US20020028434A1 - Particle or cell analyzer and method - Google Patents

Particle or cell analyzer and method Download PDF

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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
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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
Application number
US09/844,080
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English (en)
Inventor
Philippe Goix
Paul Lingane
Janette Phi-Wilson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
EMD Millipore Corp
Original Assignee
Guava Technologies Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Guava Technologies Inc filed Critical Guava Technologies Inc
Priority to US09/844,080 priority Critical patent/US20020028434A1/en
Assigned to GUAVA TECHNOLOGIES, INC. reassignment GUAVA TECHNOLOGIES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LINGANE, PAUL J., GOIX, PHILIPPE J., PHI-WILSON, JANETTE T.
Priority to AU2001288750A priority patent/AU2001288750A1/en
Priority to ES10004138T priority patent/ES2697531T3/es
Priority to PCT/US2001/027509 priority patent/WO2002021102A2/en
Priority to EP10004138.3A priority patent/EP2219021B1/de
Priority to EP01968506.4A priority patent/EP1334346B1/de
Priority to JP2002525470A priority patent/JP2004520569A/ja
Publication of US20020028434A1 publication Critical patent/US20020028434A1/en
Priority to US10/410,230 priority patent/US7410809B2/en
Priority to JP2008064290A priority patent/JP5638740B2/ja
Priority to US12/183,301 priority patent/US7972559B2/en
Priority to US13/118,838 priority patent/US8241571B2/en
Priority to US13/118,831 priority patent/US8524489B2/en
Priority to JP2013047116A priority patent/JP2013117544A/ja
Assigned to MILLIPORE CORPORATION reassignment MILLIPORE CORPORATION MERGER (SEE DOCUMENT FOR DETAILS). Assignors: GUAVA TECHNOLOGIES, INC.
Assigned to EMD MILLIPORE CORPORATION reassignment EMD MILLIPORE CORPORATION CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: MILLIPORE CORPORATION
Priority to JP2014158474A priority patent/JP6046671B2/ja
Abandoned legal-status Critical Current

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    • 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—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1404—Handling flow, e.g. hydrodynamic focusing
    • 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.

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  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Optical Measuring Cells (AREA)
US09/844,080 2000-09-06 2001-04-26 Particle or cell analyzer and method Abandoned US20020028434A1 (en)

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
AU2001288750A AU2001288750A1 (en) 2000-09-06 2001-09-05 Particle or cell analyzer and method
ES10004138T ES2697531T3 (es) 2000-09-06 2001-09-05 Analizador de partículas o células y método
PCT/US2001/027509 WO2002021102A2 (en) 2000-09-06 2001-09-05 Particle or cell analyzer and method
EP10004138.3A EP2219021B1 (de) 2000-09-06 2001-09-05 Teilchen oder zellanalysator und verfahren
EP01968506.4A EP1334346B1 (de) 2000-09-06 2001-09-05 Teilchen oder zellanalysator und verfahren
JP2002525470A JP2004520569A (ja) 2000-09-06 2001-09-05 粒子又は細胞分析器及び方法
US10/410,230 US7410809B2 (en) 2000-09-06 2003-04-08 Particle or cell analyzer and method
JP2008064290A JP5638740B2 (ja) 2000-09-06 2008-03-13 粒子分析装置
US12/183,301 US7972559B2 (en) 2000-09-06 2008-07-31 Particle or cell analyzer and method
US13/118,838 US8241571B2 (en) 2000-09-06 2011-05-31 Particle or cell analyzer and method
US13/118,831 US8524489B2 (en) 2000-09-06 2011-05-31 Particle or cell analyzer and method
JP2013047116A JP2013117544A (ja) 2000-09-06 2013-03-08 粒子分析装置
JP2014158474A JP6046671B2 (ja) 2000-09-06 2014-08-04 粒子分析装置

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

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US10/410,230 Division US7410809B2 (en) 2000-09-06 2003-04-08 Particle or cell analyzer and method

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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

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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

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US (5) US20020028434A1 (de)
EP (2) EP1334346B1 (de)
JP (4) JP2004520569A (de)
AU (1) AU2001288750A1 (de)
ES (1) ES2697531T3 (de)
WO (1) WO2002021102A2 (de)

Cited By (51)

