CN105403690A - Micro-device applied to biomedicine and use method thereof - Google Patents
Micro-device applied to biomedicine and use method thereof Download PDFInfo
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- CN105403690A CN105403690A CN201510770386.9A CN201510770386A CN105403690A CN 105403690 A CN105403690 A CN 105403690A CN 201510770386 A CN201510770386 A CN 201510770386A CN 105403690 A CN105403690 A CN 105403690A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B7/00—Microstructural systems; Auxiliary parts of microstructural devices or systems
- B81B7/02—Microstructural systems; Auxiliary parts of microstructural devices or systems containing distinct electrical or optical devices of particular relevance for their function, e.g. microelectro-mechanical systems [MEMS]
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/32—Surgical cutting instruments
- A61B17/3205—Excision instruments
- A61B17/3207—Atherectomy devices working by cutting or abrading; Similar devices specially adapted for non-vascular obstructions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/32—Surgical cutting instruments
- A61B17/3205—Excision instruments
- A61B17/3207—Atherectomy devices working by cutting or abrading; Similar devices specially adapted for non-vascular obstructions
- A61B17/320758—Atherectomy devices working by cutting or abrading; Similar devices specially adapted for non-vascular obstructions with a rotating cutting instrument, e.g. motor driven
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/34—Trocars; Puncturing needles
- A61B17/3478—Endoscopic needles, e.g. for infusion
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00017—Electrical control of surgical instruments
- A61B2017/00022—Sensing or detecting at the treatment site
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00017—Electrical control of surgical instruments
- A61B2017/00022—Sensing or detecting at the treatment site
- A61B2017/00084—Temperature
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/00234—Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
- A61B2017/00345—Micromachines, nanomachines, microsystems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/06—Measuring instruments not otherwise provided for
- A61B2090/064—Measuring instruments not otherwise provided for for measuring force, pressure or mechanical tension
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/02—Details of sensors specially adapted for in-vivo measurements
- A61B2562/028—Microscale sensors, e.g. electromechanical sensors [MEMS]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
Abstract
The invention discloses a micro-device applied to biomedicine and a use method thereof. Each micro-device comprises an external film and a peculiarity. The size scope of the micro-device is from 1 angstrom to 5 millimeters.
Description
Background technology
Although in the past one, between Two decades years, medicine and biological field achieve marked improvement, particularly in genomics.The conventional method of modern medicine, comprises as the prevention of the diseases such as cancer, Diagnosis and Treat do not become substantially, still mainly concentrates in the method for macroscopic view.Such as, the diagnosis of current disease uses macro-data and information, as chemical composition level in the body of body temperature, blood pressure, scan-image, measurement etc.Can the DNA detection technique of extensive diagnosis various diseases even emerging, do not set up yet one in real time, reliable, accurately, fast, cost effective method.The disease of many high incidences and high mortality, comprises cancer and heart disease, is difficult to early stage Accurate Diagnosis.In addition, most of existing diagnostic techniques has invasive.
About the treatment of disease, worse off.Up to the present, many operations still have very invasive, high cost, high complication risk, and need release time of growing very much.Some treatment even destroys healthy cell or tissue.One of such example uses evaporation process Therapeutic cancer, and that kills is not only cancer cell, also has normal, healthy cell.That to be the treatment of blood-related diseases be usually another example is invasive, excessive risk (as cardiac operation), very expensive and in many cases, postoperative patient cannot return to normal, positive life style.
The just prevention of another aspect, except health diet and the regular exercise of general standard, the cause of numerous disease, as cancer, still unclear.This shortage about cause of disease knowledge, the disappearance directly causing preventive medicine to be developed.
The problem of above-mentioned modern medicine in prevention, Diagnosis and Treat, be to a great extent to lack on a microscopic level (cell biology level) to the understanding of pathology, lack effective drug delivery and efficient reaction mechanism, the monitoring lacking the microscopic scale of Noninvasive and prevention mechanism and method, and the efficient target methods for the treatment of diseases of shortage Noninvasive and technology.
In recent years, there is a few thing nanometer technology being applied to biological aspect, be mainly used in external.These external work facilitate the development in this field.The people such as Pantel discuss the work using micro electronmechanical (MEMS) sensor to detect cancer cell in blood and marrow in vitro, with reference to KlausPanteletal., NatureReviews, and 2008,8,329.
Wozniak and Chen use laser optical tweezer and micropin measure the power that sample cell produces, with reference to M.A.Wozniaketal., NatureReviews, and 2009,10,34.The people such as Kubena are in U.S. Patent No. 6,922, discuss in 118 and detect biopreparate by MEMS (micro electro mechanical system) (MEMS), the people such as Weissman are in U.S. Patent No. 6,330, discuss the interpolation growth detecting biological substance with micro electronmechanical (MEMS) sensor in 885.
Due to above-mentioned all limitation, on a basic level, many problems that modern medicine faces are still unresolved, comprise targeted therapy and the cancer prevention of external microscopic scale, the treatment of normal tissue and the minimum early diagnosis of organ damage and Noninvasive.But up to the present, most publication is confined to the independent example for vitro detection always, use that structure is relatively simple, size greatly but the system that often function is limited.Also there is not the report applied with microscopic scale in advanced biomedical sector, particularly body about highly integrated, multifunction micro device (being less than or equal to 5 millimeters).
Summary of the invention
The present invention relates to novel microdevice and using method thereof, be used for realizing the prevention from suffering from the diseases on microscopic scale, diagnosis or treatment.It uses the far-ranging new function reached by the functional integration of microscopic scale, also use the manufacturing process of advanced microdevice as ic manufacturing technology.Other manufacturing process be applicable to include but not limited to mechanics, chemistry, chemico-mechanic, galvanochemistry mechanics, electric biological chemistry mechanics, biological chemistry, biological chemistry mechanics, optics, photoelectricity, Light Electrical, chemical thermodynamics, thermodynamics, thermochemistry mechanics and integrated circuit and semiconductor fabrication and technique.
In a class application wherein, microdevice comprises multiple parts, and the size of each parts is little to sub-biological cell to canonical biometric cell size (or from one micron to hundreds of micron).Multiple parts of feature richness can be integrated into one independently on microdevice to realize comprising medical diagnosis on disease on microscopic scale, treatment, the function such as clean.
According to different expectation functions, the range of size of the microdevice in the present invention is from 1 dust to 5 millimeters, the function of microdevice comprises sensing, detection, measurement, diagnosis, detection, analysis, insoluble drug release, selective absorbing, selective adsorption, performs prevention flow process and surgical intervention or above combination.
