Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
  • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
  • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N1/00—Sampling; Preparing specimens for investigation
  • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
  • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L1/00—Enclosures; Chambers
  • B01L1/50—Enclosures; Chambers for storing hazardous materials in the laboratory, e.g. cupboards, waste containers
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L1/00—Enclosures; Chambers
  • B01L1/52—Transportable laboratories; Field kits
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
  • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
  • B01L3/50855—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using modular assemblies of strips or of individual wells
• • 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
  • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
  • B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/483—Physical analysis of biological material
  • G01N33/4833—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/483—Physical analysis of biological material
  • G01N33/487—Physical analysis of biological material of liquid biological material
• • 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
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
  • B01L2200/02—Adapting objects or devices to another
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
  • B01L2200/14—Process control and prevention of errors
  • B01L2200/141—Preventing contamination, tampering
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/04—Closures and closing means
  • B01L2300/041—Connecting closures to device or container
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/06—Auxiliary integrated devices, integrated components
• • 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
  • G01N2035/00178—Special arrangements of analysers
  • G01N2035/00306—Housings, cabinets, control panels (details)
• • 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
  • G01N2035/0403—Sample carriers with closing or sealing means
  • G01N2035/0405—Sample carriers with closing or sealing means manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• • 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
  • G01N2035/0458—Multiple concentric rows of wells
• • 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
  • G01N2035/0496—Other details
  • G01N2035/0498—Drawers used as storage or dispensing means for vessels or cuvettes