* Cited by examiner, † Cited by third party
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 (de) * 2002-12-03 2005-09-14 Bay Bioscience Kabushiki Kaisha Vorrichtung zum sammeln von informationen über biopartikel
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 (de) * 2005-02-01 2010-03-24 Arryx, Inc. Verfahren und Vorrichtung zur Sortierung von Zellen
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 (zh) * 2015-05-20 2015-08-19 大连海事大学 荧光和遮挡同时测量的细胞计数装置及方法
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 (zh) * 2018-06-12 2018-12-07 西安理工大学 探测大气中雾滴和气溶胶粒径谱分布的探测仪及探测方法
CN110023741A (zh) * 2016-11-22 2019-07-16 理音株式会社 生物粒子计数系统以及生物粒子计数方法
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)

* Cited by examiner, † Cited by third party
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
AU2002220018A1 (en) 2000-11-29 2002-06-11 Colorado State University System for in-vitro fertilization with spermatozoa separated into x-chromosome 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
WO2004012837A2 (en) 2002-08-01 2004-02-12 Xy, Inc. Low pressure sperm cell separation system
US8486618B2 (en) 2002-08-01 2013-07-16 Xy, Llc Heterogeneous inseminate system
AU2003265471B2 (en) 2002-08-15 2009-08-06 Xy, Llc. High resolution flow cytometer
US7169548B2 (en) 2002-09-13 2007-01-30 Xy, Inc. Sperm cell processing and preservation systems
EP2305832B1 (de) 2003-03-28 2022-03-09 Inguran, LLC Verfahren zur Bereitstellung von nach Geschlecht sortiertem Tiersperma
NZ544103A (en) 2003-05-15 2010-10-29 Xy Llc Efficient haploid cell sorting for flow cytometer systems
EP1730266A2 (de) 2004-03-29 2006-12-13 Monsanto Technology, LLC Spermasuspensionen zur sortierung in angereicherte x- oder y-chromosomen tragende populationen
AU2005266930B2 (en) 2004-07-22 2010-09-16 Inguran, Llc Process for enriching a population of sperm cells
JP2007071794A (ja) * 2005-09-09 2007-03-22 Rion Co Ltd 粒子検出器
US20110189714A1 (en) * 2010-02-03 2011-08-04 Ayliffe Harold E Microfluidic cell sorter and method
US8616048B2 (en) * 2006-02-02 2013-12-31 E I Spectra, LLC Reusable thin film particle sensor
US9293311B1 (en) 2006-02-02 2016-03-22 E. I. Spectra, Llc Microfluidic interrogation device
US9452429B2 (en) 2006-02-02 2016-09-27 E. I. Spectra, Llc Method for mutiplexed microfluidic bead-based immunoassay
US7728974B2 (en) * 2007-02-07 2010-06-01 Cytopeia, Inc. Enhanced detection system and method
JP5171182B2 (ja) * 2007-09-20 2013-03-27 シスメックス株式会社 検体分析装置
JP4472024B2 (ja) * 2008-02-07 2010-06-02 三井造船株式会社 蛍光検出装置および蛍光検出方法
WO2010080642A1 (en) * 2008-12-18 2010-07-15 Biovigilant Systems, Inc. Compact detector for simultaneous particle size and fluorescence detection
WO2010080643A1 (en) 2008-12-18 2010-07-15 Biovigilant Systems, Inc. Integrated microbial collector
