US20020028434A1 - Particle or cell analyzer and method - Google Patents
Particle or cell analyzer and method Download PDFInfo
- Publication number
- US20020028434A1 US20020028434A1 US09/844,080 US84408001A US2002028434A1 US 20020028434 A1 US20020028434 A1 US 20020028434A1 US 84408001 A US84408001 A US 84408001A US 2002028434 A1 US2002028434 A1 US 2002028434A1
- Authority
- US
- United States
- Prior art keywords
- particles
- particle
- detector
- light
- volume
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
- G01N15/1404—Fluid conditioning in flow cytometers, e.g. flow cells; Supply; Control of flow
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
Definitions
- This invention relates generally to a particle or cell analyzer and method, and more particularly to a particle or cell analyzer and method in which the sample solution containing the particles or cells is drawn through a capillary for presentation to a shaped light beam.
- the detection and analysis of individual particles or cells is important in medical and biological research. It is particularly important to be able to measure characteristics of particles such as concentration, number, viability, identification and size.
- Individual particles or cells as herein defined include, for example, bacteria, viruses, DNA fragments, cells, molecules and constituents of whole blood.
- flow cytometers particles which are either intrinsically fluorescent or are labeled with a fluorescent marker or label, are hydrodynamically focused within a sheath fluid and caused to flow past a beam of radiant energy which excites the particles or labels to cause generation of fluorescent light.
- One or more photodetectors detect the fluorescent light emitted by the particles or labels at selected wavelengths as they flow through the light beam, and generates output signals representative of the particles.
- a photodetector is also used to measure forward scatter of the light to generate signals indicative of the presence and size of all of the particles.
- U.S. Pat. No. 5,547,849 describes a scanning imaging cytometer wherein an unprocessed biological fluid sample is reacted with a fluorescently labeled binding agent. The reacted sample undergoes minimal processing before it is enclosed in a capillary tube of predetermined size. The capillary tube with the enclosed sample is optically scanned and the fluorescent excitation is recorded from a plurality of columnar regions along the capillary tube. Each columnar region is generally defined by the spot size of the excitation beam and the depth dimension of the capillary tube. A spacial filter of sufficient pinhole diameter is selected to allow simultaneous volumetric detection of all fluorescent targets in each columnar region. The cellular components or particles are identified as is their concentration.
- a particle analyzing apparatus which analyzes particles in a sample fluid flowing through a capillary tube which has a suspended sampling end for insertion into a sample fluid, and a pump coupled to the other end for drawing the sample fluid and particles through the capillary.
- An illumination source is provided for projecting a beam of light through a predetermined volume of the capillary to impinge upon the particles that flow through that volume.
- At least one detector is disposed to receive fluorescent light emitted by excited fluorescing particles and provide an output pulse for each fluorescing particle, and another detector senses the passage of all particles which flow through the volume and provides an output signal, whereby the output signals from the detectors can be used to characterize the particles.
- a method of analyzing samples containing particles which includes drawing the sample through a capillary volume where the particles are illuminated by a light source, and scattered light and fluorescent light from labeled particles excited by the light source is detected to provide output signals which are processed to provide an analysis of the sample.
- FIG. 1 schematically shows a particle analyzer in accordance with the present invention.
- FIG. 2 is a top plan view showing the optical components shown in FIG. 1 mounted on a support shelf.
- FIG. 3 is a front elevational view partly in section of FIG. 2.
- FIG. 4 is a side elevational view of the beam-forming optical system.
- FIG. 5 is a top plan view of the beam-forming optical system of FIG. 4.
- FIG. 6 shows the sample fluid flow and pumping system.
- FIG. 7 is a perspective view of a portion of a capillary used in connection with one embodiment of the present invention.
- FIG. 8 is a perspective view of a portion of a capillary tube used in connection with another embodiment of the present invention.
- FIG. 9 schematically shows a control and data acquisition system associated with the particle analyzer.
- FIG. 10 is a timing and data acquisition diagram illustrating operation of the particle analyzer.
- FIG. 11 is a schematic view of a four-color particle analyzer.
- FIG. 12 schematically illustrates an analyzer having multiple analyzing stations along the capillary tube.
- FIG. 13 shows an impedance detector for detecting particles as they flow past a detection region.
- FIG. 14 schematically shows a circuit suitable for correlating signals from an impedance cell sensor with photomultiplier output signals
- FIG. 15 shows a particle analyzer in accordance with another embodiment of the invention.
- particles means particles or cells, for example, bacteria, viruses, DNA fragments, blood cells, molecules and constituents of whole blood.
- a capillary tube 11 has a suspended end 12 adapted to be immersed into a sample solution 13 retained in a cuvet or vial 14 . It will be apparent that, although a square capillary is illustrated, the capillary may be cylindrical or of other shape, such as a microchannel. Sample fluid is drawn into the end of the capillary as shown by the arrow 16 .
- the fluid or liquid sample is drawn through the capillary by a calibrated pump connected to the other end of the capillary.
- the size or bore of the capillary tube 11 is selected such that the particles 18 are singulated as they pass a viewing or analyzing volume 19 .
- a light source, preferably a laser, 21 emits light 22 of selected wavelength.
- the light is received by an optical focusing system 23 which focuses said light and forms and directs a beam 24 to the capillary where it passes through the analyzing volume 19 .
- the optical focusing system is configured to form a flat, thin rectangular beam which impinges on the capillary tube 11 .
- the thickness of the flat beam and the walls of the capillary define the analyzing volume.
- a beam blocker 26 is positioned to intercept the beam after it passes through the capillary tube 11 .
- Light scattered by a particle that flows through the beam is directed onto a detector 27 by lens 28 .
- the detector provides an output signal such as the one illustrated by the peak 29 , when a particle passes through the beam and scatters the light.
- the size of the peak is dependent upon the size of the particle, and the occurrence of the peak indicates that a particle in the volume 19 (fluorescent or non-fluorescent) has traversed the thin beam of light.
- Another approach is to employ an off-axis detector, such as illustrated in FIG. 15, to measure the scattered light. In such event, a beam blocker is not required.
- an impedance method of detecting particles is also described below.
- the particles are intrinsically fluorescent, or if the particles have been tagged with a fluorescent dye, they will emit light 31 at a characteristic wavelength as they pass through the volume defined by thin beam of light 24 which excites fluorescence.
- the fluorescent light is detected at an angle with respect to the beam axis so that no direct beam light is detected.
- a collector lens 32 receives the fluorescent light from the particles and focuses it at detectors 36 and 37 .
- slits 33 or 34 oriented in the direction of the thin beam to block any stray light. However, we have found that if the beam is properly focused into a thin flat beam, stray light is not a problem.
- the light impinges onto a dichroic beam splitter 38 which passes light of selected wavelengths through filter 39 to detector 36 , and deflects light of other selected wavelengths through filter 41 to photodetector 37 .
- the dichroic beam splitter reflects light having wavelengths less than 620 nm, and transmits light having a greater wavelength.
- the filters 39 and 41 are selected to pass the wavelengths corresponding to the fluorescence wavelength expected from the fluorescing particles. In one example, the filters 39 and 41 were selected to pass light at 580 nm and 675 nm, respectively. This permitted identification and counting of particles which had been tagged with fluorescent material which emits at these wavelengths in response to the optical beam.
- the outputs of the photodetectors are pulses such as those schematically illustrated at 42 and 43 , FIG. 1.
- FIGS. 2 and 3 show the components of a particle analyzer in accordance with the above-described embodiment mounted on a support plate 51 .
- the support plate 51 carries an optical block 52 adapted to receive and support the suspended capillary tube 11 .
- Capillary tube 11 includes a hub 53 , FIGS. 3 and 6, which is received in a well 54 to retain and position the capillary in the optical block.
- the capillary 11 is positioned in the optical block 52 by threading it through a narrow slot (not shown) and held in position by nylon-tipped set screws inserted in threaded holes 56 and 57 . As it is inserted through the block, the capillary tube can be viewed through the viewing port 58 .
- the end of the capillary tube is suspended and extends downwardly for insertion into a vial or cuvet 14 which contains the sample fluid or specimen. It is apparent that the capillary can be positioned and suspended by other supporting arrangements.
- a rotatable vial support member having two arms 59 is rotatably and slidably received by a guide post 60 secured to the base.
- a vial holder 61 is disposed at the end of each arm.
- the support is moved downwardly along the post 59 , rotated to bring a vial under the capillary, and moved upwardly whereby the end of the capillary is immersed in the sample fluid.
- another vial with another sample can be placed in the other holder whereby it can be brought into cooperative relationship with the capillary tip as soon as the analysis of the prior sample has been completed.
- the housing 23 for the laser and optical focusing system which forms the beam 24 is carried on mounting block 62 .
- the optical system is shown in FIGS. 4 and 5. It receives collimated light 22 from the laser 21 , and generates the light beam 24 , which impinges upon the capillary tube 1 l.
- the optical system may include, for example, a first plano-convex lens 63 , a second plano-convex lens 64 and a cylindrical lens 66 .
- the action of the lens assembly is to form a sheet-like thin rectangular beam which in one example was 20 ⁇ m in thickness along the longitudinal direction of the capillary, and 400 ⁇ m broad in the perpendicular direction, whereby a rectangular volume of sample was illuminated.
- the arrows 67 and 68 , FIGS. 4 and 5, show the thin and broad configuration of the beam, respectively.
- the photodetector 27 is mounted on the block 52 and supported axially with respect to the axis of the beam 24 .
- the beam blocker bar 26 is mounted in the block 52 and intercepts and blocks out the direct beam after it passes through the capillary 11 .
- the scattered light which passes around beam-blocking bar 26 is focused onto the detector 27 by a lens 28 .
- the scattered light will provide an output signal for any tagged or untagged particle flowing past the observation volume 19 , thus providing a total particle count.
- the output of the detector is then representative of the passage of a particle or cluster of particles and the size of the particle or cluster of particles. As will be explained below, this, taken together with the fluorescent signal, enables analysis of the sample. If the detector 27 is located off-axis, it will only receive scattered light and there is no need for a beam-blocking bar. Furthermore, this would be less sensitive to stray light in the forward direction which carries broadband laser noise which can mask out low level particle signals.
- the condenser lens 31 is carried by the block 52 .
- the lens 31 receives the fluorescent light and focuses it at the detectors 36 and 37 , which may be photomultipliers, charge-coupled diodes (CCDs), or other photodetectors. More particularly, the fluorescent light from the lens 31 impinges upon a dichroic beam splitter 38 which splits the beam into two wavelengths, one which passes through the beam splitter and one which is deflected by the dichroic beam splitter 38 .
- Filters 39 and 41 filter the transmitted and reflected light to pass only light at the wavelength of the fluorescence of the particles to reject light at other wavelengths. If slits 33 and 34 are present, they reject any stray light from regions outside of the volume 19 defined by the thin rectangular beam 24 . However, as discussed above, slits may not be required because the effect of stray light is minimized.
- the photo-multipliers or other photodetectors each provide an output signal representing the intensity of light at the filtered wavelength. As described above, the dichroic beam splitter reflects light having wavelengths less than 620 nm, and transmits light having greater wavelengths.