On the one hand, microdevice provided by the invention is for medical applications or for living biological systems.
In certain embodiments, each device includes an adventitia, and has the one being selected from following properties: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, chemistry of micro-organisms, chemistry of micro-organisms mechanics, micro-electric biological chemistry mechanics, micro-galvanochemistry mechanics, micro-electric biological chemistry mechanics, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics and micro-superconduction mechanical characteristic.The range of size of microdevice is roughly 1 dust to 5 millimeter.Such as, the microdevice with a mechanical characteristic can be described as again mechanics device, usually means that this microdevice can realize the function of an expection according to this mechanical characteristic.In certain embodiments, microdevice comprises two kinds of being selected from following characteristic: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics and micro-superconduction mechanical characteristic.In some other embodiments, microdevice and then can comprise and is selected from following characteristic: powered surfaces, chemical potential, geometric match, electromagnetism and electrochemical potential attract.One or more additional performances can make microdevice be adsorbed to target biology organ or cyto-architectural surface.
In certain embodiments, microdevice has differentiation cancer cell and Normocellular ability.Device is by measuring the microscopic characteristics of cell to realize above-mentioned functions, and microscopic characteristics includes but not limited to biological chemistry, physics, electricity, electromagnetics, biological chemistry, mechanics, acoustics, calorifics and optical characteristics.
In certain embodiments, microdevice can measure organ or eucaryotic cell structure (such as there is exploratory probe) microscopic characteristics, diagnose organ and eucaryotic cell structure on the microscale level, carry required chemical substance to required organ and eucaryotic cell structure (such as there is microsyringe or the miniature vessel of transport capacity), carry needed for medicine to organ and eucaryotic cell structure, and organ or eucaryotic cell structure selected by operating.Microdevice in non-invasive mode or real-time can realize required function.
In certain embodiments, microdevice can measure at least one be selected from following characteristic: surface charge, electrostatic potential, electrochemical potential, electromotive force, surface wettability degree, contact angle, viscosity, temperature, density, friction, hardness, surface tension, trace level chemical substance concentration, hydrophobicity, water wettability, pH value, fluid flow, pressure, optical characteristics, absorption and sorption or its combination.
Microdevice in the present invention can comprise GPS, signal transmitter, signal receiver, micro motor, microdriver or radio communication chip.So, microdevice can realize local positioning, local qualification and local message communication and location, position.
In further embodiments, microdevice and then can comprise and is selected from following function: chemicals conveying function, controlled chemistry thing conveying function, mechanical behavior, controlled mechanical behavior, selective absorbing, selective adsorption, the detection of microscopic scale, constant supply power scholarship and moral conduct is, controlled electric scholarship and moral conduct is, controlled electrochemical mechanical behavior, controlled electrochemical scholarship and moral conduct are, the behavior of controlled electrochemical study biology, controlled electrochemical study biology mechanical behavior, the triggering behavior based on above-mentioned signal and the triggering behavior based on external command.These functions can be the results after microdevice or its subelement process.
In further embodiments, microdevice can make pre-programmed to following Trigger Function, comprises chemicals conveying, mechanical action, charge injection, light transmitting, applies voltage and cool or heating organic structure.These functions can enroll the chip on device, and this chip has storage and logic function, when such as transducing signal or response signal reach preset value, can trigger the action or combination of actions startup preset.In some instances, the function of triggering can realize by using the following parameters such as the external signal that electric charge, resting potential, electromotive force, electrochemical potential, surface current, body electric current, surface wettability degree, adhesion characteristics, hydrophobicity, water wettability, flowing property, electric field, magnetic field, sound field, temperature, optical wavelength and/or intensity, friction force and friction factor, hardness, pressure and device detect that comprise.
In certain embodiments, microdevice can have the ability that (such as from 6 to 8 or from 6.8 to 7.4) dissolves within the scope of certain pH value, and dissolution time is between 30 seconds to 3 days.This means that microdevice can complete dissolving in this pH value range in above-mentioned dissolution time.
In certain embodiments, microdevice includes and is selected from following material: polymkeric substance, organic material and compatible inorganic material relative to organic material." relatively compatible " refers to usually and mammalian organism has certain bio-compatibility, can not cause infection, disorder, not accommodate other negative effects (as immunogenic effect).Microdevice can use the combination of biomaterial or biomaterial and other materials to manufacture, or is coated with one deck biomaterial as intermediate interface or surface coating.Biomaterial comprises natural material, synthetic material, or the compound substance of natural material (comprising autologous, allosome or xenogenesis) and synthetic material.The example of these materials includes but not limited to silicon, silicon dioxide, polysilicon, silicon nitride, silicon oxynitride, oxycarbide, carbonitride, the polymeric material (these materials have bio-compatibility because of himself inertia) for integrated circuit device package, fat, peptide, hydroxyapatite (HA), calcium phosphate, calcium carbonate, magnesium phosphate, ammonium magnesium phosphate, silicate, and nautilicone.
In certain embodiments, the range of size of microdevice from about 1 dust to about 100 millimeters (such as, the application relevant to eucaryotic cell structure, DNA or bacterium, to human cell's testing and analysis), from about 1 dust to about 100 microns (such as the application of selective exposure), from about 0.01 micron to about 5 millimeters, from about 10 microns to about 2 millimeters or from about 100 microns to about 1.5 millimeters.
In certain embodiments, microdevice comprises sub-device to unit of integrated multiple commaterial and realizes one or more functions.The example of suitable material includes but not limited to organic polymer, organic material, biomaterial, biochemical material, inorganic conductor, inorganic semiconductor, inorganic insulator and pottery.The example of suitable biomaterial includes but not limited to bioartificial materials, natural biologic material, the biomaterial of cultivation and the combination of natural biologic material and bioartificial materials.
In certain embodiments, microdevice is integrated microdevice, comprises and is at least selected from following a kind of function, comprises sensing, detection, measurement, calculating, analysis, diagnosis, logical process (judgement decision-making), transmits and operate or surgical functions.
