Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/02—Devices for withdrawing samples
  • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
  • G01N2001/1006—Dispersed solids
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N2035/00346—Heating or cooling arrangements
  • G01N2035/00356—Holding samples at elevated temperature (incubation)
  • G01N2035/00366—Several different temperatures used
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0439—Rotary sample carriers, i.e. carousels
  • G01N2035/0441—Rotary sample carriers, i.e. carousels for samples
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0439—Rotary sample carriers, i.e. carousels
  • G01N2035/0443—Rotary sample carriers, i.e. carousels for reagents
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0439—Rotary sample carriers, i.e. carousels
  • G01N2035/0444—Rotary sample carriers, i.e. carousels for cuvettes or reaction vessels
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0439—Rotary sample carriers, i.e. carousels
  • G01N2035/0446—Combinations of the above
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/04—Preparation or injection of sample to be analysed
  • G01N30/06—Preparation
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
  • G01N30/02—Column chromatography
  • G01N30/04—Preparation or injection of sample to be analysed
  • G01N30/24—Automatic injection systems
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
  • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
  • G01N35/1016—Control of the volume dispensed or introduced

Definitions

• the present invention relates to an automatic device for assaying different substances in biological or chemical samples, using known assay methods, for example of the type
• Apparatuses of this type are known in which samples to be analyzed, reagents and reaction cuvettes are carried by different trays rotatably mounted around vertical axes and generally arranged in a triangle, the trays of samples and reagents being on the outside of the reaction cuvettes and more or less tangent or adjacent thereto. Swivel arms are arranged between the sample and reagent trays and the reaction cuvette tray for taking determined quantities of samples and reagents and for depositing them in reaction cuvettes carried by the corresponding tray.
• the step-by-step rotation of this plate makes it possible to scroll the reaction cuvettes and successively in the stations for loading samples and reagents then in stations for heating and temperature regulation, rinsing, depositing of substrate, reading of results and optionally washing of the reaction cuvettes, the apparatus being controlled by computer to carry out previously programmed analysis cycles, corresponding to single-reactive or bi-reactive assays.
• the invention relates to an apparatus of this type, which has a relatively small footprint, which is movable or transportable, which is adaptable to any type of dosage and which can nevertheless operate at high speed to perform a relatively large number of different dosages on a relatively small number of samples or a relatively small number of different assays on a relatively large number of samples.
• an automatic device for dosing substances in biological or chemical samples comprising means for supporting reagents, means for supporting samples to be analyzed, means for supporting reaction cuvettes, means for taking samples to be analyzed and for reagents and for injecting these samples into the reaction cuvettes, means for rinsing the reaction cuvettes, and means for optically reading the results, characterized in that the support means d 'samples and the support means of the reaction cuvettes are coaxial rotary plates and in that the sampling and injection means are carried by a radial arm extending between the common axis of the plates and their periphery and are movable in translation along this arm, the latter being rotatable around the axis of the plates.
• the mounting of the sample support plates and reaction cuvettes around the same axis of rotation makes it possible to significantly reduce the overall size of the dosing device.
• the arrangement of the sampling and injection means on a radial arm which extends between the common axis of the turntables and their periphery allows samples and reagents to be taken quickly and easily to deposit them in the reaction cuvettes, without increasing the size of the device.
• the plates and the radial arm of the withdrawal and injection means can be carried by the same central tube which defines the axis of rotation of the plates and the upper end of which supports the radial arm. cited above.
• the displacement of the radial arm in rotation around the axis of the plates makes it possible in particular to accelerate the taking of samples and reagents and their deposit in the reaction cuvettes.
• this radial arm it is advantageous for this radial arm to carry two withdrawal and injection units, each mounted on a carriage guided in translation on one side of the radial arm, and means for moving the two carriages independently of one of the other on the radial arm.
• each sampling and injection unit comprises controlled means for moving a needle holder in vertical translation on the corresponding carriage.
• the reaction cuvettes are formed by bars, each of which is formed with a determined number of aligned reaction wells in a longitudinal direction of the bar, and the support plate for these bars includes means for radial and angular positioning and immobilization of said bars relative to the common axis of the plates.
• the bars are carried by supports in the form of a circular sector, which comprise fixing means, for example of the snap type, on the turntable or on the hub of this turntable. This facilitates the initial positioning of the bars as well as their replacement.
• the support plate of the bars comprises means of heating and individual thermal regulation of the bars, comprising for example electrical resistances placed on the walls of the wells of the bars and controlled means of electrical supply. of these resistances.
• the individual heating and thermal regulation of the bars makes it possible to adapt their temperature cycles to the dosages to be carried out, which may differ from one bar to another.