- the filter 39 passes light at 580 nm, while the filter 41 passes light at 675 nm.
- the output of the photo-multipliers are pulses 42 and 43 , one for each particle emitting light at the particular wavelength, such as those schematically illustrated in FIG. 1. It is apparent that the wavelengths selected for the filters depends upon the fluorescent wavelength of the marker or label affixed to the particles.
- the volume of fluid In order to identify and count the particles in the fluid in a volumetric manner, the volume of fluid must be correlated with the number of particles detected in a given volume.
- the fluid sample is drawn through the capillary tube at a constant rate by an electrically operated calibrated pump or syringe 71 , FIG. 6.
- the pump may be any other type of pump which can draw known volume samples through the capillary.
- the pump is connected to the capillary tube by a conduit or tube 72 . This permits changing capillaries 11 to substitute a clean capillary or a capillary having a different diameter which may be needed for various types and sizes of particles or cells.
- the diameter of the waste tube 74 is selected to be many times, 10 or more than that of the capillary, whereby substantially all of the fluid from the syringe is discharged into the waste. For example, if there is a factor of ten ratio in diameter, only 1/10,000 of the fluid will travel back through the capillary, a negligible amount.
- the pump is designed such that a predetermined movement of the plunger 73 will draw a known volume of sample through the capillary tube.
- the pump can be calibrated for each capillary by drawing a fluid into the pump by moving the plunger a known distance and then discharging the fluid and measuring the volume of the discharged fluid. Thereafter, for a given movement of the plunger, the volume of sample which flows through the analyzing volume is known. The volume can either be determined by measuring the movement of the plunger or measuring the time the plunger is moved if it is calibrated as a function of time.
- a syringe pump is described, other types of pumps which can draw known volumes of fluid through the capillary can be used.
- the capillary tubes are of rectangular configuration.
- FIGS. 7 and 8 show a capillary tube that includes an opaque coating 81 which is removed over an area 82 , FIG. 7, or 83 , FIG. 8.
- the beam projects through the window 82 which has a rectangular configuration to accept of the beam 24 .
- the slit masks the walls of the capillary tube and prevents diffraction of light by the walls. A combination of the two masks would confine the detected light to that emitted by a particle traveling through the capillary to block out any stray light.
- the sample vial containing the particles is positioned to immerse the end of the capillary 11 in the sample.
- the sample is then drawn through the capillary by applying a control signal from the controller 121 to start the pump 71 .
- the controller receives the command from processor 122 .
- the pump 71 is driven at a constant rate whereby the volume of sample passing through the analyzing volume 19 can be measured by timing the counting period.
- the processor After sample has been drawn from the vial for a predetermined time to assure that the new sample has reached the volume 19 , the processor begins to process the output 29 from the scatter photodetector and the outputs 42 and 43 from the photodetectors and does so for a predetermined time which will represent a known volume of sample passing through the analyzing volume.
- the processing time is schematically illustrated in FIG. 10A by the curve 123 .
- FIG. 10B illustrates the output pulses 28 from the scatter detector. It is seen that there are individual particles which provide a trace 124 and a cluster of particles which provides a trace 126 .
- FIG. 10C shows traces 126 for particles which fluoresce at a first wavelength, for example 675 nm. Of note is the fact that the cluster 126 includes three such particles.
- FIG. 10D shows traces 127 for particles which fluoresce at another wavelength, for example 750 nm.
- the processor can call for a number of analyzing cycles.
- the processor instructs the controller to open the valve 76 and reverse the pump to discharge the analyzed sample into the waste 77 .
- a new sample cuvet can then be installed and a new sample analyzed.
- the processor can be configured to average the counts over a number of cycles and to process the counts to provide outputs representing the concentration of the various particles, the number of particles, etc. Using suitable labels or markers one can conduct viability assays and antibody screening assays or monitor apoptosis.
- the apparatus has been described for a two-color analysis it can easily be modified for four-color analysis.
- This is schematically shown in FIG. 11.
- the input light beam 24 impinges upon the analyzing volume 19 .
- the photodetector 27 and associated lens 28 provide the scatter signal.
- the fluorescent light 31 is focused by lens 32 to pass through three dichroic beam splitters 81 , 82 and 83 which reflect light at three different wavelengths through filters 86 , 87 and 88 onto photodetectors 91 , 92 and 93 .
- the light at the fourth wavelength, passed by the three dichroic beam splitters 81 , 82 and 83 passes through filter 94 onto photodetector 96 .
- up to four different particles which intrinsically fluoresce or are labeled to fluoresce at four different wavelengths can be analyzed by choosing the proper reflecting wavelengths for the dichroic beam splitter and the filters.
- FIG. 12 schematically shows a system using a plurality of light sources (not shown) projecting light beams 106 , 107 and 108 to analyzing volumes 111 , 112 and 113 , which are at a predetermined distance apart.
- the scattered light indicated by arrows 114 , 116 , 117 is detected by individual detecting systems of the type described.
- the fluorescent light represented by arrows 118 , 119 and 121 is detected by individual analyzing systems of the type described above.
- This arrangement permits analyzing particles which have been tagged with different labels by selecting the wavelength of the light source to excite different fluorescent tags or markers.
- the plurality of light beams may project onto a single analyzing volume and the individual analyzing systems receive the different fluorescent wavelengths.
- a change in electrical current can detect the particles as they travel past spaced electrodes disposed on opposite sides of the flow path.
- a capillary 11 is shown with spaced electrodes 123 and 124 which extend into the capillary 11 .
- the electrodes are spaced along the capillary from the analyzing volume 19 .
- the electrically conductive working fluid is displaced and the resulting change in current (impedance) can be detected.
- This method avoids any laser noise problem. It is usually most convenient mechanically to place the electrodes along the fluid flow path either before or after the point where the laser beam 24 impinges onto the capillary.
- FIG. 14 shows the output signal 126 from the impedance cell sensor and the fluorescent signal 42 or 43 (FIG.
- the particle detector includes a light source, for example a laser, whose output is optically focused by the optics 23 to form a thin, flat beam 24 as described above.
- the beam traverses the capillary 11 to define the detection volume 19 .
- the scatter detector includes an off-axis detector assembly including a collection lens 26 a and a detector 27 a.
- an off-axis detector assembly As much as possible of the emitted fluorescent light from the tagged cells or particles is gathered or intercepted by an off-axis detector assembly. It can be gathered by a condenser lens as illustrated in FIG. 1. However, in the present embodiment, it is collected by a light guide 141 which receives the light 142 and conveys it to the beam splitter 143 . The light beam is directed to optical filters 144 and 146 and directly to detectors 147 and 148 . The output signals from the detectors and the scatter signals are processed to provide particle counts, cell viability, antibody screening, etc.
- the analyzing apparatus detects particles in a sample fluid flowing through a capillary tube which has a sampling end for insertion into a sample fluid, and a pump coupled to the other end for drawing sample through the capillary.
- a light source is provided for projecting a beam of light through a predetermined analyzing volume of the capillary tube to excite fluorescence in particles that flow through the volume.
- At least one detector is disposed to receive the fluorescent light from excited particles and another detector is disposed to provide a signal representing all particles which flow through the analyzing volume. The output of said detectors provides signals which can be processed to provide the characteristics of the particles.
Abstract
Description
- This application claims priority to provisional application Ser. No. 60/230,380 filed Sep. 6, 2000.
- This invention relates generally to a particle or cell analyzer and method, and more particularly to a particle or cell analyzer and method in which the sample solution containing the particles or cells is drawn through a capillary for presentation to a shaped light beam.
- The detection and analysis of individual particles or cells is important in medical and biological research. It is particularly important to be able to measure characteristics of particles such as concentration, number, viability, identification and size. Individual particles or cells as herein defined include, for example, bacteria, viruses, DNA fragments, cells, molecules and constituents of whole blood.
- Typically, such characteristics of particles are measured using flow cytometers. In flow cytometers, particles which are either intrinsically fluorescent or are labeled with a fluorescent marker or label, are hydrodynamically focused within a sheath fluid and caused to flow past a beam of radiant energy which excites the particles or labels to cause generation of fluorescent light. One or more photodetectors detect the fluorescent light emitted by the particles or labels at selected wavelengths as they flow through the light beam, and generates output signals representative of the particles. In most cytometers, a photodetector is also used to measure forward scatter of the light to generate signals indicative of the presence and size of all of the particles.
- U.S. Pat. No. 5,547,849 describes a scanning imaging cytometer wherein an unprocessed biological fluid sample is reacted with a fluorescently labeled binding agent. The reacted sample undergoes minimal processing before it is enclosed in a capillary tube of predetermined size. The capillary tube with the enclosed sample is optically scanned and the fluorescent excitation is recorded from a plurality of columnar regions along the capillary tube. Each columnar region is generally defined by the spot size of the excitation beam and the depth dimension of the capillary tube. A spacial filter of sufficient pinhole diameter is selected to allow simultaneous volumetric detection of all fluorescent targets in each columnar region. The cellular components or particles are identified as is their concentration.
- It is an object of the present invention to provide a particle analyzer and method having high particle selectivity.
- It is another object of the present invention to provide a compact, high-sensitivity particle analyzer.
- It is still another object of the present invention to provide a portable particle analyzer and method for use in immunology, microbiology, cell biology, hematology and cell analysis.
- It is a further object of the present invention to provide a simple-to-use, less expensive, particle analyzing apparatus for counting particles in small volumes of sample fluids and determining their characteristics.
- It is still another object of the present invention to provide a particle analyzer and method for analyzing low volumes of low-density sample fluids.
- The foregoing and other objects of the invention are achieved by a particle analyzing apparatus which analyzes particles in a sample fluid flowing through a capillary tube which has a suspended sampling end for insertion into a sample fluid, and a pump coupled to the other end for drawing the sample fluid and particles through the capillary. An illumination source is provided for projecting a beam of light through a predetermined volume of the capillary to impinge upon the particles that flow through that volume. At least one detector is disposed to receive fluorescent light emitted by excited fluorescing particles and provide an output pulse for each fluorescing particle, and another detector senses the passage of all particles which flow through the volume and provides an output signal, whereby the output signals from the detectors can be used to characterize the particles.
- A method of analyzing samples containing particles, which includes drawing the sample through a capillary volume where the particles are illuminated by a light source, and scattered light and fluorescent light from labeled particles excited by the light source is detected to provide output signals which are processed to provide an analysis of the sample.
- The foregoing and other objects of the invention will be more clearly understood from the following detailed description when read in conjunction with the accompanying drawings in which:
- FIG. 1 schematically shows a particle analyzer in accordance with the present invention.
- FIG. 2 is a top plan view showing the optical components shown in FIG. 1 mounted on a support shelf.
- FIG. 3 is a front elevational view partly in section of FIG. 2.
- FIG. 4 is a side elevational view of the beam-forming optical system.
- FIG. 5 is a top plan view of the beam-forming optical system of FIG. 4.
- FIG. 6 shows the sample fluid flow and pumping system.
- FIG. 7 is a perspective view of a portion of a capillary used in connection with one embodiment of the present invention.