In further embodiments, microdevice and then include and be selected from following hardware, comprise voltage comparator, four-point probe, arithmetical unit, logical circuit, memory cell, micro cutter, miniature hammer, minisize shielding device, miniature dyestuff, Miniature nail, micro-knife, microneedle, miniature wire clamp, miniature tweezer, Miniature optical absorber, micromirror, minisize shielding device, micro-wheels, microfilter, Optical Microchopper, micropulverizer, micropump, miniature absorber, miniature signal sensor, microbit, miniature absorber, miniature tester, miniature vessel, miniature extractor, signal projector, signal generator, friction sensor, charge sensor, temperature sensor, hardness tester, sonic generator, light wave generator, hot generator, miniature refrigerator and charge generators.These terms are well-known in the art, and its general definition is applicable to the present invention.Such as, filtrator can be microdevice (or miniature sub-device), can be isolated by the size of each component; Clearer is one and can cleans, polishing, grinds, scrubs the microdevice on required surface; Pump is the microdevice that desired substance can be transported to another place from; Pulverizer is the microdevice that can be cut into small pieces by bulk matter by blade and sharp edges.In the embodiment that some are other, microdevice comprises washer, filtrator, pulverizer, syringe and pump; Washer, filtrator, pulverizer and syringe; With the polishing unit of polishing plate; Or sensor, the mini tips for sample collection, microarray, data analysis unit and a signal transmitter for testing to collect sample.
In further embodiments, microdevice may be used for continuous sweep and analysis living systems, the miniature tester carrying out early stage disease surveillance and prevention.
Or, microdevice can in the external application of biosystem, and microdevice comprises an adventitia and is one or morely selected from following character: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, micro-electrodynamic, micro-magnetomechanics, micro-sound mechanics and micro-superconduction mechanical characteristic; And range of size is from about 1 dust to about 5 millimeters.
Microdevice can be used for medical applications, as detection and the prevention of early-stage cancer in artery cleaning and body.
Therefore, present invention also offers method microdevice of the present invention being used for clean biometric material.Each method comprises the step by microdevice and biomaterial contact, and this microdevice comprises an adventitia and has at least one and is selected from following character: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, chemistry of micro-organisms, chemistry of micro-organisms mechanics, micro-electric biological chemistry mechanics, micro-galvanochemistry mechanics, micro-electric biomechanics chemistry, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics and micro-superconduction mechanical characteristic.The range of size of microdevice is from about 1 dust to about 5 millimeters.The example of cleaned biomaterial includes but not limited to mammal medium sized vein or artery.Clean is can be realized by such as following methods: the combination of mechanical buffing, mechanical friction, chemically mechanical polishing, chemical dissolution, chemical passivation, chemical treatment, biological treatment, the polishing of use chemical dissolution liquid, laser ablation or more.
In certain embodiments, the method for claim 38 comprises the step of general area microdevice being transported to biomaterial further; Selectively, measure local temperature, local pressure, local friction, local surfaces electric charge, local resting potential, local potential, sub-surface characteristics, local part, or local flow; Selectively, cleaning function is triggered; Clean; Selectively, by miniature gatherer by cleaning after refuse collecting and transport; Selectively, by microfilter by cleaning after refuse collecting and transport.
In further embodiments, the method comprises step micro device being delivered to vein further; Selectively, the data that determination and analysis is collected, as local pressure; Selectively, clearing function is triggered when arriving target venosomes; The blood platelet of the vascular wall of cleaning target location and sediment; Optionally, the stop block required chemical agent being injected required cleaning, with the softening position cleaned, avoids the formation of piece of debris and may injuring of causing vascular wall is minimized; Selectively, dissolve microdevice after the cleaning is completed or filtered out by blood filtration system; Selectively, in cleaning course and after completing, the filtration of microdevice and fragment is completed by blood filtration step; Selectively, the process after being cleaned by microdevice.
Another aspect provides in the multiple method to the target location conveying multiple dose medicine in body, often kind of method all comprises the step transporting microdevice to target location; Carry the medicine of the first dosage to target location; After distance first time conveying certain time interval, carry the medicine of the second dosage to target location, this microdevice comprises an adventitia and at least one is selected from following characteristic: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, chemistry of micro-organisms, chemistry of micro-organisms mechanics, micro-electric biological chemistry mechanics, micro-galvanochemistry mechanics, micro-electric biomechanics chemistry, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics and micro-superconduction mechanical characteristic.The range of size of microdevice is from about 1 dust to about 5 millimeters.
In certain embodiments, the medicine of each dosage conveying is not identical.In other embodiment, medicine has different chemical characteristics and delivered the attachment selectivity that the first medicine strengthens the second medicine.
In addition, present invention also offers method microdevice being used for medical object.This microdevice includes an adventitia and has at least one and is selected from following character: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, chemistry of micro-organisms, chemistry of micro-organisms mechanics, micro-electric biological chemistry mechanics, micro-galvanochemistry mechanics, micro-electric biomechanics chemistry, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics and micro-superconduction mechanical characteristic.The range of size of microdevice is from about 1 dust to about 5 millimeters.Described medical object is from following selection: medicine input, excision, removal, polishing, transport, connection, detection, diagnosis, sensing, selective protection, target are removed, measure, the treatment of disease that cancer or blood are correlated with, carry out the function (being up to 500 micron levels) of medical assistance in eucaryotic cell structure or micro-organs level in target area.
In certain embodiments, the method is used for the treatment of cancer and comprises the following steps: the microdevice with drug delivery capabilities is optionally attached to cancer cell; Trigger the function of injection in microdevice; With by infusion of medicine cancer cell.Or the method can comprise the steps: the microdevice with high light reflectivity rate to be optionally attached on healthy cell; Unsound cell is destroyed by laser treatment; The unsound cell of laser therapy is exposed to removal.
In certain embodiments, the microdevice used in these methods has at least one and is selected from following unit: sensing unit, storage unit, Logical processing unit, signal transmitter and micrurgy; Microdevice carries out diagnosing, sensing or measurement function; The method can comprise the following steps: microdevice is transported to target location; Measurement is performed in this target location; Record data in the memory unit; Optionally, with logical process function trigger action; Selectively, operation is performed by microdevice; Fetch microdevice; And the data of analytic record.
In further embodiments, microdevice can diagnose in target location, sensing or measurement; Microdevice comprises the logical block of sensing unit, storage unit, signal transmitter, decision-making in-situ and micrurgy; Method comprises the following steps: microdevice is delivered to target location and performs diagnosis, sensing or measuring ability in this target location; By unit records data; Analyze the data that microdevice obtains; Based on the data analysis of microdevice and the logical decision of pre-programmed, determine process and the kind of microoperation; And carry out microoperation in target location.
In other embodiments, microdevice comprises an electrical performance testing unit and can detect the cancer cell of target location; The method comprises the following steps: microdevice is delivered to target location; Measure in target location and be one or morely selected from following characteristic: surface charge, electric density, resting potential, electromotive force, electrochemical potential, surface current, body electric current and current density.Microdevice and then can comprise voltage comparator, and such as this voltage comparator can carry out the voltage measurement that sensitivity is better than 1 millivolt.