Definitions

• the present invention relates to a sampling box and to a modular automaton formed by this sampling box when it is connected at a piloting station.
• the preliminary step known as sampling, which consists in positioning a given sample (or a fraction of a sample) in its location for analysis, remains a manual step which does not present all the guarantees necessary for avoid any risk of sample inversion or contamination. The consequences can be critical in an analysis.
• FIG. 1 shows the various steps of the conventional process for detecting nucleic acids by molecular biology, for example of the coronavirus SARS-CoV-2 (COVID-19).
• the sampling step (A) is manual while all the other steps of the analysis process namely, cell lysis (B), nucleic acid extraction (C) and detection by polymerization reaction real-time chain (RT-PCR) (D) are automated.
• the sampling step is all the more critical since it is the entry point for any sample in the analysis chain.
• there is today a real need for an integrated device making it possible to ensure the traceability and sampling of biological samples without risk of contamination or risk of inversion.
• the sampling of biological samples consists in inserting all or part of a biological sample, solid or liquid, in a location provided for its analysis, for example in an individual tube or in a well of a 96-posi plate. tions.
• This sample can be the head of a swab containing the biological element to be analyzed, a solid element such as for example a fragment of tissue containing genetic material or directly a biological fluid.
• cell lysis which consists of adding reagents that will break cell membranes to release nucleic acids (DNA and RNA).
• sampling is the most critical step in the entire analysis process, it must therefore be optimized in order to avoid any risk of contamination of the samples and of the operator or of positioning error to guarantee the quality of the analysis results.
• PSM microbiological safety post
• one of the aims of the present invention is to provide a sampling box which obviates the various drawbacks mentioned above.
• Another object of the invention is to connect this sampling box to a control station composed of a computer part and an electronic part to form a modular controller.
• a sampling box for biological samples, solid or liquid which is, according to the present invention, characterized in that it comprises a device supporting an assembly consisting of a 96-well plate (also called a deep-well plate or deepwell), a plug adapter having as many orifices as there are wells and placed on this deep-well plate, and plugs, each plug cooperating with a single well.
• a 96-well plate also called a deep-well plate or deepwell
• plug adapter having as many orifices as there are wells and placed on this deep-well plate, and plugs, each plug cooperating with a single well.
• sampling box is understood to mean a device making it possible to carry out step A of the conventional process of detecting nucleic acids by molecular biology as summarized in FIG. 1, that is to say a device allowing the efficient sampling of biological samples in different wells in order to be able to proceed to the following steps (B, C, D and results in FIG. 1).
• doctor is meant a human being operating the sampling, for example a laboratory technician.
• sample is understood to mean the action performed by an operator of inserting a biological sample or a sample into one of the wells of the 96-well plate.
• biological sample or “sample” is meant a solid or liquid element containing biological material. These biological samples can come from any type of environment, for example a crime scene, or a sample taken from a patient as part of a COVID-19 screening.
• 96-well plate is meant the plates also called deep-well or deepwell plates, comprising wells aligned in 8 rows x 12 columns.
• the device according to the invention can be used with any 96 wells in ANSI / SLAS (American National Standards Institute - Society for Laboratory Automation and Screening) format.
• plug adapter is understood to mean a plate making it possible to cover all the wells of a 96-well plate in order to avoid any inter-well contamination, during the insertion into each of these wells, of the samples to be analyzed whether these are solid or liquid.
• the plug adapter according to the invention has 96 holes and is designed to sit on top of a 96-well plate superimposing on the 96 holes of the sample-receiving well plate.
• This plug adapter is superimposed on said 96-well plate, and receives the plugs on its upper part, allowing the holes of said plate to be closed, in order to isolate each well of the 96-well plate from the external environment. This avoids any external contamination.
• Such an adapter thus allows the use of 96-well plates having wells of different shapes (square, rectangular, circular).
• plug is understood to mean an element making it possible to close each well independently.
• the assembly according to the invention comprises as many plugs as there are wells.
• the sampling box comprises a drawer supporting the well plate and the plug adapter.
• Drawer is meant a sliding element in the sampling box between a position internal to said sampling box and a position external to said sampling box.
• the sampling box comprises means for sliding the drawer in said sampling box which are coordinated with means for removing and replacing a plug one well at a time.
• said means is an electric actuator.
• electric actuator is understood according to the invention a device for converting the rotary movement of a motor into linear movement in order to move and position a load, namely the drawer in the case of the invention.
• Such electric actuators may for example be a guided electric actuator with ball screw drive, for example of the SMC brand of the LEFS series.
• coordinated with means for removing and replacing a plug from one well at a time is understood according to the invention that when the device supporting the whole, preferably the drawer, slides towards the operator, a single well was opened by the sampling box.
• the drawer slides between an internal position in said sampling box in which a plug is removed or replaced, and a second position external to said sampling box in which a sample to be analyzed is introduced into the well from which the plug has been removed.
• Providing only one open well allows the operator to avoid any positioning errors when inserting the sample into the plate.
• the sampling box comprises a harpoon for removing and replacing each plug.
• the drawer is composed of two parts: a base for receiving the well plate and a removable element allowing this plate to be held on this base during sampling.
• the drawer is designed to enclose and isolate the well plate to prevent external contamination.
• the design of the drawer, consisting of a base and the removable element, also makes it easier to clean and decontaminate the whole.
• the invention relates to a method for sampling biological samples, solid or liquid, using a modular automatic device according to the invention comprising the steps of: a. Scan of a solid or liquid biological sample; b. Moving the means for removing and replacing a plug from a well over a well of the plate; vs. Removing the plug from said well from step b. by said means for removing and replacing a plug from a well; d. Movement by the sampling box of the device (2) supporting the assembly (3), in front of an operator; e. Deposit by an operator of a biological sample in said open well; f. Displacement by said sampling box of the device (2) supporting the assembly (3) towards the interior of said sampling box; g.
• scan of a sample is meant the reading by the computer means of said control station of the identifier of a biological sample which was assigned to it when it was taken during a crime scene , or a sample taken from a patient as part of a COVID-19 screening,
• steps a. to g. are repeated in order to successively sample biological samples from different wells, step c. removing a different plug each time.
• FIG. f represents the different stages of the classical detection process by molecular biology
• f5 [0039]
• FIG. 2 is a front view of a sampling box according to the present invention.
• FIG. 3 is a side view of the sampling box according to Figure 2 with the drawer in the external position;
• FIG. 4 is a schematic perspective view of the sampling drawer according to 0 an exemplary embodiment of the invention.
• FIG. 5 is a perspective view of assembling a deep well plate with plug adapter and plugs