- FIG. 8 is a perspective view of a portion of a capillary tube used in connection with another embodiment of the present invention.
- FIG. 9 schematically shows a control and data acquisition system associated with the particle analyzer.
- FIG. 10 is a timing and data acquisition diagram illustrating operation of the particle analyzer.
- FIG. 11 is a schematic view of a four-color particle analyzer.
- FIG. 12 schematically illustrates an analyzer having multiple analyzing stations along the capillary tube.
- FIG. 13 shows an impedance detector for detecting particles as they flow past a detection region.
- FIG. 14 schematically shows a circuit suitable for correlating signals from an impedance cell sensor with photomultiplier output signals
- FIG. 15 shows a particle analyzer in accordance with another embodiment of the invention.
- Referring to FIG. 1, there is schematically illustrated a particle analyzer in accordance with one embodiment of the present invention. As used herein, “particles” means particles or cells, for example, bacteria, viruses, DNA fragments, blood cells, molecules and constituents of whole blood. A
capillary tube 11 has a suspendedend 12 adapted to be immersed into asample solution 13 retained in a cuvet orvial 14. It will be apparent that, although a square capillary is illustrated, the capillary may be cylindrical or of other shape, such as a microchannel. Sample fluid is drawn into the end of the capillary as shown by thearrow 16. As will be presently described, the fluid or liquid sample is drawn through the capillary by a calibrated pump connected to the other end of the capillary. The size or bore of thecapillary tube 11 is selected such that theparticles 18 are singulated as they pass a viewing or analyzingvolume 19. A light source, preferably a laser, 21 emitslight 22 of selected wavelength. The light is received by an optical focusingsystem 23 which focuses said light and forms and directs abeam 24 to the capillary where it passes through the analyzingvolume 19. The optical focusing system is configured to form a flat, thin rectangular beam which impinges on thecapillary tube 11. The thickness of the flat beam and the walls of the capillary define the analyzing volume. In order to count all particles which traverse the detection volume, that is particles which are tagged to fluoresce and untagged particles, scattered light is detected. In one embodiment, abeam blocker 26 is positioned to intercept the beam after it passes through thecapillary tube 11. Light scattered by a particle that flows through the beam is directed onto adetector 27 bylens 28. The detector provides an output signal such as the one illustrated by thepeak 29, when a particle passes through the beam and scatters the light. The size of the peak is dependent upon the size of the particle, and the occurrence of the peak indicates that a particle in the volume 19 (fluorescent or non-fluorescent) has traversed the thin beam of light. Another approach is to employ an off-axis detector, such as illustrated in FIG. 15, to measure the scattered light. In such event, a beam blocker is not required. There is also described below an impedance method of detecting particles. - If the particles are intrinsically fluorescent, or if the particles have been tagged with a fluorescent dye, they will emit light31 at a characteristic wavelength as they pass through the volume defined by thin beam of light 24 which excites fluorescence. The fluorescent light is detected at an angle with respect to the beam axis so that no direct beam light is detected. In the embodiment of FIGS. 1-3, a
collector lens 32 receives the fluorescent light from the particles and focuses it atdetectors slits dichroic beam splitter 38 which passes light of selected wavelengths throughfilter 39 todetector 36, and deflects light of other selected wavelengths throughfilter 41 tophotodetector 37. For example, the dichroic beam splitter reflects light having wavelengths less than 620 nm, and transmits light having a greater wavelength. Thefilters filters - FIGS. 2 and 3 show the components of a particle analyzer in accordance with the above-described embodiment mounted on a
support plate 51. Thesupport plate 51 carries anoptical block 52 adapted to receive and support the suspendedcapillary tube 11.Capillary tube 11 includes ahub 53, FIGS. 3 and 6, which is received in a well 54 to retain and position the capillary in the optical block. The capillary 11 is positioned in theoptical block 52 by threading it through a narrow slot (not shown) and held in position by nylon-tipped set screws inserted in threadedholes viewing port 58. The end of the capillary tube is suspended and extends downwardly for insertion into a vial orcuvet 14 which contains the sample fluid or specimen. It is apparent that the capillary can be positioned and suspended by other supporting arrangements. - In one embodiment, a rotatable vial support member having two
arms 59 is rotatably and slidably received by aguide post 60 secured to the base. Avial holder 61 is disposed at the end of each arm. In operation, the support is moved downwardly along thepost 59, rotated to bring a vial under the capillary, and moved upwardly whereby the end of the capillary is immersed in the sample fluid. As the sample is being analyzed, another vial with another sample can be placed in the other holder whereby it can be brought into cooperative relationship with the capillary tip as soon as the analysis of the prior sample has been completed. - The
housing 23 for the laser and optical focusing system which forms thebeam 24 is carried on mountingblock 62. The optical system is shown in FIGS. 4 and 5. It receives collimated light 22 from thelaser 21, and generates thelight beam 24, which impinges upon the capillary tube 1l. The optical system may include, for example, a first plano-convex lens 63, a second plano-convex lens 64 and acylindrical lens 66. The action of the lens assembly is to form a sheet-like thin rectangular beam which in one example was 20 μm in thickness along the longitudinal direction of the capillary, and 400 μm broad in the perpendicular direction, whereby a rectangular volume of sample was illuminated. Thearrows - The
photodetector 27 is mounted on theblock 52 and supported axially with respect to the axis of thebeam 24. Thebeam blocker bar 26 is mounted in theblock 52 and intercepts and blocks out the direct beam after it passes through the capillary 11. The scattered light which passes around beam-blockingbar 26 is focused onto thedetector 27 by alens 28. Thus, the scattered light will provide an output signal for any tagged or untagged particle flowing past theobservation volume 19, thus providing a total particle count. The output of the detector is then representative of the passage of a particle or cluster of particles and the size of the particle or cluster of particles. As will be explained below, this, taken together with the fluorescent signal, enables analysis of the sample. If thedetector 27 is located off-axis, it will only receive scattered light and there is no need for a beam-blocking bar. Furthermore, this would be less sensitive to stray light in the forward direction which carries broadband laser noise which can mask out low level particle signals. - As described above, light emitted by fluorescence from intrinsically fluorescent particles, or particles which have been tagged with a fluorescent dye or material, is detected at an angle with respect to the beam axis. Referring to FIG. 2, the
condenser lens 31 is carried by theblock 52. Thelens 31 receives the fluorescent light and focuses it at thedetectors lens 31 impinges upon adichroic beam splitter 38 which splits the beam into two wavelengths, one which passes through the beam splitter and one which is deflected by thedichroic beam splitter 38.Filters slits volume 19 defined by the thinrectangular beam 24. However, as discussed above, slits may not be required because the effect of stray light is minimized. The photo-multipliers or other photodetectors each provide an output signal representing the intensity of light at the filtered wavelength. As described above, the dichroic beam splitter reflects light having wavelengths less than 620 nm, and transmits light having greater wavelengths. Thefilter 39 passes light at 580 nm, while thefilter 41 passes light at 675 nm. This permits analysis of particles which have been tagged with fluorescent substances which emit light at 580 nm and 675 nm to be individually counted. The output of the photo-multipliers arepulses - In order to identify and count the particles in the fluid in a volumetric manner, the volume of fluid must be correlated with the number of particles detected in a given volume. In the present invention, the fluid sample is drawn through the capillary tube at a constant rate by an electrically operated calibrated pump or
syringe 71, FIG. 6. The pump may be any other type of pump which can draw known volume samples through the capillary. The pump is connected to the capillary tube by a conduit ortube 72. This permits changingcapillaries 11 to substitute a clean capillary or a capillary having a different diameter which may be needed for various types and sizes of particles or cells. As illustrated, the pump comprises a syringe pump in which sample fluid is drawn into the capillary by moving theplunger 73. Thepump 71 is also connected to a waste ordrain conduit 74 which includes avalve 76. When the valve is closed, the pump draws sample from the vial or cuvet through thecapillary tube 11 past thedetection volume 19. After an analysis has been completed, thevalve 76 is opened, whereby reversal of direction of theplunger 73 causes fluid to flow throughconduit 74 into thewaste container 77. In accordance with a feature of the present invention, the diameter of thewaste tube 74 is selected to be many times, 10 or more than that of the capillary, whereby substantially all of the fluid from the syringe is discharged into the waste. For example, if there is a factor of ten ratio in diameter, only 1/10,000 of the fluid will travel back through the capillary, a negligible amount. - The pump is designed such that a predetermined movement of the
plunger 73 will draw a known volume of sample through the capillary tube. The pump can be calibrated for each capillary by drawing a fluid into the pump by moving the plunger a known distance and then discharging the fluid and measuring the volume of the discharged fluid. Thereafter, for a given movement of the plunger, the volume of sample which flows through the analyzing volume is known. The volume can either be determined by measuring the movement of the plunger or measuring the time the plunger is moved if it is calibrated as a function of time. Although a syringe pump is described, other types of pumps which can draw known volumes of fluid through the capillary can be used. - Preferably, the capillary tubes are of rectangular configuration. FIGS. 7 and 8 show a capillary tube that includes an
opaque coating 81 which is removed over anarea 82, FIG. 7, or 83, FIG. 8. In the embodiment of FIG. 7, the beam projects through thewindow 82 which has a rectangular configuration to accept of thebeam 24. In FIG. 8, the slit masks the walls of the capillary tube and prevents diffraction of light by the walls. A combination of the two masks would confine the detected light to that emitted by a particle traveling through the capillary to block out any stray light. - An example of the operation of the apparatus to analyze a sample containing particles which do not fluoresce, and particles which intrinsically fluoresce or are marked or tagged to fluoresce, at two different wavelengths, for example 580 nm and 675 nm, is now provided with reference to FIGS. 9 and 10.
