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WO1993007471A1 - Detection d'un signal de radiation - Google Patents

Detection d'un signal de radiation Download PDF

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Publication number
WO1993007471A1
WO1993007471A1 PCT/US1992/008274 US9208274W WO9307471A1 WO 1993007471 A1 WO1993007471 A1 WO 1993007471A1 US 9208274 W US9208274 W US 9208274W WO 9307471 A1 WO9307471 A1 WO 9307471A1
Authority
WO
WIPO (PCT)
Prior art keywords
signal
radiation
detector
sample
focal point
Prior art date
Application number
PCT/US1992/008274
Other languages
English (en)
Inventor
Wilbur I. Kaye
Original Assignee
Beckman Instruments, 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
Priority claimed from US07/938,818 external-priority patent/US5292483A/en
Application filed by Beckman Instruments, Inc. filed Critical Beckman Instruments, Inc.
Publication of WO1993007471A1 publication Critical patent/WO1993007471A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/04—Optical or mechanical part supplementary adjustable parts
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J1/00—Photometry, e.g. photographic exposure meter
    • G01J1/02—Details
    • G01J1/04—Optical or mechanical part supplementary adjustable parts
    • G01J1/0407—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings
    • G01J1/0422—Optical elements not provided otherwise, e.g. manifolds, windows, holograms, gratings using light concentrators, collectors or condensers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0205—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows
    • G01J3/0216—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows using light concentrators or collectors or condensers
    • 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
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • G01N27/44721—Arrangements for investigating the separated zones, e.g. localising zones by optical means
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N2021/1738—Optionally different kinds of measurements; Method being valid for different kinds of measurement
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N2021/4702—Global scatter; Total scatter, excluding reflections
    • 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
    • G01N21/65—Raman scattering
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • 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
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/85—Investigating moving fluids or granular solids

