Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L9/00—Supporting devices; Holding devices
  • B01L9/06—Test-tube stands; Test-tube holders
• • 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
  • G01N35/00584—Control arrangements for automatic analysers
  • G01N35/00722—Communications; Identification
  • G01N35/00732—Identification of carriers, materials or components in automatic analysers
• • 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
  • G01N35/026—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 blocks or racks of reaction cells or cuvettes
• • 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)
• • 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
  • G01N2035/00455—Controlling humidity in analyser
• • 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
  • G01N2035/00465—Separating and mixing arrangements
  • G01N2035/00495—Centrifuges
• • 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
  • G01N35/00584—Control arrangements for automatic analysers
  • G01N35/00722—Communications; Identification
  • G01N35/00732—Identification of carriers, materials or components in automatic analysers
  • G01N2035/00742—Type of codes
  • G01N2035/00762—Type of codes magnetic code
• • 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
  • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
  • G01N2035/0412—Block or rack elements with a single row of samples
  • G01N2035/0413—Block or rack elements with a single row of samples moving in one dimension

Definitions

• the present invention relates to mu ⁇ ological or biochemical analysis using icrotitration cuvettes, and in particular an installation performing automatically the various operations of implementation of said " cuvettes " during analysis.
• microtiter plates bowls form is widespread in laboratories "medical analysis, including the implementation of type reactions
• ELISA Enzyme Linked Immuno-Sorbe ⁇ t Assay
• the microtiter plates are made of rigid and transparent polystyrene, they have an average size of 13 cm x 9 cm and have 96 cuvettes at the rate of eight rows of twelve cuvettes. These cuvettes are flat-bottomed, U-shaped or V-shaped.
• the use of such micriteration plates is advantageous for the gain in quantities used compared with traditional analysis tubes; indeed, each cuvette has a volume of the order of 150 to 200 microliters compared to the volume of the tube which is 5 to 7 ml.
• the microtitration plates therefore allowed the miniaturization of the analysis techniques; however, they are poorly suited to small series of analyzes, and even more so to unit analyzes which are commonly practiced in small laboratories.
• Bars have already been proposed comprising a limited number of bowls, from 6 to 8 bowls arranged in line. These bars are used by hand; they are difficult to use and require the implementation of a rigid bar support for their manipulation during operations, such as ce ⁇ trifugation and incubation.
• the goal set by the applicant is to propose an installation capable of carrying out in a fully automated manner all the operations of using the microtitration cuvettes during an analysis, without manual intervention for a transfer between the operations, said installation being adapted to the needs of all laboratories, including laboratories with small series of analyzes and unit analyzes.
• microtitration cuvettes which is characterized in that the microtitration cuvettes are grouped together in the form of individual modules of small dimensions, having a base. rigid and stable and, on at least one side, an information recording medium; in addition, this installation includes: a. a linear transfer chain, controlled by a stepping motor, ensuring the intermittent movement of the modules; b. treatment stations with lateral loading and unloading, each one capable of producing on one or more modules a preparation operation, said stations being placed in the immediate vicinity of the linear transfer chain; vs.
• lateral transfer stations each being associated with a processing station and capable of transversely moving a module, from the stationary chain to the associated processing station or vice versa; d. reading means, capable of reading the information recorded on each module and of activating the lateral transfer station or stations and the processing stations accordingly; e. recording means, associated with each processing station, capable of recording on the recording medium of each module entering said processing station the information relating to the processing in question.
• each module comprises four microtitration cuvettes, which are translucent in a plastic material such as polycarb ⁇ nate, and a rigid base itself in a plastic material, said base enclosing the four cuvettes.
• each module is in one piece, the microtitration cuvettes and the base being obtained by molding or thermoforming in a single operation.
• each module has a positioning asymmetry, for example a projection or a groove.
• the installation must include a loading station at the entrance and a reaction reading station at the exit.
• the loading station is provided with sampling means capable of withdrawing a predetermined quantity of the licuide to be analyzed, from its sample tube containing said liqu i, and of depositing said quantity in one or more microtiter cuvettes of a module in place in the loading station.
• Other treatment stations may have the same sampling means as the loading station, these will be reagent addition stations in which it will be a question of taking a certain quantity of a reagent contained in a tube and depositing it in one or more microtitration cuvettes a module in place in the corresponding treatment station.