- With the
syringe pump plunger 73 extended to empty the pump, the sample vial containing the particles is positioned to immerse the end of the capillary 11 in the sample. The sample is then drawn through the capillary by applying a control signal from thecontroller 121 to start thepump 71. The controller receives the command fromprocessor 122. Thepump 71 is driven at a constant rate whereby the volume of sample passing through the analyzingvolume 19 can be measured by timing the counting period. After sample has been drawn from the vial for a predetermined time to assure that the new sample has reached thevolume 19, the processor begins to process theoutput 29 from the scatter photodetector and theoutputs curve 123. FIG. 10B illustrates theoutput pulses 28 from the scatter detector. It is seen that there are individual particles which provide atrace 124 and a cluster of particles which provides atrace 126. FIG. 10C showstraces 126 for particles which fluoresce at a first wavelength, for example 675 nm. Of note is the fact that thecluster 126 includes three such particles. FIG. 10D shows traces 127 for particles which fluoresce at another wavelength, for example 750 nm. Of note is the fact that there is also onesuch particle 128 in thecluster 126. The processor can call for a number of analyzing cycles. Finally, when an analysis is completed, the processor instructs the controller to open thevalve 76 and reverse the pump to discharge the analyzed sample into thewaste 77. A new sample cuvet can then be installed and a new sample analyzed. The processor can be configured to average the counts over a number of cycles and to process the counts to provide outputs representing the concentration of the various particles, the number of particles, etc. Using suitable labels or markers one can conduct viability assays and antibody screening assays or monitor apoptosis. - Although the apparatus has been described for a two-color analysis it can easily be modified for four-color analysis. This is schematically shown in FIG. 11. The
input light beam 24 impinges upon the analyzingvolume 19. Thephotodetector 27 and associatedlens 28 provide the scatter signal. Thefluorescent light 31 is focused bylens 32 to pass through threedichroic beam splitters filters photodetectors dichroic beam splitters filter 94 ontophotodetector 96. Thus, up to four different particles which intrinsically fluoresce or are labeled to fluoresce at four different wavelengths can be analyzed by choosing the proper reflecting wavelengths for the dichroic beam splitter and the filters. - FIG. 12 schematically shows a system using a plurality of light sources (not shown) projecting
light beams volumes arrows arrows - Rather than sensing particles by light scattered by the particles, a change in electrical current can detect the particles as they travel past spaced electrodes disposed on opposite sides of the flow path. Referring to FIG. 13, a capillary11 is shown with spaced
electrodes volume 19. As the cell or particle flows between the electrodes, the electrically conductive working fluid is displaced and the resulting change in current (impedance) can be detected. This method avoids any laser noise problem. It is usually most convenient mechanically to place the electrodes along the fluid flow path either before or after the point where thelaser beam 24 impinges onto the capillary. This creates a timing problem in that the impedance detector will detect a cell at a different point in time than the fluorescence detector, and it is possible that a second cell near the first may create a signal in the fluorescence detector at the same time as the first cell creates a signal in the impedance channel. This necessitates the use of a delay element to shift one signal in time with respect to the other by an amount equal to the distance between the two detectors divided by the flow rate, so that the two signals from one cell become congruent. This delay element may be implemented in hardware with a delay line or circuit. FIG. 14 shows theoutput signal 126 from the impedance cell sensor and thefluorescent signal 42 or 43 (FIG. 1) with adelay 127 in the photomultiplier signal, whereby the signals are correlated. This can also be implemented in software by sampling the signal from each detector into its own data stream and then shifting one data stream with respect to the other. A further feature of this arrangement is that, if the physical distance between the two detectors is known, then the actual flow rate can be deduced by finding the delay that corresponds to the best correlation between the two channels; this might be helpful when trying to identify a clogged capillary. - As explained above, we have discovered that because the illumination traversing the capillary is in the form of a thin rectangular beam the detection volume is accurately defined by the thickness of the beam and the walls of the capillary11. With this in mind, we conducted experiments in which the
slits optics 23 to form a thin,flat beam 24 as described above. The beam traverses the capillary 11 to define thedetection volume 19. The scatter detector includes an off-axis detector assembly including acollection lens 26 a and adetector 27 a. As much as possible of the emitted fluorescent light from the tagged cells or particles is gathered or intercepted by an off-axis detector assembly. It can be gathered by a condenser lens as illustrated in FIG. 1. However, in the present embodiment, it is collected by alight guide 141 which receives the light 142 and conveys it to thebeam splitter 143. The light beam is directed tooptical filters detectors - There has been provided a simple-to-use particle analyzing apparatus for characterizing particles such as determining their count, viability, concentration and identification. The analyzing apparatus detects particles in a sample fluid flowing through a capillary tube which has a sampling end for insertion into a sample fluid, and a pump coupled to the other end for drawing sample through the capillary. A light source is provided for projecting a beam of light through a predetermined analyzing volume of the capillary tube to excite fluorescence in particles that flow through the volume. At least one detector is disposed to receive the fluorescent light from excited particles and another detector is disposed to provide a signal representing all particles which flow through the analyzing volume. The output of said detectors provides signals which can be processed to provide the characteristics of the particles.
- The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, to thereby enable others skilled in the art to best use the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
Claims (33)
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/844,080 US20020028434A1 (en) | 2000-09-06 | 2001-04-26 | Particle or cell analyzer and method |
EP10004138.3A EP2219021B1 (en) | 2000-09-06 | 2001-09-05 | Particle or cell analyzer and method |
AU2001288750A AU2001288750A1 (en) | 2000-09-06 | 2001-09-05 | Particle or cell analyzer and method |
JP2002525470A JP2004520569A (en) | 2000-09-06 | 2001-09-05 | Particle or cell analyzer and method |
EP01968506.4A EP1334346B1 (en) | 2000-09-06 | 2001-09-05 | Particle or cell analyzer and method |
ES10004138T ES2697531T3 (en) | 2000-09-06 | 2001-09-05 | Particle or cell analyzer and method |
PCT/US2001/027509 WO2002021102A2 (en) | 2000-09-06 | 2001-09-05 | Particle or cell analyzer and method |
US10/410,230 US7410809B2 (en) | 2000-09-06 | 2003-04-08 | Particle or cell analyzer and method |
JP2008064290A JP5638740B2 (en) | 2000-09-06 | 2008-03-13 | Particle analyzer |
US12/183,301 US7972559B2 (en) | 2000-09-06 | 2008-07-31 | Particle or cell analyzer and method |
US13/118,831 US8524489B2 (en) | 2000-09-06 | 2011-05-31 | Particle or cell analyzer and method |
US13/118,838 US8241571B2 (en) | 2000-09-06 | 2011-05-31 | Particle or cell analyzer and method |
JP2013047116A JP2013117544A (en) | 2000-09-06 | 2013-03-08 | Particle analysis device |
JP2014158474A JP6046671B2 (en) | 2000-09-06 | 2014-08-04 | Particle analyzer |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US23038000P | 2000-09-06 | 2000-09-06 | |
US09/844,080 US20020028434A1 (en) | 2000-09-06 | 2001-04-26 | Particle or cell analyzer and method |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/410,230 Division US7410809B2 (en) | 2000-09-06 | 2003-04-08 | Particle or cell analyzer and method |
Publications (1)
Publication Number | Publication Date |
---|---|
US20020028434A1 true US20020028434A1 (en) | 2002-03-07 |
Family
ID=26924172
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/844,080 Abandoned US20020028434A1 (en) | 2000-09-06 | 2001-04-26 | Particle or cell analyzer and method |
US10/410,230 Expired - Lifetime US7410809B2 (en) | 2000-09-06 | 2003-04-08 | Particle or cell analyzer and method |
US12/183,301 Expired - Fee Related US7972559B2 (en) | 2000-09-06 | 2008-07-31 | Particle or cell analyzer and method |
US13/118,831 Expired - Lifetime US8524489B2 (en) | 2000-09-06 | 2011-05-31 | Particle or cell analyzer and method |
US13/118,838 Expired - Lifetime US8241571B2 (en) | 2000-09-06 | 2011-05-31 | Particle or cell analyzer and method |
Family Applications After (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/410,230 Expired - Lifetime US7410809B2 (en) | 2000-09-06 | 2003-04-08 | Particle or cell analyzer and method |
US12/183,301 Expired - Fee Related US7972559B2 (en) | 2000-09-06 | 2008-07-31 | Particle or cell analyzer and method |
US13/118,831 Expired - Lifetime US8524489B2 (en) | 2000-09-06 | 2011-05-31 | Particle or cell analyzer and method |
US13/118,838 Expired - Lifetime US8241571B2 (en) | 2000-09-06 | 2011-05-31 | Particle or cell analyzer and method |
Country Status (6)
Country | Link |
---|---|
US (5) | US20020028434A1 (en) |
EP (2) | EP2219021B1 (en) |
JP (4) | JP2004520569A (en) |
AU (1) | AU2001288750A1 (en) |
ES (1) | ES2697531T3 (en) |
