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EP4096826A1 - Device for analysing solid biological elements and device for implementing same - Google Patents

Device for analysing solid biological elements and device for implementing same

Info

Publication number
EP4096826A1
EP4096826A1 EP21702660.8A EP21702660A EP4096826A1 EP 4096826 A1 EP4096826 A1 EP 4096826A1 EP 21702660 A EP21702660 A EP 21702660A EP 4096826 A1 EP4096826 A1 EP 4096826A1
Authority
EP
European Patent Office
Prior art keywords
tube
plate
deep well
tubes
well plate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21702660.8A
Other languages
German (de)
French (fr)
Inventor
Amaury PUSSIAU
Sylvain HUBAC
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ministere de lInterieur
Original Assignee
Ministere de lInterieur
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ministere de lInterieur filed Critical Ministere de lInterieur
Publication of EP4096826A1 publication Critical patent/EP4096826A1/en
Pending legal-status Critical Current

Links

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
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • 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
    • B01L3/54—Labware with identification means
    • 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
    • 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
    • B01L9/56—Means for indicating position of a recipient or sample in an array
    • 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
    • B01L2200/021—Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
    • 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
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • 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
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • 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
    • B01L2300/042—Caps; Plugs
    • 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
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/048—Function or devices integrated in the closure enabling gas exchange, e.g. vents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0605—Valves, specific forms thereof check valves
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S215/00—Bottles and jars
    • Y10S215/902—Vent