• FIG. 6 is an internal schematic view, viewed from above, of the swimming sample housing with the drawer extended;
• FIG. 7 is an internal schematic view, viewed from above, of the swimming sample housing with the drawer in the closed position.
• a sampling box f comprises, according to the present invention, a device 2 supporting an assembly 3 consisting of a well plate 4, a plug adapter 5 and plugs 6, each plug 30 cooperating with a single orifice of the adapter 5 placed on the well plate 4.
• the plug adapter 5 makes it possible to cover all the wells of a 96-well plate 4 in order to avoid any inter-well contamination, during the insertion into each of these wells, of the samples to be analyzed, as those - these are solid or liquid.
• the plug adapter 5 has 96 holes and is designed to sit above a well plate 4 regardless of the manufacturer: the 96 holes of this one being perfectly posed to the 96 holes of the well plate 4 receiving the samples.
• the addition of plugs 6 then makes it possible to isolate each well from the well plate 4. With such a device 2, it is possible to carry out manual sampling of the well plate 4. It is then necessary to remove a stopper 6 using sterile forceps in order to be able to insert the element to be analyzed into the well thus opened. The stopper 6 is then replaced manually using the pliers in its original location. The risk of contamination is controlled by opening only one well at a time thanks to the presence of independent plugs 6.
• the device 2 is a drawer which can slide inside and outside the sampling box 1.
• the drawer 2 being designed to accommodate a 96-well plate to the ANSI / SLAS standard such as, for example, a deepwell or PCR plate.
• the drawer 2 as well as the plug adapter 5 are made of an easily decontaminable material such as aluminum or stainless steel.
• the sampling box 1 is composed of the following elements:
• a sliding drawer 2 composed of a base 7 for receiving any type of 96-well plate 4 (Deepwell or PCR plate for example) and a removable element 8 allowing it to be held on the base 7.
• the assembly 3 is placed in this drawer 2 when the element 8 is withdrawn.
• the assembly 3 is inserted into the drawer 2 thanks to specific guide rails 9 of the plug adapter 5 and of the 96-well plate 4 in order to guarantee the correct positioning of the assembly 3.
• the removable element 8 is repositioned on the drawer 2 after insertion of the assembly 3 in order to block the assembly 3 in the drawer 2.
• the removable element 8 comprises guide rods 10 making it possible to ensure its correct positioning on the drawer 2. L
• the use of guide rails 9 makes it possible to slide the assembly 3 in the drawer without exerting any particular pressure.
• An orifice 11 on its front facade (that is to say that facing the operator) which is adjusted to the shape of the drawer 2 preventing the operator from any risk of injury when closing the drawer 2.
• the cap in- raised remains attached to the harpoon during the phases of opening the drawer, sampling, swimming a sample, and closing the drawer.
• a vertical camera 13 making it possible to take a photograph of each well of the plate 4. This functionality makes it possible to ensure that a plug 6 is indeed present before opening, that the well of interest is indeed empty before sampling then filled with a biological sample and that the stopper 6 has been repositioned on the well after insertion of this sample.
• An internal bar code reader 14 for identifying the well plate 4 when a bar code is attached to it.
• the drawer 2 can move only along the Y axis (front / rear) 15 which allows to center the assembly 3 under the harpoon 12 to remove and reposition, specifically ment, a plug 6 of a column plug adapter 5.
• the harpoon 12 can move on an X axis (left / right) 16 and a Z axis (up / down) 17 and can only remove or replace a single plug 6 at a time.
• the movement of the harpoon 12 along the X axis makes it possible to specifically remove a plug 6 from a line of the adapter 5. It moves in a known manner on the axes 16 and 17 arranged above the drawer 2, in the sample box 1.
• the drawer 2 of the sampling box 1 is in the closed (internal) position when the harpoon 12 has to remove a plug 6 from the plug adapter. To do this, the movements of the harpoon along the X axis and of the slide along the Y axis make it possible to remove a specific plug. The action of the harpoon along the Z axis makes it possible to remove the plug 6 from the plug adapter 5.
• the drawer 2 then opens to reveal only one open location, all the other wells being closed thus avoiding any inter-well contami nation. After inserting the sample into the well in question, the drawer is closed and the stopper replaced.
• the drawer 2 is movable between a first position in which it is returned in the sampling box 1, placed under the harpoon 12 and out of reach of the operator, and a second position in which it has slid towards the operator so that the latter can introduce a sample into the only open well of the well plate 4, without risk of contamination and without risk of positioning error.
• the sampling box 1 is small in order to contain only a minimum of mechanical elements linked to the movements of the drawer and of the harpoon.
• the sampling unit can thus be connected to a control station made up of a computer part and an electronic part: the computer part makes it possible to control the actions of the sampling unit 1 following a defined processing sequence. .
• said computer part can be configured so that when a sample from, for example, a crime scene, or a sample taken from a patient as part of a COVID-19 screening, is to sample, the operator scans the identifier of said sample, which will initiate a processing sequence (predefined by the operator) and the movement of the harpoon will open a well where the sample can be deposited by the operator after movement of the device supporting the assembly in front of the operator.
• the computer part makes it possible to integrate the cards and electronic components necessary for the operation of the sampling box 1.
• a pedal can be connected to it which will actuate the harpoon 12 for the removal and replacement of the caps 6 in order to to work in "hands-free” mode. The operator can thus reserve the use of both hands for handling the samples without having to touch the automatic device, thus avoiding any risk of contamination of the device during its use.
• the sampling box therefore constitutes, with the piloting station, a seemingly modular one.
• the sampling box (1) can be integrated into the control station.
• the modular automaton can then include a control station which integrates a sampling box (1).
• the modular controller can be formed by the sampling box (1) and which is connected to the control station, thus forming two distinct units.
• said sampling box and the piloting station are connected and form the modular automaton, but said sampling box and said piloting station are distinct from one another, said piloting station is n ' not integrating said sampling box.
• the sampling box is as compact as possible to be positioned in a type 2 microbiological safety station (PSM) or any other type of safety station allowing to protect the operator with regard to the nature of the sample.
• PSM microbiological safety station
• This compact appearance of the sampling box according to the present invention also makes it possible to position it in a mobile laboratory or on any laboratory bench.
• each side of said sampling box has a dimension of less than 40 cm.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Physics & Mathematics (AREA)
• Biomedical Technology (AREA)
• Analytical Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Clinical Laboratory Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Biochemistry (AREA)
• Hematology (AREA)
• Molecular Biology (AREA)
• Biophysics (AREA)
• Medicinal Chemistry (AREA)
• Food Science & Technology (AREA)
• Urology & Nephrology (AREA)
• Optics & Photonics (AREA)
• Dispersion Chemistry (AREA)
• Automatic Analysis And Handling Materials Therefor (AREA)
• Sampling And Sample Adjustment (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)

Applications Claiming Priority (2)

Publications (1)

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• 2020
  • 2020-05-20 FR FR2005169A patent/FR3110696B1/fr active Active
• 2021
  • 2021-05-20 US US17/999,095 patent/US20230175934A1/en active Pending
  • 2021-05-20 WO PCT/FR2021/050910 patent/WO2021234308A1/fr unknown
  • 2021-05-20 EP EP21733490.3A patent/EP4153355A1/de active Pending

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