• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    This flow cytometry system comprises a measuring chamber (11), an injection device (12) arranged to inject a stream of biological particles to be analyzed into the measuring chamber (11), an evacuation device (13). arranged to evacuate outside the cytometry system the flow of biological particles injected into the measuring chamber (11), a measuring assembly arranged to measure at least one optical property of the biological particles to be analyzed, the measuring assembly comprising an emission device (42) arranged to emit a light beam towards the measuring chamber (11) and able to cross the stream of biological particles, and at least one collection device (43a) arranged to collect light rays from the measuring chamber (11). The flow cytometry system further comprises a support (6) on which are mounted the injection device (12), the evacuation device (13), the emission device (42) and the at least one collecting device (43a).
    公开号:FR3022998A1
    申请号:FR1456230
    申请日:2014-06-30
    公开日:2016-01-01
    发明作者:Alain Rousseau
    申请人:ALAIN ROUSSEAU TECH & INNOVATIONS ARTEION；
    IPC主号:
    专利说明:

    [0001] The present invention relates to a flow cytometry system for the analysis of biological particles. The document FR 2 653 885 discloses a flow cytometry system comprising: a measuring cell delimiting at least part of a measuring chamber; an injection device arranged to inject a stream of biological particles to be analyzed in the chamber of measurement, the injection device comprising: - an injection nozzle defining an internal chamber and comprising an injection orifice fluidly connected to the measuring chamber, - a first supply duct opening into the internal chamber and intended to supply the internal chamber with a liquid sample containing the biological particles to be analyzed in suspension, and - a second supply duct opening into the internal chamber and intended to supply the inner chamber with a first cladding fluid, the injection nozzle and the second feed duct being configured such that the first cladding fluid introduced into the inner chamber is fit to cheerful hydrodynamically the liquid sample introduced into the internal chamber, - an evacuation device arranged to evacuate outside the cytometry system the flow of biological particles injected into the measuring chamber, and - a measuring assembly arranged to measure at least one optical property of the biological particles to be analyzed, the measuring assembly comprising: a transmission device arranged to emit a light beam in the direction of the measuring chamber and able to cross the flow of biological particles, the device transmission device comprising a light source arranged to generate the light beam, and a collection device arranged to collect light rays from the measurement chamber, and more particularly light rays diffused or diffracted by each biological particle introduced into the light source. measuring chamber and crossing the light beam. The hydrodynamic cladding of the liquid sample containing the biological particles to be analyzed makes it possible to stretch the liquid sample before it passes through the injection orifice, and therefore on the one hand to precisely confine the biological particles and to on the other hand to optimize the centering of the flow of biological particles in the measuring chamber. These arrangements thus make it possible to facilitate the relative positioning of the incident light beam and of the flow of biological particles, and thus to improve the quality of the measurements of the optical properties of the biological particles to be analyzed. The flow cytometry system described in document FR 2 653 885 also makes it possible to limit the consumption of reaction liquids because of the small volume of the measurement chamber delimited by the measuring cell. Nevertheless, such a flow cytometry system requires the use of expensive and complex adjustment systems to align the incident light beam with the flow of biological particles. In addition, the control systems used for such a flow cytometry system have insufficient accuracy. Thus, the optical measurements made with such a flow cytometry system can be further improved. The present invention aims to remedy all or part of these disadvantages. The technical problem underlying the invention consists in particular in providing a flow cytometry system that is simple in structure and economical, while allowing reliable optical measurements to be made. To this end, the present invention relates to a flow cytometry system for the analysis of biological particles, comprising: a measurement cell delimiting at least in part a measurement chamber, an injection device arranged for injecting a stream of biological particles to be analyzed in the measuring chamber, the injection device comprising: an injection nozzle delimiting an internal chamber and comprising an injection orifice fluidly connected to the measuring chamber; a first conduit; feeding device opening into the internal chamber and intended to supply the internal chamber with a liquid sample containing the biological particles to be analyzed in suspension, and a second supply duct opening into the internal chamber and intended to feed the internal chamber with a first cladding fluid, the injection nozzle and the second supply duct being configured so that the first a sheathing fluid introduced into the internal chamber is capable of hydrodynamically sheathing the liquid sample introduced into the internal chamber; an evacuation device arranged to evacuate outside the cytometry system the flow of biological particles injected into the chamber; a third supply conduit fluidly connected to the measuring chamber and for supplying the measuring chamber with a second sheathing fluid, the measuring chamber and the third supply duct being configured so that the second cladding fluid introduced into the measuring chamber is capable of hydrodynamically sheathing the flow of biological particles in the measurement chamber; a measuring assembly arranged to measure at least one optical property of the biological particles to be analyzed, such as the intensity of the absorption of biological particles, the measuring assembly comprising: at least one emitting device A ssion arranged to emit a light beam in the direction of the measuring chamber and able to cross the flow of biological particles, the at least one transmitting device comprising a light source arranged to generate the light beam, - at least one device collector arranged to collect light rays from the measuring chamber, and - a support on which are mounted the injection device, the evacuation device, the at least one transmission device and the at least one 25 collection device, the support defining a receiving housing in which is housed the measuring cell. The fact of mounting the transmission and collection devices on the same support, referred to as reference, makes it possible to improve the stability and the relative positioning of the transmission and collection devices, and therefore the reliability of the optical measurements made. In addition, the fact of mounting the injection and evacuation devices on a reference support makes it possible to produce the injection and evacuation devices from molded or overmolded parts of low precision, which reduces the manufacturing costs of the flow cytometry system according to the present invention.
    [0002] It should be noted that the cladding of the flow of biological particles in the measuring chamber makes it possible to keep the stream of biological particles centered and stabilized during its journey in the measurement chamber. According to one embodiment of the invention, the at least one transmission device 5 is arranged to emit a laser beam. According to one embodiment of the invention, the at least one transmission device comprises a focusing device arranged to focus the light beam in the measurement chamber and on the flow of biological particles. According to one embodiment of the invention, the focusing device comprises: a first mounting part equipped with an optical focusing element arranged on the optical path of the light beam; a second mounting part on which is mounted the light source, the first and second mounting portions of the focusing device being movable relative to each other in a first direction of movement substantially parallel to the optical path of the light beam, and - a first adjustment element, such as a micrometer screw, arranged to adjust the relative position of the first and second mounting portions of the focusing device along the first direction of travel. According to one embodiment of the invention, the optical focusing element comprises a focusing lens. According to one embodiment of the invention, the focusing device comprises at least one immobilization element arranged for realizing the first mounting part with respect to the support, the second mounting portion of the focusing device being mounted movably relative to at the first mounting part of the focusing device. According to one embodiment of the invention, the at least one immobilizing element comprises at least one immobilizing screw. According to one embodiment of the invention, the first mounting portion of the focusing device delimits a guide duct in which is slidably mounted at least a portion of the second mounting portion of the focusing device.
    [0003] According to one embodiment of the invention, the first adjustment element comprises a first threaded portion arranged to cooperate with a first threaded bore formed on the first mounting portion of the focusing device, and a second threaded portion arranged to cooperate with a second threaded bore formed on the second mounting portion of the focusing device, the first and second threaded portions having threads of different pitch. According to one embodiment of the invention, the flow cytometry system comprises at least one orientation adjustment device, also called attitude control device, arranged to adjust the orientation of the light beam emitted by the at least one transmitting device. According to one embodiment of the invention, the orientation adjustment device is arranged to adjust the orientation of the light beam emitted by the at least one emission device so that the optical path of the light beam extends substantially orthogonally to the flow direction of the flow of biological particles. According to one embodiment of the invention, the orientation adjustment device comprises: an adjustment cushion disposed between the support and the at least one transmission device, the adjustment cushion being at least partly elastically deformable, and - a set of deformation arranged to deform the compression cushion so as to adjust the orientation of the light beam emitted by the at least one transmission device. According to one embodiment of the invention, the adjustment cushion is annular. For example, the adjustment pad defines a central passageway through which at least a portion of the transmitting device extends. According to one embodiment of the invention, the first mounting portion of the focusing device comprises a bearing portion arranged to bear against the adjustment cushion. According to one embodiment of the invention, the bearing portion of the first mounting part comprises a through hole through which the at least one immobilizing element extends. According to one embodiment of the invention, the deformation assembly is formed by the at least one immobilizing element and the bearing portion of the first mounting part.
