WO2001027590A2 - Element optique pour cytometrie en flux - Google Patents

Element optique pour cytometrie en flux Download PDF

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Publication number
WO2001027590A2
WO2001027590A2 PCT/US2000/041151 US0041151W WO0127590A2 WO 2001027590 A2 WO2001027590 A2 WO 2001027590A2 US 0041151 W US0041151 W US 0041151W WO 0127590 A2 WO0127590 A2 WO 0127590A2
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WO
WIPO (PCT)
Prior art keywords
optical element
reflective surface
aspheric
optical
flow channel
Prior art date
Application number
PCT/US2000/041151
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English (en)
Other versions
WO2001027590A3 (fr
Inventor
William J. Treytl
Original Assignee
Becton Dickinson And Company
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 Becton Dickinson And Company filed Critical Becton Dickinson And Company
Publication of WO2001027590A2 publication Critical patent/WO2001027590A2/fr
Publication of WO2001027590A3 publication Critical patent/WO2001027590A3/fr

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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—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1434—Optical arrangements
    • G01N15/1436—Optical arrangements the optical arrangement forming an integrated apparatus with the sample container, e.g. a flow cell

Definitions

  • the present invention relates to an optical element for collecting and projecting light scattered or emitted by the passage of particulate material through a beam of light. More specifically, the present invention relates to an optical element that combines the functions of a fluid flow delivery system, and a high-efficiency light gathering optic into a compact unit for use in a flow cytometer.
  • Flow cytometers are used in biomedical research for counting, characterizing and sorting cells and other particulate material in a fluid.
  • a typical flow cytometer works by passing individual cells or particles in a flow stream through an excitation site, where they are intersected by a high-intensity light beam or laser beam. If a particle is present, light from the beam is scattered by the particle, collected, and directed to a sensor that measures properties of the light to count and characterize the particles. Additional measurements may be made by staining the cells with fluorescent dyes or by reacting the cells with fluorescent reagents that are biologically reactive with the cells, using the laser beam to induce fluorescence, and using the sensor to detect properties of the light emitted due to fluorescence to characterize various properties of the cells.
  • Flow cytometers are widely known and have been used for more than two decades. Numerous improvements and modifications have been developed that enable measurement of a variety of cellular properties, and enhance the accuracy and efficiency of the measurements. Also, many advancements in improving optical efficiency of the light gathering optics of flow cytometers have been achieved.
  • Some previously known systems improve the efficiency of light gathering by placing the excitation site within an ellipsoidal reflective chamber (typically referred to as a flow cell), or within a reflective chamber formed by a combination of spherical, ellipsoidal and other conic reflectors.
  • These previously known systems typically are constructed so that the excitation site is located at a first focal point of the optical system, and light scattered or emitted by the sample is collected by a sensor positioned at a second focal point of the optical system.
  • U.S. Patent No. 3,946,239 to Salzman et al. U.S. Patent No. 4,188,543 to Brunsting et al.
  • U.S. Patent No. 4,189,236 to Hogg et al. and U.S. Patent No. 4,871,249 to Watson all describe systems that use enclosed reflective chambers.
  • the chambers include windows for illuminating the sample stream and for light collection, and typically also have openings for introducing and removing the sample stream.
  • the light collection efficiency of the foregoing devices may be high, enclosed reflective chambers collect light scattered in all directions and direct the light to the focal spot by different paths using different numbers of surfaces, and thus do not form a true image of the sample.
  • U.S. Patent 3,989,381 to Fulwyler describes an optical chamber or flow cell having a spherical reflective portion for use in a flow cytometer. Instead of enclosing the excitation site within a reflective chamber to collect light scattered in all directions, however, Fulwyler uses a spherical reflective portion to reflect some of the scattered light, and direct it back through the sample towards a collection lens. Light passing through the collection lens is refracted into parallel beams, and is directed towards a photodetector . Thus, the spherical reflective surface functions as a light gathetering enhancer, rather than as an imaging optical element.
  • Refractive light collection systems may cause optical and chromatic aberrations. Such aberrations may be particularly severe near the edges of the lens, or wherever a significant refractive discontinuity is encountered. Such refractive discontinuities in the optical path also may reduce the light collection efficiency of the system.
  • Systems that use refractive elements typically attempt to reduce such aberrations by filling the flow cell with a fluid having an index of refraction similar to the index of refraction of the material from which the collection lens is formed, thereby decreasing the number of refractive discontinuities in the optical system.
  • Optical aberrations may also be reduced by passing light through refractive boundaries or discontinuities at normal or near-normal angles. In view of the foregoing, it would be desirable to provide an optical element for use in a flow cytometer that provides high-efficiency light gathering, and that produces high-quality images with reduced chromatic aberration.
