduced is stated a given number of thing.For instance, in order to help to understand, appending claims possibly use introductory phrase " at least one " and " one or more " to introduce claim statement thing.Yet; The use of these phrases should not be interpreted as hint and require all to be limited to the claim that only contains this kind statement thing to any specific rights that contains this claim of introducing statement thing through the claim statement thing that indefinite article " " or " " introduce; Even when same claim comprises introductory phrase " one or more " or " at least one " and for example also is so (for example, " one " and/or " one " should be interpreted as usually and mean " at least one " or " one or more ") during indefinite article such as " " or " "; Introduce the use that claim is stated the definite article of thing for being used for, situation also is like this.In addition; Even state the given number of the claim of being introduced a statement thing clearly; This statement thing also should be interpreted as usually mean this statement thing at least number (for example; There is not the plain statement of " two statement things " of other modifier to mean at least two statement things usually, perhaps two or more statement things).In addition; Be similar in use in those instances of convention of " at least one among A, B and the C "; To be configured on the meaning of this convention be set (for example, " at least one a system that has among A, B and the C " will comprise but be not limited to have A separately, have B separately, have C separately, have A and B jointly, have A and C jointly, have B and C jointly and/or have the system of A, B and C or the like jointly) to this kind substantially.Be similar in use in those instances of convention of " at least one among A, B or the C etc. "; To be configured on the meaning of this convention be set (for example, " at least one a system that has among A, B or the C " will comprise but be not limited to have A separately, have B separately, have C separately, have A and B jointly, have A and C jointly, have B and C jointly and/or have the system of A, B and C or the like jointly) to this kind substantially.Usually; No matter be in description, claims or diagram; Separation property word and/or the phrase that presents two or more selectivity terms all is to be understood that any one or the possibility of these two terms that has comprised in one in these terms, these terms for having considered, only if regulation made in addition in context.For instance, phrase " A or B " will be generally understood as the possibility that comprises " A " or " B " or " A and B ".

About appended claims, wherein the operation of statement can be carried out with any order substantially.And, though be to present various operating processes in order, should be appreciated that, can carry out various operations with the order that is different from illustrated order, perhaps can side by side carry out various operations.The instance of these alternative order can comprise order overlapping, staggered, that interrupt, that reorder, that increase progressively, preparation, that replenish, simultaneously, reversing or other variation is only if regulation made in addition in context.In addition, for example " in response to ", " relating to " or the adjectival term of other past tense substantially and be not intended to and get rid of these modification, only if regulation made in addition in context.

Though this paper has disclosed various aspects and embodiment, other aspect and embodiment are also considered.Various aspects and embodiment that this paper discloses are for illustrative purposes, and are not that intention limits, and wherein real scope and spirit are indicated by appended claims.

Claims (43)

1. details in a play not acted out on stage, but told through dialogues indirect illumination equipment comprises:

A dark ground illuminator comprises

An agent structure; This agent structure has an aperture and a plurality of waveguide sub-assembly; These a plurality of waveguide sub-assemblies comprise the one or more electromagnetic energy waveguides that are configured to be connected at least one electromagnetic energy emitter, and one or more incidence angles place that these a plurality of waveguide sub-assemblies are oriented in respect to an optical axis of an optical package focuses on electromagnetic energy at least one focal zone in this aperture; And

Be used for adjusting along an optical axis of an optical axis that is parallel to this optical package substantially the device of a dark ground illuminator distance with respect to an optical package.

2. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1; Wherein this is used for comprising a calculation element with respect to the device of this dark ground illuminator distance of optical package adjustment; But this calculation element is connected to a rotatable adjustment structure, threaded adjustment structure or one with mode of operation and slidably adjusts in the structure at least one, and this calculation element is configured to slidably to adjust in the structure at least one via this rotatable adjustment structure, this threaded adjustment structure or this and actuates this dark ground illuminator with respect to the carry out displacement of an optical package along an axis of an optical axis that is parallel to this optical package substantially.

3. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, wherein this dark ground illuminator is configured to many electromagnetic energy beams are delivered on the focal zone in this aperture at two or more places, azimuths with respect to an optical axis of an optical package.

4. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, wherein this dark ground illuminator is configured to electromagnetic energy is delivered on two or more positions, focal zone at two or more incidence angle places.

5. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1, wherein at least one in these a plurality of waveguide sub-assemblies comprises at least one polarizer.

6. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1 further comprises:

Be used to adjust the device of an incidence angle of the electromagnetic energy of sending by this dark ground illuminator.

7. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 6; Wherein this device that is used to adjust this incidence angle of the electromagnetic energy of being sent by this dark ground illuminator comprises a calculation element, but this calculation element is connected in a mechanical optics assembly, electro-optical package or the acousto-optic assembly at least one with mode of operation.

8. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 6; Wherein this device that is used to adjust this incidence angle of the electromagnetic energy of being sent by this dark ground illuminator comprises a calculation element; But this calculation element is connected at least one optical waveguide with mode of operation, and this optical waveguide is configured to change an incidence angle by one or more electromagnetic energy sent in these a plurality of waveguide sub-assemblies.

9. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 1 further comprises:

A draw bail, this draw bail are configured to this details in a play not acted out on stage, but told through dialogues indirect illumination equipment is attached to an optical package with removably.

10. details in a play not acted out on stage, but told through dialogues indirect illumination equipment as claimed in claim 9, wherein this draw bail is configured to through a bayonet socket connection, a frictional fit connection, a snap connection or a thread connection this details in a play not acted out on stage, but told through dialogues indirect illumination equipment is attached to this optical package with removably.

11. a malaria checkout equipment comprises:

An optical package, this optical package have a sample side, a detector side and pass an optical axis wherein;

A dark ground illuminator, this dark ground illuminator approach this sample side of this optical package, and this dark ground illuminator comprises

A plurality of waveguide sub-assemblies, and

An agent structure, this agent structure have an aperture, and this aperture is along an axis alignment that is parallel to an optical axis substantially;

Be used for adjusting the device of a dark ground illuminator with respect to the distance of this optical package along an axis of an optical axis that is parallel to an optical package substantially;

This optical package be configured to receive come a sample that free this dark ground illuminator inquires after, through the electromagnetic energy of scattering; And

A detector, this detector be configured to take with this sample that comes free this dark ground illuminator to inquire after, these one or more microphotos that are associated through the electromagnetic energy of scattering.

12. a system comprises:

A testing circuit, this testing circuit are configured to obtain at place, one or more visual field one or more microphotos of a biological specimen;

A resolution ratio is revised circuit, and this resolution ratio is revised circuit and is configured to revise a pixel counts of at least one microphoto and produces at least one first modified microphoto;

One is filtered nuclear and produces circuit; This filtration nuclear produces circuit and is configured to produce one and is used for coming nuclear that a plurality of pixels that form this first modified microphoto are filtered based on a filtering feature, and produces at least one first conspicuousness image of this at least one modified microphoto of expression; And

An object identification circuit; This object identification circuit is configured to be identified in a plurality of pixel group in this first conspicuousness image; One or more objects that these pixel group indications form images in this at least one microphoto; And this object identification circuit is configured to produce the one or more continuous part of a curve map representing a plurality of pixel groups, these one or more objects that these pixel groups indications form images in this at least one microphoto.

13. system as claimed in claim 12 further comprises:

A circuit; This circuit is configured to the one or more continuous part of this curve map that is produced and the references object information that is stored in one or more data structures are compared, and relatively produces a response based on this of the one or more continuous part of this curve map that is produced and this references object information.

14. system as claimed in claim 13; Wherein this circuit that is configured to the one or more continuous part of this curve map that comparison produces comprises one or more data structures; Store references object information in these one or more data structures, this references object information comprises the red blood cell plot information, receive the red blood cell plot information of malaria infection or in the hemozoin plot information at least one.

15. system as claimed in claim 12 further comprises:

A spatial frequency produces circuit, is configured to

Confirm a spatial frequency spectrum of at least one first pixel sub group of this at least one microphoto,

With this spatial frequency spectrum of this first pixel sub group with compare with reference to spatial frequency spectrum information, and

Relatively produce a response based on this spatial frequency spectrum of this first pixel sub group and this with reference to this of spatial frequency spectrum information.