    [0004] According to one embodiment of the invention, the adjustment cushion comprises a through hole through which the at least one immobilizing element extends. According to one embodiment of the invention, the at least one collection device 5 comprises: a first mounting part comprising a first optical collection element; a second mounting part comprising at least one second optical collection element; the first and second mounting portions of the collecting device being movable relative to one another in a second direction of movement, and - a second adjusting element, such as a micrometer screw, arranged to adjust the relative position of the first and second mounting portions of the collection device along the second direction of travel. According to one embodiment of the invention, the at least one collection device comprises at least one immobilization element arranged for real estate the first mounting portion of the collection device relative to the support, the second mounting part of the device the collection member being movably mounted relative to the first mounting portion of the collection device. According to one embodiment of the invention, the first mounting portion of the collection device defines a guide duct in which is slidably mounted at least a portion of the second mounting portion of the collection device. According to one embodiment of the invention, the second adjusting element comprises a first threaded portion arranged to cooperate with a first threaded bore formed on the first mounting portion of the collection device, and a second threaded portion arranged to cooperate with a second threaded bore formed on the second mounting portion 30 of the collection device, the first and second threaded portions having threads of different pitch. According to one embodiment of the invention, the first optical collection element comprises an optical lens which can for example form a collimator.
    [0005] According to one embodiment of the invention, the at least one second optical collection element comprises at least one optical collection fiber. According to one embodiment of the invention, the second mounting portion of the collection device comprises a plurality of collection optical fibers. According to one embodiment of the invention, the second mounting portion of the collection device comprises a central collection optical fiber, and peripheral collection optical fibers. For example, the central collection optical fiber is intended to collect the light rays coming from the measurement chamber according to the optical path of the incident light beam, that is to say at 0 °, and the peripheral optical collection fibers are intended to collect light rays from the measuring chamber at low angles, for example less than 15 °. The second mounting part of the collection device may for example comprise at least one peripheral optical fiber for collecting light rays coming from the measurement chamber at an angle of the order of 4 ° and at least one optical fiber. Peripheral collection intended to collect light rays coming from the measuring chamber at an angle of the order of 9 °. According to one embodiment of the invention, the flow cytometry system comprises an electrical impedance variation measuring device arranged to measure the variation of electrical impedance generated by the passage of the biological particles through the orifice of injection, the electrical impedance variation measuring device comprising a first and a second electrode respectively disposed on either side of the injection orifice, the first and second electrodes being intended to be in electrical contact with the flow of biological particles so as to establish an electric field through the injection port. Such an electrical impedance variation measuring device makes it possible to count the number of biological particles passing through the injection orifice, and also to determine the size, and more precisely the volume of the biological particles. According to one embodiment of the invention, the measuring assembly comprises a plurality of collection devices angularly offset with respect to the measuring cell, and more precisely with respect to the axis of the flow of biological particles.
    [0006] According to one embodiment of the invention, the at least one collection device is disposed substantially opposite the emission device relative to the measuring cell. According to one embodiment of the invention, the flow cytometry system comprises a plurality of emission devices angularly offset with respect to the measuring cell, and more precisely with respect to the axis of the flow of biological particles. According to one embodiment of the invention, the evacuation device comprises a discharge conduit fluidly connected to the measuring chamber and intended to evacuate the flow of biological particles injected into the measurement chamber, and in addition the third supply duct. These arrangements make it possible to substantially symmetrically distribute the inflow and outflow of fluids relative to the support, and thus to facilitate the assembly of the flow cytometry system 15 according to the invention and to make access to the various inputs easier. and fluid outlets. These arrangements also make it easier to manufacture the injection and evacuation devices, since certain component parts thereof can then be manufactured from the same mold or from a mold provided with inserts or parts enabling to adapt its shape. According to one embodiment of the invention, the flow cytometry system is shaped such that the pressure of the second cladding fluid injected into the measurement chamber is less than the pressure of the first cladding fluid injected into the chamber. internal. According to one embodiment of the invention, the injection device 25 comprises a first discharge conduit fluidly connected to the inner chamber and intended to discharge the contents of the internal chamber outside the cytometry system. The first discharge conduit is more particularly intended to discharge outside the cytometry system a first rinsing fluid introduced into the internal chamber via the second feed duct. According to one embodiment of the invention, the flow cytometry system further comprises a first discharge valve fluidly connected to the first discharge pipe and movable between a closed position in which the first discharge valve prevents a flow of water. fluid from the internal chamber to the outside of the cytometry system via the first discharge line, and an open position in which the first discharge valve allows fluid flow from the internal chamber to the outside of the cytometry system via the first discharge pipe. According to one embodiment of the invention, the at least one evacuation device comprises a second discharge conduit fluidly connected to the measurement chamber and intended to discharge the contents of the chamber to the outside of the cytometry system. measurement. The second discharge conduit is more particularly intended to discharge outside the cytometry system a second rinsing fluid introduced into the measurement chamber 10 via the third supply duct and the fluid to be measured which passes through the orifice. injection and comes from the internal chamber. According to one embodiment of the invention, the flow cytometry system further comprises a second discharge valve fluidly connected to the second discharge pipe and movable between a closed position in which the second discharge valve prevents a flow of water. fluid from the measurement chamber to the outside of the cytometry system via the second discharge pipe, and an open position in which the second discharge valve allows fluid flow from the measurement chamber to the outside of the system cytometry via the second delivery line. According to one embodiment of the invention, the first discharge valve and / or the second discharge valve is a solenoid valve. According to one embodiment of the invention, the support comprises at least a first passage opening through which at least a portion of the emission device extends, a second passage opening through which at least one a part of the at least one collection device, a third passage opening through which at least a portion of the injection device extends, and at least a fourth passage opening through which at least one part of the evacuation device 30, the first, second, third and fourth passage openings opening into the receiving housing. According to one embodiment of the invention, the first and second supply ducts respectively comprise first and second ends opening into the internal chamber, the second end being further from the injection orifice than the first end. .
    [0007] According to one embodiment of the invention, the first supply duct comprises a first tubular supply portion opening into the internal chamber, and the second supply duct comprises a second tubular supply portion opening into the internal chamber. the second tubular supply portion extending around the first tubular supply portion. The first and second tubular supply portions may for example extend coaxially. According to one embodiment of the invention, the end of the third supply duct facing the measuring chamber is further away from the injection orifice than the end of the evacuation duct facing the chamber. measured. According to one embodiment of the invention, the evacuation duct comprises a tubular evacuation portion opening into the measuring chamber, and the third supply duct comprises a third opening tubular supply portion 15 fluidly connected to the measuring chamber, the third tubular supply portion extending around the tubular discharge portion. The tubular discharge portion and the third tubular supply portion may, for example, extend coaxially. According to one embodiment of the invention, the first supply duct 20 opens out opposite the injection orifice. According to one embodiment of the invention, the measuring cell is fluidly isolated from the receiving housing. According to one embodiment of the invention, the measuring cell is interposed in a sealed manner between the injection and discharge devices. According to one embodiment of the invention, the measuring cell is at least partly transparent to the light beam emitted by the transmitting device According to one embodiment of the invention, the measuring cell 30 is made of a material electrically insulating. According to one embodiment of the invention, the injection and evacuation devices are made of an electrically insulating material. According to one embodiment of the invention, the emission device is arranged such that the optical path of the light beam extends substantially perpendicular to the flow direction of the flow of biological particles.