• the incubation station includes a conditioned enclosure and a mat intermittently moving a given module, placed on the mat, from the entrance of the enclosure where the module is introduced to the exit of the enclosure from where it is evacuated, and this for a predetermined time.
• the mat has a bell shape, with an ascending part and a descending part lying between a detour element, and it is equipped with wedging means capable of holding each module in place during its movement on said mat during the time d 'incubation.
• the centrifuge station is powered and has a side outlet; it includes a mobile carousel rotating around a vertical axis.
• the detection reading station includes reading equipment of the photometer or shape recognition system type.
• the information recording medium affixed to one face of each module, consists for example of a magnetic strip glued on said face.
• the installation comprises computer means connected to the reading means and to the recording means, and which are programmed to actuate the lateral transfer stations as a function of the information read from the recording media of a module.
• FIG. 1 is a perspective view of a module with four microtitration cuvettes
• FIG. 2 is a partial sectional view of the module of FIG. 1 along the plane A-A '
• FIG. 3 is a schematic representation in the form of a diagram of the installation
• Figure 4 is a schematic sectional view of the incubation station.
• the individual microtitration module 1 comprises four cuvettes 2 made of transparent polycarbonate, embedded in a base 3, made of rigid plastic material, for example colored.
• the four bowls 2 are obtained by thermoforming and form a unit 4 in one piece, the edges 5 of which are clipped onto the base 3 using a cover 6.
• the base 3 has vertical uprights 7 at the periphery ensuring the stability of the module 1. In its inner part, it also includes vertical uprights 8 delimiting recesses in which the microtitration bowls 2 are placed.
• the upper part 8_a_ of said vertical uprights 8 has a profile complementary to that of the conical bowl 2 corresponding ( Figure 2), and ensures the maintenance of the bowl 1 in particular during ce ⁇ trifugation.
• Module 1 has the general shape of a rectangular parallelepiped, 50 mm long, 17 mm wide and 20 mm high.
• the other large side face is provided with a positioning notch 11.
• Each bowl 2 has a useful volume of the order of 150 to 200 microliters.
• FIG. 3 shows in a very diagrammatic form the automatic installation carrying out the immunological or biochemical analysis from the modules described above.
• the transfer chain 12 ensures the linear movement of each module 1 throughout the installation. It consists of a flexible plastic strip stretched between two rollers 13,14, one of which is driven by a set of pulleys and belts by a stepping motor 15.
• the outer face of the strip 16 includes transverse extra thicknesses 17 regularly spaced and delimiting the placement zones of the modules 1.
• the motor 15 drives the strip 16 by a step corresponding to the distance between two transverse thicknesses 17 every thirty seconds for example, which gives the installation a throughput of 480 tests per hour.
• the installation entry station is the loading station 18, with which is associated a sample tube support 19 for the liquid to be analyzed.
• the loading station 18 comprises locations 20 determined for a certain number of microtitration modules 1 and a sampling device 21 comprising a suction nozzle for a predetermined quantity of the liquid contained in the tube 19, mounted in rotation around a vertical axis 22.
• lateral transfer stations 23 The function of these stations is either to move a module 1 located on the strip 16 to a processing station or to move a module 1 placed at the outlet of a processing station to the strip 16.
• Each station 23 for lateral transfer is constituted of a jack whose rod 24 is terminated by a flat surface capable of bearing on a small lateral face 25 of the module 1. It is understood that the stroke of the jack is a function of the distance which must be traveled by the module 1 between the treatment station and strip 16 or vice versa.
• the identification station 26 includes means for reading the magnetic strip 10 placed on the side face 9 of the module 1, namely a magnetic reading head. These means are connected to an electronic circuit 27, itself connected to the various lateral transfer stations 23 and programmed to actuate one or the other station in synchronization with the advancement of the strip 16 according to the information read by the read head on the magnetic strip 10.
• FIG. 4 shows the incubation module 28.
• This module 28 comprises an enclosure 29 of substantially triangular section equipped with conditioning means, not shown, capable of maintaining the interior of the enclosure 29 under temperature conditions and predetermined humidity.
• a belt 30 forms a closed loop between three detour rollers 31, 32, 33, one of these rollers being controlled in rotation by a stepping motor. Between the first 31 and the second 32 detour rollers, the belt 30 has an ascending path; between the second 32 and the third 33, it has a descending route.
• the modules 1 are held in place by teeth 34 on which they bear while the belt 30 is moving inside the enclosure 29.
• the stepping motor makes it possible to ensure the intermittent movement of the belt 30 so as to set the incubation time.
• the passage through the enclosure, corresponding to the incubation time can be of the order of 10 minutes, for a capacity of approximately 20 modules. If longer times are required, the installation may include several incubation stations like the one just described.