Definitions

  • the present invention relates to a device for analyzing solid biological elements and to a device for its implementation.
  • the "Forensic Spin Filter basket” device marketed by the company MidSci is composed of a filtration unit with a perforated bottom making it possible to collect a biological sample and of a 2 mL collection tube with an integral cap.
  • the cap may be integral with the filtration unit instead of being attached to the collecting tube, or the filtration unit as well as the collecting tube may both have a integral cap.
  • the first step of the analysis process consists of inserting the solid biological element also called a sample or sample (e.g. piece of tissue, cigarette filter paper, hair, etc.) into the filtration unit, which is then inserted into the collecting tube.
  • a buffer or solvent suitable for lysis of the cells is added thereto in order to cover the sample.
  • the sample is thus immersed in the buffer at the filtration unit.
  • the device is closed using the cap attached to the collection tube or the filtration unit and then incubated for a given time.
  • the whole is then centrifuged in a microcentrifuge to separate the buffer from the biological sample, the buffer passing through the micro-pores at the bottom of the filtration unit to end up in the collection tube.
  • the filtration unit can be directly removed from the collection tube, or require a preliminary step of opening the cap.
  • the collection tube containing the lysate is then used to perform DNA purification.
  • the device described above is not suitable for processing more than one sample at a time. It is necessary to multiply the number of devices as many times as necessary according to the number of samples to be processed, which increases the number of manual steps to be performed by as many times as necessary.
  • WO-2009074177-A relates to a sampling device for collecting solid forensic samples in order to extract biological material.
  • the device includes a compartment in which the sample is inserted, then the lysis buffer. After incubation, the buffer is transferred to a well of a microplate located below via a vertical pouring channel, the transfer being carried out by a siphon.
  • this device can only process up to 24 samples simultaneously.
  • the device generally used to carry out the sampling and the lysis of several samples simultaneously consists of a 96 spin basket plate hereinafter referred to as a tube plate, a 96 deep well plate and a means for separating both, this means being referred to hereinafter as an elevator.
  • a means for separating both this means being referred to hereinafter as an elevator.
  • To perform the sampling simply insert the items to be analyzed, for example cigarette filter paper, a compress, a piece of cloth, etc., one by one into each of the tubes of the tube plate.
  • the traceability of the samples that is to say the identification of the position of each of the elements to be analyzed is ensured by software internal to each laboratory.
  • the lysis solution is added to each tube in order to immerse the element to be analyzed;
  • the plate of tubes is covered with an adhesive film in order to close the free end of the tubes and thus to avoid any subsequent contamination during the analysis process;
  • This assembly is placed in a heating system in order to carry out cell lysis with stirring;
  • the tube plate is lifted while keeping it nested in the deep well plate with the elevator and the samples are wrung out by centrifugation so that the lysis solution is completely found in the deep wells;
  • the deep well plate which therefore contains the lysate, is ready for the next step of nucleic acid purification.
  • the length of the tubes of the tube plates currently in use is not adapted to the depth of the deep wells of the deep well plate: in fact, the sample is not completely immersed in the determined volume of solution of lysis.
  • one of the aims of the present invention is to provide a device for analyzing solid biological elements making it possible to ensure the non-contamination of the elements to be analyzed as well as their traceability.
  • Another object is to provide such a device which allows the item to be analyzed to immerse as much as possible in the lysis solution.
  • An additional aim of the present invention is to provide a method which obviates the drawbacks set out above.
  • a device for analyzing solid biological elements comprising, on the one hand, a plate of tubes, the lower ends of which are perforated and the upper ends of which are open. to allow the introduction of an element to be analyzed which may contain biological material, and, on the other hand, a deep well plate in which the tube plate is fitted, the deep well plate comprising several deep wells, the device further comprising an elevator for raising the tube plate from the deep well plate, each tube of the tube plate having towards its upper end at least one orifice passing right through the wall of the tube to allow passage of water. air, the device further comprising, for each tube of the tube plate, a plug which closes the upper end of the tube.
  • the orifice is a groove made in the wall of the tube, and opening out to the upper end of the tube.
  • a groove makes it possible to balance the air pressure between the inside and the outside of the tube.
  • the groove has a slot shape, such a slot shape being particularly suitable for optimizing the air pressure balancing between the inside and the outside of the tube.
  • such a groove also makes it possible, by virtue of its shape, to make the orifice visible from the top of the plate when no stopper is inserted in the tube.
  • the operator can easily visualize that the sample does not come into direct contact with the bleeding, or else, failing that, that no element that can become detached from the sample obstructs this bleeding during the insertion of the sample in the tube.
  • the slot of the bleeding defines a kind of linear guide which makes it possible to facilitate the unblocking of the bleeding in the event that an element should obstruct the latter.
  • Such an unblocking is for example very easily carried out via the insertion by the operator of a needle through the groove.
  • the groove has a width in the range of 0.1 mm to 5 mm.
  • each tube comprises a membrane positioned on or within the groove, preferably along the entire length of the groove, such a membrane being configured to allow only air to pass.
  • a membrane thus configured, thus prevents volatile compounds (and / or liquid) from escaping from the tube or passing into the tube from the outside, in order to avoid any inter-sample contamination within the plate. of tubes.
  • the stopper obstructs the upper part of the groove at the upper end of the tube.
  • the deep wells have square sections and the orifice (s) are arranged along the diagonals of this square section.
  • each tube comprises on its outer wall a non-return membrane cooperating with the inner wall of the corresponding deep well.
  • this membrane is embedded in a reinforcement of the tube.
  • the tube plate comprises at one of its angles a keying device, which is preferably breakable.
  • the tube plate has a height difference on its edges allowing it to fit on the elevator in order to block the assembly between the tube plate and the elevator.
  • the shape of the edges of the tube plate makes it possible to affix a barcode type identifier thereon.
  • the device according to the invention is designed to process up to 96 samples simultaneously while respecting the plate format standards defined by the ANSI / SLAS (American National Standards Institute - Society for Laboratory Automation and Screening) for the automation of processes. analyzes.
  • the present invention also relates to a method for analyzing solid biological elements using the above device and comprising in particular the following steps:
  • the method comprises a step carried out following the first step, consisting in repeating, for each tube of the plate of tubes, sequentially, the operation consisting in removing the stopper from the tube, in depositing an element to be analyzed. in this tube, and to close the tube by its stopper. This is to prevent any inter-sample contamination between the tubes.
  • Figure 1 is a perspective view of a device according to the present invention comprising a plate of tubes with plugs nested in a deep well plate;
  • Figure 2 is a sectional view of the device according to Figure 1, some tubes being with plug and others without;
  • figure 3 shows in perspective the device according to figure 1, the plate of tubes being lifted in the plate of deep tubes;
  • Figure 4 shows schematically in section a tube of the tube plate, according to the present invention, stoppered after introduction of a sample
  • Figure 5 shows schematically in section a deep well of the deep well plate into which a lysis solution is poured;
  • Figure 6 shows schematically in section the fitting of a tube of the tube plate into a deep well of the deep well plate
  • Figure 7 shows schematically in section the entire tube and deep well during the cell lysis phase
  • Figure 8 shows schematically in section the spinning phase, the tube plate being lifted into the deep well plate
  • Figure 9 shows schematically in section the deep well after removal of the tube
  • Figure 10 is a perspective view, partially cut away, of tubes of part of the tube plate having at least one orifice;
  • Figure 11 is a schematic sectional view, seen from above, of some tubes inserted in deep wells;
  • Figure 12 is a cutaway view of a tube with a backflow preventer in a deep well.
  • a device for analyzing solid biological elements comprises, on the one hand, a plate of tubes, designated as a whole by the reference 1: the lower end 2 of each tube 3 is perforated and the end upper 4 open at the level of the tube plate 1 to allow the introduction of an element to be analyzed 5 and, on the other hand, a deep well plate, generally designated by the reference 6 in which the plate is fitted of tubes 1.
  • This device also comprises a means for separating the plate of tubes from the plate of deep wells such as an elevator 7.
  • This elevator 7 is for example constituted by a U-shaped fork which is placed on the outer edges of the deep well plate 6 and under the outer edges of the tube plate 1 in order to raise the latter above the deep well plate 6.
  • Each tube 3 of the tube plate 1 is closed by a stopper 8 which ensures the non-contamination of the elements to be analyzed.
  • each tube 3 has a shape which conforms to the shape of the bottom of the deep well plate 6 without being in contact with it.
  • each tube 3 of the tube plate 1 has towards its upper end 4, at least one orifice 9 passing right through the wall of the tube 3 to allow air to pass.
  • This orifice 9 is a groove which is made in the wall of the tube 3 and which opens out at the level of the upper end 4 of the tube 3.
  • This groove 9, which is made in the wall of the tube 3 has the function of balancing the atmospheric air pressure between the inner part and the outer part of the tube 3 when a plug 8 is present.
  • the length of this groove 9 begins at the upper end 4 of the tube 3 and stops, for its lower part, preferably just below the position of the stopper 8 once the latter has been inserted into the tube 3.
  • the lower end of the bleeding 9 may be a few millimeters longer compared to the position of the stopper 8 but is not intended to come into contact with the lysis buffer.
  • Such a groove 9 is in fact located as high as possible on the tube 3 so as not to be in contact with the lysis solution 13 or the sample 5.
  • This groove 9 preferably has a width of at least 0.1 mm, in particular between 0.1mm and 5mm, in order to create an air exchange space between the inside and the outside of the tube 3.
  • the groove 9 is provided with a membrane 9a permeable to air only.
  • This membrane 9a positioned on or in the groove 9, preferably over the entire length of the groove 9, makes it possible to prevent volatile compounds separating from the sample 5 from escaping from the tube 3 through the groove 9 during the insertion of the sample 5, thus avoiding any risk of inter-sample contamination within the tube plate 1.
  • the membrane 9a is positioned on the groove 9 and covers the latter.
  • the width of the groove 9 may be equal to the width of the membrane 9a.
  • the membrane 9a can for example be made of paper filter or plastic or any other material allowing only air to pass or be in the form of a flexible membrane split in the middle which would open according to the change in pressure of air.
  • the groove 9 may comprise two parts of different dimensions and optionally forming an angle between them.
  • the stopper 8 closes the upper part of the groove 9 at the level of the upper end 4 of the tube 3, thus preventing any contamination of the tube by exogenous elements.
  • the number of orifices 9 is between 1 and 4.
  • the deep wells 11 have square sections and the orifice (s) 9 are arranged along the diagonal (s) of this square section.
  • Each tube 3 may include on its outer wall a non-return membrane 12 cooperating with the inner wall of the corresponding deep well 11. According to one embodiment, this membrane 12 is embedded in a reinforcement of the tube 3.
  • the tube plate 3 comprises a key 15 located at one of its angles so as to allow only one direction of insertion of the tube plate 3 into the deep well plate 6 and thus prevent any inversion of the device.
  • This key 15 is breakable so that the tube plate 3 can adapt to any other model of deep well plate if necessary.
  • the tube plate 3 comprises flanges 16 which fit onto the elevator 7 to block the assembly between the tube plate 3 and the elevator 7.
  • These flanges 16 have a cross section. higher central 17 in order to affix a barcode type identifier.
  • the present invention also relates to a method for analyzing solid biological elements using the device described above and comprising in particular the following steps:
  • the method also comprises a step carried out following the first step, consisting in repeating, for each tube 3 of the plate of tubes 1, sequentially, the operation consisting in removing the stopper 8 from the tube 3, to deposit an element to be analyzed 5 in this tube 3, and to close the tube 3 with its cap 8. This makes it possible to avoid any inter-sample contamination between the tubes 3.
  • the lysis solution 13 is introduced directly into each deep well 11 and the tube plate 1 is then fitted into the deep well plate 6 so that the lysis solution 13 penetrates in each tube 3 by the lower end 2 thereof which has holes generally seven in number.
  • the orifice 9 makes it possible to exchange air between the inside and the outside of the tube 3 when the stopper 8 is present at the level of the upper end 4 of the tube 3.
  • the orifice 9 has the effect of promoting the leveling of the lysis solution liquid 13 between the interior of the tube 3 and the interior of the deep well 11 of so that the element to be analyzed 5 is entirely immersed in the lysis solution 13.
  • the tube 3 can also be provided with a flexible membrane 12 cooperating with the internal wall of the deep well 11: this flexible wall prevents the lysis solution 13 from rising too much between the tubes 3 and the deep wells 11 and thus contributes to making the lysis solution 13 penetrate the tube 3 through the holes located at its lower end 2.
  • the holes located at the the lower end 2 of the tubes 3 are exclusively oriented so vertical so that no hole is in the direction of another tube 3. Only the holes located at the lower end 2 of the tube 3 allow liquid to be transferred between the inside and the outside of the tubes 3.
  • the lower end 2 of the tube 3 can also be provided with a filter 15 arranged above the holes that it comprises. The particular function of this filter is to prevent small particles originating from the sample present in the tube 3 from passing through the holes and thus from passing into the lysis solution 13 present in the corresponding deep well 11.
  • the device according to the present invention therefore ensures that each tube 3 of the tube plate 1 is free from any contamination before and during its use because all the tubes 3 of the tube plate 1 are closed by a cap 8.
  • an automatic device can be used which will remove the stopper 8 of a tube 3 determined for the introduction into this tube 3 of an element to be analyzed without risk of contamination of the tubes 3. adjacent which are still blocked.
  • the automaton will only lift a plug 8 at a time and put it back in place once the element to be analyzed has been introduced into the tube 3.
  • the automaton can be equipped with an optical system to take an image of each element to be analyzed in order to ensure traceability of operations.
  • the stopper 8 of a tube 3 is only handled once in order to insert an element to be analyzed in the tube 3. This makes it possible to ensure that no cross-contamination can occur during the process. treatment.
  • this device is easily automated and can be coupled with traceability software in order to control the opening and closing of each tube 3 and thus guarantee the correct positioning of each sample.
  • the device for analyzing solid biological elements makes it possible, in particular in the medical field or the field of forensics, to meet the requirements of the international standard ISO / IEC 17025 relating to analysis laboratories and 'test.
  • the requirements of the standard focus in particular on the fight against contamination and the traceability of samples from receipt of the sample in the laboratory until the results are returned.
  • the preliminary step known as sampling, which consists of positioning a given sample (or a fraction of a sample) in its location for analysis, as well as the cell lysis step, are the two steps covered by of the method of the present invention, and have all the guarantees necessary to avoid any risk of sample inversion or contamination.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention relates to a device for analysing solid biological elements and to a device for implementing same. The device comprises a plate (1) of tubes, the lower ends (2) of which are perforated and the upper ends (4) of which are open on the tube plate (1) to allow the introduction of an analyser element (5), a deep well plate (6) into which the tube plate (1) is inserted and a lifter (7) for raising the tube plate (1) from the deep well plate (6). Each tube (3) in the tube plate (1) comprises at least one opening (9) towards its upper end (4) to allow air to pass through and each tube (3) can be closed at its upper end (4) with a stopper (8). The invention is applicable particularly in the medical, agri-food and forensic science fields.