• the support plate for samples to be analyzed comprises, at its radially external periphery, means for receiving tubes or the like intended to receive the samples to be analyzed, these tubes being distributed over the plate along 'at least one arc of a circle.
• the reagent support means are fixed and arranged in an arc around the plates of support for samples to be analyzed and reaction cuvettes.
• these support means are equipped with refrigeration means, making it possible to maintain the temperature of the reactants at an appropriate value below ambient temperature.
• the rotational movements of the plates and of the radial arm are controlled by data processing means, of the microcomputer type, which are programmed to optimize the taking and injecting of samples and reagents according to the number and nature of the assays to be carried out and for passing the reaction cuvettes through the reading means at the end of the assay reaction, without loss of time.
• data processing means of the microcomputer type, which are programmed to optimize the taking and injecting of samples and reagents according to the number and nature of the assays to be carried out and for passing the reaction cuvettes through the reading means at the end of the assay reaction, without loss of time.
• the reaction cuvettes are brought to the means for reading results, not in the order in which they are on their support plate, but in the order of completion of the assay reactions carried out in these cuvettes. This increases the operating rate of the device according to one invention.
• the means for reading the results of the assays are of the optical type and include different systems, for example one for measuring the light absorption of the contents of the reaction cuvettes at determined wavelengths, another for measuring chemiluminescence of the contents of these cuvettes, and another for the measurement of light emission, following a light excitation, of the contents of the cuvettes (fluorescence).
• the device according to the invention can also be used in combination with other measuring devices, for example of the flow cytometry type or of the HPLC (High Performance Liquid Chro atography) type, the device according to the invention used to prepare mixtures of cells which are then analyzed by the associated devices.
• other measuring devices for example of the flow cytometry type or of the HPLC (High Performance Liquid Chro atography) type, the device according to the invention used to prepare mixtures of cells which are then analyzed by the associated devices.
• the reaction bars are characterized in that certain wells of each bar are sealed in a sealed manner with a removable cover and contain determined quantities of specific reagents for the determination of at least one sample in the other wells of the strip.
• the lids sealing the wells containing the reagents it suffices to remove the lids sealing the wells containing the reagents and to place the strips on the corresponding support plate in the apparatus according to the invention.
• the reagents are taken from the corresponding wells of the strip and deposited in the adjacent wells, with the samples to be analyzed.
• FIG. 2 is a schematic view in axial section of this device
• Figure 3 is a schematic perspective view of this device.
• the metering device according to the invention shown in the drawings, comprises a chassis 10 of mechanically welded tubes, which carries a vertical central tube 12 on which two axially spaced plates 14, 16 are mounted and guided in rotation by means of bearings with bearings.
• the upper plate 14 is intended to support sets of reaction cuvettes which are formed by bars 18 each comprising several reaction wells 20 aligned in the longitudinal direction of the bar, the number of wells per bar being eight in this example.
• the bars 18 are positioned radially on the plate 14 relative to the common axis 22 of rotation of the plates 14 and 16 and are held in position by means with spring blades.
• the surface of the plate 14 is divided into a certain number of circular sectors which are independent of each other and which are fixed to the hub of the plate 14, for example by elastic snap-fitting or the like.
• the bars 18 are placed and fixed ably on supports in the form of circular sectors which are positioned and removably fixed on the plate 14.
• tools can be placed on these supports consumables, such as for example tubular sampling and injection cones, which are intended to be used each once for collecting a sample and depositing it in a well of a bar 18 and which are discarded after use.
• These removable supports S can each carry 4, 6 or 8 bars 18 and the consumable tools correspondents, for example, and have been shown schematically in dotted lines in FIG. 1.
• the lower plate 16 is intended for the support of samples to be analyzed, contained in liquid form in tubes 24 which are received in supports 26 arranged at the external periphery of the plate 16 and distributed in an arc of a circle, the tube supports 26 being 10 in number in the example of Figure 1.
• the plates 14 and 16 are rotated step by step about the axis 22 independently of one another by means of belts toothed by electric motors.
• a surface 28 for reagent support is fixedly mounted on the chassis 10 and extends in an arc of a circle over approximately 180 ° around the axis 22, radially outside the plate 16 and substantially at the level thereof.
• This surface 28 is intended to carry a certain number of sets 30 of reagents, each corresponding to a different assay to be carried out on the samples to be analyzed.
• the surface 28 may also include a zone 32 for receiving samples to be analyzed and a zone 34 for supporting the bottles 36 which may contain, inter alia, substrates, antibodies, sera, etc.
• the part of the surface 28 which supports the sets of reagents 30 is equipped with refrigeration means, making it possible to maintain these reagents at a determined temperature of 4 ° C. for example.
• the surface 38 also supports a system 44 for optical reading of the assay results by measuring the light absorption of certain wavelengths by the contents of the wells 20 of the reaction bars, this reading system 44 being followed by another system. 46 for reading the results by measuring the chemiluminescence of the liquids contained in the wells of the reaction strips 20.