  • an optical element having a base portion defining a flow channel, and a mirror portion defining an aspheric concave reflective surface.
  • the mirror portion preferably comprises a convex aspheric shape coated with a layer of reflective material to form an aspheric concave reflective surface relative to the flow channel.
  • the aspheric concave reflective surface preferably has a relatively large collection angle to provide high- efficiency light collection and to direct collected light to form an image an a plane external to the optical element.
  • the optical element is constructed from an optically clear material, and the base and mirror portions of the optical element may be integrally formed.
  • the base and mirror portions may be assembled from separate components, for example, a plano-convex element, reflectively coated on the aspheric surface, and a base element.
  • the components are optically coupled with a coupling material having a refractive index matching the components joined, so as to reduce refractive discontinuities in the optical path.
  • the sample stream preferably comprises a fluid selected to have an index of refraction that closely matches the index of refraction of the material from which the optical element is constructed.
  • FIG. 1 is a block diagram of a previously known flow cytometer
  • FIGS. 2A and 2B are, respectively, a cutaway perspective view and a side view of an illustrative optical element constructed in accordance with the principles of the present invention
  • FIG. 3 illustrates a ray trace resulting from use of the optical element of FIGS. 2;
  • FIG. 4 is an exploded view of an alternative embodiment of an optical element of the present invention.
  • FIG. 1 a block diagram of a previously known flow cytometer is described. Such a system is described, for example, in U.S. Patent No.
  • Flow cytometer 10 generally includes pressurized sheath fluid tank 11 coupled via inlet line 12 to sheath flow tube 13, pressurized sample fluid tank 14 coupled via inlet line 15 to sample tube 16, flow cell 17, light source 18, light collector 19, light detector 20, processing circuit 21, and waste tank 22.
  • Light source 18 may comprise, for example, one or more lasers having different wavelengths, depending upon the intended application of flow cytometer 10.
  • a sample to be analyzed or sorted by flow cytometer 10 is mixed with saline solution or distilled water in sample tank 14 to form a sample fluid.
  • the sample may be treated with stains, fluorescent reagents or dyes to provide emissions in predetermined wavelength regions when subjected to predetermined types of illumination.
  • the sample fluid is injected under pressure into sample tube 16.
  • Sheath fluid which generally comprises the same fluid used to form the sample fluid, is injected into sheath flow tube 13 and forms an annular flow coaxial with the sample fluid. Because the sheath fluid travels past the exit of sample tube 16 at much greater velocity than the sample fluid, the sheath fluid entrains the slower moving sample fluid. As the sample fluid attains the velocity of the surrounding sheath fluid, the diameter of the sample fluid stream generally is reduced to a diameter on the order of the thickness of a single cell or particle suspended in the sample fluid.
  • the resulting sample stream comprising the reduced diameter sample fluid coaxially surrounded by the sheath fluid, passes through flow cell 17, where it is illuminated by beam 24 generated by light source 18. Beam 24 intersects the sample stream at excitation site 23. As described in the above-incorporated Fulwyler patent, flow cell 17 may be filled with quiescent sheath fluid through which the high-velocity sample stream passes with relatively little loss of sample material. The sample stream then passes into waste tank 22.
  • Flow cell 17 may include one or more spherical reflective elements that direct light from the excitation site to light collector 19. When a cell or other particulate material in the sample stream passes through the beam, the light is scattered.
  • the cells in the sample may have been dyed using a fluorescent dye or a fluorescent reagent, causing them to fluoresce when the cells pass through the beam.
  • Some of the scattered or emitted light is reflected by the reflective interior of flow cell 17 toward light collector 19, typically a lens or other optical system, which focuses the collected light onto light detector 20.
  • a spectral discriminating device typically an optical filter or spectrally dispersing device 19a is placed in the optical path before the detector 20 to limit the light incident on the detector to the desired wavelength regions.
  • Light detector 20 produces a signal indicative of properties of the detected light, and sends the signal to processing circuit 21, typically a microcomputer programmed to function as a data recorder.
  • Processing circuit 21 may be used to count or characterize the cells or other particulate material in the sample stream.
  • system 10 may redirect some of the sample stream into a sorting chamber (not shown) , based on the characterization of a sample obtained when the sample passed through flow chamber 17. Accordingly, flow cytometer may be employed for sorting cells or other particulate material having certain characteristics, as is known in the art.
  • FIGS. 2A and 2B a perspective view of optical element 30 constructed in accordance with the principles of the present invention is described.
  • Optical element 30 constitutes an aspheric reflective imaging viewing orifice and may be substituted in place of flow cell 17 in flow cytometer system 10 of FIG. 1.
  • Optical element 30 preferably comprises base portion 31 and mirror portion 32.