    [0008] According to one embodiment of the invention, the evacuation device is mounted on the support opposite the injection device relative to the measuring cell. According to one embodiment of the invention, the support is in one piece. According to one embodiment of the invention, the at least one emission device and the at least one collection device extend in a plane substantially perpendicular to the flow direction of the flow of biological particles.
    [0009] According to one embodiment of the invention, the measurement assembly comprises at least one detection element associated with the at least one collection device and arranged to output at least one measurement signal determined as a function of the light rays. collected by the at least one collection device. The at least one detection element may for example be a photodetector, such as a photodiode or a photomultiplier. According to one embodiment of the invention, the biological particles to be analyzed may be biological cells and in particular blood cells such as leucocytes or erythrocytes, or blood platelets, or even yeasts, fungi, spores, microbes, bacteria, etc. Biological particles may also be elements such as crystals. According to one embodiment of the invention, the injection nozzle comprises an injection member, such as a ruby or a synthetic sapphire, in which is formed the injection port. However, the injection port could also be directly molded into the body of the injection nozzle. According to one embodiment of the invention, the emission device is arranged in such a way that the distance between the injection orifice and the light beam substantially corresponds to one third or less of the distance separating the evacuation duct. and the injection port. According to one embodiment of the invention, the emission device is arranged such that the distance between the injection orifice and the light beam corresponds substantially to half or less of the height of the measuring chamber. . According to one embodiment of the invention, the first and / or second cladding fluid is a diluting liquid, such as a physiological fluid.
    [0010] According to one embodiment of the invention, the first and / or the second rinsing fluid is a dilution liquid, such as a physiological liquid. The present invention further relates to a set of flow cytometry comprising at least one flow cytometry system according to the invention. According to one embodiment of the invention, the flow cytometry assembly comprises a housing in which the at least one flow cytometry system is mounted. According to one embodiment of the invention, the flow cytometry assembly comprises a pre-amplification unit arranged to filter and pre-amplify the measurement signals supplied at the output of the at least one detection element. Such a pre-amplification unit may for example comprise an acquisition electronic card to which is attached the at least one detection element. According to one embodiment of the invention, the pre-amplification unit is mounted in the housing. According to one embodiment of the invention, the flow cytometry assembly comprises a control device arranged to control the opening and closing of the first discharge valve and / or the second discharge valve. The present invention further relates to an in vitro diagnostic analysis device, comprising at least one set of flow cytometry according to the invention. Such an analysis device may for example be similar to that described in the document FR2998057. According to one embodiment of the invention, the analysis device comprises a processing unit arranged to analyze the measurement signals provided by the at least one detection element. The processing unit is for example arranged to differentiate and / or identify the biological particles, and in particular to determine the structure and / or the shape of the biological particles. The treatment unit is, for example, also designed to determine the concentration and / or the distribution of the biological particles, and for example the concentration and / or the distribution of the leucocytes in lymphocytes, monocytes, neutrophils, eosinophils and basophils. The present invention furthermore relates to an assembly comprising a flow cytometry system according to the invention and an adjustment bench on which the flow cytometry system is intended to be mounted, in which the adjustment bench comprises at least a first translation adjustment device arranged to adjust in translation the position of the transmission device relative to the support.
    [0011] According to one embodiment of the invention, the first translation adjustment device is arranged to adjust in translation the position of the transmission device relative to the support in at least a first direction of translation adjustment orthogonal to the direction of translation. flow of the biological particle stream.
    [0012] According to one embodiment of the invention, the first translation adjustment device is arranged to adjust in translation the position of the transmission device relative to the support in at least a second direction of translation adjustment parallel to the direction of translation. flow of the biological particle stream.
    [0013] According to one embodiment of the invention, the first translational adjustment device comprises: a first attachment part fixed on a support part of the adjustment bench, such as a support plate, a mounted support element movable in translation relative to the first fastening portion in the first translational adjustment direction, and - a second fastening portion for connection to the transmitting device, the second fastening portion being movable in translation relative to to the support member in the second translational direction of translation. Such a translation adjustment device makes it possible to easily and accurately adjust the position of the emission device, and thus to ensure optimal alignment of the light beam on the flow of biological particles. According to one embodiment of the invention, the support element 30 is a support bracket comprising a first and a second support arm, the first support arm being movable in translation relative to the first attachment portion the first direction of adjustment in translation, the second fixing portion being movably mounted in translation relative to the second support arm in the second direction of translation adjustment.
    [0014] According to one embodiment of the invention, the flow cytometry system comprises an attachment bracket comprising a first attachment branch mounted on the support and on which the transmission device is mounted, and a second attachment branch intended to be fixed on the second fixing part. According to one embodiment of the invention, the adjustment cushion is interposed between the first mounting portion of the focusing device and a portion of the fixing bracket. According to one embodiment of the invention, the translation adjustment device 10 is a micrometric translation adjustment device. According to one embodiment of the invention, the flow cytometry system comprises at least one fixing screw arranged to fix the first attachment branch on the support, the first attachment branch comprising at least one through hole through which is able to extend the at least one fixing screw. According to one embodiment of the invention, the passage opening is oblong or has dimensions greater than those of the body of the fixing screw. According to one embodiment of the invention, the adjustment bench comprises at least one second translational adjustment device arranged to adjust in translation the position of the at least one collection device with respect to the support. According to one embodiment of the invention, the second translation adjustment device is arranged to adjust in translation the position of the collection device relative to the support in at least a first direction of translation adjustment orthogonal to the direction of translation. flow of the biological particle stream. According to one embodiment of the invention, the second translation adjustment device is arranged to adjust in translation the position of the collection device relative to the support in at least a second direction of adjustment in translation parallel to the direction of translation. flow of the biological particle stream. According to an embodiment of the invention, the second device for adjusting in translation comprises: a first fixing part fixed on the support part of the adjustment bench; a support element mounted to move in translation relative to the first fixing part according to the first direction of adjustment in translation, and a second fixing part intended to be connected to the collection device 5, the second fixing part being mounted movable in translation with respect to the support element according to the second direction of adjustment in translation. According to one embodiment of the invention, the support element belonging to the second translation adjustment device is a support bracket 10 comprising a first and a second support arm, the first support arm mounted in translation relative to at the first fixing part in the first direction of translation adjustment, the second fixing part being mounted in translation relative to the second support arm in the second translational adjustment direction. According to one embodiment of the invention, the flow cytometry system comprises at least one attachment bracket associated with the at least one collection device and comprising a first attachment branch mounted on the support and on which is mounted the collection device, and a second securing branch for attachment to the second attachment portion. According to one embodiment of the invention, the second translational adjustment device is a micrometric translation adjustment device. According to one embodiment of the invention, the flow cytometry system comprises at least one fixing screw arranged to fix on the support the first attachment branch on which the collection device is mounted, said first attachment branch comprising at least one through hole through which is adapted to extend the at least one fastening screw. According to one embodiment of the invention, the passage opening is oblong or has dimensions greater than those of the body of the corresponding fixing screw. In any case, the invention will be better understood with the aid of the description which follows with reference to the appended diagrammatic drawing showing, by way of nonlimiting examples, two embodiments of this flow cytometry system.