Definitions

  • This invention relates to the efficient collection and detection of low levels of radiation arising within microliter volumes of sample.
  • the radiation may be in the form of luminescence from a chemical reaction or result from the interaction of an intense light source and the sample.
  • the processes of light scattering, Raman scattering, fluorescence and- phosphorescence may be used.
  • the technique of light scattering is particularly useful in the detection of particle ⁇ , and two broad cla ⁇ sifications of in ⁇ truments can be identified.
  • Particles of diameters significantly smaller than the wavelength of probe light scatter isotropically, i.e. equally in all directions. This type of scattering is usually called Rayleigh scattering.
  • This type of scattering is usually called Mie scattering.
  • the intensity of forward scattered light varies as the sixth power of the particle diameter; hence, special precautions must be taken when attempting to measure the light scattered from very small particles.
  • the present invention permits for the determi ⁇ nation of relative particle size and/or concentration of very small particles, particularly in a flowing system.
  • Intense light sources such as lasers are used for studying small particles.
  • the use of such sources introduces problems associated with discrimination of light scattered by instrumental components from that scattered by the sample.
  • the intensity of light scattered from small particles may be less than one millionth the intensity of laser radiation.
  • To measure such low intensities it is necessary to collect as much of the light scattered by the sample as possible, yet reject that scattered by the instrument.
  • Raman scattering is used for the chemical characterization of the samples rather than particle size. Like Rayleigh scattering, the signal intensities are very low and it is important to capture as large a solid angle of Raman scattered light as possible while also u ⁇ ing very intense sources of incident radiation.
  • the Raman scattered signals are of different wavelength from the incident light.
  • Chemical characterization of the sample is determined by the difference between the frequency of the Raman signal and the frequency of the exciting radiation. It is customary to use a blocking filter to reject the incident radiation followed by a monochromator to determine the frequency of the Raman signal. While this frequency difference helps in the discrimination between exciting and Raman signals, the Raman bands are often narrow; hence, the signals are very weak. It is important to use whatever geometric means are available to minimize the detection of the incident radiation and maximize the detection of the weak Raman radiation from the sample.
  • Fluorescence techniques are used when the sample or some component(s) of the sample can be tagged with a fluorescing dye.
  • the sample is then excited by an intense beam of exciting radiation, usually from a laser.
  • the wavelength of the exciting radiation is chosen to correspond to the wavelength of maximum sample excitation.
  • the wavelength of the fluorescing radiation will usually be greater than the exciting wavelength, and a filter or monochromator will be chosen to pass only that radiation corresponding to the wavelength of maximum fluorescence emission.
  • a filter or monochromator will be chosen to pass only that radiation corresponding to the wavelength of maximum fluorescence emission.
  • Phosphorescence techniques are employed where the sample, itself, or the tagged sample continues to emit radiation a significant time after excitation. Time as well as wavelength can then be used to discriminate between exciting and emitting radiation.
  • Luminescence techniques are u ⁇ ed when the sample or some component of the sample emits radiation as a re ⁇ ult of a chemical reaction of the sample with a reagent. No external exciting radiation is needed; hence, all of the radiated light may be detected without recourse to filtering.
  • the luminescence signals are usually very weak and depend on the number of reacting molecules within the detected sample volume. A compromise must usually be made between detected sample volume and concentration of reacting molecules. The efficient collection and detection of the radiation emitted within the detected sample volume is of great importance.
  • a generated radiation signal from an excited sample is collected over a large solid angle by means of a reflecting curvilinear surface of revolution and is directed to a detector.
  • the angle should preferably be between about 35° and 145°.
  • the sample enters a detection volume in a flowing stream and the axis of sample flow is collinear with the axis of revolution of the reflecting curvilinear surface of revolution.
  • the scattering volume which is part of the detection volume, is retained relatively small.
  • the radiation signal after the above interaction has the same wavelength as the radiation signal incident on the sample.
  • This type of interaction is called "light scattering."
  • the incident radiation is of high intensity and is usually produced by a laser. There are means for directing this laser beam along an axis of the curvilinear reflection means.
  • sample flow past the point of interaction.
  • the axis of sample flow is coaxial with the axis of a reflective light collector.
  • the scattered light ray output is the generated signal at the focus of the reflecting means.
  • the output reflection signal from the reflective means can be a collimated beam which is directed to a detector directly.