Description

DESCRIPTION DESCRIPTION

Titre : Dispositif pour analyser des éléments solides biologiques et dispositif pour sa mise en oeuvre Title: Device for analyzing solid biological elements and device for its implementation

La présente invention concerne un dispositif pour analyser des éléments solides biologiques et un dispositif pour sa mise en œuvre. The present invention relates to a device for analyzing solid biological elements and to a device for its implementation.

Historiquement, les dispositifs d’échantillonnage et de lyse cellulaire étaient conçus pour ne traiter qu’un seul échantillon à la fois. Par exemple, le dispositif « Forensic Spin Filter basket » commercialisé par la société MidSci est composé d’une unité de filtration à fond perforé permettant de recueillir un prélèvement biologique et d’un tube collecteur de 2 mL avec un capuchon solidaire. Dans des versions alternatives de ce type de dispositif, le capuchon peut être solidaire de l’unité de filtration au lieu d’être rattaché au tube collecteur, ou bien l’unité de filtrations ainsi que le tube collecteur peuvent tous deux disposer d’un capuchon solidaire. Historically, cell sampling and lysis devices were designed to process only one sample at a time. For example, the "Forensic Spin Filter basket" device marketed by the company MidSci is composed of a filtration unit with a perforated bottom making it possible to collect a biological sample and of a 2 mL collection tube with an integral cap. In alternative versions of this type of device, the cap may be integral with the filtration unit instead of being attached to the collecting tube, or the filtration unit as well as the collecting tube may both have a integral cap.

La première étape du processus d’analyse consiste à insérer l’élément solide biologique appelé également prélèvement ou échantillon (ex : morceau de tissu, papier filtre de cigarette, cheveu...) dans l’unité de filtration, qui est ensuite inséré dans le tube collecteur. Un tampon ou solvant approprié à la lyse des cellules y est ajouté afin de recouvrir le prélèvement. Le prélèvement est ainsi immergé dans le tampon au niveau de l’unité de filtration. Le dispositif est fermé à l’aide du capuchon solidaire du tube collecteur ou de l’unité de filtration puis incubé pendant un temps donné. L’ensemble est ensuite centrifugé dans une micro-centrifugeuse afin de séparer le tampon du prélèvement biologique, le tampon passant au travers des micro-pores situés au fond de l’unité de filtration pour se retrouver dans le tube collecteur. En fonction des dispositifs, l’unité de filtration peut être directement retirée du tube collecteur, ou nécessiter une étape préalable d’ouverture du capuchon. Le tube collecteur contenant le lysat est ensuite utilisé pour réaliser la purification de l’ADN. The first step of the analysis process consists of inserting the solid biological element also called a sample or sample (e.g. piece of tissue, cigarette filter paper, hair, etc.) into the filtration unit, which is then inserted into the collecting tube. A buffer or solvent suitable for lysis of the cells is added thereto in order to cover the sample. The sample is thus immersed in the buffer at the filtration unit. The device is closed using the cap attached to the collection tube or the filtration unit and then incubated for a given time. The whole is then centrifuged in a microcentrifuge to separate the buffer from the biological sample, the buffer passing through the micro-pores at the bottom of the filtration unit to end up in the collection tube. Depending on the devices, the filtration unit can be directly removed from the collection tube, or require a preliminary step of opening the cap. The collection tube containing the lysate is then used to perform DNA purification.

Le dispositif décrit ci-dessus n’est pas adapté pour traiter plus d’un échantillon à la fois. Il est nécessaire de multiplier autant de fois que nécessaire le nombre de dispositifs en fonction du nombre d’échantillons à traiter, ce qui augmente autant de fois le nombre d’étapes manuelles à réaliser. The device described above is not suitable for processing more than one sample at a time. It is necessary to multiply the number of devices as many times as necessary according to the number of samples to be processed, which increases the number of manual steps to be performed by as many times as necessary.

Dans le document US-5888831-A est décrit un récipient de collecte et d’extraction permettant de récupérer le tampon de lyse à l’aide d’une seringue sans nécessité de retirer le panier filtrant contenant le prélèvement, et sans nécessité de rouvrir le capuchon du tube collecteur. Néanmoins, ce dispositif ne permet pas non plus de traiter plusieurs échantillons à la fois et nécessite une étape de pipetage à l’aide d’une seringue pour récupérer le tampon de lyse. In the document US-5888831-A is described a collection and extraction container making it possible to recover the lysis buffer using a syringe without the need to remove the filter basket containing the sample, and without the need to reopen the collector tube cap. However, this device does not allow no more processing multiple samples at once and requires a pipetting step using a syringe to collect the lysis buffer.

Le dispositif décrit dans le document US-2010248213-A repose sur le même principe que le dispositif précédent avec l’avantage de pouvoir traiter plusieurs échantillons simultanément. Néanmoins, le procédé utilisé présente des risques de contaminations croisés au cours du processus d’échantillonnage du fait que les récipients contenant le matériel biologique ne sont scellés qu’après l’insertion de tous les échantillons et ajout du tampon de lyse. The device described in document US-2010248213-A is based on the same principle as the previous device with the advantage of being able to process several samples simultaneously. However, the method used presents risks of cross-contamination during the sampling process as the containers containing the biological material are not sealed until after all samples have been inserted and lysis buffer added.

Le document WO-2009074177-A concerne un dispositif d’échantillonnage pour collecter des échantillons médico-légaux solides afin d’en extraire du matériel biologique. Le dispositif comprend un compartiment dans lequel est inséré l’échantillon, puis le tampon de lyse. Après incubation, le tampon est transféré dans un puits d'une microplaque situé en dessous via un canal vertical de coulée, le transfert étant réalisé par un siphon. Cependant, ce dispositif ne permet de traiter que jusqu’à 24 échantillons simultanément. WO-2009074177-A relates to a sampling device for collecting solid forensic samples in order to extract biological material. The device includes a compartment in which the sample is inserted, then the lysis buffer. After incubation, the buffer is transferred to a well of a microplate located below via a vertical pouring channel, the transfer being carried out by a siphon. However, this device can only process up to 24 samples simultaneously.

Actuellement, le dispositif généralement utilisé pour réaliser l’échantillonnage et la lyse de plusieurs échantillons simultanément est constitué par une plaque de 96 « spin basket » dénommée par la suite plaque de tubes, par une plaque de 96 puits profonds et par un moyen pour désolidariser les deux, ce moyen étant appelé par la suite élévateur. Pour réaliser l’échantillonnage, il suffit d’insérer les éléments à analyser, par exemple du papier filtre de cigarette, une compresse, un morceau de tissu, etc.., un par un dans chacun des tubes de la plaque de tubes. La traçabilité des échantillons, c’est-à-dire l’identification de la position de chacun des éléments à analyser est assurée par un logiciel interne à chaque laboratoire. Currently, the device generally used to carry out the sampling and the lysis of several samples simultaneously consists of a 96 spin basket plate hereinafter referred to as a tube plate, a 96 deep well plate and a means for separating both, this means being referred to hereinafter as an elevator. To perform the sampling, simply insert the items to be analyzed, for example cigarette filter paper, a compress, a piece of cloth, etc., one by one into each of the tubes of the tube plate. The traceability of the samples, that is to say the identification of the position of each of the elements to be analyzed is ensured by software internal to each laboratory.