    [0015] Figure 1 is a perspective view of a set of flow cytometry comprising two flow cytometry systems according to a first embodiment of the invention. Figure 2 is a perspective view of a flow cytometry system of Figure 1. Figure 3 is a partial perspective view of the flow cytometry system of Figure 2. Figure 4 is a top view of the flow cytometry system. Figure 5 is a sectional view along line VV of Figure 4. Figures 6 and 7 are enlarged scale views of details of Figure 5. Figure 8 is a diagrammatic view of Figure 5. FIG. 9 is an enlarged view of details of FIG. 8. FIG. 12 is a front view of a portion of a collection device belonging to the line VIII-VIII of FIG. to the flow cytometry system of Figure 2. Figures 13 to 15 are partial perspective views of a flow cytometry system installed on a bench. Figures 16 and 17 are front and rear perspective views of an in vitro diagnostic analysis device according to the invention. Figures 18 and 19 are sectional views of a flow cytometry system according to a second embodiment of the invention. FIGS. 1 to 15 show a first embodiment of a set of flow cytometry 2, also called a cytometric measurement set, intended for the analysis of biological particles, and for example of biological cells, such as blood cells . As shown in FIG. 1, the flow cytometry assembly 2 comprises in particular at least one flow cytometry system 4, also called a cytometric measurement head. According to the embodiment shown in FIG. 1, the flow cytometry set 2 comprises two flow cytometry systems 4. Nevertheless, the flow cytometry set 2 could comprise a single flow cytometry system 4 or more. of two flow cytometry systems 4. The flow cytometry system 4 comprises a monoblock support 6 which can be for example metallic. The support 6 is parallelepipedic and delimits an internal receiving housing 7. The support 6 has six openings 8a to 8f formed respectively on the six external faces of the support 6. The flow cytometry system 4 further comprises a measuring cell 9 which at least partially delimits a measuring chamber 11, a device injection device 12 arranged to inject a flow of biological particles F into the measuring chamber 11, and an evacuation device 13 arranged to evacuate outside the flow cytometry system 4 the flow of biological particles F injected into the measuring chamber 11.
    [0016] As shown in Figures 5 and 8, the measuring cell 9 is annular and is interposed in a sealed manner between the injection and discharge devices 12, 13. The measuring cell 9 is housed in the receiving housing 7 delimited by the support 5, and is fluidly isolated from the receiving housing 7. The measuring cell 9 is advantageously made of an electrically insulating material and transparent to light, for example plastic such as polymethyl methacrylate. The injection and evacuation devices 12, 13 are respectively fixed on two opposite external faces of the support 6, and for example on the upper and lower outer faces of the support 6.
    [0017] As shown more particularly in FIGS. 6 and 9, the injection device 12 comprises an injection nozzle 14 delimiting an internal chamber 15. The injection nozzle 14 is provided at its upper end with an orifice of injection 16 opening into the measuring chamber 11 and arranged to connect fluidly to the inner chamber 15 to the measuring chamber 11. According to the embodiment shown in Figures 1 to 15, the injection nozzle 14 comprises on the one hand a nozzle body 14a extending partly through the passage opening 8a of the support 6 and made of an electrically insulating material, such as a plastic material, and on the other hand an injection member 14b mounted on the nozzle body 14a and in which is formed the injection port 16. The injection member may be formed for example by a ruby or synthetic sapphire, or be made of plastic. According to an alternative embodiment of the invention, the injection orifice 16 could be injected directly with the nozzle body 14a.
    [0018] The injection device 12 further comprises a tubular supply conduit 17 for supplying the inner chamber 15 with a liquid sample containing, in suspension, the biological particles to be analyzed. The supply duct 17 extends partly in the inner chamber 15 and has an upper end 18 opening into the inner chamber 15 near the injection port 16 and facing the latter. The injection device 12 further comprises a supply conduit 19 for supplying the inner chamber 15 with a sheath fluid. The injection nozzle 14 and the supply duct 19 are configured such that the cladding fluid introduced into the internal chamber 15 via the supply duct 19 is capable of hydrodynamically sheathing the liquid sample introduced into the internal chamber. Before the liquid sample passes through the injection port 16. Such a hydrodynamic cladding may also be referred to as a hydraulic or hydrodynamic focusing of the liquid sample.
    [0019] According to the embodiment shown in Figures 1 to 15, the injection device 12 comprises a supply portion 21 sealingly mounted on a lower face of the nozzle body 14a, and the supply conduit 19 comprises of firstly a first portion of conduit 19a formed by a tubular insert mounted on the feed portion 21, and secondly a second portion of tubular conduit 19b fluidly connected to the first conduit portion 19a. The feed portion 21 may for example be made of an electrically insulating material, and in particular plastic. The second conduit portion 19b may for example be formed on the feed portion 21 or be formed by a tubular insert mounted on the latter. The tubular insert forming the first conduit portion 19a may for example be overmolded. According to the embodiment shown in FIGS. 1 to 15, the first duct portion 19a comprises an end portion projecting from the supply portion 21 and intended to be connected to a first source of cladding fluid (not shown in the figures). The second duct portion 19b extends into the inner chamber 15 and around the supply duct 17, the supply duct 17 and the second duct portion 19b extending coaxially. The second duct portion 19b has an upper end 22 opening into the internal chamber 15.
    [0020] The upper end 22 of the second conduit portion 19b is further away from the injection port 16 than the upper end 18 of the supply conduit 17. According to the embodiment shown in FIGS. 1 to 15, the feed duct 17 includes an end portion extending through a through hole in the supply portion 21. The end portion of the supply duct 17 projects from the supply portion 21 and is intended to be connected to a source of liquid sample (not shown in the figures). As shown in FIGS. 5 and 6, the injection device 12 furthermore comprises a discharge conduit 26 fluidly connected to the internal chamber 15 and intended to discharge the content of the chamber to the outside of the flow cytometry system 4 15. The delivery conduit 26 is more particularly intended to discharge outside the flow cytometry system 4 a rinsing fluid introduced into the internal chamber 15 via the supply conduit 19. According to the embodiment shown in FIG. 1 to 15, the discharge conduit 26 opens into the internal chamber 15, and for example at the base thereof, and is formed by a tubular insert mounted on the nozzle body 14a and having an end portion protruding from the nozzle body 14a. The flow cytometry assembly 2 further comprises a first discharge valve (not shown in the figures) fluidly connected to the discharge pipe 26 and movable between a closed position in which the first discharge valve prevents a fluid flow of the internal chamber 15 towards the outside of the flow cytometry system 4 via the discharge conduit 26, and an open position in which the first discharge valve allows a flow of fluid from the internal chamber 15 to the outside of the flow cytometry system 4via the discharge conduit 26.
    [0021] The evacuation device 13 comprises a discharge piece 28 bearing against the support 6 and delimiting an internal chamber 29 opening into the measuring chamber 11. A part of the evacuation piece 28 extends through the opening 8b of the support 6. The discharge part 28 may for example be made of an electrically insulating material, including plastic.
    [0022] The evacuation device 13 further comprises a tubular evacuation conduit 31 fluidly connected to the measurement chamber 11 and intended to evacuate the flow of biological particles F injected into the measuring chamber 11 towards the outside of the cytometry system. flow 4. The exhaust duct 31 extends partly into the inner chamber 29 and has a lower end 32 opening into the measuring chamber 11 facing the injection port 16. The discharge device 13 comprises in addition, a supply duct 33 fluidly connected to the measuring chamber 11 and for supplying the measuring chamber 11 with a sheathing fluid. The measuring chamber 11 and the supply duct 33 are configured in such a way that the cladding fluid introduced into the measurement chamber 11 via the supply duct 33 is able to hydrodynamically buffer the flow of biological particles F flowing. through the measuring chamber 11.