  • Base portion 31 comprises an optically clear material having a portion defining flow channel 33 having inlet 34 and outlet 35.
  • Mirror portion 32 also preferably formed from an optically clear material, includes convex aspheric portion 36.
  • Convex aspheric portion 36 is coated with thin layer 37 of a broadband reflecting material, such as aluminum, a broadband dielectric interference stack, or gold, which is deposited using techniques that are per se known, for example, by vapor deposition.
  • convex aspheric portion 36 When coated with reflective material, convex aspheric portion 36 forms aspheric concave reflective surface 38 having optical axis 39.
  • Excitation site 40 is located within flow channel 33 along optical axis 39 of aspheric concave reflective surface 38.
  • a beam of high-intensity light is directed through lateral face 41 of base portion 31 to intersect the sample stream passing through flow channel 33 at excitation site 40.
  • Optical element 30 preferably may be manufactured as a single compact monolithic unit, and preferably comprises a transparent optical material, such as laser grade fused silica, quartz, or an optical grade plastic or appropriate optical glass with low base refractive index or high dispersive power ("ABBE value") .
  • a transparent optical material such as laser grade fused silica, quartz, or an optical grade plastic or appropriate optical glass with low base refractive index or high dispersive power ("ABBE value") .
  • Monolithic construction of optical element 30 facilitates easy assembly and replacement of the optical system in a flow cytometer, and results in an optical system that is significantly more compact than the optical systems used in a previously known flow cytometers .
  • High optical collection efficiency is achieved by refractive matching of the fluid passing through flow channel 33 with the transparent material from which optical element 30 is constructed.
  • aspheric concave reflective surface 38 preferably has a relatively large collection angle (i.e. numerical aperture greater than 1.0) and covers an area such that light is collected from a cone
  • a collection angle of 90° will result in approximately 20% of the total light emitted being collected by aspheric concave reflective surface 38, and used to form an image. Because aspheric optics are used to form reflective surface 38, near diffraction-limited performance is provided for on-axis operation, despite the large collection angle.
  • Optical element 30 may be inserted in the system of FIG. 1 in place of flow cell 17.
  • the sample stream either with or without an outer annulus of sheath fluid, enters optical element 30 through inlet 34.
  • the sample stream completely fills flow channel 33.
  • the sample stream exits optical element 30 through outlet 35.
  • laser 42 generates focused excitation beam L, which is directed through lateral face 41 of base portion 31 orthogonal to flow channel 33.
  • Excitation beam L intersects and illuminates the sample stream at excitation site 40.
  • illumination by excitation beam L causes scattered emitted light, such as fluorescence, phosphorescence and/or other types of emission to occur, depending upon the dyes, stains or reagents used in the sample stream, and the types of illumination employed.
  • Image I may be detected using any of a variety of known photodetection means, and may be used for spectral processing and detection, or other measurements as is known in the field of flow cytometry.
  • an apertured screen may be placed just before the image plane in alignment with optical axis 39 to mask the detector from such unfocused light. Applicant expects that contributions to the light impinging on a photodetector may be reduced, for example, to less than 0.2%, by using such an apertured screen.
  • the reflective optics used to collect, redirect, and generate the image in the optical element of the present invention are expected to introduce little or no chromatic aberrations.
  • the light travels through refractive materials (i.e. the optical element), and encounters boundaries having significant refractive discontinuity (e.g. when the light exits the optical element) , chromatic aberration is expected to be insignificant, because the light crosses such boundaries at near normal angles.
  • the fluid that fills flow channel 33 preferably has its refractive index matched to that of the material of optical element 30, the number of refractive discontinuities encountered is reduced. Referring now to FIG. 4, an exploded view of an alternative embodiment of an optical element constructed in accordance with the present invention is described.
  • Optical element 50 comprises two separate components: aspheric plano-convex element 52 having thin layer 53 of reflective coating disposed on aspheric convex surface 54 to form aspheric concave reflective surface 55; and base cuvette 56 defining flow channel 56.
  • Aspheric plano-convex element 52 and base cuvette 56 preferably are constructed of the same optically clear material, and preferably are coupled together using layer 57 of a suitable optical adhesive or gel that closely matches the refractive index of the material from which components 52 and 56 are constructed. While manufacturing optical element 50 from separate components may introduce assembly tolerance issues resulting in slight losses in optical efficiency and image quality, optical element 50 may be much easier to manufacture.
  • aspheric plano- convex elements 52 having different curvatures may be coupled to base cuvette 56, depending upon the intended application of the flow cytometer.
  • optical element of the present invention may be constructed in other ways. For example, an optical element that is split at the position of the flow channel may provide some additional benefit in ease of manufacture.