WO (1) | WO2002021102A2 (en) |
Cited By (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002093138A2 (en) * | 2001-05-16 | 2002-11-21 | Guava Technologies, Inc. | Exchangeable flow cell assembly with a suspended capillary |
WO2004037157A2 (en) * | 2002-10-25 | 2004-05-06 | Guava Technologies, Inc. | Automatic analysis apparatus |
US20050068536A1 (en) * | 2001-12-12 | 2005-03-31 | Schwabe Nikolai Franz Gregor | Device and method for investigating analytes in liquid suspension or solution |
EP1574838A1 (en) * | 2002-12-03 | 2005-09-14 | Bay Bioscience Kabushiki Kaisha | Device for collecting information on biological particle |
US20050214747A1 (en) * | 2003-09-17 | 2005-09-29 | Robert Danielzadeh | Compositions and methods for analysis of target analytes |
US20050218319A1 (en) * | 2004-03-25 | 2005-10-06 | Bandura Dmitry R | Method and apparatus for flow cytometry linked with elemental analysis |
US20060237665A1 (en) * | 2003-03-10 | 2006-10-26 | Barney William S | Bioaerosol discrimination |
US20070025879A1 (en) * | 2005-07-27 | 2007-02-01 | Dakocytomation Denmark A/S | Method and apparatus for syringe-based sample introduction within a flow cytometer |
US20070127863A1 (en) * | 2005-12-07 | 2007-06-07 | Accuri Instruments Inc. | System and method for guiding light from an interrogation zone to a detector system |
US20070172388A1 (en) * | 2004-05-14 | 2007-07-26 | Honeywell International Inc. | Portable sample analyzer system |
US20070212262A1 (en) * | 2006-03-08 | 2007-09-13 | Rich Collin A | Fluidic system for a flow cytometer |
US20070224684A1 (en) * | 2006-03-22 | 2007-09-27 | Olson David C | Transportable flow cytometer |
US20070243106A1 (en) * | 2006-04-17 | 2007-10-18 | Rich Collin A | Flow cytometer system with sheath and waste fluid measurement |
US20080055595A1 (en) * | 2006-08-30 | 2008-03-06 | Olson David C | System and method of capturing multiple source excitations from a single location on a flow channel |
US20080092961A1 (en) * | 2006-03-08 | 2008-04-24 | Bair Nathaniel C | Flow cytometer system with unclogging feature |
US20080156379A1 (en) * | 2005-12-07 | 2008-07-03 | Rich Collin A | Pulsation attenuator for a fluidic system |
US20080221812A1 (en) * | 2006-09-29 | 2008-09-11 | Richard Pittaro | Differentiation of flow cytometry pulses and applications |
US20080228444A1 (en) * | 2005-08-22 | 2008-09-18 | David Olson | User interface for a flow cytometer system |
US20080268469A1 (en) * | 2007-04-12 | 2008-10-30 | Friedrich Srienc | Systems and Methods for Analyzing a Particulate |
US20090104075A1 (en) * | 2005-10-13 | 2009-04-23 | Rich Collin A | User interface for a fluidic system of a flow cytometer |
US20090170151A1 (en) * | 2006-07-19 | 2009-07-02 | Gary Owen Shaw | Flow-through cell and method of use |
US20090174881A1 (en) * | 2007-12-17 | 2009-07-09 | Rich Collin A | Optical system for a flow cytometer with an interrogation zone |
US20090201501A1 (en) * | 2006-02-22 | 2009-08-13 | Bair Nathaniel C | Optical System for a Flow Cytometer |
US20090260701A1 (en) * | 2005-12-07 | 2009-10-22 | Rich Collin A | Pulsation attenuator for a fluidic system |
US20090268195A1 (en) * | 2006-04-11 | 2009-10-29 | Guava Technologies, Inc. | Asymmetric capillary for capillary-flow cytometers |
US20090293910A1 (en) * | 2006-03-08 | 2009-12-03 | Ball Jack T | Fluidic system with washing capabilities for a flow cytometer |
US20090325183A1 (en) * | 2006-12-14 | 2009-12-31 | Life Technologies Corporation | Sequencing methods |
EP2166340A1 (en) * | 2005-02-01 | 2010-03-24 | Arryx, Inc. | Method and apparatus for sorting cells |
WO2010100501A1 (en) | 2009-03-04 | 2010-09-10 | Malvern Instruments Limited | Particle characterization |
US20100245821A1 (en) * | 2009-03-04 | 2010-09-30 | Jason Cecil William Corbett | Particle characterization |
US20100302536A1 (en) * | 2009-06-02 | 2010-12-02 | Ball Jack T | Data collection system and method for a flow cytometer |
US20100319469A1 (en) * | 2005-10-13 | 2010-12-23 | Rich Collin A | Detection and fluidic system of a flow cytometer |
US20110058163A1 (en) * | 2007-12-17 | 2011-03-10 | Rich Collin A | Optical system for a flow cytometer with an interrogation zone |
US20110204259A1 (en) * | 2010-02-23 | 2011-08-25 | Rogers Clare E | Method and system for detecting fluorochromes in a flow cytometer |
US20110235030A1 (en) * | 2008-12-02 | 2011-09-29 | C2 Diagnostics | Method and device for flow cytometry without sheath fluid |
US20110315757A1 (en) * | 2007-12-31 | 2011-12-29 | Joshua Lewis Colman | Tube verifier |
US20120103112A1 (en) * | 2010-10-29 | 2012-05-03 | Becton Dickinson And Company | Dual feedback vacuum fluidics for a flow-type particle analyzer |
US8229684B2 (en) | 2006-12-22 | 2012-07-24 | Accuri Cytometers, Inc. | Detection system and user interface for a flow cytometer system |
US8445286B2 (en) | 2006-11-07 | 2013-05-21 | Accuri Cytometers, Inc. | Flow cell for a flow cytometer system |
US8507279B2 (en) | 2009-06-02 | 2013-08-13 | Accuri Cytometers, Inc. | System and method of verification of a prepared sample for a flow cytometer |
US8715573B2 (en) | 2006-10-13 | 2014-05-06 | Accuri Cytometers, Inc. | Fluidic system for a flow cytometer with temporal processing |
CN104849444A (en) * | 2015-05-20 | 2015-08-19 | 大连海事大学 | Cell counting device and method capable of synchronously measuring fluorescence and occlusion |
US9218949B2 (en) | 2013-06-04 | 2015-12-22 | Fluidigm Canada, Inc. | Strategic dynamic range control for time-of-flight mass spectrometry |
WO2016022276A1 (en) * | 2014-08-06 | 2016-02-11 | Beckman Coulter, Inc. | Evaluation of multi-peak events using a flow cytometer |
US9280635B2 (en) | 2010-10-25 | 2016-03-08 | Accuri Cytometers, Inc. | Systems and user interface for collecting a data set in a flow cytometer |
US9551600B2 (en) | 2010-06-14 | 2017-01-24 | Accuri Cytometers, Inc. | System and method for creating a flow cytometer network |
US9677988B1 (en) * | 2015-07-10 | 2017-06-13 | David E. Doggett | Integrating radiation collection and detection apparatus |
CN108956391A (en) * | 2018-06-12 | 2018-12-07 | 西安理工大学 | The survey meter and detection method of the gentle aerosol particle size Spectral structure of droplet in atmospheric sounding |
CN110023741A (en) * | 2016-11-22 | 2019-07-16 | 理音株式会社 | Biomone number system and biomone method of counting |
US10732095B2 (en) | 2015-09-18 | 2020-08-04 | Sysmex Corporation | Particle imaging device and particle imaging method |
US11022538B2 (en) * | 2018-05-15 | 2021-06-01 | Government Of The United States Of America, As Represented By The Secretary Of Commerce | Quantum flow cytometer |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2279574C (en) | 1997-01-31 | 2007-07-24 | The Horticulture & Food Research Institute Of New Zealand Ltd. | Optical apparatus |
US6149867A (en) | 1997-12-31 | 2000-11-21 | Xy, Inc. | Sheath fluids and collection systems for sex-specific cytometer sorting of sperm |
US7208265B1 (en) | 1999-11-24 | 2007-04-24 | Xy, Inc. | Method of cryopreserving selected sperm cells |
CA2468772C (en) | 2000-11-29 | 2013-10-29 | George E. Seidel | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
US7713687B2 (en) | 2000-11-29 | 2010-05-11 | Xy, Inc. | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
NZ538462A (en) | 2002-08-01 | 2008-06-30 | Xy Inc | Low pressure sperm cell separation system |
US8486618B2 (en) | 2002-08-01 | 2013-07-16 | Xy, Llc | Heterogeneous inseminate system |
US7855078B2 (en) | 2002-08-15 | 2010-12-21 | Xy, Llc | High resolution flow cytometer |
US7169548B2 (en) | 2002-09-13 | 2007-01-30 | Xy, Inc. | Sperm cell processing and preservation systems |
EP2308416B1 (en) | 2003-03-28 | 2015-01-07 | Inguran, LLC | Apparatus and methods for providing sex-sorted animal sperm |
AU2004242121B2 (en) | 2003-05-15 | 2010-06-24 | Xy, Llc. | Efficient haploid cell sorting for flow cytometer systems |
US7892725B2 (en) | 2004-03-29 | 2011-02-22 | Inguran, Llc | Process for storing a sperm dispersion |
AR049732A1 (en) | 2004-07-22 | 2006-08-30 | Monsanto Co | PROCESS TO ENRICH A Sperm Cell Population |
JP2007071794A (en) * | 2005-09-09 | 2007-03-22 | Rion Co Ltd | Particle detector |
US8616048B2 (en) * | 2006-02-02 | 2013-12-31 | E I Spectra, LLC | Reusable thin film particle sensor |
US9452429B2 (en) | 2006-02-02 | 2016-09-27 | E. I. Spectra, Llc | Method for mutiplexed microfluidic bead-based immunoassay |
US20110189714A1 (en) * | 2010-02-03 | 2011-08-04 | Ayliffe Harold E | Microfluidic cell sorter and method |
US9293311B1 (en) | 2006-02-02 | 2016-03-22 | E. I. Spectra, Llc | Microfluidic interrogation device |
US7728974B2 (en) * | 2007-02-07 | 2010-06-01 | Cytopeia, Inc. | Enhanced detection system and method |
JP5171182B2 (en) * | 2007-09-20 | 2013-03-27 | シスメックス株式会社 | Sample analyzer |
JP4472024B2 (en) | 2008-02-07 | 2010-06-02 | 三井造船株式会社 | Fluorescence detection apparatus and fluorescence detection method |
JP5667079B2 (en) * | 2008-12-18 | 2015-02-12 | アズビル株式会社 | Compact detector for simultaneous detection of particle size and fluorescence |
US8358411B2 (en) * | 2008-12-18 | 2013-01-22 | Biovigilant Systems, Inc. | Integrated microbial collector |
US8467054B2 (en) | 2009-01-23 | 2013-06-18 | University Of Washington | Virtual core flow cytometry |
WO2010091311A2 (en) * | 2009-02-05 | 2010-08-12 | The Regents Of The University Of California | A nanowire afm probe for imaging soft materials |
US20100198188A1 (en) * | 2009-02-05 | 2010-08-05 | Abbott Diabetes Care Inc. | Devices and Methods for Metering Insoluble Active Agent Particles |
US20100220315A1 (en) * | 2009-02-27 | 2010-09-02 | Beckman Coulter, Inc. | Stabilized Optical System for Flow Cytometry |
US9500645B2 (en) | 2009-11-23 | 2016-11-22 | Cyvek, Inc. | Micro-tube particles for microfluidic assays and methods of manufacture |
US9759718B2 (en) | 2009-11-23 | 2017-09-12 | Cyvek, Inc. | PDMS membrane-confined nucleic acid and antibody/antigen-functionalized microlength tube capture elements, and systems employing them, and methods of their use |