    [0023] According to the embodiment shown in FIGS. 1 to 15, the evacuation device 13 comprises a supply portion 34 sealingly mounted on an upper face of the evacuation piece 28, and the supply duct 33 comprises firstly a first portion of conduit 33a formed by a tubular insert mounted on the feed portion 34, and secondly a second portion of tubular conduit 33b fluidly connected to the first conduit portion 33a. The supply portion 34 may for example be made of an electrically insulating material, and in particular plastic. The second conduit portion 33b may for example be provided on the feed portion 34 or be formed by a tubular insert mounted on the latter. The tubular insert forming the first portion of conduit 33a may for example be overmolded. According to the embodiment shown in FIGS. 1 to 15, the first conduit portion 33a comprises an end portion projecting from the supply portion 34 and intended to be connected to a second source of cladding fluid (not shown in the figures). The second conduit portion 33b extends partly into the inner chamber 29 and around the exhaust duct 31, the exhaust duct 31 and the second duct portion 33b extending coaxially. The second conduit portion 33b has a lower end 35 opening into the inner chamber 29.
    [0024] The lower end 35 of the second conduit portion 33b is further away from the injection port 16 than the lower end 32 of the evacuation conduit 31. According to one embodiment of the invention, the cytometry system 4 is shaped so that the pressure of the cladding fluid injected into the measuring chamber 11 via the supply duct 33 is less than the pressure of the cladding fluid injected into the internal chamber 15 via the supply duct 26. According to the embodiment shown in FIGS. 1 to 15, the exhaust duct 31 comprises an end portion extending through a passage opening on the supply portion 34, and projecting from the feed portion 34. According to one embodiment of the invention, the nozzle body 14a, the feed portion 21, the discharge piece 28 and the feed portion 34 are each made by molding. As shown in FIGS. 5 and 7, the evacuation device 13 furthermore comprises a delivery duct 40 fluidly connected to the measurement chamber 11 and intended to discharge the contents of the flow cytometry system 4 outside the flow cytometry system 4. the measuring chamber 11. The discharge duct 40 is more particularly intended to discharge outside the flow cytometry system 4 a rinsing fluid introduced into the measuring chamber 11 via the supply duct 33. According to the embodiment shown in Figures 1 to 15, the discharge conduit 40 opens into the inner chamber 29, and is formed by a tubular insert mounted on the discharge member 28. The discharge pipe 40 is fluidly connected to the measuring chamber 11 via the internal chamber 29. The flow cytometry assembly 2 further comprises a second discharge valve (not shown in the figures) fluidly connected to the discharge pipe 40 and movable between a closing position in which the second discharge valve prevents a flow of fluid from the measuring chamber 11 to the outside of the flow cytometry system 4 via the discharge pipe 40, and a position of opening in which the second discharge valve allows a flow of fluid from the measuring chamber 11 to the outside of the flow cytometry system 4 via the discharge conduit 40.
    [0025] The flow cytometry system 4 further comprises a measuring assembly arranged to measure at least one optical property of the biological particles to be analyzed. According to the embodiment shown in FIGS. 1 to 15, the measuring assembly comprises a transmission device 42 arranged to emit a light beam towards the measurement chamber 11 and able to cross, that is to say ie intersect, the stream of biological particles introduced into the measuring chamber 11, and several collection devices 43a, 43b, 43c angularly offset relative to the flow of biological particles and arranged to collect light rays from the measurement chamber 11. Nevertheless, the measuring assembly could comprise for example several emission devices angularly offset with respect to the flow of biological particles, and also only one or more collection devices. The emission and collection devices are mounted on the lateral faces of the support 6 and extend in a plane substantially perpendicular to the flow direction of the flow of biological particles F. The collection device 43a is for example disposed to the opposite of the emission device 42 with respect to the measuring cell 9, while the collection devices 43b and 43c are arranged perpendicularly to the emission device 42 with respect to the measurement cell 9. emission and collection 43a-43c respectively extend partly through the passage openings 8c to 8f of the support 6. The emission device 42 comprises a light source 44 25 arranged to generate the light beam. The light source 44 may for example be a laser source arranged to generate a laser beam. The transmission device 42 comprises a focusing device 45 arranged to focus the light beam emitted by the light source 44, in the measurement chamber 11 and on the flow of biological particles F. According to the embodiment shown in the figures 1 to 15, the focusing device 45 comprises a first mounting portion 46 intended to be immobilized relative to the support 6, and a second mounting portion 47 on which the light source 44 is mounted. The second mounting portion 47 is mounted movable in translation relative to the first mounting portion 46 in a direction of displacement D1 parallel to the optical path of the light beam.
    [0026] As shown in FIG. 8, the first mounting portion 46 comprises a tubular guide portion 48 delimiting a guide duct. The guide portion 48 is equipped with an optical focusing element 49 arranged on the optical path of the light beam. The optical focusing element 49 comprises for example a focusing lens 51. The first mounting portion 46 also comprises an annular support portion 52 extending radially from the guide portion 48. The bearing portion 52 comprises a plurality of passage orifices 53 for the passage of immobilizing screws 54 arranged for real estate the first mounting portion 46 relative to the support 6. The passage orifices 53 are for example angularly offset relative to the axis d extension of the first mounting portion 46. According to the embodiment shown in Figures 1 to 15, the first mounting portion 46 comprises three passage holes 53 regularly angularly offset, and three immobilizing screws 54. The second part mounting member 47 comprises a tubular guided portion 55 slidably mounted in the guide duct delimited by the first mounting portion 46. The guided portion 55 limit a housing in which is mounted the light source 44. The guided portion 55 comprises for example an opening disposed opposite the optical focusing element 49 and through which extends an emission portion of the light source 44. The second mounting portion 47 further includes an annular portion 56 extending radially from the guided portion 55. The focusing device 45 further includes a micrometer adjusting member 57 arranged to adjust the relative position of the first and second mounting parts along the direction of movement Dl. According to the embodiment shown in FIGS. 1 to 15, the micrometric adjustment element 57 comprises a first threaded portion 57a arranged to cooperate with a first threaded bore 58 formed on the first mounting portion 46 of the focusing device, and a second threaded portion 57b arranged to cooperate with a second threaded bore 59 formed on the second mounting portion 47 of the focusing device, the first and second threaded portions 57a, 57b having threads of different pitch.
    [0027] The flow cytometry system 4 further comprises an orientation adjustment device 61, also called attitude control device, arranged to adjust the orientation or attitude of the light beam emitted by the emission device of such so that the optical path of the light beam extends substantially orthogonal to the direction of flow of the flow of biological particles F. The orientation adjustment device 61 comprises an annular adjustment cushion 62 arranged between the support 6 and the portion of the support 52 of the first mounting portion 46 of the focusing device 45. The adjusting cushion 62 is at least partially elastically deformable. According to the embodiment shown in FIGS. 1 to 15, the adjustment cushion 62 defines a passage central through which extends the guide portion 48 of the first mounting portion 46, and has a plurality of through holes 63 through which tending the immobilizing screws 54. Such an arrangement and such a configuration of the adjustment cushion 62 allow an operator to easily adjust the attitude of the light beam emitted by the light source 44 simply by screwing and / or unscrewing the various immobilizing screws 54 which cause an elastic deformation of the adjustment cushion 62. As shown more particularly in FIGS. 13 and 15, the flow cytometry system 4 can be fixed on an adjustment bench 3 with the aid of FIG. a base 5 for adjusting the position of the transmission device 42. The adjustment bench 3 comprises a translation adjustment device 64 arranged to adjust in translation the position of the transmission device 42 relative to the support. 6 in a first direction of translation adjustment D2 orthogonal to the flow direction of the flow of biological particles F and a second direction of adjustment in transla D3 parallel to the direction of flow of the flow of biological particles F. The first translational adjustment device 64 comprises a first fixing portion 65 fixed on a plate of the adjustment bench 3. The first translational adjustment device 64 further comprises a support bracket 66 comprising a first and a second support arm 66a, 66b perpendicular to each other. The first support arm 66a is movably mounted in translation on the first attachment portion 65 in the first translation adjustment direction D2.