• Another system for reading results by measuring fluorescence can be provided in the apparatus according to the invention, in addition to systems 44 and 46 or in place of one of them, this other system comprising means for light excitation of the contents of the reaction cuvettes and of the means for measuring the light emission resulting from this excitation.
• a radial arm 48 is rotatably mounted on the upper end of the central tube 12 and extends horizontally between the axis of rotation 22 and the periphery of the device.
• This arm 48 carries two withdrawal and injection units 50 which are movable independently of one another in translation along the arm 48.
• Each unit 50 comprises a carriage 52 guided in translation on a horizontal rail 54 of the arm 48 and driven by an electric motor.
• Each carriage 52 comprises a vertical upright 56 carrying a rail 58 for guiding a needle holder 60 movable in translation on the rail 58 by an electric motor.
• the arm 48 is secured to a vertical plate 62 which supports a linear actuator of the syringe pump type, as well as a syringe and a solenoid valve connected by tubes 64 to needles 60 of the aforementioned units 50 for sampling and injection.
• a pushing liquid is contained in the syringe, the solenoid valve and part of the tubes 64, which makes it possible to withdraw and inject by means of the needles 60 small quantities of liquid, determined with precision.
• a central well 66 allows the needles 60 to be cleaned after each use.
• the radial arm 48 is rotated by an electric motor and a toothed belt.
• the reaction bars 18 which are used in the apparatus according to the invention are made of glass or transparent plastic material, to allow the optical reading of the assay results. These bars can be of a reusable type, after washing and decontamination, or else disposable after a single use.
• reaction wells 20 can undergo a treatment which makes them specific to the substances to be detected, this treatment comprising for example the deposition of an antibody coating on the inner wall of reaction wells 20.
• reaction bars include individual heating and thermal regulation means, comprising electrical resistances, formed of wires or films deposited or glued to the external lateral surface of these wells.
• the means provided on the plate 14 for positioning and immobilizing the bars include controlled means for supplying electrical power to the heating resistors of the wells of the bars, for a heating and individual thermal regulation of each bar.
• each reaction strip can comprise a certain number of wells which will be used to store specific reagents for one or more determined determinations.
• four wells of a strip comprising eight reaction wells can contain determined quantities of specific reagents of a given assay and are sealed with a removable or tear-off seal. For their use, these bars are placed on the plate 14 after removal or tearing of the aforementioned lids.
• the reagents corresponding to the assays to be carried out are placed on the support surface 28 fixed around the plates 14 and 16.
• Reaction bars 18, preferably new, are placed on the plate 14.
• Samples to be analyzed are contained in the tubes 26 placed in the housings 24 of the lower plate 16.
• the start-up of the apparatus controlled by computer, makes it possible to take, by means of the units 50, predetermined quantities of samples in the tubes 26 and of reagents in sets 30 and deposit them in the wells of the reaction bars.
• the sample tubes 26 are identified and identified by bar code labels, readable by a reader mounted adjacent to the periphery of the plate 16.
• the reaction bars 18 are identified by their angular position relative to a radial reference on the plate 14, these positions being numbered from 1 to 30 in the example shown.
• the two sampling units 50 mounted on the arm 48 make it possible to accelerate the deposition of samples and reagents in the wells of the reaction bars 18, in the following manner: when a unit 50 is used to take a sample or a reagent and to deposit it in a reaction well, the other unit 50 is moved towards the axis 22 for cleaning its needle. Then, this other unit 50 is used for removal and deposition, and the first unit 50 is moved towards the axis 22 for cleaning its needle.
• the plate 14 is rotated in one direction, then in the other, to place the wells of a bar 18 in radial alignment with the needle 60 of the unit 50 used for depositing a sample or reagent.
• the rotations of the plates 14 and 16 allow the bars and the samples to be brought into alignment.
• the temperatures of the bars 18 are regulated bar by bar.
• each bar is brought, by rotation of the plate 14, to the reading means 44 or 46 in the order of completion of the reactions in the wells of the bars.
• the apparatus according to the invention can also be used with other means for measuring results, for example with means for cytometric or chromatographic measurement. It then essentially serves as an apparatus for preparing cell mixtures and is associated by means of sampling and deposition either with a system of the HPLC type (High Performance Liquid Chromatography) or with a flow cytometry system. As is known, such a system allows the study and characterization of cells after marking with fluorescent markers and comprises fluidic means for presenting the cells one by one in front of optical detection means associated with light excitation means (for example laser), and with signal and data processing means . Three types of signals are measured:

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• 2000
  • 2000-11-29 FR FR0015701A patent/FR2817350B1/fr not_active Expired - Fee Related
• 2001
  • 2001-11-21 WO PCT/FR2001/003686 patent/WO2002044740A2/fr not_active Application Discontinuation
  • 2001-11-21 AU AU2002222020A patent/AU2002222020A1/en not_active Abandoned
  • 2001-11-21 EP EP01998838A patent/EP1337860A2/de not_active Withdrawn
• 2003
  • 2003-05-29 US US10/447,600 patent/US20040009099A1/en not_active Abandoned

Non-Patent Citations (1)

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