Avec un tel dispositif, les différentes étapes sont :With such a device, the different steps are:

- on dépose dans chaque tube de la plaque de tubes, qui est emboîtée dans la plaque de puits profonds, un élément à analyser ;- Is deposited in each tube of the tube plate, which is nested in the deep well plate, an element to be analyzed;

- on ajoute la solution de lyse dans chaque tube afin d’immerger l’élément à analyser ;- the lysis solution is added to each tube in order to immerse the element to be analyzed;

- on recouvre la plaque de tubes par un film adhésif afin de fermer l’extrémité libre des tubes et ainsi d’éviter toute contamination ultérieure au cours du processus d’analyse ;- the plate of tubes is covered with an adhesive film in order to close the free end of the tubes and thus to avoid any subsequent contamination during the analysis process;

- on dépose cet ensemble dans un système chauffant pour réaliser une lyse cellulaire sous agitation ;- This assembly is placed in a heating system in order to carry out cell lysis with stirring;

- à l’issue de cette lyse, on soulève la plaque de tubes tout en la maintenant emboîtée dans la plaque de puits profonds avec l’élévateur et on essore les échantillons par centrifugation pour que la solution de lyse se retrouve entièrement dans les puits profonds ; - at the end of this lysis, the tube plate is lifted while keeping it nested in the deep well plate with the elevator and the samples are wrung out by centrifugation so that the lysis solution is completely found in the deep wells;

- on retire la plaque de tubes ainsi que l’élévateur de la plaque de puits profonds. La plaque de puits profonds, qui contient donc le lysat, est prête pour l’étape suivante de purification des acides nucléiques. - remove the tube plate as well as the elevator from the deep well plate. The deep well plate, which therefore contains the lysate, is ready for the next step of nucleic acid purification.

Il est relevé qu’il n’existe aucune sécurité assurant une absence de contamination entre les tubes d’une même plaque pendant et après le dépôt d’un échantillon. Cette sécurité n’est donc pas assurée tant que tous les tubes de la plaque ne sont pas recouverts par un film adhésif, ce qui correspond à attendre la fin de l’échantillonnage de tous les éléments. It is noted that there is no security ensuring an absence of contamination between the tubes of the same plate during and after the deposit of a sample. This security is therefore not guaranteed until all the tubes of the plate are covered by an adhesive film, which corresponds to waiting for the end of the sampling of all the elements.

Par ailleurs, la longueur des tubes des plaques de tubes actuellement utilisés n’est pas adaptée à la profondeur des puits profonds de la plaque de puits profonds : en effet, l’échantillon n’est pas totalement immergé dans le volume déterminé de solution de lyse. Furthermore, the length of the tubes of the tube plates currently in use is not adapted to the depth of the deep wells of the deep well plate: in fact, the sample is not completely immersed in the determined volume of solution of lysis.

Aussi un des buts de la présente invention est-il de fournir un dispositif pour analyser des éléments solides biologiques permettant d’assurer la non contamination des éléments à analyser ainsi que leur traçabilité. Also one of the aims of the present invention is to provide a device for analyzing solid biological elements making it possible to ensure the non-contamination of the elements to be analyzed as well as their traceability.

Un autre but est de fournir un tel dispositif qui permet à l’élément à analyser de plonger le plus possible dans la solution de lyse. Another object is to provide such a device which allows the item to be analyzed to immerse as much as possible in the lysis solution.

Un but supplémentaire de la présente invention est de fournir un procédé obviant les inconvénients exposés ci-dessus. An additional aim of the present invention is to provide a method which obviates the drawbacks set out above.

Ces buts, ainsi que d’autres qui apparaîtront par la suite, sont atteints par un dispositif pour analyser des éléments solides biologiques comprenant, d’une part, une plaque de tubes, dont les extrémités inférieures sont perforées et dont les extrémités supérieures sont ouvertes pour permettre l’introduction d’un élément à analyser pouvant contenir du matériel biologique, et, d’autre part, une plaque de puits profonds dans laquelle est emboîtée la plaque de tubes, la plaque de puits profonds comportant plusieurs puits profonds, le dispositif comportant en outre un élévateur permettant de surélever la plaque de tube de la plaque de puits profonds, chaque tube de la plaque de tubes comportant vers son extrémité supérieure au moins un orifice traversant de part en part la paroi du tube pour laisser passer de l’air, le dispositif comportant en outre, pour chaque tube de la plaque de tubes, un bouchon venant fermer l’extrémité supérieure du tube. L’orifice est une saignée ménagée dans la paroi du tube, et débouchant jusqu’à l’extrémité supérieure du tube. Une telle saignée permet d’équilibrer la pression d'air entre l'intérieur et l'extérieur du tube. En effet, la saignée présente une forme en fente, une telle forme en fente étant particulièrement adaptée pour optimiser l’équilibrage de pression d’air entre l’intérieur et l’extérieur du tube. Par ailleurs, une telle saignée permet également, de par sa forme, de rendre l'orifice visible par le dessus de la plaque lorsqu'aucun bouchon n'est inséré dans le tube. Ainsi l'opérateur pourra facilement visualiser que l'échantillon ne rentre pas en contact direct avec la saignée, ou bien à défaut, qu'aucun élément pouvant se désolidariser de l'échantillon ne vienne obstruer cette saignée lors de l'insertion de l'échantillon dans le tube. A l’inverse, la présence d’un trou circulaire dans la paroi du tube ne permet pas à un opérateur de visualiser depuis le dessus qu’aucun échantillon n’obstrue le trou. Enfin, la fente de la saignée définit une sorte de guide linéaire qui permet de faciliter le débouchage de la saignée au cas où un élément viendrait obstruer cette dernière. Un tel débouchage est par exemple très facilement effectué via l’insertion par l’opérateur d’une aiguille à travers la saignée. These goals, as well as others which will appear later, are achieved by a device for analyzing solid biological elements comprising, on the one hand, a plate of tubes, the lower ends of which are perforated and the upper ends of which are open. to allow the introduction of an element to be analyzed which may contain biological material, and, on the other hand, a deep well plate in which the tube plate is fitted, the deep well plate comprising several deep wells, the device further comprising an elevator for raising the tube plate from the deep well plate, each tube of the tube plate having towards its upper end at least one orifice passing right through the wall of the tube to allow passage of water. air, the device further comprising, for each tube of the tube plate, a plug which closes the upper end of the tube. The orifice is a groove made in the wall of the tube, and opening out to the upper end of the tube. Such a groove makes it possible to balance the air pressure between the inside and the outside of the tube. Indeed, the groove has a slot shape, such a slot shape being particularly suitable for optimizing the air pressure balancing between the inside and the outside of the tube. Moreover, such a groove also makes it possible, by virtue of its shape, to make the orifice visible from the top of the plate when no stopper is inserted in the tube. Thus the operator can easily visualize that the sample does not come into direct contact with the bleeding, or else, failing that, that no element that can become detached from the sample obstructs this bleeding during the insertion of the sample in the tube. Conversely, the presence of a circular hole in the wall of the tube does not allow an operator to visualize from above that no sample is obstructing the hole. Finally, the slot of the bleeding defines a kind of linear guide which makes it possible to facilitate the unblocking of the bleeding in the event that an element should obstruct the latter. Such an unblocking is for example very easily carried out via the insertion by the operator of a needle through the groove.

De préférence, la saignée présente une largeur comprise dans la plage de 0.1 mm à 5 mm. Preferably, the groove has a width in the range of 0.1 mm to 5 mm.

De préférence, chaque tube comprend une membrane positionnée sur ou au sein de la saignée, de préférence sur toute la longueur de la saignée, une telle membrane étant configurée pour ne laisser passer que de l’air. Une telle membrane, ainsi configurée, empêche ainsi des composés volatiles (et/ou du liquide) de s’échapper du tube ou de passer dans le tube depuis l’extérieur, afin d'éviter toute contamination inter-échantillons au sein de la plaque de tubes. Preferably, each tube comprises a membrane positioned on or within the groove, preferably along the entire length of the groove, such a membrane being configured to allow only air to pass. Such a membrane, thus configured, thus prevents volatile compounds (and / or liquid) from escaping from the tube or passing into the tube from the outside, in order to avoid any inter-sample contamination within the plate. of tubes.