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  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Optical Measuring Cells (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention se rapporte à un élément optique conçu pour être utilisé dans un cytomètre en flux et comportant un élément de base ayant une partie définissant un canal d'écoulement, et une surface réfléchissante, concave, asphérique, ayant un axe optique formant une intersection avec le canal d'écoulement. Une certaine quantité de lumière diffusée ou émise par les cellules ou toute autre matière particulaire présente dans un courant échantillon qui s'écoule dans le canal d'écoulement est recueillie et réfléchie par la surface réfléchissante, concave, asphérique de sorte qu'une image peut être formée sur un plan image externe à l'élément optique.
PCT/US2000/041151 1999-10-12 2000-10-11 Element optique pour cytometrie en flux WO2001027590A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41647399A 1999-10-12 1999-10-12
US09/416,473 1999-10-12

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WO2001027590A2 true WO2001027590A2 (fr) 2001-04-19
WO2001027590A3 WO2001027590A3 (fr) 2001-12-13

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6683314B2 (en) 2001-08-28 2004-01-27 Becton, Dickinson And Company Fluorescence detection instrument with reflective transfer legs for color decimation
WO2007137119A2 (fr) * 2006-05-17 2007-11-29 Luminex Corporation systÈmes de type cytomÈtres en flux sur circuits intÉgrÉs pour analyser des particules marquÉes de maniÈre fluorescente
EP1907820A2 (fr) * 2005-05-02 2008-04-09 Jmar Research, Inc. Systemes et procedes destines a un instrument a angle de capture eleve et a diffusion de lumiere a angles multiples (mals)
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
US8233146B2 (en) 2009-01-13 2012-07-31 Becton, Dickinson And Company Cuvette for flow-type particle analyzer
WO2015084676A1 (fr) 2013-12-04 2015-06-11 Iris International, Inc. Cytomètre en flux
JP2017062247A (ja) * 2012-05-30 2017-03-30 アイリス インターナショナル， インコーポレイテッド フローサイトメータ
US9746412B2 (en) 2012-05-30 2017-08-29 Iris International, Inc. Flow cytometer
US20190391069A1 (en) * 2018-06-25 2019-12-26 Shinko Electric Industries Co., Ltd. Flow cell
WO2022156303A1 (fr) * 2021-01-22 2022-07-28 Beckman Coulter Biotechnology (Suzhou) Co., Ltd. Ensemble cuvette, cuve à circulation comprenant l'ensemble cuvette, et processeur d'échantillons contenant l'ensemble cuvette ou la cuve à circulation
WO2023118708A1 (fr) * 2021-12-20 2023-06-29 Diagdev Elément pour système de mesure optique