In further embodiments, the cancer cell that the method can be used for target location detects, and comprises the steps: microdevice to be transported to target location and is selected from following one or more parameters in target location measurement: concentration, pH value, fluid flow, pressure, optical characteristics, absorption and sorption characteristic or more the combination of surface charge, resting potential, electrochemical potential, electromotive force, surface current, body electric current, surface wettability, contact angle, adhesion property, temperature, density, friction, hardness, surface tension, trace level chemical substance.
Microdevice of the present invention can use one or more known method manufactures of this area, such as method for manufacturing integrated circuit, semiconductor making method, mechanical manufacturing method, chemical treatment method, synthetic method, electrochemical process for treating, bioremediation, biochemistry treatment method, mechanical manufacturing method and laser processing.
Therefore, another aspect of the present invention is the usage of microdevice, thus reach and obtain in the real time data of eucaryotic cell structure level and information, as used miniature voltage comparator, four-point probe and other circuit design to measure cell surface charge in the mode of Noninvasive.The difference of cell surface charge is the health or the unhealthy condition that determine a cell, and to the key factor of the suitable treatment of cell time if necessary.One of example uses this device measured surface and/or body electrical properties comprise the difference of resting potential and surface charge thus distinguish normal cell and cancer cell.
Another aspect of the present invention is the usage of microdevice, is used for drug delivery also to distinguish healthy and unhealthy cell (as cancer cell) to the target location in body.This can by microdevice selective adsorption or absorption be healthy or unhealthy cell (as cancer cell) realizes.Such as, in order to remove a part of unsound organ with laser surgey, the microdevice with high reflectance can be used for selective adsorption on healthy cell, thus the cell that protects the health is not removed by laser treatment and/or melts.
Term as used herein "or", refers to and both comprises "AND" and "or".
"a" or "an" as referred to herein adds the odd number of noun, also comprises the implication of its noun plurality.
" microdevice " as referred to herein or " micro element " can have material, character, shape, complicacy and integrated level widely, or theirs is appropriately combined.The scope that this word is suitable for usually comprises from a kind of device of homogenous material to comprising multiple material, multiple subelement, multi-functional very complicated device.The range in complexity of the present invention's expection is from having the very little single particle of required character to comprising various multi-functional unit, quite complicated integrated unit.Such as, a simple microdevice can be a simple spheroidal particle, and its diameter is 100 dusts, has required hardness, surface charge or has required organic chemicals to be adsorbed on its surface.More complicated microdevice can be the device of 1 millimeter, with the sensor be integrated on this device, simple counter, storage unit, logical block and cutter.In the previous case, particle can be formed by gas phase process or in colloidal precipitation process, and is integrated with multipart device different integrated circuit fabrication process can be adopted to realize.
The scope of the microdevice in the present invention (as diameter) is dimensionally from about 1 dust to 5 millimeters of magnitudes.Such as, in the present invention, 10 dusts can be used for undersized biomolecule, biosome or biologic artifact as the target of eucaryotic cell structure, DNA, bacterium etc. is located to the microdevice of 100 microns; And for example in the present invention, another kind of range of size can be used for relatively large biological substance such as the target of part human organ from the microdevice of 1 micron to 5 millimeters and locates.Such as, in the present invention, simple microdevice can be that diameter is less than 100 dusts, have required character of surface (as surface charge or immersion coating) makes the simple particle of Preferential adsorption or absorption to the cell of target.
" absorption " one word mean surface and be connected to the physical connection (in this case, absorb to surface) between the material on surface.On the other hand, " absorption " usually mean stronger chemical bonding between the two.These characteristics are extremely important in the present invention; because they can effectively for the attachment of microdevice and target target; thus (a) measures at microscopic scale; b () is removed unsound cell and (c) targetedly and to be protected the health cell, as during laser surgey.
" chemical agent " or " chemicals " used in the present patent application one word be often referred to the chemical substance (compound as large or little) with certain effect or one can with the compound of of a target transfer position material phase reaction.
By novel microdevice, its novel compositions and operating process that is integrated and that integrate, many problems of current medical science can solve.Special needs to be pointed out is, a kind of micro device of the present invention can be used for " cleaning " biologic-organ, as patch and adipopexis in cleaning vein blood vessel, blocks with prevention of cardiac, apoplexy and blood.
Accompanying drawing explanation
Fig. 1 be used as the microdevice of microsyringe before action of injection and action of injection complete after skeleton view.
Fig. 2 is the skeleton view of the microdevice being used as miniature burnisher.
Fig. 3 is the skeleton view of the microdevice being used as miniature burnisher, microfilter, microsyringe, microsensor and miniature pulverizer.
Fig. 4 is the skeleton view of the microdevice being used as micro-knife.
Fig. 5 is the skeleton view of the microdevice being used as microfilter.
Fig. 6 is the skeleton view of the microdevice being used as minisize shielding device.
Fig. 7 is the skeleton view of microdevice when vascular wall patch in blood vessel.
Fig. 8 is that in blood vessel, microdevice to sense near vascular wall patch pressure change to trigger skeleton view during microdevice cleaning function.
Fig. 9 is the figure of microdevice after cleaning vascular wall patch in blood vessel.
Figure 10 is the close-up perspective view of one group of healthy cell and one group of unsound cancer cell.
Figure 11 is that one group of healthy cell and one group of unsound cancer cell and microdevice are used as the close-up perspective view of voltage comparator on two groups of cells.
Figure 12 is the close-up perspective view of one group of healthy cell and one group of unsound cancer cell.
Figure 13 is one group of healthy cell and one group of unsound cancer cell and the close-up perspective view of microdevice only absorbing or be adsorbed in healthy cell.
Figure 14 is a close-up perspective view incorporating the microdevice of multiple subelement, comprises micro cutter, microneedle, storage unit, analysis and Logical processing unit, microsensor and signal transmitter.
Figure 15 is with sensing unit, the skeleton view of the microdevice of logical block and microsyringe.
Embodiment
The invention provides the new micro device for biologic applications, be expected to solve the many key issues in modern medicine method.These problems comprise the pathology lacked as some fatal diseases and understand, to the prevention of some fatal diseases, to the non-intrusion type of various disease, the efficient diagnosis of microcosmic, and the treatment of the effective fatal disease such as targeted drug jettison system and such as cancer.
Microdevice range of size of the present invention from about 1 dust to about 5 millimeters (as from 1 dust to 100 microns; Or from 100 microns to 5 millimeters).Less microdevice (as from 1 dust to 100 microns) can be used in sensing, measurement and diagnosis etc., particularly obtains information and the data of eucaryotic cell structure level or molecule (as DNA, RNA or protein) level; And larger device (as from about 100 microns to about 5 millimeters) is except the operation for eucaryotic cell structure level, also can be used for machinery or the operation of human organ or tissue.