De préférence, le bouchon obstrue la partie supérieure de la saignée au niveau de l’extrémité supérieure du tube. Preferably, the stopper obstructs the upper part of the groove at the upper end of the tube.

Selon un mode de réalisation de l’invention, les puits profonds sont de sections carrées et le ou les orifices sont disposés selon les diagonales de cette section carrée. According to one embodiment of the invention, the deep wells have square sections and the orifice (s) are arranged along the diagonals of this square section.

Avantageusement, chaque tube comprend sur sa paroi extérieure une membrane anti-retour coopérant avec la paroi interne du puits profond correspondant. Advantageously, each tube comprises on its outer wall a non-return membrane cooperating with the inner wall of the corresponding deep well.

De préférence, cette membrane est incrustée dans un renfort du tube. Preferably, this membrane is embedded in a reinforcement of the tube.

Avantageusement la plaque de tubes comprend à un de ses angles un détrompeur, qui est, de préférence, sécable. Advantageously, the tube plate comprises at one of its angles a keying device, which is preferably breakable.

De préférence, la plaque de tubes présente sur ses rebords une différence de hauteur lui permettant de s’emboîter sur l’élévateur afin de bloquer l’assemblage entre la plaque de tubes et l’élévateur. Avantageusement, la forme des rebords de la plaque de tubes permet d’y apposer un identifiant de type code-barres. Preferably, the tube plate has a height difference on its edges allowing it to fit on the elevator in order to block the assembly between the tube plate and the elevator. Advantageously, the shape of the edges of the tube plate makes it possible to affix a barcode type identifier thereon.

Le dispositif selon l’invention est conçu pour traiter jusqu'à 96 prélèvements simultanément en respectant les standards de formats de plaques définis par l’ANSI/SLAS (American National Standards Institute - Society for Laboratory Automation and Screening) pour l'automatisation des procédés d'analyses. The device according to the invention is designed to process up to 96 samples simultaneously while respecting the plate format standards defined by the ANSI / SLAS (American National Standards Institute - Society for Laboratory Automation and Screening) for the automation of processes. analyzes.

La présente invention concerne également un procédé pour analyser des éléments solides biologiques mettant en œuvre le dispositif ci-dessus et comprenant notamment les étapes ci-après :The present invention also relates to a method for analyzing solid biological elements using the above device and comprising in particular the following steps:

- retirer le bouchon d’un tube d’une plaque de tubes et déposer l’élément à analyser dans ce tube et fermer ledit tube par ce même bouchon ;- remove the stopper of a tube from a plate of tubes and place the element to be analyzed in this tube and close said tube with the same stopper;

- introduire dans chaque puits profond d’une plaque de puits profonds une solution de lyse ;- introduce a lysis solution into each deep well of a deep well plate;

- emboîter la plaque de tubes dans la plaque de puits profonds, la solution de lyse pénétrant alors dans chaque tube de la plaque de tubes par leur extrémité inférieure perforée; - Fit the tube plate into the deep well plate, the lysis solution then entering each tube of the tube plate through their perforated lower end;

- incuber sous agitation l’ensemble constitué de la plaque de tubes emboîtée dans la plaque de puits profonds;- incubate, with shaking, the assembly consisting of the tube plate nested in the deep well plate;

- insérer l’élévateur entre la plaque de tubes et la plaque de puits profonds tout en les maintenant emboîtées pour procéder à l’essorage de l’élément à analyser contenu dans chaque tube;- insert the elevator between the plate of tubes and the plate of deep wells while keeping them nested to proceed to the spinning of the element to be analyzed contained in each tube;

- retirer la plaque de tubes et l’élévateur de la plaque de puits profonds. La plaque de puits profonds qui contient le lysat est prête pour l’étape suivante de purification des acides nucléiques. - remove the tube plate and the elevator from the deep well plate. The deep well plate that contains the lysate is ready for the next step of nucleic acid purification.

Avantageusement, le procédé comprend une étape effectuée à la suite de la première étape, consistant à répéter, pour chaque tube de la plaque de tubes, de manière séquentielle, l’opération consistant à enlever le bouchon du tube, à déposer un élément à analyser dans ce tube, et à fermer le tube par son bouchon. Ceci permet d’éviter toute contamination inter-échantillons entre les tubes. Advantageously, the method comprises a step carried out following the first step, consisting in repeating, for each tube of the plate of tubes, sequentially, the operation consisting in removing the stopper from the tube, in depositing an element to be analyzed. in this tube, and to close the tube by its stopper. This is to prevent any inter-sample contamination between the tubes.

La description qui va suivre et qui ne présente aucun caractère limitatif doit être lue en regard des figures annexées parmi lesquelles : The description which will follow and which is in no way limiting should be read with reference to the appended figures, among which:

[Fig. 1] la figure 1 est une vue en perspective d’un dispositif selon la présente invention comprenant une plaque de tubes avec bouchons emboîtée dans une plaque de puits profonds ; [Fig. 2] la figure 2 est une vue en coupe du dispositif selon la figure 1 , certains tubes étant avec bouchon et d’autres sans ; [Fig. 1] Figure 1 is a perspective view of a device according to the present invention comprising a plate of tubes with plugs nested in a deep well plate; [Fig. 2] Figure 2 is a sectional view of the device according to Figure 1, some tubes being with plug and others without;

[Fig. 3] la figure 3 représente en perspective le dispositif selon la figure 1, la plaque de tubes étant soulevée dans la plaque de tubes profonds ; [Fig. 3] figure 3 shows in perspective the device according to figure 1, the plate of tubes being lifted in the plate of deep tubes;

[Fig. 4] la figure 4 représente schématiquement en coupe un tube de la plaque de tubes, selon la présente invention, bouché après introduction d’un échantillon ; [Fig. 4] Figure 4 shows schematically in section a tube of the tube plate, according to the present invention, stoppered after introduction of a sample;

[Fig. 5] la figure 5 représente schématiquement en coupe un puits profond de la plaque de puits profonds dans lequel une solution de lyse est versée ; [Fig. 5] Figure 5 shows schematically in section a deep well of the deep well plate into which a lysis solution is poured;

[Fig. 6] la figure 6 représente schématiquement en coupe l’emboîtement d’un tube de la plaque de tubes dans un puits profond de la plaque de puits profonds ; [Fig. 6] Figure 6 shows schematically in section the fitting of a tube of the tube plate into a deep well of the deep well plate;

[Fig. 7] la figure 7 représente schématiquement en coupe l’ensemble tube et puits profond pendant la phase de lyse cellulaire ; [Fig. 7] Figure 7 shows schematically in section the entire tube and deep well during the cell lysis phase;

[Fig. 8] la figure 8 représente schématiquement en coupe la phase d’essorage, la plaque de tubes étant soulevée dans la plaque de puits profonds ; [Fig. 8] Figure 8 shows schematically in section the spinning phase, the tube plate being lifted into the deep well plate;

[Fig. 9] la figure 9 représente schématiquement en coupe le puits profond après retrait du tube ; [Fig. 9] Figure 9 shows schematically in section the deep well after removal of the tube;

[Fig. 10] la figure 10 est une vue en perspective, avec arrachement partiel, de tubes d’une partie de la plaque de tubes comportant au moins un orifice ; [Fig. 10] Figure 10 is a perspective view, partially cut away, of tubes of part of the tube plate having at least one orifice;

[Fig. 11] la figure 11 est une vue schématique en coupe, vue du dessus de quelques tubes insérés dans des puits profonds ; [Fig. 11] Figure 11 is a schematic sectional view, seen from above, of some tubes inserted in deep wells;

[Fig. 12] la figure 12 est une vue écorchée d’un tube avec une membrane antiretour dans un puits profond. [Fig. 12] Figure 12 is a cutaway view of a tube with a backflow preventer in a deep well.