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US4871249A (en) * 1987-07-10 1989-10-03 Medical Research Council Light collecting device with chamber including ellipsoidal surface and spherical surface
WO1993007471A1 (fr) * 1991-10-08 1993-04-15 Beckman Instruments, Inc. Detection d'un signal de radiation
US5430541A (en) * 1993-01-12 1995-07-04 Applied Biosystems Inc. High efficiency fluorescence flow cell for capillary liquid chromatography or capillary electrophoresis
US5471299A (en) * 1992-02-21 1995-11-28 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Apparatus and method for the analysis of particle characteristics using monotonically scattered light

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US4871249A (en) * 1987-07-10 1989-10-03 Medical Research Council Light collecting device with chamber including ellipsoidal surface and spherical surface
WO1993007471A1 (fr) * 1991-10-08 1993-04-15 Beckman Instruments, Inc. Detection d'un signal de radiation
US5471299A (en) * 1992-02-21 1995-11-28 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Apparatus and method for the analysis of particle characteristics using monotonically scattered light
US5430541A (en) * 1993-01-12 1995-07-04 Applied Biosystems Inc. High efficiency fluorescence flow cell for capillary liquid chromatography or capillary electrophoresis

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6683314B2 (en) 2001-08-28 2004-01-27 Becton, Dickinson And Company Fluorescence detection instrument with reflective transfer legs for color decimation
US7129505B2 (en) 2001-08-28 2006-10-31 Becton Dickinson And Company Fluorescence detection instrument with reflective transfer legs for color decimation
EP1907820A2 (fr) * 2005-05-02 2008-04-09 Jmar Research, Inc. Systemes et procedes destines a un instrument a angle de capture eleve et a diffusion de lumiere a angles multiples (mals)
EP1907820A4 (fr) * 2005-05-02 2011-07-06 Jmar Res Inc Systemes et procedes destines a un instrument a angle de capture eleve et a diffusion de lumiere a angles multiples (mals)
WO2007137119A2 (fr) * 2006-05-17 2007-11-29 Luminex Corporation systÈmes de type cytomÈtres en flux sur circuits intÉgrÉs pour analyser des particules marquÉes de maniÈre fluorescente
WO2007137119A3 (fr) * 2006-05-17 2008-05-08 Luminex Corp systÈmes de type cytomÈtres en flux sur circuits intÉgrÉs pour analyser des particules marquÉes de maniÈre fluorescente
US9810707B2 (en) 2006-05-17 2017-11-07 Luminex Corporation Chip-based flow cytometer type systems for analyzing fluorescently tagged particles
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
US8233146B2 (en) 2009-01-13 2012-07-31 Becton, Dickinson And Company Cuvette for flow-type particle analyzer
CN107014741A (zh) * 2012-05-30 2017-08-04 艾瑞斯国际有限公司 流式细胞仪
US11703443B2 (en) 2012-05-30 2023-07-18 Iris International, Inc. Flow cytometer
EP3206010A1 (fr) 2012-05-30 2017-08-16 Iris International, Inc. Cytomètre de flux
US9746412B2 (en) 2012-05-30 2017-08-29 Iris International, Inc. Flow cytometer
JP2017062247A (ja) * 2012-05-30 2017-03-30 アイリス インターナショナル， インコーポレイテッド フローサイトメータ
US10126227B2 (en) 2012-05-30 2018-11-13 Iris International, Inc. Flow cytometer
US10209174B2 (en) 2012-05-30 2019-02-19 Iris International, Inc. Flow cytometer
US10330582B2 (en) 2012-05-30 2019-06-25 Iris International, Inc. Flow cytometer
EP4332547A2 (fr) 2012-05-30 2024-03-06 Iris International, Inc. Cytomètre en flux
US11255772B2 (en) 2012-05-30 2022-02-22 Iris International, Inc. Flow cytometer
WO2015084676A1 (fr) 2013-12-04 2015-06-11 Iris International, Inc. Cytomètre en flux
US20190391069A1 (en) * 2018-06-25 2019-12-26 Shinko Electric Industries Co., Ltd. Flow cell
WO2022156303A1 (fr) * 2021-01-22 2022-07-28 Beckman Coulter Biotechnology (Suzhou) Co., Ltd. Ensemble cuvette, cuve à circulation comprenant l'ensemble cuvette, et processeur d'échantillons contenant l'ensemble cuvette ou la cuve à circulation
WO2023118708A1 (fr) * 2021-12-20 2023-06-29 Diagdev Elément pour système de mesure optique

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