• the reagent addition station 45 is of the same type as the loading station 18. It is associated with a tube support 46 containing the complementary reagent to be added to one and / or the other cuvette 2 of a module 1.
• the centrifugation station 35 comprises an enclosure 36 with an inlet 37 and an outlet 38, and a carousel 39 movable in rotation about a vertical axis 40.
• the carousel 39 has four arms 41, arranged symmetrically at 90 °, terminated by module supports 42 in the form of a basket, open at both ends to allow the module to be inserted and removed.
• the centrifuge can therefore ê -e performed for one, two or four modules in preparation s: ⁇ .tanêment.
• the duration of loading, centrifuging and discharging i for four modules is of the order of 2 minutes.
• the speed of rotation of the axis 40 is defined for obtain the acceleration required for centrifugation.
• the reaction reading station 43 has predetermined locations for the modules 1, by means of which the bottoms 44 of the cuvettes 2 are located opposite the reading cells of a photometer and / or of a shape recognition system.
• Each of the processing stations comprises magnetic recording means, placed at a given location of the station facing the large lateral face 9 of the module 1 supporting the magnetic strip 10. These means write magnetically on the strip 10 the information corresponding to the processing. that was performed in the post in question.
• the operation of the installation is as follows.
• the operator places a module 1 in the loading station 18 at the reserved location, intended for a specific type of analysis.
• the visual identification of the module can be obtained by writing on the free space 45 of the cover 6, which supplements the indications previously carried on the magnetic strip 10 and which correspond to the type of analysis.
• the notch 11 fits into a lug, ensuring positioning accuracy.
• the suction nozzle at the end of the pivoting arm 21 takes from the tube 19 hundred and fifty microliters of the plasma; the arm 21 pivots about its axis 22 and the nozzle injects the plasma into a first bowl 2 of the module 1; the first operation is repeated for a second bowl 2 '.
• Another nozzle takes a reference liquid from another tube and injects it into the third and fourth cuvettes 2 "and 2" 'of module 1.
• the module 1, once loaded, is sent to the identification station 26; the read head decrypts the information carried on the magnetic tape 10 and transfers it to the electronic circuit 27.
• the information in question is integrated into the analysis program so that the electronic circuit 27 will then actuate delayed according to the adequate and coordinated sequencing the operation of the stepping motor 15 and therefore the intermittent movement of the strip 16, the operation of the lateral transfer stations 23 and of the various treatment stations.
• the module 1 is pushed by the rod 24 of a jack on the strip 16 in an area delimited by two transverse thickeners 17.
• the strip 16 advances in the direction of the arrow F as far as the entrance to the incubation station 28 .
• the module 1 is pushed into the enclosure 29 and placed in the teeth 34.
• the belt 30 moves intermittently ensuring the transfer of the module 1 in its upward path then downward in the thermostatically controlled atmosphere of the enclosure 29 for a given time corresponding to the duration programmed for incubation. Then the module 1 is pushed back onto the strip 16.
• the module 1 is transported, by the displacement of the strip 16, as far as the station 45 for adding reagent, where it is introduced. There, reagent contained in the tube 46 is withdrawn and injected into the first and third cuvettes 2 and 2 "of the module 1. Then the module 1 is pushed back onto the strip 16.
• the module is transported in front of the entrance 37 of the centrifugation station 35. It is pushed by the rod 24 of a jack in the nacelle 42 which is opposite the entry 37 of the enclosure 36.
• the carousel 39 is rotated at speed and for the programmed time. Then the carousel stops so that the module 1 is facing the outlet 38 of 1) enclosure 36, and the module 1 is pushed back onto the strip 16.
• the module 1 is transported to the entrance of the reading station 43 reactions. It is pushed into the reserved location, the bottom 44 of the cuvettes 2 being located opposite the photometer reading cell. Once the reading of the reactions is finished, the module is pushed back onto the strip 16 from where it is evacuated either manually or automatically.
• the indications concerning the operation carried out in said station have been entered in each station; thus the module 1 includes, at the end of the installation, on its magnetic strip 10 the detail of all the operations, which allows possible subsequent verifications.
• module 1 may be in one piece, obtained in one piece by thermoforming for example; it may also include a different number of bowls 2.

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Biochemistry (AREA)
• Physics & Mathematics (AREA)
• Life Sciences & Earth Sciences (AREA)
• Analytical Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Clinical Laboratory Science (AREA)
• Automatic Analysis And Handling Materials Therefor (AREA)

Applications Claiming Priority (2)

Publications (1)

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ID=9388171

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• 1989
  • 1989-11-24 FR FR8916068A patent/FR2655151B1/fr not_active Expired - Lifetime
• 1990
  • 1990-11-21 EP EP19900917656 patent/EP0455788A1/de not_active Ceased
  • 1990-11-21 WO PCT/FR1990/000834 patent/WO1991008491A1/fr not_active Application Discontinuation

Non-Patent Citations (1)

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