Comme représenté sur ces figures, un dispositif pour analyser des éléments solides biologiques comprend, d’une part, une plaque de tubes, désignée dans son ensemble par la référence 1 : l’extrémité inférieure 2 de chaque tube 3 est perforée et l’extrémité supérieure 4 ouverte au niveau de la plaque de tubes 1 pour permettre l’introduction d’un élément à analyser 5 et, d’autre part, une plaque de puits profonds, désignée dans son ensemble par la référence 6 dans laquelle est emboîtée la plaque de tubes 1. Ce dispositif comprend aussi un moyen pour désolidariser la plaque de tubes de la plaque de puits profonds tel qu’un élévateur 7. Cet élévateur 7 est par exemple constitué par une fourche en U qui vient se placer sur les bords externes de la plaque de puits profonds 6 et sous les bords externes de la plaque de tubes 1 afin de surélever cette dernière par rapport à la plaque de puits profonds 6. Chaque tube 3 de la plaque de tubes 1 est obturé par un bouchon 8 qui permet d’assurer la non contamination des éléments à analyser. As shown in these figures, a device for analyzing solid biological elements comprises, on the one hand, a plate of tubes, designated as a whole by the reference 1: the lower end 2 of each tube 3 is perforated and the end upper 4 open at the level of the tube plate 1 to allow the introduction of an element to be analyzed 5 and, on the other hand, a deep well plate, generally designated by the reference 6 in which the plate is fitted of tubes 1. This device also comprises a means for separating the plate of tubes from the plate of deep wells such as an elevator 7. This elevator 7 is for example constituted by a U-shaped fork which is placed on the outer edges of the deep well plate 6 and under the outer edges of the tube plate 1 in order to raise the latter above the deep well plate 6. Each tube 3 of the tube plate 1 is closed by a stopper 8 which ensures the non-contamination of the elements to be analyzed.

Selon la présente invention, l’extrémité inférieure 2 de chaque tube 3 a une forme qui épouse la forme du fond de la plaque à puits profond 6 sans pour cela être en contact avec. According to the present invention, the lower end 2 of each tube 3 has a shape which conforms to the shape of the bottom of the deep well plate 6 without being in contact with it.

Selon la présente invention, chaque tube 3 de la plaque de tubes 1 comporte vers son extrémité supérieure 4, au moins un orifice 9 traversant de part en part la paroi du tube 3 pour laisser passer de l’air. Cet orifice 9 est une saignée qui est réalisée dans la paroi du tube 3 et qui débouche au niveau de l’extrémité supérieure 4 du tube 3. Cette saignée 9, qui est réalisée dans la paroi du tube 3, a pour fonction d'équilibrer la pression d'air atmosphérique entre la partie intérieure et la partie extérieure du tube 3 lorsqu'un bouchon 8 est présent. La longueur de cette saignée 9 débute à l'extrémité supérieure 4 du tube 3 et s’arrête, pour sa partie inférieure, préférentiellement juste en dessous de la position du bouchon 8 une fois ce dernier inséré dans le tube 3. L'extrémité inférieure de la saignée 9 peut être plus longue de quelques millimètres par rapport à la position du bouchon 8 mais n'a pas vocation à entrer en contact avec le tampon de lyse. Une telle saignée 9 se situe en effet le plus haut possible sur le tube 3 afin de ne pas être en contact avec la solution de lyse 13 ou l'échantillon 5. Cette saignée 9 présente de préférence une largeur au minimum de 0,1mm, notamment comprise entre 0,1mm et 5mm, afin de créer un espace d'échange d'air entre l'intérieur et l'extérieur du tube 3. According to the present invention, each tube 3 of the tube plate 1 has towards its upper end 4, at least one orifice 9 passing right through the wall of the tube 3 to allow air to pass. This orifice 9 is a groove which is made in the wall of the tube 3 and which opens out at the level of the upper end 4 of the tube 3. This groove 9, which is made in the wall of the tube 3, has the function of balancing the atmospheric air pressure between the inner part and the outer part of the tube 3 when a plug 8 is present. The length of this groove 9 begins at the upper end 4 of the tube 3 and stops, for its lower part, preferably just below the position of the stopper 8 once the latter has been inserted into the tube 3. The lower end of the bleeding 9 may be a few millimeters longer compared to the position of the stopper 8 but is not intended to come into contact with the lysis buffer. Such a groove 9 is in fact located as high as possible on the tube 3 so as not to be in contact with the lysis solution 13 or the sample 5. This groove 9 preferably has a width of at least 0.1 mm, in particular between 0.1mm and 5mm, in order to create an air exchange space between the inside and the outside of the tube 3.

Le positionnement de la saignée 9 jusqu'au niveau de l'extrémité supérieure 4 du tube 3 permet de rendre l'orifice visible par le dessus de la plaque 1 lorsqu'aucun bouchon 8 n'est inséré dans le tube 3. Ainsi l'opérateur pourra veiller à ce que l'échantillon 5 ne rentre pas en contact direct avec la saignée 9, ou bien qu'à défaut, qu'aucun élément pouvant se désolidariser de l'échantillon 5 ne vienne obstruer cette saignée 9 lors de l'insertion de l'échantillon 5 dans le tube 3. The positioning of the groove 9 up to the level of the upper end 4 of the tube 3 makes it possible to make the orifice visible from the top of the plate 1 when no plug 8 is inserted in the tube 3. Thus the The operator will be able to ensure that the sample 5 does not come into direct contact with the bleeding 9, or else, failing that, that no element which can become detached from the sample 5 obstructs this bleeding 9 during the insert sample 5 into tube 3.

Préférentiellement, et comme visible sur la figure 10, la saignée 9 est munie d'une membrane 9a perméable à l'air uniquement. Cette membrane 9a positionnée sur ou dans la saignée 9, de préférence sur toute la longueur de la saignée 9, permet d’empêcher que des composés volatiles se désolidarisant de l'échantillon 5 ne s'échappent du tube 3 par la saignée 9 lors de l'insertion de l'échantillon 5, évitant ainsi tout risque de contamination inter-échantillons au sein de la plaque de tubes 1. Dans l’exemple de réalisation particulier illustré sur la figure 10, la membrane 9a est positionnée sur la saignée 9 et recouvre cette dernière. En variante, la largeur de la saignée 9 peut être égale à la largeur de la membrane 9a. La membrane 9a peut par exemple être en filtre papier ou en plastique ou toute autre matière ne laissant passer que l'air ou se présenter sous la forme d'une membrane souple fendue au milieu qui s'ouvrirait en fonction du changement de pression d'air. Preferably, and as visible in FIG. 10, the groove 9 is provided with a membrane 9a permeable to air only. This membrane 9a positioned on or in the groove 9, preferably over the entire length of the groove 9, makes it possible to prevent volatile compounds separating from the sample 5 from escaping from the tube 3 through the groove 9 during the insertion of the sample 5, thus avoiding any risk of inter-sample contamination within the tube plate 1. In the particular embodiment illustrated in FIG. 10, the membrane 9a is positioned on the groove 9 and covers the latter. As a variant, the width of the groove 9 may be equal to the width of the membrane 9a. The membrane 9a can for example be made of paper filter or plastic or any other material allowing only air to pass or be in the form of a flexible membrane split in the middle which would open according to the change in pressure of air.

Selon un exemple de réalisation non limitatif, la saignée 9 peut comporter deux parties de dimensions différentes et éventuellement formant entre elles un angle. According to a nonlimiting exemplary embodiment, the groove 9 may comprise two parts of different dimensions and optionally forming an angle between them.

Le bouchon 8 obture la partie supérieure de la saignée 9 au niveau de l’extrémité supérieure 4 du tube 3 évitant ainsi toute contamination du tube par des éléments exogènes. The stopper 8 closes the upper part of the groove 9 at the level of the upper end 4 of the tube 3, thus preventing any contamination of the tube by exogenous elements.

Le nombre d’orifices 9 est compris entre 1 et 4. Lorsque le tube 3 comporte 4 orifices 9, les puits profonds 11 sont de sections carrées et le ou les orifices 9 sont disposés selon la ou les diagonales de cette section carrée. The number of orifices 9 is between 1 and 4. When the tube 3 has 4 orifices 9, the deep wells 11 have square sections and the orifice (s) 9 are arranged along the diagonal (s) of this square section.