US8928881B2 (en) * 2009-01-23 2015-01-06 University Of Washington Cytometer with automatic continuous alignment correction
US20100198188A1 (en) * 2009-02-05 2010-08-05 Abbott Diabetes Care Inc. Devices and Methods for Metering Insoluble Active Agent Particles
WO2010091311A2 (en) * 2009-02-05 2010-08-12 The Regents Of The University Of California A nanowire afm probe for imaging soft materials
US20100220315A1 (en) * 2009-02-27 2010-09-02 Beckman Coulter, Inc. Stabilized Optical System for Flow Cytometry
US9651568B2 (en) 2009-11-23 2017-05-16 Cyvek, Inc. Methods and systems for epi-fluorescent monitoring and scanning for microfluidic assays
US10065403B2 (en) 2009-11-23 2018-09-04 Cyvek, Inc. Microfluidic assay assemblies 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
US9500645B2 (en) 2009-11-23 2016-11-22 Cyvek, Inc. Micro-tube particles for microfluidic assays 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
JP5815123B2 (ja) 2011-05-05 2015-11-17 イー・エム・デイー・ミリポア・コーポレイシヨン 毛細管ベースのフローサイトメトリーにおける集光効率を高めるための装置及び方法
TWI435080B (zh) 2011-06-09 2014-04-21 Univ Nat Pingtung Sci & Tech 細胞或粒子檢測裝置
KR101139776B1 (ko) 2011-12-09 2012-04-26 국방과학연구소 입자계수기용 또는 형광검출장비용 빔 덤퍼
JP2013137267A (ja) * 2011-12-28 2013-07-11 Sony Corp マイクロチップ及びマイクロチップ型微小粒子測定装置
EP2822688B1 (de) 2012-03-08 2019-09-25 Cyvek, Inc. Anordnungen mikrofluidischer assays und verfahren zur herstellung
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 (zh) * 2012-07-23 2014-10-22 河海大学 使用激光粒度仪实测微囊藻密度及群体大小的方法
US11110458B2 (en) 2013-02-01 2021-09-07 Bio-Rad Laboratories, Inc. System for detection of spaced droplets
JP6117093B2 (ja) * 2013-12-20 2017-04-19 アズビル株式会社 粒子検出装置及び粒子の検出方法
CN103868595B (zh) * 2014-03-06 2016-03-02 湖南大学 一种空间分离的泵浦-探测瞬态吸收光谱仪及实现方法
WO2016112035A1 (en) 2015-01-08 2016-07-14 University Of Washington Systems and methods for immersion flow cytometry
KR102258807B1 (ko) * 2015-02-24 2021-06-09 (주)미디어에버 미세 먼지 및 미생물 검출 장치
US10365226B2 (en) 2015-04-30 2019-07-30 Hewlett-Packard Development Company, L.P. Microfluidic optical fluid sensor
US10228367B2 (en) 2015-12-01 2019-03-12 ProteinSimple Segmented multi-use automated assay cartridge
CN106596498B (zh) * 2017-01-19 2018-09-04 大连理工大学 一种空气微生物快速检测装置
CN113474084B (zh) 2017-06-28 2024-02-09 生物辐射实验室股份有限公司 用于液滴检测的系统和方法
US11045805B2 (en) 2017-11-01 2021-06-29 Bio-Rad Laboratories, Inc. Microfluidic system and method for arranging objects
CN208833783U (zh) * 2018-08-14 2019-05-07 三诺生物传感股份有限公司 一种光学检测机构及全自动生化分析仪
US20220034785A1 (en) * 2018-09-14 2022-02-03 The Regents Of The University Of California Cell sorting device and method
CN109587327A (zh) * 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 一种可集成于智能手机的致病细菌激光快速查杀系统

Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE26055E (en) * 1962-07-02 1966-07-05 Automatic sample handling apparatus
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 (ja) * 1983-12-27 1985-07-25 Shimadzu Corp 自動分析装置
JPS6193932A (ja) * 1984-10-15 1986-05-12 Hitachi Ltd 粒子分析装置
JPS61262639A (ja) * 1985-09-03 1986-11-20 Olympus Optical Co Ltd 自動分析装置
JPS6188158A (ja) * 1985-09-03 1986-05-06 Olympus Optical Co Ltd 自動分析装置
JPH0719847B2 (ja) 1985-12-28 1995-03-06 株式会社東芝 ダイナミツクメモリセルの製造方法
US4827143A (en) * 1986-03-26 1989-05-02 Hitachi, Ltd. Monitor for particles of various materials
JPS62156856U (de) * 1986-03-28 1987-10-05
JPS63135152A (ja) 1986-11-28 1988-06-07 オリンパス光学工業株式会社 超音波処置用内視鏡
JPS63135152U (de) * 1987-02-25 1988-09-05
JPS63225143A (ja) * 1987-03-16 1988-09-20 Sasakura Eng Co Ltd 流体中の不純微粒子計測方法及び計測装置
JPH0614008B2 (ja) * 1988-03-22 1994-02-23 キヤノン株式会社 粒子解析装置
JPH0776713B2 (ja) * 1988-03-22 1995-08-16 株式会社島津製作所 電子天びん
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 (ja) * 1988-06-30 1990-01-18 Canon Inc 粒子測定装置
US5597733A (en) * 1988-07-25 1997-01-28 Precision Systems, Inc. Automatic multiple-sample multiple-reagent dispensing method in chemical analyzer
JPH0658318B2 (ja) * 1988-08-16 1994-08-03 リオン株式会社 光散乱式粒子検出器
US5132088A (en) * 1988-11-17 1992-07-21 Kabushiki Kaisha Nittec Automatic medical sampling device
JP2749912B2 (ja) * 1989-12-15 1998-05-13 キヤノン株式会社 検体測定装置及び検体測定方法
JPH02289808A (ja) * 1989-04-28 1990-11-29 Olympus Optical Co Ltd 照明光学系
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 (ja) * 1989-08-31 1991-04-15 Nikkiso Co Ltd 表面積測定装置における校正用ガス流通路切り替え装置
AU642444B2 (en) * 1989-11-30 1993-10-21 Mochida Pharmaceutical Co., Ltd. Reaction vessel
JPH0738839Y2 (ja) * 1990-05-15 1995-09-06 オムロン株式会社 流れ式粒子分析装置
JP3084295B2 (ja) * 1991-02-27 2000-09-04 シスメックス株式会社 フローイメージサイトメータ
US5529679A (en) * 1992-02-28 1996-06-25 Hitachi, Ltd. DNA detector and DNA detection method
JPH04337446A (ja) * 1991-05-15 1992-11-25 Hitachi Ltd 微粒子計測方法、定量方法および微粒子計測装置
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 (ja) * 1991-09-20 2000-10-23 シスメックス株式会社 粒子分析装置
US5548395A (en) 1991-09-20 1996-08-20 Toa Medical Electronics Co., Ltd. Particle analyzer
JP3232145B2 (ja) * 1991-12-27 2001-11-26 シスメックス株式会社 網赤血球測定方法
JP2565844B2 (ja) * 1992-02-07 1996-12-18 アボツト・ラボラトリーズ 細胞溶解処理条件下で異種細胞集団を正確に計数し，感受性に関する格付けを行う方法
US5495105A (en) * 1992-02-20 1996-02-27 Canon Kabushiki Kaisha Method and apparatus for particle manipulation, and measuring apparatus utilizing the same
JP2756397B2 (ja) * 1992-02-20 1998-05-25 キヤノン株式会社 粒子操作方法及び装置、並びにこれを用いた測定装置
JP3185335B2 (ja) 1992-02-27 2001-07-09 石川島播磨重工業株式会社 熱間材料の接合方法
JP3076144B2 (ja) 1992-05-01 2000-08-14 キヤノン株式会社 生体微量成分検査装置
JPH05332992A (ja) * 1992-05-29 1993-12-17 Shimadzu Corp 電気泳動装置
DE69224380T2 (de) * 1992-08-04 1998-05-20 Hewlett Packard Gmbh Vorrichtung zur Behandlung von Fiolen in einem "Analyseapparat"
JPH06194299A (ja) * 1992-12-24 1994-07-15 Canon Inc フローセル装置
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 (no) * 1993-06-08 1995-01-05 Oddbjoern Gjelsnes Anordning for anvendelse ved væskeströmscytometri
JP3103709B2 (ja) * 1993-10-15 2000-10-30 リオン株式会社 粒子計数装置及び粒子計数方法
US5656499A (en) * 1994-08-01 1997-08-12 Abbott Laboratories Method for performing automated hematology and cytometry analysis
JP3375203B2 (ja) * 1994-08-08 2003-02-10 シスメックス株式会社 細胞分析装置
JPH08145869A (ja) * 1994-11-25 1996-06-07 Hitachi Ltd 粒子分析装置
US5833827A (en) * 1995-09-29 1998-11-10 Hitachi, Ltd. Capillary array electrophoresis system
EP2302368B1 (de) * 1997-06-09 2017-04-05 EMD Millipore Corporation Verfahren und Vorrichtung zur Erkennung von Mikropartikeln in Fluidproben
JP2000000458A (ja) * 1998-04-13 2000-01-07 Jsr Corp 水性分散体と水性分散体中の粗大粒子の測定方法
JP3734125B2 (ja) * 1998-04-24 2006-01-11 松下電器産業株式会社 微生物数測定装置
JP2000000468A (ja) 1998-06-18 2000-01-07 Petroleum Energy Center Found 窒素酸化物を接触還元するための触媒及び方法
US6077713A (en) * 1998-06-30 2000-06-20 Dade Behring Inc. Method and apparatus for extracting liquid samples from a closed container
JP4377064B2 (ja) * 1998-07-27 2009-12-02 興和株式会社 花粉計数方法および花粉計数装置
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 (ja) * 2000-06-27 2006-12-06 三菱重工業株式会社 ナトリウム精製システム
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3827304A (en) * 1971-07-20 1974-08-06 Gilson W Sample handling method