    [0028] The first translational adjustment device 64 also comprises a second fixing portion 67 on which the emission device 42 is intended to be mounted. The second fixing portion 67 comprises a fastener 68 mounted to be movable in translation on the second branch support 66b of the support bracket 66 in the second direction of translation adjustment D2. The translational adjustment device 64 also comprises a micrometric screw 71 arranged to adjust the position of the support bracket 66 relative to the first attachment portion 65, and a micrometer screw 72 arranged to adjust the position of the fastener part. 68 with respect to the support bracket 66. The flow cytometry system 4 further comprises an attachment bracket 69 comprising a first attachment branch 69a fixed on the support 6 and on which the transmission device 42 is mounted, and a second attachment branch 69b for attachment to the attachment piece 68. The flow cytometry system 4 also includes a plurality of attachment screws 73 arranged to attach the first attachment branch 69a of the attachment bracket 69 on the support 6, and the first attachment branch 69a has a plurality of through-holes 74 through which the fixing screws 73 extend. the embodiment shown in Figures 1 to 15, each passage opening 74 has dimensions greater than those of the body of the corresponding fixing screw 73. In order to precisely adjust the position of the transmission device 42 with respect to the support 6 and thus to ensure an optimal crossing of the light beam and the flow of biological particles F in the measurement chamber 11, an operator must first of all install the flow cytometry system 4 on the adjustment bench 3 and fix the second attachment branch 69b to the fastener 68, then loosen the fastening screws 74, then actuate the micrometer screw 71 on the one hand. to adjust horizontally the position of the light beam and secondly the micrometer screw 72 so as to adjust vertically the position of the light beam, and finally tighten the fastening screws 74 so as to immobilize the fastening bracket 69 relative to the support 6. The translation adjustment device 64 thus allows easy adjustment of the position of the transmission device 42.
    [0029] According to the embodiment shown in FIGS. 1 to 15, the adjustment cushion 62 is interposed between the first attachment branch 69a of the attachment bracket 69 and the first mounting portion 46 of the focusing device 45.
    [0030] As shown in FIGS. 5 and 8, each collection device 43a, 43b, 43c comprises a first mounting portion 75 intended to be immobilized relative to the support 6, and a second mounting portion 76 mounted to be movable in translation relative to the first mounting part 75 according to the direction of movement.
    [0031] According to the embodiment shown in Figures 1 to 15, the first mounting portion 75 of each collection device comprises a tubular guide portion 77 defining a guide duct. The guide portion 77 is equipped with a collection optical element 78 disposed near the measuring cell 9. The optical collecting element 78 comprises for example an optical lens 79. The first mounting portion 75 of each device collection also comprises an annular support portion 81 extending radially from the corresponding guide portion 77. Each bearing portion 81 comprises a plurality of through holes 82 for the passage of immobilizing screws 83 arranged for real estate the corresponding first mounting portion 75 relative to the support 6. The through holes 83 provided on each portion of support 81 are for example offset angularly with respect to the axis of extension of the corresponding first mounting part 75. According to the embodiment shown in Figures 1 to 15, each first mounting portion 75 comprises three passage holes 82 regularly angularly offset, and three locking screws 83. The second mounting portion 76 comprises a mounted tubular guided portion 84 sliding in the guide duct delimited by the first mounting portion 75, and an annular portion 85 extending radially from the guided portion 84. The guided portion 84 has an end wall 84a facing the measuring cell 9 and wherein is provided at least one mounting hole 84b in which a collection optical fiber 86 is mounted. Each collection device 43a-43c further comprises a micrometer adjusting member 87 arranged to adjust the relative position of the first and second mounting portions 75, 76 of the corresponding collecting device along the corresponding direction of movement. According to the embodiment shown in Figures 1 to 15, each micrometric adjustment element 87 comprises a first threaded portion 87a arranged to cooperate with a first threaded bore 88 formed on the corresponding first mounting portion 75, and a second threaded portion 87b arranged to cooperate with a second threaded bore 89 formed on the corresponding second mounting portion 76, the first and second threaded portions 87a, 87b having threads of different pitch. According to the embodiment shown in FIGS. 1 to 15 and as it follows more particularly from FIG. 2, the collection device 43a comprises a plurality of collection optical fibers, and more particularly a central collection optical fiber 86a, and optical fiber collection devices 86b, 86c. For example, the central collection optical fiber 86a is intended to collect the light rays coming from the measurement chamber 11 according to the optical path of the incident light beam, that is to say at 0 °, at least one optical fiber of Peripheral collection 86b is intended to collect light rays coming from the measurement chamber 11 at an angle of the order of 4 ° and at least one peripheral optical fiber 86c is intended to collect light rays coming from the measurement chamber 11 at an angle of the order of 9 °. The collection device 43a may for example comprise a plurality of peripheral optical collection fibers 86b intended to collect light rays coming from the measurement chamber 11 at an angle of the order of 4 ° and several peripheral optical collecting fibers 86c intended to collect light rays from the measuring chamber 11 at an angle of the order of 9 °. According to the embodiment shown in FIGS. 1 to 15, each of the collection devices 43b, 43c comprises a single central collection optical fiber. The adjustment bench 3 further comprises three translation adjustment devices 64 'intended to be each associated with one of the collection devices 43a-43c. According to the embodiment shown in FIGS. 1 to 15, the translational adjustment devices 64 'are identical to the adjustment device 64 intended to be associated with the transmission device 42. Each translational adjustment device 64' comprises a first fixing portion 65 'fixed on the plate of the adjustment bench 3 and a support bracket 66' comprising a first and a second support arm 66a ', 66b' perpendicular to each other. The first support branch 66a 'of each support bracket 66' is mounted to move in translation on the corresponding first fixing portion 65 'in the first direction of translation adjustment orthogonal to the flow direction of the flow of biological particles F. Each translational adjustment device 64 'also includes a second attachment portion 67' on which the corresponding collection device is to be mounted. The second fastening portion 67 'of each translational adjustment device 64' comprises a fixing piece 68 'mounted to move in translation on the second support branch 66b' of the corresponding support bracket 66 'in a second direction of adjustment in translation parallel to the flow direction of the flow of biological particles F. Each translational adjustment device 64 'also comprises a micrometric screw 71' arranged to adjust the position of the support bracket 66 'of said translational adjustment device 64 'relative to the corresponding first fastener portion 65', and a micrometer screw 72 arranged to adjust the position of the fastener 68 'of said translation adjuster 64' relative to the corresponding support bracket 66 ' . The flow cytometry system 4 further comprises a fixing bracket 69 'associated with each collection device. Each fixing bracket 69 'comprises a first attachment branch 69a' fixed on the support 6 and on which the corresponding collection device 42 is mounted, and a second attachment branch 69b 'intended to be fixed on the attachment piece 68' corresponding. The flow cytometry system 4 also comprises a plurality of attachment screws 73 'arranged to fix the first attachment branch 69a' of each attachment bracket 69 'to the support 6, and each first attachment branch 69a' comprises a plurality passage holes 74 'through which the corresponding fixing screws 73' extend. According to the embodiment shown in Figures 1 to 15, each passage opening 74 'has dimensions greater than those of the body of the corresponding fixing screw 73'.