Chaque tube 3 peut comporter sur sa paroi extérieure une membrane anti- retour 12 coopérant avec la paroi interne du puits profond 11 correspondant. Selon un mode de réalisation, cette membrane 12 est incrustée dans un renfort du tube 3. Each tube 3 may include on its outer wall a non-return membrane 12 cooperating with the inner wall of the corresponding deep well 11. According to one embodiment, this membrane 12 is embedded in a reinforcement of the tube 3.

Dans une version préférée, la plaque de tubes 3 comprend un détrompeur 15 situé à un de ses angles de manière à ne permettre qu’un seul sens d’insertion de la plaque de tubes 3 dans la plaque de puits profonds 6 et empêcher ainsi toute inversion du dispositif. Ce détrompeur 15 est sécable pour que la plaque de tubes 3 puisse s’adapter à tout autre modèle de plaque à puits profonds si nécessaire. In a preferred version, the tube plate 3 comprises a key 15 located at one of its angles so as to allow only one direction of insertion of the tube plate 3 into the deep well plate 6 and thus prevent any inversion of the device. This key 15 is breakable so that the tube plate 3 can adapt to any other model of deep well plate if necessary.

Dans une version encore plus préférée, la plaque de tubes 3 comporte des rebords 16 venant s’emboîter sur l’élévateur 7 pour bloquer l’assemblage entre la plaque de tubes 3 et l’élévateur 7. Ces rebords 16 disposent d’une section centrale plus haute 17 afin d’y apposer un identifiant de type code-barres. In an even more preferred version, the tube plate 3 comprises flanges 16 which fit onto the elevator 7 to block the assembly between the tube plate 3 and the elevator 7. These flanges 16 have a cross section. higher central 17 in order to affix a barcode type identifier.

La présente invention concerne également un procédé pour analyser des éléments solides biologiques mettant en œuvre le dispositif décrit ci-dessus et comprenant notamment les étapes ci-après :The present invention also relates to a method for analyzing solid biological elements using the device described above and comprising in particular the following steps:

- retirer le bouchon 8 et déposer l’élément à analyser 5 dans un tube 3 d’une plaque de tubes 1 et refermer ce tube 3 par ce bouchon 8 ;- remove the cap 8 and place the element to be analyzed 5 in a tube 3 of a plate of tubes 1 and close this tube 3 with this cap 8;

- dispenser dans chaque puits profond 11 de la plaque de puits profonds 6 la solution de lyse 13;- Dispense in each deep well 11 of the deep well plate 6 the lysis solution 13;

- emboîter la plaque de tubes 1 dans la plaque de puits profonds 6, la solution de lyse 13 pénétrant alors dans chaque tube 3 par l’extrémité inférieure perforée 2 ; - incuber sous agitation l’ensemble constitué par la plaque de tubes 1 emboîtée dans la plaque de puits profonds 6 ;- Fit the tube plate 1 into the deep well plate 6, the lysis solution 13 then entering each tube 3 through the perforated lower end 2; - incubating, with stirring, the assembly formed by the tube plate 1 nested in the deep well plate 6;

- soulever la plaque de tubes 1 au moyen de l’élévateur 7 de telle sorte que les extrémités inférieures 2 ne soient plus au contact de la solution de lyse 13 pour effectuer une phase d’essorage par centrifugation ; - lift the plate of tubes 1 by means of the elevator 7 so that the lower ends 2 are no longer in contact with the lysis solution 13 to carry out a spin phase by centrifugation;

- retirer la plaque de tubes 1 hors de la plaque de puits profonds 6. - remove the tube plate 1 from the deep well plate 6.

Avantageusement, le procédé comprend également une étape effectuée à la suite de la première étape, consistant à répéter, pour chaque tube 3 de la plaque de tubes 1 , de manière séquentielle, l’opération consistant à enlever le bouchon 8 du tube 3, à déposer un élément à analyser 5 dans ce tube 3, et à fermer le tube 3 par son bouchon 8. Ceci permet d’éviter toute contamination inter-échantillons entre les tubes 3. Advantageously, the method also comprises a step carried out following the first step, consisting in repeating, for each tube 3 of the plate of tubes 1, sequentially, the operation consisting in removing the stopper 8 from the tube 3, to deposit an element to be analyzed 5 in this tube 3, and to close the tube 3 with its cap 8. This makes it possible to avoid any inter-sample contamination between the tubes 3.

Comme aura pu le noter l’homme du métier, la solution de lyse 13 est introduite directement dans chaque puits profond 11 et la plaque de tubes 1 est ensuite emboîtée dans la plaque de puits profonds 6 de telle sorte que la solution de lyse 13 pénètre dans chaque tube 3 par l’extrémité inférieure 2 de celui-ci qui comporte des trous généralement au nombre de sept. As those skilled in the art will have noted, the lysis solution 13 is introduced directly into each deep well 11 and the tube plate 1 is then fitted into the deep well plate 6 so that the lysis solution 13 penetrates in each tube 3 by the lower end 2 thereof which has holes generally seven in number.

La présence de l’orifice 9 permet d’effectuer un échange d’air entre l’intérieur et l’extérieur du tube 3 lorsque le bouchon 8 est présent au niveau de l’extrémité supérieure 4 du tube 3. Lors de l’insertion de la plaque de tubes 1 dans la plaque de puits profonds 6, l’orifice 9 a pour effet de favoriser la mise à niveau du liquide de solution de lyse 13 entre l’intérieur du tube 3 et l’intérieur du puits profond 11 de manière que l’élément à analyser 5 soit entièrement immergé dans la solution de lyse 13. Dans une version alternative, le tube 3 peut être également munit d’une membrane souple 12 coopérant avec la paroi interne du puits profond 11 : cette paroi souple empêche la solution de lyse 13 de trop remonter entre les tubes 3 et les puits profonds 11 et contribue ainsi à faire pénétrer la solution de lyse 13 dans le tube 3 par l’intermédiaire des trous situés à son extrémité inférieure 2. Les trous situés à l'extrémité inférieure 2 des tubes 3 sont exclusivement orientés de façon verticale afin qu'aucun trou ne soit en direction d'un autre tube 3. Seuls les trous situés à l'extrémité inférieure 2 du tube 3 permettent d'effectuer un transfert de liquide entre l'intérieur et l'extérieur des tubes 3. L’extrémité inférieure 2 du tube 3 peut également être munie d’un filtre 15 disposé au-dessus des trous qu’elle comporte. Ce filtre a notamment pour fonction d’empêcher des petites particules issues de l’échantillon présent dans le tube 3 de traverser les trous et ainsi de passer dans la solution de lyse 13 présente dans le puits profond 11 correspondant. The presence of the orifice 9 makes it possible to exchange air between the inside and the outside of the tube 3 when the stopper 8 is present at the level of the upper end 4 of the tube 3. During the insertion of the tube plate 1 in the deep well plate 6, the orifice 9 has the effect of promoting the leveling of the lysis solution liquid 13 between the interior of the tube 3 and the interior of the deep well 11 of so that the element to be analyzed 5 is entirely immersed in the lysis solution 13. In an alternative version, the tube 3 can also be provided with a flexible membrane 12 cooperating with the internal wall of the deep well 11: this flexible wall prevents the lysis solution 13 from rising too much between the tubes 3 and the deep wells 11 and thus contributes to making the lysis solution 13 penetrate the tube 3 through the holes located at its lower end 2. The holes located at the the lower end 2 of the tubes 3 are exclusively oriented so vertical so that no hole is in the direction of another tube 3. Only the holes located at the lower end 2 of the tube 3 allow liquid to be transferred between the inside and the outside of the tubes 3. The lower end 2 of the tube 3 can also be provided with a filter 15 arranged above the holes that it comprises. The particular function of this filter is to prevent small particles originating from the sample present in the tube 3 from passing through the holes and thus from passing into the lysis solution 13 present in the corresponding deep well 11.