WO2013134740A1 (en) | 2012-03-08 | 2013-09-12 | Cyvek, Inc. | Methods and systems for epi-fluorescent monitoring and scanning for microfluidic assays |
US10022696B2 (en) | 2009-11-23 | 2018-07-17 | Cyvek, Inc. | Microfluidic assay systems employing micro-particles and methods of manufacture |
US9700889B2 (en) | 2009-11-23 | 2017-07-11 | Cyvek, Inc. | Methods and systems for manufacture of microarray assay systems, conducting microfluidic assays, and monitoring and scanning to obtain microfluidic assay results |
US9855735B2 (en) | 2009-11-23 | 2018-01-02 | Cyvek, Inc. | Portable microfluidic assay devices and methods of manufacture and use |
US10065403B2 (en) | 2009-11-23 | 2018-09-04 | Cyvek, Inc. | Microfluidic assay assemblies and methods of manufacture |
WO2012151112A1 (en) | 2011-05-05 | 2012-11-08 | Emd Millipore Corporation | Apparatus and method for increasing collection efficiency in capillary based flowcytometry |
TWI435080B (en) | 2011-06-09 | 2014-04-21 | Univ Nat Pingtung Sci & Tech | Cell or particle detecting apparatus |
KR101139776B1 (en) | 2011-12-09 | 2012-04-26 | 국방과학연구소 | A beam dumper for a particle counter or a fluorescence detector |
JP2013137267A (en) * | 2011-12-28 | 2013-07-11 | Sony Corp | Microchip and microchip-type fine-particle measuring device |
US8804105B2 (en) | 2012-03-27 | 2014-08-12 | E. I. Spectra, Llc | Combined optical imaging and electrical detection to characterize particles carried in a fluid |
CN102818755B (en) * | 2012-07-23 | 2014-10-22 | 河海大学 | Method for actual measurement of microcystis density and population size by using laser particle analyzer |
WO2014121241A1 (en) | 2013-02-01 | 2014-08-07 | Bio-Rad Laboratories, Inc. | System for detection of spaced droplets |
JP6117093B2 (en) * | 2013-12-20 | 2017-04-19 | アズビル株式会社 | Particle detection apparatus and particle detection method |
CN103868595B (en) * | 2014-03-06 | 2016-03-02 | 湖南大学 | The pumping-detection transient state absorption spectrometer that a kind of space is separated and implementation method |
WO2016112035A1 (en) | 2015-01-08 | 2016-07-14 | University Of Washington | Systems and methods for immersion flow cytometry |
KR102258807B1 (en) * | 2015-02-24 | 2021-06-09 | (주)미디어에버 | Detection apparatus for micro dust and organism |
CN107209107A (en) | 2015-04-30 | 2017-09-26 | 惠普发展公司有限责任合伙企业 | Microfluidic optical fluid sensor |
US10228367B2 (en) | 2015-12-01 | 2019-03-12 | ProteinSimple | Segmented multi-use automated assay cartridge |
CN106596498B (en) * | 2017-01-19 | 2018-09-04 | 大连理工大学 | A kind of air microbe device for fast detecting |
US11499183B2 (en) | 2017-06-28 | 2022-11-15 | Bio-Rad Laboratories, Inc. | System and method for droplet detection |
US11045805B2 (en) | 2017-11-01 | 2021-06-29 | Bio-Rad Laboratories, Inc. | Microfluidic system and method for arranging objects |
CN208833783U (en) * | 2018-08-14 | 2019-05-07 | 三诺生物传感股份有限公司 | A kind of optical de-tection means and automatic clinical chemistry analyzer |
CN112996900A (en) * | 2018-09-14 | 2021-06-18 | 加利福尼亚大学董事会 | Cell sorting device and method |
CN109587327A (en) * | 2018-11-12 | 2019-04-05 | 中国航空工业集团公司洛阳电光设备研究所 | A kind of quick killing system of pathogenic bacteria laser being integrated in smart phone |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3827304A (en) * | 1971-07-20 | 1974-08-06 | Gilson W | Sample handling method |
Family Cites Families (71)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1051716A (en) * | 1962-07-02 | 1900-01-01 | ||
US3413464A (en) * | 1965-04-29 | 1968-11-26 | Ibm | Method for measuring the nucleic acid in biological cells after enhancement in an acidic solution |
US3591290A (en) * | 1969-04-04 | 1971-07-06 | Battelle Development Corp | Urological apparatus and method |
US3826899A (en) * | 1969-08-15 | 1974-07-30 | Nuclear Res Ass Inc | Biological cell analyzing system |
JPS5681451A (en) * | 1979-12-07 | 1981-07-03 | Olympus Optical Co Ltd | Separately-injecting nozzle |
US4350892A (en) * | 1980-07-31 | 1982-09-21 | Research Corporation | X'-, Y'-, Z'- axis multidimensional slit-scan flow system |
JPS5798862A (en) * | 1980-12-12 | 1982-06-19 | Olympus Optical Co Ltd | Distributor |
US4510438A (en) * | 1982-02-16 | 1985-04-09 | Coulter Electronics, Inc. | Coincidence correction in particle analysis system |
JPS60140156A (en) * | 1983-12-27 | 1985-07-25 | Shimadzu Corp | Automatic analytical apparatus |
JPS6193932A (en) * | 1984-10-15 | 1986-05-12 | Hitachi Ltd | Particle analysis instrument |
JPS6188158A (en) * | 1985-09-03 | 1986-05-06 | Olympus Optical Co Ltd | Automatic analysis instrument |
JPS61262639A (en) * | 1985-09-03 | 1986-11-20 | Olympus Optical Co Ltd | Automatic analyser |
JPH0719847B2 (en) | 1985-12-28 | 1995-03-06 | 株式会社東芝 | Method of manufacturing dynamic memory cell |
US4827143A (en) * | 1986-03-26 | 1989-05-02 | Hitachi, Ltd. | Monitor for particles of various materials |
JPS62156856U (en) * | 1986-03-28 | 1987-10-05 | ||
JPS63135152A (en) | 1986-11-28 | 1988-06-07 | オリンパス光学工業株式会社 | Endoscope for ultrasonic treatment |
JPS63135152U (en) * | 1987-02-25 | 1988-09-05 | ||
JPS63225143A (en) * | 1987-03-16 | 1988-09-20 | Sasakura Eng Co Ltd | Method and apparatus for measuring impure fine particles in fluid |
JPH0776713B2 (en) * | 1988-03-22 | 1995-08-16 | 株式会社島津製作所 | Electronic balance |
JPH0614008B2 (en) * | 1988-03-22 | 1994-02-23 | キヤノン株式会社 | Particle analyzer |
US4837446A (en) * | 1988-03-31 | 1989-06-06 | International Paper Company | Apparatus and process for testing uniformity of pulp |
US6001230A (en) * | 1988-04-29 | 1999-12-14 | Beckman Coulter, Inc. | Automated capillary electrophoresis apparatus |
JPH0213830A (en) * | 1988-06-30 | 1990-01-18 | Canon Inc | Article measuring apparatus |
US5597733A (en) * | 1988-07-25 | 1997-01-28 | Precision Systems, Inc. | Automatic multiple-sample multiple-reagent dispensing method in chemical analyzer |
JPH0658318B2 (en) * | 1988-08-16 | 1994-08-03 | リオン株式会社 | Light scattering particle detector |
US5132088A (en) * | 1988-11-17 | 1992-07-21 | Kabushiki Kaisha Nittec | Automatic medical sampling device |
JP2749912B2 (en) * | 1989-12-15 | 1998-05-13 | キヤノン株式会社 | Sample measuring device and sample measuring method |
JPH02289808A (en) * | 1989-04-28 | 1990-11-29 | Olympus Optical Co Ltd | Lighting optical system |
US5074658A (en) * | 1989-07-31 | 1991-12-24 | Syracuse University | Laser capillary spectrophotometric acquisition of bivariate drop size and concentration data for liquid-liquid dispersion |
US5030002A (en) * | 1989-08-11 | 1991-07-09 | Becton, Dickinson And Company | Method and apparatus for sorting particles with a moving catcher tube |
JPH0389143A (en) * | 1989-08-31 | 1991-04-15 | Nikkiso Co Ltd | Gas passage switching apparatus for calibration in surface area measuring apparatus |
AU642444B2 (en) * | 1989-11-30 | 1993-10-21 | Mochida Pharmaceutical Co., Ltd. | Reaction vessel |
JPH0738839Y2 (en) * | 1990-05-15 | 1995-09-06 | オムロン株式会社 | Flow particle analyzer |
JP3084295B2 (en) * | 1991-02-27 | 2000-09-04 | シスメックス株式会社 | Flow image cytometer |
US5529679A (en) * | 1992-02-28 | 1996-06-25 | Hitachi, Ltd. | DNA detector and DNA detection method |
JPH04337446A (en) * | 1991-05-15 | 1992-11-25 | Hitachi Ltd | Method and device for measuring fine grain and constant quantity method |
US5286452A (en) * | 1991-05-20 | 1994-02-15 | Sienna Biotech, Inc. | Simultaneous multiple assays |
US5178750A (en) * | 1991-06-20 | 1993-01-12 | Texaco Inc. | Lubricating oil process |
US5488469A (en) * | 1991-08-30 | 1996-01-30 | Omron Corporation | Cell analyzing apparatus |
JP3102925B2 (en) * | 1991-09-20 | 2000-10-23 | シスメックス株式会社 | Particle analyzer |
US5548395A (en) * | 1991-09-20 | 1996-08-20 | Toa Medical Electronics Co., Ltd. | Particle analyzer |
JP3232145B2 (en) * | 1991-12-27 | 2001-11-26 | シスメックス株式会社 | Reticulocyte measurement method |
EP0626067A4 (en) * | 1992-02-07 | 1997-06-25 | Abbott Lab | Method for accurately enumerating and sensitively qualifying heterogeneous cell populations in cytolytic processing conditions. |
US5495105A (en) * | 1992-02-20 | 1996-02-27 | Canon Kabushiki Kaisha | Method and apparatus for particle manipulation, and measuring apparatus utilizing the same |
JP2756397B2 (en) * | 1992-02-20 | 1998-05-25 | キヤノン株式会社 | Particle operation method and apparatus, and measurement apparatus using the same |
JP3185335B2 (en) | 1992-02-27 | 2001-07-09 | 石川島播磨重工業株式会社 | Hot material joining method |
JP3076144B2 (en) | 1992-05-01 | 2000-08-14 | キヤノン株式会社 | Biological trace component inspection system |
JPH05332992A (en) * | 1992-05-29 | 1993-12-17 | Shimadzu Corp | Electrophoresis device |
DE69224380T2 (en) * | 1992-08-04 | 1998-05-20 | Hewlett Packard Gmbh | Device for treating fioles in an "analysis apparatus" |
JPH06194299A (en) * | 1992-12-24 | 1994-07-15 | Canon Inc | Flow cell apparatus |
US5547849A (en) | 1993-02-17 | 1996-08-20 | Biometric Imaging, Inc. | Apparatus and method for volumetric capillary cytometry |
GB9310557D0 (en) * | 1993-05-21 | 1993-07-07 | Smithkline Beecham Plc | Novel process and apparatus |
NO932088L (en) * | 1993-06-08 | 1995-01-05 | Oddbjoern Gjelsnes | Device for use in liquid flow cytometry |
JP3103709B2 (en) * | 1993-10-15 | 2000-10-30 | リオン株式会社 | Particle counting device and particle counting method |
US5656499A (en) * | 1994-08-01 | 1997-08-12 | Abbott Laboratories | Method for performing automated hematology and cytometry analysis |
JP3375203B2 (en) * | 1994-08-08 | 2003-02-10 | シスメックス株式会社 | Cell analyzer |
JPH08145869A (en) * | 1994-11-25 | 1996-06-07 | Hitachi Ltd | Particle analyzer |
US5833827A (en) * | 1995-09-29 | 1998-11-10 | Hitachi, Ltd. | Capillary array electrophoresis system |
JP4754661B2 (en) * | 1997-06-09 | 2011-08-24 | ミリポア・コーポレイション | Method and apparatus for detecting microparticles in a fluid sample |
JP2000000458A (en) * | 1998-04-13 | 2000-01-07 | Jsr Corp | Water based dispersion and measuring method of coarse particle in water based dispersion |