16. method as claimed in claim 20, wherein this spatial frequency produces circuit and further is configured to use at least one this spatial frequency spectrum with this at least the first pixel sub group in the following to be divided into one or more information groups: Fuzzy C mean value troop scheme, graph theory scheme, layering troop scheme, K mean value troop scheme, position sensing hash scheme, mixed Gaussian scheme, the modeling scheme based on the scheme of trooping of model, the weighting of trooping, expectation maximization scheme, principal component analysis scheme or splitting scheme.

17. system as claimed in claim 12; Wherein this testing circuit comprises one or more detectors, and these one or more detectors are configured to obtain at place, one or more visual field and at one or more depths of focus place one or more microphotos of a biological specimen.

18. system as claimed in claim 12, wherein this resolution ratio modification circuit comprises the one or more calculation elements that are configured to revise a microphoto pixel resolution.

19. system as claimed in claim 12; Wherein this resolution ratio modification circuit comprises at least one calculation element and one or more data structure; These one or more data structures can be operated producing and to store a threshold value fiducial value, and produce and store one based on this threshold value fiducial value and be used for nuclear that a plurality of pixels that form a microphoto are filtered.

20. a method comprises:

Use a testing circuit to come to obtain one or more microphotos of a biological specimen at place, one or more visual field;

Revise in these one or more microphotos at least one a resolution ratio and produce at least one first modified microphoto;

Produce one first microphoto through this at least the first modified microphoto being filtered through filtering based on a filtering scheme; And

A plurality of objects through discerning this this biological specimen in the microphoto that filters are confirmed a kind of morbid state.

21. method as claimed in claim 20 is wherein revised this microphoto resolution ratio and comprised prioritization scheme of execution, this prioritization scheme is adjusted the size of the one or more pixels in this microphoto based on an object detection scheme.

22. method as claimed in claim 20 wherein produces this and first comprises in the following at least one through the microphoto that filters: filters nuclear with one and carry out convolution to produce the microphoto of a warp filtration with one or more pixel parameters that are associated with this first modified microphoto; With a plurality of parts that link to each other that filter that nuclear and these one or more pixel parameters are carried out convolution and confirm to be directed against a curve map of a plurality of pixels based on a result of this convolution; Or use in troop scheme or the study scheme at least one that this at least one microphoto is divided into this one or more pixel sub groups.

23. method as claimed in claim 20 confirms that wherein this morbid state comprises

Receive with the comparison of threshold value index or with this biological specimen based on a probable value image one of malaria infection a level of confidence joining of definite probability correlation confirm in a plurality of parts that link to each other of a curve map at least one, the contents of object in this first modified microphoto of this graphical representation.

24. an equipment comprises:

A dark ground illuminator has

An agent structure, this agent structure defines at least one aperture,

A plurality of devices of inquiring after; These are inquired after device and comprise a waveguide sub-assembly separately; This waveguide sub-assembly comprises the one or more electromagnetic energy waveguides that are configured to be connected at least one electromagnetic energy emitter, and these are a plurality of inquires after one or more incidence angles place that device is oriented in respect to an optical axis of an optical package electromagnetic energy is focused at least one focal zone in this at least one aperture; And

A plurality of sensors, these sensors be configured to capture come a sample that free this dark ground illuminator inquires after, through the electromagnetic energy of scattering.

25. equipment as claimed in claim 1, but wherein a plurality of independently sensors in these a plurality of sensors are connected to this with mode of operation and a plurality ofly inquire after in the device one or more, right to form one or more sensors-inquire after device.

26. equipment as claimed in claim 25, wherein this one or more sensors-inquire after device is to obtaining in electromagnetic energy scattered information that depends on angle or the electromagnetic energy scattered information that depends on wavelength at least one.

27. equipment as claimed in claim 25; Wherein a plurality of independently sensors in these a plurality of sensors are positioned in the light path; This light path has been avoided not the electromagnetic energy from the sample scattering substantially, and this sample is to inquire after in the device one or more and inquire after this of a part is a plurality of by forming these sensors-inquire after device.

28. equipment as claimed in claim 1, wherein these a plurality of devices of inquiring after side by side or sequentially focus on electromagnetic energy at least one focal zone in this at least one aperture at the one or more incidence angles place with respect to an optical axis of an optical package.