In this statement, general terms " microdevice " can refer to far-ranging material, character, shape, complicacy and an integrated level or their combination.In complicacy limit of consideration of the present invention from very little, that there is desirable characteristics single particle to the complex unit being integrated with multiple functional subunits.
Such as, simple microdevice can be a spherical particle, and radius is little to be had required hardness, surface charge or adsorption have required organic chemistry agent to 100 dusts.More complicated microdevice can be the device of 1 millimeter, is integrated with sensor, simple operation device, storage unit, logical block and cutter.In the previous case, particle can be formed by such as gas phase or colloidal precipitation process, and the microdevice being integrated with multiple parts can adopt different integrated circuit fabrication process manufactures.
Microdevice of the present invention has and designs widely, 26S Proteasome Structure and Function, comprise as voltage comparator, four-point probe, arithmetical unit, logical circuit, storage unit, micro cutter, miniature hammer, minisize shielding device, miniature dyestuff, Miniature nail, micro-knife, microneedle, miniature wire clamp, miniature tweezer, Miniature optical absorber, micromirror, micro-wheels, microfilter, Optical Microchopper, micropulverizer, micropump, miniature absorber, miniature signal sensor, miniature drill, miniature extractor, miniature tester, miniature vessel, signal transmitter, signal generator, friction sensor, charge sensor, temperature sensor, hardness tester, sonic generator, light wave generator, heater, miniature refrigerator and charge generators.
Disclosed by this patent, microdevice, due to the ability of its property qualitative diversity, high complexity and degree of integration and miniaturization, can produce in extensive range, extremely powerful function and application.
In addition, it should be noted that nowadays advanced manufacturing technology can make the far-ranging device of manufacture and integrated various function become feasible effective with cost in single microdevice.The characteristic dimension of human cell is 10 microns.When the state-of-the-art ic manufacturing technology of employing, the minimum feature size that microdevice defines can be as small as 0.1 micron.Therefore, microdevice of the present invention is applied to biological field is desirable.
With regard to the material of microdevice, common principle is the compatibility of material and biomaterial.The time contacted with biomaterial (as biomolecule, such as DNA, RNA or protein, cell, cell mass, tissue or organ) is variable, depends on its applicable cases.Microdevice of the present invention or any subelement can select different material manufactures.In some cases, material can dissolve in a controlled manner under specific pH value, therefore can be elected to be suitable material.Other factors that need consider comprise cost, simply, easy-to-use, practical.Along with micro-processing technology is as the major progress of ic manufacturing technology, the little manufacture to 0.1 micron of microdevice of highly integrated, minimum feature size can effectively reduce cost and commercialization.One of example is the Design and manufacture of MEMS (micro electro mechanical system) (MEMS), is widely used at present at integrated circuit industry.
Chapters and sections below comprise several application all kinds microdevice of the present invention in the brand-new example of biologic applications.
Sensing, measures and diagnosis
Before making the present invention, do not utilize probe in biological living, at cellular level, microscopic characteristics is carried out to the technology detected in real time.The microdevice of novelty disclosed by the invention can the cell characteristics of sense organ live body.Expectedly these Detection Information can be retrieved on-the-fly, as a diagnostic tool.
Such as, the mode that microdevice of the present invention may be used for Noninvasive in biological living organ detects cancer cell.Figure 10 illustrates at certain position of human body with the health of some (or normal) cell " a " 39 and unhealthy (or abnormal cell) " b " 40.Electric property such as electric charge and the resting potential of normal cell " a " 39 are different from abnormal cell " b " 40.First, microdevice with a voltage comparator for measuring the surface charge (or voltage) of known healthy cell.Next, as shown in figure 11, for the region comprising healthy cell 39 and unhealthy cell 40 simultaneously, with the microdevice 41 of voltage comparator 42 for scanning this region.By contrast cell surface voltage (difference of electric charge or electromotive force), healthy cell 39 and non-health cell 40 can be distinguished easily.By integrated voltage comparator, logic processing circuit and for the micro-syringe (or micropin) to cancer cell transmission or injection cancer therapy drug), microdevice 41 can be easy to expand the function having differentiation, measurement and treatment cancer cell.
Drug delivery
Up to the present, although the medicine of many Therapeutic cancer proves successful in the test of use for laboratory mouse, human trial does not receive Expected Results.It is believed that, subject matter is about success and effectively conducts drugs to cancer target cell.Normally adopt the form of tablet due to this kind of medicine or enter in body by injection, arriving in cancer focus process at medicine and also can there is serious problem.Even if medicine can reach target location, its intensity (concentration) and chemical composition may change, and make it partially or completely invalid.Then will inevitably increase spinoff and the increase of mortality ratio may be caused increasing dosage by this way.
In the present invention, new, effective targeted drug delivery system is expected to solve the problem.Employ a kind of microdevice 64 in Figure 15, this device comprises sensing unit 62, logical block 63 and micro-syringe 61.Microdevice 64 is designed to Preferential adsorption (or absorption) in unhealthy cell.Selectively, sensor 62 by detecting by the specific physics of scanning cell, chemistry, electricity and biological property, can detect unsound cell and can be attached to unhealthy cell.Once microdevice 64 is attached to unhealthy cell, it will be injected into tumour cell by micro-syringe 61 one or more anticancer agents.Can not be injected into medicine because of adhering to by mistake in order to ensure healthy cell, the data being attached cell that logical block 63 can detect based on sensor 62 judge.Because this method is a kind of targeted approach, cancer therapy drug is directly delivered to unhealthy cell, estimates that compared with the standard treatment that the method and the routine of current Therapeutic cancer use, its effect can be improved greatly.
Cleaning
Another major domain that invention focuses on is a kind of novel microdevice for biological " cleaning ", particularly, for " cleaning " of the artery and vein of the mankind.Fig. 7 illustrates vascular wall 30, along the microdevice 32 of 33 direction movements, and clot 36, the place of reducing blood pressure P134 and the place P235 that reduces blood pressure.In this kind of application, the microdevice 32 that the present invention relates to has at least a clearer to adhere on it.A more complete microdevice also at least comprises a sensor, a clearer, a microfilter, microsyringe, a pulverizer and a pump.