JP3734125B2 (en) * | 1998-04-24 | 2006-01-11 | 松下電器産業株式会社 | Microbe count measuring device |
JP2000000468A (en) | 1998-06-18 | 2000-01-07 | Petroleum Energy Center Found | Catalyst for catalytically reducing nitrogen oxide and method thereof |
US6077713A (en) * | 1998-06-30 | 2000-06-20 | Dade Behring Inc. | Method and apparatus for extracting liquid samples from a closed container |
ATE286246T1 (en) * | 1998-07-27 | 2005-01-15 | Kowa Co | METHOD AND DEVICE FOR COUNTING POLLEN GRAINS |
US6074880A (en) * | 1998-08-28 | 2000-06-13 | Transgenomic, Inc. | Sample analyte containing solution fraction collection system, and method of use |
US6228652B1 (en) * | 1999-02-16 | 2001-05-08 | Coulter International Corp. | Method and apparatus for analyzing cells in a whole blood sample |
US20030040105A1 (en) * | 1999-09-30 | 2003-02-27 | Sklar Larry A. | Microfluidic micromixer |
US6641993B1 (en) * | 2000-02-22 | 2003-11-04 | Ortho Clinical Diagnostics, Inc. | Aspirating and mixing of liquids within a probe tip |
JP3854475B2 (en) * | 2000-06-27 | 2006-12-06 | 三菱重工業株式会社 | Sodium purification system |
US7320775B2 (en) * | 2001-05-16 | 2008-01-22 | Guava Technologies, Inc. | Exchangeable flow cell assembly with a suspended capillary |
US6833062B2 (en) * | 2003-02-28 | 2004-12-21 | Combisep, Inc. | Multiplexed, absorbance-based capillary electrophoresis system and method |
-
2001
- 2001-04-26 US US09/844,080 patent/US20020028434A1/en not_active Abandoned
- 2001-09-05 EP EP10004138.3A patent/EP2219021B1/en not_active Expired - Lifetime
- 2001-09-05 JP JP2002525470A patent/JP2004520569A/en active Pending
- 2001-09-05 ES ES10004138T patent/ES2697531T3/en not_active Expired - Lifetime
- 2001-09-05 AU AU2001288750A patent/AU2001288750A1/en not_active Abandoned
- 2001-09-05 EP EP01968506.4A patent/EP1334346B1/en not_active Expired - Lifetime
- 2001-09-05 WO PCT/US2001/027509 patent/WO2002021102A2/en active Application Filing
-
2003
- 2003-04-08 US US10/410,230 patent/US7410809B2/en not_active Expired - Lifetime
-
2008
- 2008-03-13 JP JP2008064290A patent/JP5638740B2/en not_active Expired - Lifetime
- 2008-07-31 US US12/183,301 patent/US7972559B2/en not_active Expired - Fee Related
-
2011
- 2011-05-31 US US13/118,831 patent/US8524489B2/en not_active Expired - Lifetime
- 2011-05-31 US US13/118,838 patent/US8241571B2/en not_active Expired - Lifetime
-
2013
- 2013-03-08 JP JP2013047116A patent/JP2013117544A/en active Pending
-
2014
- 2014-08-04 JP JP2014158474A patent/JP6046671B2/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3827304A (en) * | 1971-07-20 | 1974-08-06 | Gilson W | Sample handling method |
Cited By (116)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002093138A3 (en) * | 2001-05-16 | 2003-02-27 | Guava Technologies Inc | Exchangeable flow cell assembly with a suspended capillary |
WO2002093138A2 (en) * | 2001-05-16 | 2002-11-21 | Guava Technologies, Inc. | Exchangeable flow cell assembly with a suspended capillary |
US7320775B2 (en) | 2001-05-16 | 2008-01-22 | Guava Technologies, Inc. | Exchangeable flow cell assembly with a suspended capillary |
US20140070092A1 (en) * | 2001-07-17 | 2014-03-13 | Perkinelmer Health Sciences, Inc. | Elemental flow cytometer |
US7245379B2 (en) * | 2001-12-12 | 2007-07-17 | Proimmune Limited | Device and method for investigating analytes in liquid suspension or solution |
US7477384B2 (en) | 2001-12-12 | 2009-01-13 | Proimmune Limited | Device and method for investigating analytes in liquid suspension or solution |
US20050068536A1 (en) * | 2001-12-12 | 2005-03-31 | Schwabe Nikolai Franz Gregor | Device and method for investigating analytes in liquid suspension or solution |
US20110216319A1 (en) * | 2001-12-12 | 2011-09-08 | Prolmmune Limited | Device and method for investigating analytes in liquid suspension or solution |
WO2004037157A2 (en) * | 2002-10-25 | 2004-05-06 | Guava Technologies, Inc. | Automatic analysis apparatus |
WO2004037157A3 (en) * | 2002-10-25 | 2004-06-17 | Guava Technologies Inc | Automatic analysis apparatus |
US20040136870A1 (en) * | 2002-10-25 | 2004-07-15 | Kochy Thomas E. | Automatic analysis apparatus |
EP1574838A1 (en) * | 2002-12-03 | 2005-09-14 | Bay Bioscience Kabushiki Kaisha | Device for collecting information on biological particle |
EP1574838A4 (en) * | 2002-12-03 | 2011-09-28 | Bay Bioscience Kabushiki Kaisha | Device for collecting information on biological particle |
US20060237665A1 (en) * | 2003-03-10 | 2006-10-26 | Barney William S | Bioaerosol discrimination |
US20100173325A1 (en) * | 2003-09-17 | 2010-07-08 | Millipore Corporation | Composition and Method for Analysis of Target Analytes |
JP2010204120A (en) * | 2003-09-17 | 2010-09-16 | Guava Technologies Inc | Composition and method for analyzing target specimen |
US20050214747A1 (en) * | 2003-09-17 | 2005-09-29 | Robert Danielzadeh | Compositions and methods for analysis of target analytes |
US20070281325A1 (en) * | 2003-09-17 | 2007-12-06 | Robert Danielzadeh | Compositions and methods for analysis of target analytes |
US7479630B2 (en) * | 2004-03-25 | 2009-01-20 | Bandura Dmitry R | Method and apparatus for flow cytometry linked with elemental analysis |
US10436698B2 (en) | 2004-03-25 | 2019-10-08 | Fluidigm Corporation | Mass spectrometry based multi-parametric particle analyzer |
US20050218319A1 (en) * | 2004-03-25 | 2005-10-06 | Bandura Dmitry R | Method and apparatus for flow cytometry linked with elemental analysis |
US9952134B2 (en) | 2004-03-25 | 2018-04-24 | Fluidigm Corporation | Mass spectrometry based multi-parametric particle analyzer |
US10180386B2 (en) | 2004-03-25 | 2019-01-15 | Fluidigm Corporation | Mass spectrometry based multi-parametric particle analyzer |
US20070172388A1 (en) * | 2004-05-14 | 2007-07-26 | Honeywell International Inc. | Portable sample analyzer system |
US8323564B2 (en) * | 2004-05-14 | 2012-12-04 | Honeywell International Inc. | Portable sample analyzer system |
CN102128778A (en) * | 2005-02-01 | 2011-07-20 | 阿尔利克斯公司 | Method and apparatus for sorting cells |
EP2166340A1 (en) * | 2005-02-01 | 2010-03-24 | Arryx, Inc. | Method and apparatus for sorting cells |
US8628723B2 (en) | 2005-07-27 | 2014-01-14 | Beckman Coulter, Inc. | Method and apparatus for syringe-based sample introduction within a flow cytometer |
US20070025879A1 (en) * | 2005-07-27 | 2007-02-01 | Dakocytomation Denmark A/S | Method and apparatus for syringe-based sample introduction within a flow cytometer |
US20100112679A1 (en) * | 2005-07-27 | 2010-05-06 | Beckman Coulter, Inc. | Method And Apparatus For Syringe-Based Sample Introduction Within A Flow Cytometer |
US7996188B2 (en) | 2005-08-22 | 2011-08-09 | Accuri Cytometers, Inc. | User interface for a flow cytometer system |
US20080228444A1 (en) * | 2005-08-22 | 2008-09-18 | David Olson | User interface for a flow cytometer system |
US8229707B2 (en) | 2005-08-22 | 2012-07-24 | Accuri Cytometers, Inc. | User interface for a flow cytometer system |
US20090104075A1 (en) * | 2005-10-13 | 2009-04-23 | Rich Collin A | User interface for a fluidic system of a flow cytometer |
US20100319469A1 (en) * | 2005-10-13 | 2010-12-23 | Rich Collin A | Detection and fluidic system of a flow cytometer |
US8303894B2 (en) | 2005-10-13 | 2012-11-06 | Accuri Cytometers, Inc. | Detection and fluidic system of a flow cytometer |
US7776268B2 (en) | 2005-10-13 | 2010-08-17 | Accuri Cytometers, Inc. | User interface for a fluidic system of a flow cytometer |
US8470246B2 (en) | 2005-10-13 | 2013-06-25 | Accuri Cytometers, Inc. | Detection and fluidic system of a flow cytometer |
US20080156379A1 (en) * | 2005-12-07 | 2008-07-03 | Rich Collin A | Pulsation attenuator for a fluidic system |
US7857005B2 (en) | 2005-12-07 | 2010-12-28 | Accuri Cytometers, Inc. | Pulsation attenuator for a fluidic system |
US7520300B2 (en) | 2005-12-07 | 2009-04-21 | Accuri Cytometers, Inc. | Pulsation attenuator for a fluidic system |
US20070127863A1 (en) * | 2005-12-07 | 2007-06-07 | Accuri Instruments Inc. | System and method for guiding light from an interrogation zone to a detector system |
US20090260701A1 (en) * | 2005-12-07 | 2009-10-22 | Rich Collin A | Pulsation attenuator for a fluidic system |
US20090201501A1 (en) * | 2006-02-22 | 2009-08-13 | Bair Nathaniel C | Optical System for a Flow Cytometer |
US8149402B2 (en) | 2006-02-22 | 2012-04-03 | Accuri Cytometers, Inc. | Optical system for a flow cytometer |
US8262990B2 (en) | 2006-03-08 | 2012-09-11 | Accuri Cytometers, Inc. | Flow cytometer system with unclogging feature |
US8187888B2 (en) | 2006-03-08 | 2012-05-29 | Accuri Cytometers, Inc. | Fluidic system for a flow cytometer |
US20070212262A1 (en) * | 2006-03-08 | 2007-09-13 | Rich Collin A | Fluidic system for a flow cytometer |
US7780916B2 (en) | 2006-03-08 | 2010-08-24 | Accuri Cytometers, Inc. | Flow cytometer system with unclogging feature |
US20100319786A1 (en) * | 2006-03-08 | 2010-12-23 | Bair Nathaniel C | Flow cytometer system with unclogging feature |
US8283177B2 (en) | 2006-03-08 | 2012-10-09 | Accuri Cytometers, Inc. | Fluidic system with washing capabilities for a flow cytometer |
US8017402B2 (en) | 2006-03-08 | 2011-09-13 | Accuri Cytometers, Inc. | Fluidic system for a flow cytometer |
US20090293910A1 (en) * | 2006-03-08 | 2009-12-03 | Ball Jack T | Fluidic system with washing capabilities for a flow cytometer |
US20080092961A1 (en) * | 2006-03-08 | 2008-04-24 | Bair Nathaniel C | Flow cytometer system with unclogging feature |
US20070224684A1 (en) * | 2006-03-22 | 2007-09-27 | Olson David C | Transportable flow cytometer |
US7978318B2 (en) | 2006-04-11 | 2011-07-12 | Millipore Corporation | Asymmetric capillary for capillary-flow cytometers |
US20090268195A1 (en) * | 2006-04-11 | 2009-10-29 | Guava Technologies, Inc. | Asymmetric capillary for capillary-flow cytometers |
US20070243106A1 (en) * | 2006-04-17 | 2007-10-18 | Rich Collin A | Flow cytometer system with sheath and waste fluid measurement |