  • the reflecting curvilinear surface of revolution producing a collimated beam is selectively a paraboloid.
  • the collimated beam may also be focused onto a detector by a focusing lens.
  • the curvilinear means can reflect the generated signal directly to a remote focal point.
  • the curvilinear means for doing this is preferably an ellipsoid.
  • the generated radiation signal may arise selectively from light scattering, Raman scattering, fluore ⁇ cence, phosphorescence or luminescence.
  • Figure 1 shows the invention used to monitor some property of a sample as it changes in time as a result of pas ⁇ age through a ⁇ eparation means.
  • the sample may be mixed with a reagent, and the geometric axes in the vicinity of the point of radiation generation are illustrated.
  • Figures 2A and 2B are respectively a side diagrammatic view and end diagrammatic view of the sy ⁇ tem for detection of scattered light.
  • Figure 3 shows the details of the containment ves ⁇ el in ⁇ ert fitting into the curvilinear reflecting surface.
  • Figure 4 shows an alternate design of the insert in a configuration optimized for the detection of sample luminescence.
  • Figure 5 is a diagrammatic view of an embodiment wherein an annular aperture determines the detected scattering angle of a scattering signal.
  • Figure 6 is a diagrammatic view of a monochromator suitable for addition to any of the above light collection systems.
  • a Fery prism is used to disperse the radiation onto one or more detectors.
  • An aperture plate in the focal surface and in front of the detector( ⁇ ) determines the portion of the spectrum detected.
  • an array detector may be located at the focal surface of the prism and the spectrum measured.
  • Figure 7 is an embodiment illustrating an ellipsoidal version of the reflective surface, and is similar to Figures 2A and 2B.
  • Figure 1 identifies the major components of the system.
  • a sample processed by some type of separation system such as a chromatograph column, mixes with a reagent from a delivery ⁇ y ⁇ tem 2 at point 3. The mixture enter ⁇ a ⁇ ample containment ve ⁇ sel 4.
  • An intense light source 5 such as a laser produces a beam 102 which is filtered by a filter 6 and focu ⁇ ed by a len ⁇ 7 onto a point of radiation generation 8.
  • Thi ⁇ generation point 8 corresponds to a focal point of a curvilinear surface of revolution 9 milled into a block 10.
  • the curvilinear surface 9 is a paraboloid.
  • the surface 9 of this paraboloid is reflecting and collimates the radiation generated at the point 8. From the point 8, there is generated a beam 111 of incident radiation which is directed through a large solid angle to reflective surface 9.
  • the collimated beam 100 of reflected radiation is filtered by a filter 11 and focused by a lens 12 onto an aperture 13 in a plate 14. Radiation passing through the aperture 13 is detected by a detector 15.
  • An imaginary straight line 101 from the intense light source 5 to the aperture 13 defines the axis of the curvilinear surface 9 and also the axis of sample flow in the vicinity of the point of generation 8. Where pertinent, this imaginary line 101 defines the axis of the exciting light beam 102 in the vicinity of the point 8 of radiation generation.
  • Figure 2A shows an embodiment of the invention specifically for the detection of scattered light.
  • the light beam 102 from a laser 5 is focused by the lens 7 and directed by means of a two-axis adjusting device 16 down the axis of a channel 17 in the sample containment vessel 4 which screws into the block 10 of the para- boloid.
  • the sample from point 3 enters the containment vessel 4 at 18 and exits at 19.
  • the laser beam 102 must not strike the walls of the channel 17 in the sample containment vessel 4. Alignment is accomplished by viewing the generation point 8 by means of viewing lens 20 and a hole 21 in block 10 into which the curvilinear surface 9 is formed.
  • the lens 12 and the aperture in plate 14 serve as a spatial filter and allow only the radiation generated at 8 from passing to the detector 15. In some applications, this spatial filter is unnecessary, but the photosensitive area of the detector 15 must then be as large as the mouth of the paraboloid.
  • Figure 2B is an end view of the apparatus looking down the axis 101 of the curvilinear surface 9. Looking into the open end of the paraboloid, one "sees" the end of the end cap 27 of the containment vessel. The inner edge 103 and outer edge 104 of the paraboloid mouth as well as the outer edge of the lens 12 are visible.
  • Figure 3 shows the details of the sample containment vessel 4 and the end cap 27.
  • the .parts are made of a material such as black "Delrin.”
  • the containment vessel 4 is threaded at 105 to fit into the paraboloid block 10 which has mating threads and position the generation point 8 at the focal point of the paraboloid surface 9.
  • the sample enters at 18 through a stainless steel tube 22 tightly inserted in a hole 23 drilled into the black plastic.
  • a second hole 24, at 90° to the first hole 23, is drilled into the black plastic and conveys the sample mixture to channel 107 running down the axis of the containment ves ⁇ el.
  • the second hole 24 is closed by plug 25 to keep the sample mixture from escaping from the de ⁇ ired channel 24.
  • a glas ⁇ tube 26 fit ⁇ tightly into bore 107 in the sample containment vessel 4 and extends into the second black pla ⁇ tic end cap 27.
  • a gla ⁇ s plate 28 ⁇ erves as a window to allow laser radiation 102 to pass into the containment vessel while keeping the sample in its channel 24.