As shown in Figure 8, microdevice 32 is integrated with sensing (for local pressure test) and cleaning function 37, can be used in the cleaning of artery and vein.In vascular wall 30, clot 36 is positioned at P235 place, and localised blood pressure is higher in this case.Microdevice moves to clot 36 in vascular wall along 33 directions.The rising of device 32 sensing localised blood pressure while progressively close to clot, and then trigger cleaning function 37.
Fig. 9 illustrate utilize the cleaning function 37 of microdevice 32 by clot in vascular wall 30 38 wash after, the situation of vascular wall 30.This to be microdevice disclosed by the invention as " intelligence " device be applied to Noninvasive, real-time mode in numerous examples of biological field.
As shown in Figure 3, the invention discloses a more accurate microdevice 17, it is made up of cleaning arm 8 and washer 9, sensor 15, microfilter 13 and 14, miniature pulverizer 11 and micro-syringe 16.The object of this design is to assist clean flow process, and to guarantee that cleaning fragment reduces to less sheet, it can not cause clot at the other field of human body by being completely removed like this.Clearer has polishing or brush-wash function usually, and filtrator prevents them from moving to other parts of health for the fragment filtering cleaning process generation, causes blockage problem.Chip from microdevice washer dissolves for discharging pharmaceutical dissolution by syringe; It also may be used for transporting medicament to assist " cleaning " (polishing) process.Micro mist millstone 11 is for pulverizing the larger chip produced in cleaning process.More specifically, cleaning unit can be the polishing pad 9 that can be used in polishing or scrub with certain roughness be made up of polymeric material.Avoiding the large chip of clot breakage formation to introduce glossing to reduce mechanical stress, employing microsyringe 16 simultaneously.Preferred method is, with controlled speed by clot from level to level (about 10 dusts of one deck are thick) rub off.The chemically mechanical polishing of compromise is method for optimizing, and introduce surface chemical reaction and mechanical wear, mechanical wear controls in extremely low speed to avoid the breakage of clot simultaneously.Meanwhile, microfilter 13 and 14 is in order to guarantee that not having large fragment to stay cleaning position causes damage to other position of human body.Ink vessel transfusing is had to the patient of deposition tendency, utilize method periodic cleaning disclosed by the invention can reduce heart attack and the risk of apoplexy and the difficulty be reduced in cleaning process subsequently.
Due to typically having a diameter from several millimeters (about 2 millimeters to 4 millimeters) of major arteries, the range of size of (for clean aortal) microdevice of such cleaning can from about 10 microns to being less than 2 millimeters, such as, from about 100 microns to about 1.5 millimeters.
Targeted therapy
Microdevice disclosed in the present invention is applicable to carrying out targeted therapy very much, to remove or to destroy unsound cell or partial organ, reduces the infringement to healthy cell or organ to greatest extent simultaneously.This method has selectivity highly, Noninvasive also can complete under microcosmic.
There are the healthy cell 39 of some and the unhealthy cell 40 of some in certain position that Figure 12 illustrates the person.In Figure 13, for employing the laser surgey of two-phonon process, first healthy cell 39 is covered by the microdevice 43 (being called minisize shielding device) of high reflectance.Next, unhealthy cell 40 such as cancer cell is removed by optical instrument, and healthy cell 39 is protected by minisize shielding device 43 simultaneously.Make between microdevice and healthy cell, there is adsorption (or absorption) effect by the sensing process of microdevice and/or the character (as charge attraction) of particular microchannel device, thus make microdevice 43 become possibility to the attachment of healthy cell selectivity.Such as, microdevice can be designed or be programmed to, and by the mode mentioned in surface charge measurement and logical decision subsequently and above-mentioned Figure 11, these microdevices are only adsorbed in healthy cell.
A kind of use of microdevice being integrated with logical process, sensor, function of injection about another embodiment of targeted therapy in the present invention.First microdevice uses sensing function to locate its target.Then target is attached to.Finally, microdevice is to cancer cell injection cancer therapy drug.
Micro-operation
As disclosed herein, various microdevice can carry out surgical functions widely, thus completes concrete object.Some examples that can carry out operating microdevice refer to Fig. 1 to Fig. 6.
Fig. 1 illustrates the microdevice before triggering 6 and the microdevice 7 after triggering.Device 6 comprises adventitia 1, sensing unit 2, base plate 3 and region 4, and wherein region 4 is for depositing the various preparations before triggering.Device 7 after triggering has a region 5, once base plate 3 is vertically promoted to remove the preparation in region 4, region 5 is an empty region 5.Fig. 2 illustrates microdevice 10, that includes the burnisher/sleeker 9 of an attachment on the adjutage 8 of adventitia outside.Fig. 4 illustrates microdevice 20, and with an adventitia 1 and annex 19, wherein 19 with blade type end 18.Fig. 5 illustrates microdevice 25 with an end face 24, adventitia 21, and end face 24 is with a series of opening 22, and opening 22 runs through microdevice 25 to bottom surface 26 by passage 23 is whole.Fig. 6 illustrates microdevice 29 with an individuality 27, and wherein reflecting part 28 is attached to the top of individual 27.
It should be emphasized that in actual operation application, be preferably integrated with the multifunction micro device with several functions assembly, they will become the most effectively, operation tool the most flexibly.The clear superiority of those disclosed in the present invention " intelligence " devices it is possible to carry out Minimally Invasive Surgery, has the high precision on microstructure layer, high selectivity, and the minimal damage to healthy cell and organ.
As an embodiment, integrated microdevice at least comprises a sensor, a storage unit, a Logical processing unit, a signal projector, signal receiver, at least one microsyringe, multiple micro-knife, multiple microneedle, at least one pair of micro-clipper and at least one miniature thread forceps.This integrated micro device can perform some basic operation techniques.The example of this kind of integrated micro device is shown in Figure 14.Figure 14 shows integrated micro device 43, it is with adventitia 44, be attached to the sensing unit 47 of pickup arm 48, wherein pickup arm 48 is connected with storage unit 50 by path 49, storage unit 50 is connected with analysis/logical block 52 by path 51, logical block 52 is connected with signal projector 45 by path 46, logical block 52 is connected with microneedle unit 55 by path 53, 55 connect outside by the pin 54 extending adventitia 44, logical block 52 is connected with a micro cutter 57 by path 56 simultaneously, micro cutter 57 is with an adjutage 58 and a blade 59.