US7981661B2 (en) | 2006-04-17 | 2011-07-19 | Accuri Cytometers, Inc. | Flow cytometer system with sheath and waste fluid measurement |
US20090170151A1 (en) * | 2006-07-19 | 2009-07-02 | Gary Owen Shaw | Flow-through cell and method of use |
US20080055595A1 (en) * | 2006-08-30 | 2008-03-06 | Olson David C | System and method of capturing multiple source excitations from a single location on a flow channel |
US8077310B2 (en) | 2006-08-30 | 2011-12-13 | Accuri Cytometers, Inc. | System and method of capturing multiple source excitations from a single location on a flow channel |
US20110063602A1 (en) * | 2006-09-29 | 2011-03-17 | Millipore Corporation | Differentiation of flow cytometry pulses and applications |
US7847923B2 (en) | 2006-09-29 | 2010-12-07 | Millipore Corporation | Differentiation of flow cytometry pulses and applications |
US8885153B2 (en) | 2006-09-29 | 2014-11-11 | Emd Millipore Corporation | Differentiation of flow cytometry pulses and applications |
US8184271B2 (en) | 2006-09-29 | 2012-05-22 | Emd Millipore Corporation | Differentiation of flow cytometry pulses and applications |
US20080221812A1 (en) * | 2006-09-29 | 2008-09-11 | Richard Pittaro | Differentiation of flow cytometry pulses and applications |
US8715573B2 (en) | 2006-10-13 | 2014-05-06 | Accuri Cytometers, Inc. | Fluidic system for a flow cytometer with temporal processing |
US8445286B2 (en) | 2006-11-07 | 2013-05-21 | Accuri Cytometers, Inc. | Flow cell for a flow cytometer system |
US20090325183A1 (en) * | 2006-12-14 | 2009-12-31 | Life Technologies Corporation | Sequencing methods |
US8229684B2 (en) | 2006-12-22 | 2012-07-24 | Accuri Cytometers, Inc. | Detection system and user interface for a flow cytometer system |
US20080268469A1 (en) * | 2007-04-12 | 2008-10-30 | Friedrich Srienc | Systems and Methods for Analyzing a Particulate |
US8409509B2 (en) | 2007-04-12 | 2013-04-02 | Regents Of The University Of Minnesota | Systems and methods for analyzing a particulate |
US8432541B2 (en) | 2007-12-17 | 2013-04-30 | Accuri Cytometers, Inc. | Optical system for a flow cytometer with an interrogation zone |
US20090174881A1 (en) * | 2007-12-17 | 2009-07-09 | Rich Collin A | Optical system for a flow cytometer with an interrogation zone |
US7843561B2 (en) | 2007-12-17 | 2010-11-30 | Accuri Cytometers, Inc. | Optical system for a flow cytometer with an interrogation zone |
US20110058163A1 (en) * | 2007-12-17 | 2011-03-10 | Rich Collin A | Optical system for a flow cytometer with an interrogation zone |
US8720772B2 (en) | 2007-12-31 | 2014-05-13 | Oridion Medical 1987 Ltd. | Tube verifier |
US8967461B2 (en) | 2007-12-31 | 2015-03-03 | Oridion Medical (1987) Ltd. | Tube verifier |
US9206932B2 (en) | 2007-12-31 | 2015-12-08 | Oridion Medical (1987) Ltd. | Tube verifier |
US8763892B2 (en) * | 2007-12-31 | 2014-07-01 | Oridon Medical 1987 Ltd. | Tube verifier |
US8763895B2 (en) | 2007-12-31 | 2014-07-01 | Oridion Medical 1987 Ltd. | Tube verifier |
US9480832B2 (en) | 2007-12-31 | 2016-11-01 | Oridion Medical 1987 Ltd. | Tube verifier |
US20110315757A1 (en) * | 2007-12-31 | 2011-12-29 | Joshua Lewis Colman | Tube verifier |
US20110235030A1 (en) * | 2008-12-02 | 2011-09-29 | C2 Diagnostics | Method and device for flow cytometry without sheath fluid |
US9243992B2 (en) * | 2008-12-02 | 2016-01-26 | C2 Diagnostics | Method and device for flow cytometry without sheath fluid |
US8675197B2 (en) * | 2009-03-04 | 2014-03-18 | Malvern Instruments, Ltd. | Particle characterization |
US20100253945A1 (en) * | 2009-03-04 | 2010-10-07 | Jason Cecil William Corbett | Particle characterization |
US8614792B2 (en) | 2009-03-04 | 2013-12-24 | Malvern Instruments, Ltd. | Particle characterization |
US20100245821A1 (en) * | 2009-03-04 | 2010-09-30 | Jason Cecil William Corbett | Particle characterization |
WO2010100501A1 (en) | 2009-03-04 | 2010-09-10 | Malvern Instruments Limited | Particle characterization |
CN102439413A (en) * | 2009-03-04 | 2012-05-02 | 马尔文仪器有限公司 | Particle characterization |
US8004674B2 (en) | 2009-06-02 | 2011-08-23 | Accuri Cytometers, Inc. | Data collection system and method for a flow cytometer |
US9523677B2 (en) | 2009-06-02 | 2016-12-20 | Accuri Cytometers, Inc. | System and method of verification of a prepared sample for a flow cytometer |
US20100302536A1 (en) * | 2009-06-02 | 2010-12-02 | Ball Jack T | Data collection system and method for a flow cytometer |
US8507279B2 (en) | 2009-06-02 | 2013-08-13 | Accuri Cytometers, Inc. | System and method of verification of a prepared sample for a flow cytometer |
US20110204259A1 (en) * | 2010-02-23 | 2011-08-25 | Rogers Clare E | Method and system for detecting fluorochromes in a flow cytometer |
US8779387B2 (en) | 2010-02-23 | 2014-07-15 | Accuri Cytometers, Inc. | Method and system for detecting fluorochromes in a flow cytometer |
US9551600B2 (en) | 2010-06-14 | 2017-01-24 | Accuri Cytometers, Inc. | System and method for creating a flow cytometer network |
US9280635B2 (en) | 2010-10-25 | 2016-03-08 | Accuri Cytometers, Inc. | Systems and user interface for collecting a data set in a flow cytometer |
US10481074B2 (en) | 2010-10-25 | 2019-11-19 | Becton, Dickinson And Company | Systems and user interface for collecting a data set in a flow cytometer |
US11125674B2 (en) | 2010-10-25 | 2021-09-21 | Becton, Dickinson And Company | Systems and user interface for collecting a data set in a flow cytometer |
US10031064B2 (en) | 2010-10-25 | 2018-07-24 | Accuri Cytometers, Inc. | Systems and user interface for collecting a data set in a flow cytometer |
US20120103112A1 (en) * | 2010-10-29 | 2012-05-03 | Becton Dickinson And Company | Dual feedback vacuum fluidics for a flow-type particle analyzer |
US8528427B2 (en) * | 2010-10-29 | 2013-09-10 | Becton, Dickinson And Company | Dual feedback vacuum fluidics for a flow-type particle analyzer |
US9092034B2 (en) | 2010-10-29 | 2015-07-28 | Becton, Dickinson And Company | Dual feedback vacuum fluidics for a flow-type particle analyzer |
US9218949B2 (en) | 2013-06-04 | 2015-12-22 | Fluidigm Canada, Inc. | Strategic dynamic range control for time-of-flight mass spectrometry |
WO2016022276A1 (en) * | 2014-08-06 | 2016-02-11 | Beckman Coulter, Inc. | Evaluation of multi-peak events using a flow cytometer |
CN106574891A (en) * | 2014-08-06 | 2017-04-19 | 贝克曼考尔特公司 | Evaluation of multi-peak events using a flow cytometer |
CN104849444A (en) * | 2015-05-20 | 2015-08-19 | 大连海事大学 | Cell counting device and method capable of synchronously measuring fluorescence and occlusion |
US9677988B1 (en) * | 2015-07-10 | 2017-06-13 | David E. Doggett | Integrating radiation collection and detection apparatus |
US10732095B2 (en) | 2015-09-18 | 2020-08-04 | Sysmex Corporation | Particle imaging device and particle imaging method |
CN110023741A (en) * | 2016-11-22 | 2019-07-16 | 理音株式会社 | Biomone number system and biomone method of counting |
US11022538B2 (en) * | 2018-05-15 | 2021-06-01 | Government Of The United States Of America, As Represented By The Secretary Of Commerce | Quantum flow cytometer |
US11768147B2 (en) | 2018-05-15 | 2023-09-26 | Government Of The United States Of America, As Represented By The Secretary Of Commerce | Quantum flow cytometer |
CN108956391A (en) * | 2018-06-12 | 2018-12-07 | 西安理工大学 | The survey meter and detection method of the gentle aerosol particle size Spectral structure of droplet in atmospheric sounding |
Also Published As
Publication number | Publication date |
---|---|
EP2219021A2 (en) | 2010-08-18 |
JP5638740B2 (en) | 2014-12-10 |
US20080283773A1 (en) | 2008-11-20 |
WO2002021102A2 (en) | 2002-03-14 |
US8241571B2 (en) | 2012-08-14 |
US20110226964A1 (en) | 2011-09-22 |
US7972559B2 (en) | 2011-07-05 |
US20040005635A1 (en) | 2004-01-08 |
US8524489B2 (en) | 2013-09-03 |
JP2014206549A (en) | 2014-10-30 |
EP2219021A3 (en) | 2014-09-03 |
JP2013117544A (en) | 2013-06-13 |
ES2697531T3 (en) | 2019-01-24 |
EP1334346A2 (en) | 2003-08-13 |
JP2008191163A (en) | 2008-08-21 |
US7410809B2 (en) | 2008-08-12 |
EP1334346B1 (en) | 2019-04-24 |
JP6046671B2 (en) | 2016-12-21 |
JP2004520569A (en) | 2004-07-08 |
WO2002021102A3 (en) | 2003-06-12 |
EP2219021B1 (en) | 2018-11-07 |
US20110233422A1 (en) | 2011-09-29 |
AU2001288750A1 (en) | 2002-03-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7410809B2 (en) | Particle or cell analyzer and method | |
JP3102938B2 (en) | Particle image analyzer | |
US5547849A (en) | Apparatus and method for volumetric capillary cytometry | |
US7528384B2 (en) | Methods and devices for characterizing particles in clear and turbid media | |
JP3098273B2 (en) | Urine cell analyzer | |
EP0068404A1 (en) | Analyzer for simultaneously determining volume and light emission characteristics of particles | |
JPH10512952A (en) | Flow fluorescence method and apparatus | |
CN107003239B (en) | Self-triggering flow cytometer | |
JPH05322885A (en) | Instrument for analyzing cell in urine | |
EP0465534A1 (en) | Method and apparatus for the identification of particles. | |
US20140152987A1 (en) | System and Method for Separating Samples in a Continuous Flow | |
US7320775B2 (en) | Exchangeable flow cell assembly with a suspended capillary | |
RU2190208C2 (en) | Device measuring luminescence of biological specimens | |
EP1070952A2 (en) | Method and means for particle measurement | |
CN114907960A (en) | Label-free living cell screening system and method based on droplet microfluidics |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: GUAVA TECHNOLOGIES, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GOIX, PHILIPPE J.;LINGANE, PAUL J.;PHI-WILSON, JANETTE T.;REEL/FRAME:011749/0966;SIGNING DATES FROM 20010420 TO 20010423 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |
|
AS | Assignment |
Owner name: MILLIPORE CORPORATION, MASSACHUSETTS Free format text: MERGER;ASSIGNOR:GUAVA TECHNOLOGIES, INC.;REEL/FRAME:031160/0923 Effective date: 20091221 Owner name: EMD MILLIPORE CORPORATION, MASSACHUSETTS Free format text: CHANGE OF NAME;ASSIGNOR:MILLIPORE CORPORATION;REEL/FRAME:031188/0680 Effective date: 20111212 |