  • the glass plate 28 is held against an "O ring" 29 by means of retainer 30.
  • the glas ⁇ tube 26 does not come in optical contact with the glass plate 28. Thereby, the light scattered at the surface of the glass plate 28 does not channel into the glass tube 26. Were a significant fraction of the light scattered by glass plate 28 to enter tube 25, some unwanted radiation could escape from tube 26 in the vicinity of the generation point 8.
  • the end cap 27 allows the sample to exit the sy ⁇ tem through hole 108 and al ⁇ o act ⁇ a ⁇ a light trap for * the exce ⁇ incident radiation from la ⁇ er beam 102.
  • the black glas ⁇ plate fits against the wall of the black plastic by means of a threaded plug 32.
  • Another "O-ring” 33 seals against escape of the sample stream.
  • a 10 second plug 25 again confines the sample to the desired stream.
  • a short piece of stainless steel tubing 34 fitted into a hole 110 conveys the sample stream to a
  • Teflon tubing 35 which mates with still another piece 36 of stainless steel tubing by which the sample stream exits the containment vessel at 19.
  • the plastic tubing 35 blocks only a negligible portion of the scattered rays from falling on the paraboloid.
  • the end cap 27 is dimensioned to slip through the hole in the paraboloid block 10 at its ba ⁇ e.
  • the solid angle 112 of incident radiation is 25 between about 45° and 135° relative to the axis 101.
  • the end face 113 of the vessel 4 defines one limit of the angle 112.
  • the end face 114 of the end cap 27 can define a second limit of the angle 112.
  • the limit 103 of the parabaloid surface 9 30 can limit the extent of the angle, as illustrated in Figure ⁇ l and 2.
  • Figure 4 how ⁇ another embodiment of the containment vessel 4 and its end cap 27.
  • 35 the sample mixture is introduced to the generation point by means of a capillary tubing 41.
  • a chemiluminescence reagent is introduced through entry 18.
  • This embodiment is primarily intended for use with chemiluminescent samples. Exciting light source is not necessary in this application. It is presumed that the luminescence resulting from the chemical reaction is of short lifetime, hence, has a maximum intensity at the point of reaction which in this case occurs at the generation point.
  • Plate 43 with an annular aperture 42 is inserted into the apparatus where the beam from the sample is collimated.
  • the inner and outer diameters of this annular aperture determine the solid angle 112 of detected scattered light.
  • Figure 6 is an extension of Figure 2A and shows the focused radiation 106 passing through the aperture 13 in plate 14 and on to a Fery prism 44 which disperse ⁇ the radiation 116 and focu ⁇ e ⁇ a ⁇ pectrum on a curved plate 45.
  • the location and size of the aperture 47 in plate 45 determine ⁇ the wavelength and wavelength interval of radiation detected by detector 46.
  • a multiplicity of apertures and detectors may be used when it is desired to monitor different spectral intervals simultaneously.
  • means other than a Fery prism may be used to disperse radiation 106.
  • an array detector may be positioned in place of the aperture plate.
  • the signal from the array of detectors 46 may be processed in the usual manner to provide the dynamic changing spectra as samples flow through the system. It should be apparent that any type of dispersing system may be employed in Figure 6. However, the Fery prism 44 affords a high efficiency along with low stray light.
  • surface 9 of block 10 may be in the shape of an ellipsoid. As shown in Figure 7, the beam 106 is then focused directly onto aperture plate 14 and lens 12 is not needed.
  • the apparatus in its light scattering configuration is useful in the study of antigen-antibody reactions.
  • the antigen specific to an antibody mixes with a solution containing the antibody, there is a reaction producing aggregates of rapidly increasing size. If the concentration of antibody and antigens is sufficiently high, the aggregates may become large enough to see with the naked eye. However, at low concentration, the limiting aggregate size may be submicroscopic and detectable only by very sensitive light scattering techniques.
  • the above invention is applicable to the screening of antibody-antigen reactions wherein a separation technique isolates fractions of either antibodies or antigens. A ⁇ the components elute from the separations means 1 and mix with a potential conjugate steadily flowing from 2, the sample generates an elevated scattered light signal, indicative of an aggregating pair.
  • the detector means 15 can be set up to respond to a spatial or temporal signal from the generating point 8.
  • Raman spectra often characterize particular classes of molecular structure.
  • a detector can sense when sample fractions having that particular class of structure elute from a chromatograph column 11.
  • Fluorescence and phosphorescence techniques provide for extremely sensitive detection of classes of samples eluting from a separation system when certain classes of effluent can be tagged with a fluorescent dye or set of dyes. For example, DNA fragments of different size may be chromatographed to separate fragments by molecular weight. At the same time, there are only four possible end groups and these can be dyed with fluorophores specific to the end groups. The above apparatus can identify the end group of the eluting fractions.
  • Certain oxidation-reduction reactions can be sensitively detected by chemiluminescence.
  • the above apparatus can provide a good detector when an eluting sample triggers a chemiluminescence reaction.