Therefore, obviously, the microdevice of biologic applications disclosed according to the present invention, is used in particular for carrying out the disease detection of microscopic scale in biological living, the microdevice for the treatment of and prevention can meet requirement of the present invention and advantage.Although list specific embodiment herein, those skilled in the art can make modifications and variations under the prerequisite not departing from spirit of the present invention.Therefore, the present invention is not limited to instructions.The present invention contain microdevice disclosed in the present application and for biological field common extended device between combination in any.In addition, it is integrated arbitrarily that the present invention also covers on disclosed microdevice basis, comes, for disease detection, prevention and therapy in human body, to comprise operation.Therefore, the present invention includes and allly reach the arrangement of identical object and all modifications in Claims scope and change.
It is noted that openly check for the public together with this instructions with document with all papers that instructions is submitted simultaneously, and the content of these papers and document is hereby incorporated by.Unless specifically indicated, all structures disclosed in instructions (comprising any subsidiary claim, summary and figure) can by any reach other equivalent structures of identical object substitute.Therefore unless specifically indicated, each disclosed structure is an example in a series of equivalence or similar universal architecture.
Do not explicitly point out " approach " " method " " step " realizing certain concrete function in claim to should not be construed as " method " or " step " of specifying in U.S.C. § 112 the 35th section the 6th section.
All publications above-mentioned and full content thereof are incorporated to herein by reference.
Claims (37)
1. one kind is applied to the microdevice in biosystem, comprise an adventitia, described adventitia has the one in following character: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, chemistry of micro-organisms, chemistry of micro-organisms mechanics, micro-electric biological chemistry mechanics, micro-galvanochemistry mechanics, micro-electric biological chemistry mechanics, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics, microthermodynamics, low-grade fever electricity, low-grade fever electrodynamic and micro-superconduction mechanical characteristic, and wherein the range of size of microdevice is from 1 dust to 100 millimeters;
Described microdevice, degrades under specific pH value, and the scope of degradation time was from 30 seconds to 3 days; Described microdevice comprises clearer, filtrator, pulverizer, syringe further.
2. microdevice as claimed in claim 1, it is characterized in that, described microdevice comprises two kinds in following properties: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics, microthermodynamics, low-grade fever chemico-mechanic, low-grade fever electricity, low-grade fever electrodynamic and micro-superconduction mechanical characteristic.
3. as the microdevice in claim 1, comprise the one in following character further: the attractive force that surface charge, electromotive force, chemical potential, geometric match, electromagnetism, ion gradient, thermal gradient, surface tension, mechanical force, electrochemical potential are relevant with physical force.
4. microdevice as defined in claim 1, it is characterized in that, described microdevice can distinguish cancer cell and normal cell.
5. microdevice as claimed in claim 1, it is characterized in that, described microdevice can sense organ and cyto-architectural microscopic property, at microscopic scale, organ and eucaryotic cell structure diagnosed, carry specific chemical agent at microscopic scale to organ and eucaryotic cell structure, carry specific medicine at microscopic scale to organ and eucaryotic cell structure, and at microscopic scale, selected organ and eucaryotic cell structure to be operated.
6. microdevice as claimed in claim 5, it is characterized in that, described microdevice can with non-invasive mode practical function.
7. microdevice as claimed in claim 5, is characterized in that, described microdevice can practical function in real time.
8. microdevice as claimed in claim 5, it is characterized in that, described microdevice can detect the one in following properties: the combination of surface charge, resting potential, electrochemical potential, electromotive force, wettability of the surface, contact angle, viscosity, temperature, density, friction, hardness, surface tension, microchemistry concentration, hydrophobicity level, level of hydrophilicity, pH value, flow rate of liquid, pressure, optical characteristics, absorption and sorption and these characteristics.
9. microdevice as claimed in claim 1, it is characterized in that, described microdevice comprises GPS (GPS), signal transmission device, signal receiver, tiny engine, Mini-type spiral oar, radio communication chip, logical circuit and a memory circuit further.
10. microdevice as claimed in claim 1, it is characterized in that, described microdevice comprises the one of following function further: chemical agent conveying function, control chemical agent conveying function, mechanical action, control mechanical action, selective absorbing, selective adsorption, microcosmic point detect, the dynamo-electric action of timing, the electronic work of controller, control electrochemical machinery action, control electric Biology seed coating, control electrochemica biological action, control electrochemica biological behavior, control electrochemica biological mechanical behavior and according to the signal detected or external command trigger action.
11. microdevices as claimed in claim 1, it is characterized in that, described microdevice has pre-programmed Trigger Function, and selectivity triggers and is selected from following action: chemical agent conveying, mechanical action, charge injection, light are launched, apply voltage and cooled or heating organic structure.
12. microdevices as claimed in claim 11, it is characterized in that, described Trigger Function is selected from following gain of parameter by introducing: the external signal that the wavelength of electric charge, resting potential, electromotive force, electrochemical potential, surface current, body electric current, surface wettability, adhesiveness, hydrophobicity, water wettability, flowing property, electric field, magnetic field, sound field, temperature, light and/or light intensity, friction force and coefficient, hardness, pressure and units test arrive.
13. microdevices as claimed in claim 1, it is characterized in that, described microdevice comprises the one in llowing group of materials: polymkeric substance, organic material and compatible inorganic material relative to organic system.
14. microdevices as claimed in claim 1, it is characterized in that, the range of size of described microdevice is from 1 dust to 5 millimeters.
15. microdevices as claimed in claim 1, it is characterized in that, the range of size of described microdevice is from 1 dust to 100 microns.
16. microdevices as claimed in claim 1, it is characterized in that, described microdevice comprises a kind of material, and wherein multiple subassembly is integrated in the unit that at least has a kind of function.
17. microdevices as claimed in claim 1, it is characterized in that, described microdevice comprises the one in llowing group of materials further: polymkeric substance, organic material, biomaterial, biochemical material, inorganic conductor material, inorganic semiconductor material, inorganic insulator material and pottery.
18. microdevices as claimed in claim 17, it is characterized in that, described biomaterial is selected from the one of llowing group of materials: the combination of the biomaterial of bioartificial materials, natural biologic material, cultivation and natural biologic material and bioartificial materials.
19. microdevices as claimed in claim 18, is characterized in that, the range of size of described microdevice is from 0.01 micron to 5 millimeters.
20. microdevices as claimed in claim 1, it is characterized in that, described microdevice is an integrated micro device and the one comprised in following function: sensing, detection, measurement, calculating, analysis, diagnosis, logical process, transmission, operation or surgical functions.