    [0032] In order to precisely adjust the position of each collection device 43a-43c relative to the support 6 and thus to ensure optimal collection of the light rays from the measurement chamber 11, an operator must first install the cytometry system in flow 4 on the adjustment bench 3 and fix the second securing branches 69b 'on the respective fasteners 68', then loosen the fastening screws 74 'associated with each translation adjusting device 64', then actuating firstly the micrometric screws 71 'so as to adjust horizontally the position of the different collection devices and secondly the micrometer screws 72 so as to adjust the position of the different collection devices vertically, and finally tighten the fixing screws 74' so as to immobilize the different fastening brackets 69 'with respect to the support 6. Each translational adjustment device 64' thus allows adjustment in easy translation of the position of the corresponding collecting device 43a-43c. The measurement assembly further comprises a plurality of detection elements 90 each associated with a collection device 43a-43c. Each detection element 90 is arranged to output a measurement signal determined as a function of the light rays collected by the corresponding collection device. At the passage of each biological particle through the incident light beam, each measurement signal output from each detection element 90 is for example proportional to the amount of light absorbed or re-emitted by said biological particle. Each detection element 90 may for example be a photodetector, such as a photodiode or also photomultiplier. The flow cytometry assembly 2 further comprises a pre-amplification unit 94 arranged to filter and pre-amplify the measurement signals output from the different detection elements 90. The pre-amplification unit 94 comprises in particular a acquisition electronic card 95 on which the detection elements 90 are fixed. The flow cytometry assembly 2 also comprises a housing 96 in which each flow cytometry system 4, the detection elements 90 and Pre-amplification unit 94. The flow cytometry system 4 further comprises an electrical impedance variation measuring device arranged to measure the variation of electrical impedance generated by the passage of the biological particles through the orifice. 16. The electrical impedance variation measuring device comprises, for example, first and second electrodes 91, 92 disposed respectively on either side of the injection port 16. The first and second electrodes 91, 92 are intended to be in electrical contact with the flow of biological particles F so as to establish an electric field through the injection port 16. Such an electrical impedance variation measuring device makes it possible to count the number of biological particles passing through the injection orifice 16, and also to determine the size, and more precisely the volume of the biological particles. . The operation of such an electrical impedance variation measuring device is known to those skilled in the art and is therefore not described in detail. It should however be noted that the passage of each biological particle through the injection port 16 causes an electrical pulse proportional to the size or volume of said biological particle and to count electrically the number of particles. Figures 16 and 17 show an analysis device 97 for in vitro diagnostics, and for example to perform blood tests, such as tests on whole blood. Such an analysis device 97 comprises in particular a set of flow cytometry 2 and a processing unit 98 arranged to analyze the measurement signals provided by each detection element 90. The processing unit 98 is for example arranged to differentiate and and / or identifying the biological particles, and in particular for determining the structure and / or the shape of the biological particles from the measurement signals provided by the detection elements 90. The processing unit 98 can also be arranged to determine the concentration and / or the distribution of biological particles. Such a processing unit 98 is known to those skilled in the art and is therefore not described in detail.
    [0033] FIGS. 18 and 19 show a flow cytometry system 4 according to a second embodiment of the invention which differs from that of supply 34a, 34b, which are distinct from one another, in that the first portion of the conduit 19a is provided on the first feed member 21a, in that the discharge conduit 26 is provided on the nozzle body 14a, in that the first conduit portion 33a is provided on the first feed portion 34a and the discharge duct 40 is arranged on the discharge part 28 shown in FIGS. 1 to 15 essentially in that the supply portion 21 is formed by a first and second separate feed members 21a, 21b one of the other, in that the supply portion 34 is formed by a first and second part According to this embodiment of the invention, the injection device 12 comprises a first connecting piece 23 fluidly connected at the first conduit portion 19a and mounted on the first power supply portion 21a, a second connection tip 25 for connection to the liquid sample source and mounted on the second power supply portion 21b, and a third connecting piece 27 fluidly connected to the discharge conduit 26 and mounted on the nozzle body 14a. According to this embodiment of the invention, the evacuation device 13 comprises a first connection endpiece 36 intended to be connected to the second fluid source 10 of cladding and mounted on the first supply portion 34a, a second endpiece connecting piece 38 fluidly connected to the discharge duct 31 and mounted on the second supply portion 34b, and a third connection piece 41 mounted on the discharge piece 28 and fluidly connected to the discharge duct 40.
    [0034] According to another embodiment of the invention not shown in the figures, the first and second electrodes of the electrical impedance variation measuring device could be formed by the supply and discharge conduits 17, 31 or by the conduit portions 19b, 33b.
    [0035] According to another embodiment of the invention not shown in the figures, the measuring assembly could comprise two emission devices 42 angularly offset, and two sets of collection devices each associated with one of the devices of FIG. emission 42, each series comprising for example three collection devices 43a-43c angularly offset. According to such an embodiment, the support 6 may for example have an octagonal shape. According to such an embodiment, the emission devices 42 may have different light sources. For example, one of the emitters 42 could be arranged to emit a blue laser beam and the other emitter 42 could be arranged to emit a red laser beam. As goes without saying, the invention is not limited to the embodiments of this flow cytometry system, described above as examples, it encompasses all the variants.
    权利要求:
    Claims (17)
    [0001]
    REVENDICATIONS1. Flow cytometry system (4) comprising: - a measuring cell (9) delimiting at least in part a measurement chamber (11), - an injection device (12) arranged to inject a flow of biological particles to analyzing in the measuring chamber (11), the injection device (12) comprising: - an injection nozzle (14) delimiting an internal chamber (15) and comprising an injection orifice (16) fluidly connected to the measurement chamber (11), - a first supply duct (17) opening into the internal chamber (15) and intended to feed the internal chamber with a liquid sample containing the biological particles to be analyzed, and 15 - a second duct supply valve (19) opening into the internal chamber (15) and intended to feed the inner chamber with a first cladding fluid, the injection nozzle (14) and the second supply duct (19) being configured such that so that the first cladding fluid introduced into the internal chamber is capable of hydrodynamically sheathing the liquid sample introduced into the internal chamber, an evacuation device (13) arranged to evacuate outside the cytometry system the flow of biological particles injected into the measurement chamber (11), - a third supply duct (33) fluidly connected to the measuring chamber (11) and for supplying the measuring chamber with a second cladding fluid, the measuring chamber (11) and the third feeding duct (33) being configured such that the second cladding fluid introduced into the measuring chamber (11) is capable of hydrodynamically sheathing the stream of biological particles in the measuring chamber (11), - a set measuring device arranged to measure at least one optical property of the biological particles to be analyzed, the measuring assembly comprising: at least one transmission device (42) arranged to emit a beam of light x in the direction of the measuring chamber (11) and able to cross the stream of biological particles, the at least one emission device (42) comprising a light source (44) arranged to generate the light beam, - at least a collection device (43a-43c) arranged to collect light rays coming from the measuring chamber (11), characterized in that the flow cytometry system further comprises a support (6) on which are mounted the device for injection (12), the evacuation device (13), the at least one emission device (42) and the at least one collection device (43a-43c), the support (5) delimiting a housing receiver (7) in which the measuring cell (9) is housed.