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  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

La focalisation d'un signal de rayonnement généré sur un détecteur s'effectue par l'intermédiaire d'une surface curviligne. Le signal du faisceau de rayonnement provenant de la surface de réflexion est collimatée ou focalisée sur le détecteur. Des signaux de rayonnement diffusés par la lumière, de Raman, de fluorescence, de chimioluminescence, de phosphorescence par des particules suite à un processus chimique ou à une réaction chimique sont augmentés par cette technique de focalisation. Le signal intensifié qui est détecté est mesuré ultérieurement par des techniques de détection différentes.
PCT/US1992/008274 1991-10-08 1992-09-29 Detection d'un signal de radiation WO1993007471A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US77282391A 1991-10-08 1991-10-08
US772,823 1991-10-08
US07/938,818 US5292483A (en) 1991-06-28 1992-09-01 Detecting a radiation signal
US938,818 1992-09-01

Publications (1)

Publication Number Publication Date
WO1993007471A1 true WO1993007471A1 (fr) 1993-04-15

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Application Number Title Priority Date Filing Date
PCT/US1992/008274 WO1993007471A1 (fr) 1991-10-08 1992-09-29 Detection d'un signal de radiation

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AU (1) AU2761392A (fr)
WO (1) WO1993007471A1 (fr)

Cited By (15)

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Publication number Priority date Publication date Assignee Title
EP0582865A1 (fr) * 1992-07-24 1994-02-16 Sumitomo Electric Industries, Limited Procédé de détection de matériaux étrangers dans un fluide
WO1994029695A1 (fr) * 1993-06-08 1994-12-22 Gjelsnes Oddbjoern Cytometre de flux liquide
US5495333A (en) * 1992-07-24 1996-02-27 Sumitomo Electric Industries, Ltd. Method and apparatus of detecting impurities in fluid
EP0704699A3 (fr) * 1994-09-29 1996-08-21 Hitachi Software Eng Appareil d'électrophorèse capillaire
WO1997030338A1 (fr) * 1996-02-16 1997-08-21 Inphocyte, Inc. Systeme et procede d'analyse rapide de cellules par cytometrie spectrale
WO2001027590A3 (fr) * 1999-10-12 2001-12-13 Becton Dickinson Co Element optique pour cytometrie en flux
WO2004059312A1 (fr) * 2002-12-20 2004-07-15 Corning Incorporated Dispositif et procede d'essai a capillaires
WO2007011726A1 (fr) * 2005-07-14 2007-01-25 Battelle Memorial Institute Dispositif de declenchement d'aerosol et procedes de detection de particules d'interet au moyen d'un dispositif de declenchement d'aerosol
US7518710B2 (en) 2005-07-14 2009-04-14 Battelle Memorial Institute Optical devices for biological and chemical detection
DE102009045075A1 (de) 2009-09-28 2011-04-07 Carl Zeiss Ag Messung des Dispergierungszustandes von nanoskaligen Füllstoffen in flüssigen und viskosen Medien
US8101426B2 (en) 2007-03-02 2012-01-24 Icyt Mission Technology, Inc. System and method for the measurement of multiple fluorescence emissions in a flow cytometry system
CN106594553A (zh) * 2017-01-11 2017-04-26 哈尔滨理工大学 一种新生儿鼻孔照明装置
CN106641799A (zh) * 2017-01-11 2017-05-10 哈尔滨理工大学 婴儿用鼻孔照明装置
US9746412B2 (en) 2012-05-30 2017-08-29 Iris International, Inc. Flow cytometer
CN110553955A (zh) * 2019-08-30 2019-12-10 华中科技大学 一种基于光散射场的颗粒物粒径分布测量方法及系统

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US4606636A (en) * 1983-10-25 1986-08-19 Universite De Saint-Etienne Optical apparatus for identifying the individual multiparametric properties of particles or bodies in a continuous flow
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US2551542A (en) * 1948-11-10 1951-05-01 Charles R Marsh Fluorophotometer
US2852693A (en) * 1953-01-13 1958-09-16 Standard Oil Co Method and apparatus for measuring the optical properties of liquids
US3248551A (en) * 1962-10-22 1966-04-26 Joseph C Frommer Optical arrangement for sensing very small particles
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US4200802A (en) * 1979-03-28 1980-04-29 The United States Of America As Represented By The United States Department Of Energy Parabolic cell analyzer
US4606636A (en) * 1983-10-25 1986-08-19 Universite De Saint-Etienne Optical apparatus for identifying the individual multiparametric properties of particles or bodies in a continuous flow
EP0421156A2 (fr) * 1989-09-12 1991-04-10 Packard Instrument Company, Inc. Procédé et appareil pour mesurer la fluorescence

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Cited By (27)

* Cited by examiner, † Cited by third party
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