21. microdevices as claimed in claim 1, it is characterized in that, described microdevice comprises the one of following hardware further: voltage comparator, four-point probe, arithmetical unit, logical circuit, storage unit, micro cutter, miniature hammer, minisize shielding device, miniature dyestuff, Miniature nail, micro-knife, microneedle, miniature wire holding clamp, micro-clipper, Miniature optical absorber, micromirror, minisize shielding device, micro-wheels, microfilter, Optical Microchopper, micropulverizer, micropump, miniature absorber, miniature signal detector, miniature drill, miniature extractor, miniature tester, miniature vessel, miniature puller, signal transmitter, signal generator, friction sensor, charge sensor, temperature sensor, hardness tester, sonic generator, light wave generator, thermodynamics device, thermochemistry mechanics device, thermoelectricity mechanics device, heater, micro-refrigerator, miniature signal transmitter, miniature signal receiver and charge generators.
22. microdevice as claimed in claim 1, is characterized in that the one manufacture of described microdevice by following method: method for manufacturing integrated circuit, method, semi-conductor device manufacturing method, mechanical manufacturing method, chemical treatment method, synthetic method, electrochemical process for treating, bioremediation, biochemical processing method, mechanical manufacturing method and laser processing.
23. microdevices as claimed in claim 1, it is characterized in that, described microdevice comprises clearer, filtrator, pulverizer, syringe, pump further.
24. microdevices as claimed in claim 1, it is characterized in that, described microdevice comprises the polishing unit with polishing pad further.
25. microdevices as claimed in claim 1, is characterized in that, the range of size of described microdevice is from 10 microns to 2 millimeters.
26. microdevices as claimed in claim 1, is characterized in that, the range of size of described microdevice is from 100 microns to 1.5 millimeters.
27. microdevices as claimed in claim 1, is characterized in that, described microdevice is a micro-detector, scan and analyze, thus can carry out early detection and the prevention of disease for continuing to biological living system.
28. microdevice as claimed in claim 1, is characterized in that, described microdevice comprises sensor, micro-scale sampler, microarray, data analysis unit and signal projector for collected specimens further.
29. microdevices as claimed in claim 1, is characterized in that, the range of size of described microdevice is from 1 micron to 100 microns.
30. microdevices as claimed in claim 1, is characterized in that, the range of size of described microdevice is from 10 microns to 5 millimeters.
31. microdevices as claimed in claim 1, it is characterized in that, the range of size of described microdevice is from 2 dusts to 500 microns.
32. microdevices as claimed in claim 1, is characterized in that, described microdevice is used for artery cleaning.
33. microdevices as claimed in claim 1, it is characterized in that, described microdevice can be used for early detection and the prevention of the cancer in body.
34. 1 kinds of methods using microdevice to clean biomaterial, comprise the step by microdevice and biomaterial contact, wherein microdevice comprises the one in an adventitia and following character: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, chemistry of micro-organisms, chemistry of micro-organisms mechanics, micro-electric biological chemistry mechanics, micro-galvanochemistry mechanics, micro-electric biological chemistry mechanics, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics, microthermodynamics, low-grade fever chemico-mechanic, low-grade fever electricity, low-grade fever electrodynamic and micro-superconduction mechanical characteristic; Wherein the range of size of microdevice is from 1 dust to 5 millimeter; Described cleaning is realized by mechanical buffing, mechanical friction, chemically mechanical polishing, chemical dissolution, chemical passivation, chemical treatment, biological treatment, chemical dissolution polishing, laser ablation or their combination.
35. methods as claimed in claim 35, it is characterized in that, described biomaterial is mammiferous vein or artery.
36. methods as claimed in claim 35, it is characterized in that, described method is further comprising the steps of: to the general area conveying microdevice of biomaterial; Measure local temperature, local pressure, local friction, local surfaces electric charge, local resting potential, local potential, sub-surface characteristics, local part or partial fluid flow velocity; Trigger cleaning function; Clean; Collect the fragment of cleaning process generation by micro-gatherer and transport away; Collect fragment by a microfilter and fragment is transported away.
37. 1 kinds are applied to the microdevice outside biosystem, and comprise an adventitia, described adventitia has the one in following character: micro mechanics, macro, micro-chemico-mechanic, micro-optic, microsonics, microbiology, micro-electrodynamic, micro-electromagnetism mechanics, micro-sound mechanics and micro-superconduction mechanical property; Wherein, the range of size of described microdevice is from 1 dust to 5 millimeters; Described microdevice can have the ability of dissolving within the scope of certain pH value, and dissolution time is between 30 seconds to 3 days.
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| CN201510770386.9A CN105403690A (en) | 2010-09-17 | 2010-09-17 | Micro-device applied to biomedicine and use method thereof |
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| CN201510770386.9A CN105403690A (en) | 2010-09-17 | 2010-09-17 | Micro-device applied to biomedicine and use method thereof |
| CN201080070042.2A CN103237492B (en) | 2010-09-17 | 2010-09-17 | Be applied to microdevice in biomedicine and using method thereof |
| PCT/US2010/049298 WO2012036697A1 (en) | 2010-09-17 | 2010-09-17 | Micro devices biomedical applications and uses of the same |
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| TW202109037A (en) | 2012-07-16 | 2021-03-01 | 大陸商昌和生物醫學科技（揚州）有限公司 | Devices and methods for enhanced detection and identification of diseases |
| WO2014139482A1 (en) | 2013-03-15 | 2014-09-18 | Anpac Bio-Medical Science (Lishui) Co., Ltd. | Methods and apparatus for enhanced detection of diseases |
| JPWO2015166977A1 (en) * | 2014-05-02 | 2017-04-20 | 公立大学法人大阪府立大学 | Polymer membrane for cancer cell detection, method for producing the same, and cancer cell detection apparatus using the same |
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| BR112013006299B8 (en) | 2021-07-27 |
| EP2615968A4 (en) | 2014-03-12 |
| CN103237492B (en) | 2016-02-17 |
| ZA201302375B (en) | 2014-02-26 |
| KR20130124484A (en) | 2013-11-14 |
| KR101761259B1 (en) | 2017-07-25 |
| BR112013006299A2 (en) | 2016-06-07 |
| CN103237492A (en) | 2013-08-07 |
| AU2017200356A1 (en) | 2017-02-02 |
| AU2010360764A1 (en) | 2013-04-11 |
| WO2012036697A1 (en) | 2012-03-22 |
| AU2010360764A8 (en) | 2013-04-18 |
| IL225284A0 (en) | 2013-06-27 |
| CA2812189C (en) | 2021-09-21 |
| CA2812189A1 (en) | 2012-03-22 |
| BR112013006299B1 (en) | 2020-12-22 |
| JP5917522B2 (en) | 2016-05-18 |
| JP2013539669A (en) | 2013-10-28 |
| EP2615968A1 (en) | 2013-07-24 |
| IL225284B (en) | 2018-11-29 |
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