    [0002]
    Flow cytometry system according to claim 1, wherein the at least one emission device (42) comprises a focusing device (45) arranged to focus the light beam in the measuring chamber (11) and on the flow of biological particles (F).
    [0003]
    The flow cytometry system of claim 2, wherein the focusing device (45) comprises: a first mounting portion (46) equipped with an optical focusing element (49) disposed on the optical path of the light beam; - a second mounting portion (47) on which the light source (44) is mounted, the first and second mounting portions (46, 47) of the focusing device (45) being movable relative to one another; to the other in a first direction of movement (D1) substantially parallel to the optical path of the light beam, and - a first adjusting member (57) arranged to adjust the relative position of the first and second mounting portions (46, 47 ) of the focusing device (45) along the first direction of movement (D1).
    [0004]
    The flow cytometry system according to claim 3, wherein the focusing device (45) comprises at least one immobilization element (54) arranged for realizing the first mounting portion (46) relative to the support (6). ), the second mounting portion (46) of the focusing device (45) being movably mounted relative to the first mounting portion (46) of the focusing device (45).
    [0005]
    The flow cytometry system according to any one of claims 1 to 4, which comprises an orientation adjusting device (61) arranged to adjust the orientation of the light beam emitted by the at least one device. broadcast (42).
    [0006]
    The flow cytometry system according to claim 5, wherein the orientation adjusting device (61) comprises: - an adjustment cushion (62) disposed between the support (6) and the at least one device emission (42), the adjusting cushion (62) being at least 5 partly elastically deformable, and - a set of deformations arranged to deform the compression cushion (62) so as to adjust the orientation of the light beam emitted by the at least one transmitting device (42).
    [0007]
    The flow cytometry system of claim 6 in combination with claim 3, wherein the first mounting portion (46) of the focusing device (45) includes a bearing portion (52) arranged to abut against the adjustment cushion (62).
    [0008]
    The flow cytometry system of claim 7 in combination with claim 4, wherein the deformation assembly is formed by the at least one immobilizing member and the bearing portion (52) of the first mounting portion (46).
    [0009]
    The flow cytometry system of any one of claims 1 to 8, wherein the at least one collection device (43a-c) comprises: a first mounting portion (75) comprising a first optical element collector (78), - a second mounting part (76) comprising at least a second optical pick-up element (86), the first and second mounting parts (75, 76) of the at least one collecting device being movable relative to each other in a second direction of movement, and - a second adjusting member (87) arranged to adjust the relative position of the first and second mounting portions (75, 76) of the at least one collection device (43a-43c) along the second direction of travel. 30
    [0010]
    The flow cytometry system according to claim 9, wherein the at least one collection device (43a-43c) comprises at least one immobilization element (83) arranged for real estate the first mounting part (75) of said collecting device relative to the support (6), the second mounting portion (76) of said collection device being movably mounted relative to the first mounting portion of said collection device.
    [0011]
    The flow cytometry system of any one of claims 8 to 10, wherein the at least one second optical collection element (86) comprises at least one optical collection fiber.
    [0012]
    The flow cytometry system of any one of claims 1 to 11, which comprises an electrical impedance variation measuring device arranged to measure a variation of electrical impedance generated by the passage of biological particles through the body. the injection orifice (16), the electrical impedance variation measuring device comprising a first and a second electrode (91, 92) disposed respectively on either side of the injection orifice (16) the first and second electrodes (91, 92) being intended to be in electrical contact with the flow of biological particles.
    [0013]
    13. flow cytometry system according to one of claims 1 to 12, wherein the evacuation device (13) comprises: - an exhaust duct (31) fluidly connected to the measuring chamber (11) and intended to evacuate the flow of biological particles injected into the measuring chamber, and - the third supply duct (33).
    [0014]
    14. Flow cytometry assembly (2) comprising at least one flow cytometry system (4) according to any one of claims 1 to 13.
    [0015]
    The in vitro diagnostic assay (97) comprising a flow cytometry assay (2) according to claim 14.
    [0016]
    16. An assembly comprising a flow cytometry system according to any one of claims 1 to 13 and an adjustment bench (3) on which said flow cytometry system is intended to be mounted, in which the adjustment bench (3) ) comprises at least a first translational adjustment device (64) arranged to adjust in translation the position of the transmission device (42) relative to the support (6).
    [0017]
    17. The assembly of claim 16, wherein the adjustment bench (3) comprises at least a second translational adjustment device (64 ') arranged to adjust in translation the position of the at least one collection device (43a). 43c) relative to the support (6).
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    同族专利:
    公开号 | 公开日
    JP2020073918A|2020-05-14|
    RU2017101980A3|2018-12-13|
    MX2017000068A|2017-05-01|
    EP3161451A1|2017-05-03|
    FR3022998B1|2016-07-15|
    JP2017524925A|2017-08-31|
    RU2686525C2|2019-04-29|
    KR20170066308A|2017-06-14|
    CN106796170A|2017-05-31|
    US20170146443A1|2017-05-25|
    BR112016030749B1|2021-04-27|
    JP6991257B2|2022-01-12|
    AU2015282588A1|2017-02-09|
    ZA201700734B|2021-01-27|
    WO2016001522A1|2016-01-07|
    US10267722B2|2019-04-23|
    CA2953055A1|2016-01-07|
    KR102328003B1|2021-11-17|
    AU2015282588B2|2020-04-30|
    RU2017101980A|2018-07-30|
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    优先权:
    申请号 | 申请日 | 专利标题
    FR1456230A|FR3022998B1|2014-06-30|2014-06-30|SYSTEM AND ASSEMBLY FOR FLOW CYTOMETRY, ANALYSIS DEVICE COMPRISING SUCH A CYTOMETRY ASSEMBLY AND ASSEMBLY COMPRISING SUCH A CYTOMETRY SYSTEM|FR1456230A| FR3022998B1|2014-06-30|2014-06-30|SYSTEM AND ASSEMBLY FOR FLOW CYTOMETRY, ANALYSIS DEVICE COMPRISING SUCH A CYTOMETRY ASSEMBLY AND ASSEMBLY COMPRISING SUCH A CYTOMETRY SYSTEM|
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    BR112016030749-6A| BR112016030749B1|2014-06-30|2015-06-23|FLOW CYTOMETRY SYSTEM AND GROUPING AND ANALYSIS DEVICE|
    AU2015282588A| AU2015282588B2|2014-06-30|2015-06-23|Flow cytometry assembly and system, analysing device comprising such a cytometry assembly and assembly comprising such a cytometry system|
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    US15/322,098| US10267722B2|2014-06-30|2015-06-23|Flow cytometry assembly and system, analyzing device comprising such a cytometry assembly and assembly comprising such a cytometry system|
    PCT/FR2015/051677| WO2016001522A1|2014-06-30|2015-06-23|Flow cytometry assembly and system, analysing device comprising such a cytometry assembly and assembly comprising such a cytometry system|
    MX2017000068A| MX2017000068A|2014-06-30|2015-06-23|Flow cytometry assembly and system, analysing device comprising such a cytometry assembly and assembly comprising such a cytometry system.|
    EP15756182.0A| EP3161451A1|2014-06-30|2015-06-23|Flow cytometry assembly and system, analysing device comprising such a cytometry assembly and assembly comprising such a cytometry system|
    ZA2017/00734A| ZA201700734B|2014-06-30|2017-01-30|Flow cytometry assembly and system, analysing device comprising such a cytometry assembly and assembly comprising such a cytometry system|
    JP2020009074A| JP6991257B2|2014-06-30|2020-01-23|A flow cytometry system and an apparatus, an in vitro diagnostic analyzer equipped with the flow cytometry apparatus, and an apparatus including the flow cytometry system.|
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