Cited By (116)

* Cited by examiner, † Cited by third party
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 (de) * 2002-12-03 2005-09-14 Bay Bioscience Kabushiki Kaisha Vorrichtung zum sammeln von informationen über biopartikel
EP1574838A4 (de) * 2002-12-03 2011-09-28 Bay Bioscience Kabushiki Kaisha Vorrichtung zum sammeln von informationen über biopartikel
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 (ja) * 2003-09-17 2010-09-16 Guava Technologies Inc 標的被検体を分析するための組成物および方法
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 (zh) * 2005-02-01 2011-07-20 阿尔利克斯公司 用于分选细胞的方法和设备
EP2166340A1 (de) * 2005-02-01 2010-03-24 Arryx, Inc. Verfahren und Vorrichtung zur Sortierung von Zellen
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
US8229707B2 (en) 2005-08-22 2012-07-24 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
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
US8470246B2 (en) 2005-10-13 2013-06-25 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
US20090104075A1 (en) * 2005-10-13 2009-04-23 Rich Collin A User interface for a fluidic system of a flow cytometer
US7857005B2 (en) 2005-12-07 2010-12-28 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
US7520300B2 (en) 2005-12-07 2009-04-21 Accuri Cytometers, Inc. Pulsation attenuator for a fluidic system
US20080156379A1 (en) * 2005-12-07 2008-07-03 Rich Collin A Pulsation attenuator for a fluidic 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
US20080092961A1 (en) * 2006-03-08 2008-04-24 Bair Nathaniel C Flow cytometer system with unclogging feature
US20070212262A1 (en) * 2006-03-08 2007-09-13 Rich Collin A Fluidic system for a flow cytometer
US20100319786A1 (en) * 2006-03-08 2010-12-23 Bair Nathaniel C Flow cytometer system with unclogging feature
US20090293910A1 (en) * 2006-03-08 2009-12-03 Ball Jack T Fluidic system with washing capabilities for a flow cytometer
US7780916B2 (en) 2006-03-08 2010-08-24 Accuri Cytometers, Inc. Flow cytometer system with unclogging feature
US8262990B2 (en) 2006-03-08 2012-09-11 Accuri Cytometers, Inc. Flow cytometer system with unclogging feature
US8017402B2 (en) 2006-03-08 2011-09-13 Accuri Cytometers, Inc. Fluidic system for a flow cytometer
US8187888B2 (en) 2006-03-08 2012-05-29 Accuri Cytometers, Inc. Fluidic system for a flow cytometer
US8283177B2 (en) 2006-03-08 2012-10-09 Accuri Cytometers, Inc. Fluidic system with washing capabilities for a flow cytometer
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
US8763895B2 (en) 2007-12-31 2014-07-01 Oridion Medical 1987 Ltd. Tube verifier
US8763892B2 (en) * 2007-12-31 2014-07-01 Oridon 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 (zh) * 2009-03-04 2012-05-02 马尔文仪器有限公司 粒子表征
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 (zh) * 2014-08-06 2017-04-19 贝克曼考尔特公司 使用流式细胞仪评价多峰事件
CN104849444A (zh) * 2015-05-20 2015-08-19 大连海事大学 荧光和遮挡同时测量的细胞计数装置及方法
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 (zh) * 2016-11-22 2019-07-16 理音株式会社 生物粒子计数系统以及生物粒子计数方法
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 (zh) * 2018-06-12 2018-12-07 西安理工大学 探测大气中雾滴和气溶胶粒径谱分布的探测仪及探测方法

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US7410809B2 (en) 2008-08-12
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US20110226964A1 (en) 2011-09-22
US7972559B2 (en) 2011-07-05
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US20110233422A1 (en) 2011-09-29
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US20040005635A1 (en) 2004-01-08
US8241571B2 (en) 2012-08-14
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US8524489B2 (en) 2013-09-03
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US20080283773A1 (en) 2008-11-20
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