29. equipment as claimed in claim 1; Wherein this a plurality of inquire after device side by side or sequentially with at least one first inquire after stimulate and one second inquire after to stimulate and be directed on the focal zone, this second inquire after stimulate have be different from this first inquire after stimulation an incidence angle.

30. equipment as claimed in claim 1; Wherein this a plurality of inquire after device side by side or sequentially with at least one first inquire after stimulate and one second inquire after to stimulate and be directed on the focal zone, this second is inquired after to stimulate to have and is different from this and first inquires after the peak value radiation wavelength of stimulation.

31. equipment as claimed in claim 1, wherein this a plurality of inquire after device side by side or sequentially at two or more incidence angle places with a plurality of inquire after to stimulate be provided on two or more positions, focal zone.

32. equipment as claimed in claim 1 further comprises:

Be used for adjusting the device of a dark ground illuminator with respect to the distance of this optical package along an axis of an optical axis that is parallel to an optical package substantially; And

Be used to adjust device by an incidence angle of these a plurality of electromagnetic energies of inquiring after the device radiation.

33. a malaria checkout equipment comprises:

An optical package, this optical package have a sample side, a detector side and pass an optical axis wherein; And

A dark ground illuminator, this dark ground illuminator approach this sample side of this optical package, and this dark ground illuminator comprises

A plurality of waveguide sub-assemblies,

A sensor cluster, this sensor cluster comprises one or more sensors, these one or more sensors be configured to receive come a sample that free this dark ground illuminator inquires after, through the electromagnetic energy of scattering; And

An agent structure, this agent structure has at least one aperture, and this at least one aperture is along an axis alignment that is parallel to an optical axis substantially.

34. malaria checkout equipment as claimed in claim 33 further comprises:

Be used for adjusting the device of a dark ground illuminator with respect to the distance of this optical package along an axis of an optical axis that is parallel to this optical package substantially.

35. malaria checkout equipment as claimed in claim 33 further comprises:

Be used to adjust the device of an incidence angle of the electromagnetic energy of sending by this dark ground illuminator.

36. malaria checkout equipment as claimed in claim 33 further comprises:

A detector, this detector be configured to take with this sample that comes free this dark ground illuminator to inquire after, these one or more microphotos that are associated through the electromagnetic energy of scattering.

37. a dark ground illuminator comprises:

An agent structure, this agent structure defines at least one aperture;

A plurality of devices of inquiring after; These are inquired after device and comprise a waveguide sub-assembly separately; This waveguide sub-assembly comprises the one or more electromagnetic energy waveguides that are configured to be connected at least one electromagnetic energy emitter, and these are a plurality of inquires after one or more incidence angles place that device is oriented in respect to an optical axis of an optical package electromagnetic energy is focused at least one focal zone in this at least one aperture; And

A plurality of sensors, these sensors be configured to capture come a sample that free this dark ground illuminator inquires after, through the electromagnetic energy of scattering.

38. dark ground illuminator as claimed in claim 37, but wherein these a plurality of sensors are connected to this with mode of operation and a plurality ofly inquire after a plurality of in the device and independently inquire after device, and be configured to obtain the electromagnetic energy scattered information that depends on angle.

39. dark ground illuminator as claimed in claim 37, but wherein these a plurality of sensors are connected to this with mode of operation and a plurality ofly inquire after a plurality of in the device and independently inquire after device, and be configured to obtain the electromagnetic energy scattered information that depends on wavelength.

40. dark ground illuminator as claimed in claim 37 further comprises:

A draw bail, this draw bail are configured to through a bayonet socket connection, a frictional fit connection, a snap connection or a thread connection this dark ground illuminator is attached to an optical package with removably.

41. a dark ground illuminator system comprises:

Inquire after stimulation circuit for one, this is inquired after stimulation circuit and is configured to an electromagnetic energy stimulation is directed on one or more volume of focus of a sample; And

A testing circuit, this testing circuit be configured to obtain at one or more incidence angles place free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.

42. dark ground illuminator as claimed in claim 41 system, wherein this testing circuit obtain at place, one or more azimuths with respect to an optical axis free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.

43. dark ground illuminator as claimed in claim 41 system; Wherein this testing circuit comprises one or more detectors, in order to obtain at place, one or more visual fields and at one or more depths of focus place free this inquire after a sample that stimulation circuit inquires after, through the electromagnetic energy of scattering.

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