Le dispositif selon la présente invention assure donc que chaque tube 3 de la plaque de tubes 1 est exempt de toute contamination avant et pendant son usage du fait que tous les tubes 3 de la plaque de tubes 1 sont fermées par un bouchon 8. The device according to the present invention therefore ensures that each tube 3 of the tube plate 1 is free from any contamination before and during its use because all the tubes 3 of the tube plate 1 are closed by a cap 8.

Pour la mise en œuvre du procédé décrit ci-dessus, il peut être utilisé un automate qui retirera le bouchon 8 d’un tube 3 déterminé pour l’introduction dans ce tube 3 d’un élément à analyser sans risque de contamination des tubes 3 adjacents qui eux sont encore bouchés. L’automate ne soulèvera qu’un bouchon 8 à la fois et le remettra en place une fois l’élément à analyser introduit dans le tube 3. De plus, l’automate peut être équipé d’un système optique pour prendre une image de chaque élément à analyser afin d’assurer une traçabilité des opérations. For the implementation of the method described above, an automatic device can be used which will remove the stopper 8 of a tube 3 determined for the introduction into this tube 3 of an element to be analyzed without risk of contamination of the tubes 3. adjacent which are still blocked. The automaton will only lift a plug 8 at a time and put it back in place once the element to be analyzed has been introduced into the tube 3. In addition, the automaton can be equipped with an optical system to take an image of each element to be analyzed in order to ensure traceability of operations.

Selon la présente invention, le bouchon 8 d’un tube 3 n’est manipulé qu’une fois afin d’insérer un élément à analyser dans le tube 3. Ceci permet de garantir qu’aucune contamination croisée ne puisse se produire en cours de traitement. According to the present invention, the stopper 8 of a tube 3 is only handled once in order to insert an element to be analyzed in the tube 3. This makes it possible to ensure that no cross-contamination can occur during the process. treatment.

De plus, comme déjà mentionné, ce dispositif est facilement automatisable et peut être couplé à un logiciel de traçabilité afin de contrôler l’ouverture et la fermeture de chaque tube 3 et ainsi garantir le bon positionnement de chaque échantillon. In addition, as already mentioned, this device is easily automated and can be coupled with traceability software in order to control the opening and closing of each tube 3 and thus guarantee the correct positioning of each sample.

Ainsi, le dispositif d’analyse d’éléments solides biologiques selon la présente invention permet, notamment dans le domaine médical ou le domaine de la criminalistique, de répondre aux exigences de la norme internationale ISO/CEI 17025 relative aux laboratoires d’analyses et d’essai. Les exigences de la norme sont notamment axées sur la lutte contre les contaminations et la traçabilité des échantillons depuis la réception du prélèvement au laboratoire jusqu’au rendu des résultats. L’étape préliminaire, dite d’échantillonnage, qui consiste à positionner un échantillon (ou une fraction d’échantillon) donné dans son emplacement pour l’analyse, ainsi que l’étape de lyse cellulaire, sont les deux étapes faisant l’objet du procédé de la présente invention, et présentent toutes les garanties nécessaires pour éviter tout risque d’inversion d’échantillon ou de contamination. Thus, the device for analyzing solid biological elements according to the present invention makes it possible, in particular in the medical field or the field of forensics, to meet the requirements of the international standard ISO / IEC 17025 relating to analysis laboratories and 'test. The requirements of the standard focus in particular on the fight against contamination and the traceability of samples from receipt of the sample in the laboratory until the results are returned. The preliminary step, known as sampling, which consists of positioning a given sample (or a fraction of a sample) in its location for analysis, as well as the cell lysis step, are the two steps covered by of the method of the present invention, and have all the guarantees necessary to avoid any risk of sample inversion or contamination.

Claims

REVENDICATIONS 1 . Dispositif pour analyser des éléments solides biologiques comprenant une plaque de tubes (1), dont les extrémités inférieures (2) sont perforées et les extrémités supérieures (4) ouvertes au niveau de la plaque de tubes (1) pour permettre l’introduction d’un élément à analyser (5), et une plaque de puits profonds (6) dans laquelle est emboîtée la plaque de tubes (1), la plaque de puits profonds comportant plusieurs puits profonds (11), le dispositif comportant en outre un élévateur (7) permettant de surélever la plaque de tube (1) de la plaque de puits profonds (6), chaque tube (3) de la plaque de tubes (1) comportant vers son extrémité supérieure (4) au moins un orifice (9) traversant de part en part la paroi du tube (3) pour laisser passer de l’air, le dispositif comportant en outre, pour chaque tube (3) de la plaque de tubes (1), un bouchon (8) venant fermer l’extrémité supérieure (4) du tube (3) ; caractérisé par le fait que l’orifice (9) est une saignée ménagée dans la paroi du tube (3), et débouchant jusqu’à l’extrémité supérieure (4) du tube (3). 1. Device for analyzing solid biological elements comprising a plate of tubes (1), the lower ends (2) of which are perforated and the upper ends (4) open at the level of the plate of tubes (1) to allow the introduction of an element to be analyzed (5), and a deep well plate (6) in which the tube plate (1) is fitted, the deep well plate comprising several deep wells (11), the device further comprising an elevator ( 7) allowing the tube plate (1) to be raised from the deep well plate (6), each tube (3) of the tube plate (1) having towards its upper end (4) at least one orifice (9) passing right through the wall of the tube (3) to allow air to pass, the device further comprising, for each tube (3) of the tube plate (1), a plug (8) closing the upper end (4) of the tube (3); characterized in that the orifice (9) is a groove formed in the wall of the tube (3), and opening up to the upper end (4) of the tube (3). 2. Dispositif selon la revendication 1 , caractérisé par le fait que la saignée (9) présente une largeur comprise dans la plage de 0.1 mm à 5 mm. 2. Device according to claim 1, characterized in that the groove (9) has a width within the range of 0.1 mm to 5 mm. 3. Dispositif selon la revendication 1 ou 2, caractérisé par le fait que chaque tube (3) comprend une membrane (9a) positionnée sur ou au sein de la saignée (9), de préférence sur toute la longueur de la saignée (9), une telle membrane (9a) étant configurée pour ne laisser passer que de l’air. 3. Device according to claim 1 or 2, characterized in that each tube (3) comprises a membrane (9a) positioned on or within the groove (9), preferably over the entire length of the groove (9) , such a membrane (9a) being configured to allow only air to pass. 4. Dispositif selon l’une quelconque des revendications précédentes, caractérisé par le fait que la partie supérieure de la saignée (9) au niveau de l’extrémité supérieure (4) du tube (3) est fermée par le bouchon (8). 4. Device according to any one of the preceding claims, characterized in that the upper part of the groove (9) at the upper end (4) of the tube (3) is closed by the stopper (8). 5. Dispositif selon l’une quelconque des revendications précédentes, caractérisé par le fait que, les puits profonds (11) sont de sections carrés et que le ou les orifices (9) sont disposés selon la ou les diagonales de cette section carrée. 5. Device according to any one of the preceding claims, characterized in that the deep wells (11) are of square sections and that the orifice (s) (9) are arranged along the diagonal (s) of this square section. 6. Dispositif selon l’une quelconque des revendications 1 à 5, caractérisé par le fait que chaque tube (3) comprend sur sa paroi extérieure une membrane anti-retour (12) coopérant avec la paroi interne du puits profond (11) correspondant. 6. Device according to any one of claims 1 to 5, characterized in that each tube (3) comprises on its outer wall a non-return membrane (12) cooperating with the inner wall of the corresponding deep well (11). 7. Dispositif selon la revendication 6, caractérisé par le fait que cette membrane (12) est incrustée dans un renfort du tube (3). 7. Device according to claim 6, characterized in that this membrane (12) is embedded in a reinforcement of the tube (3). 8. Dispositif selon l’une quelconque des revendications précédentes, caractérisé par le fait que la plaque de tubes (3) comprend à un de ses angles un détrompeur (15). 8. Device according to any one of the preceding claims, characterized in that the tube plate (3) comprises at one of its angles a key (15). 9. Dispositif selon la revendication 8, caractérisé par le fait que le détrompeur (15) est sécable. 9. Device according to claim 8, characterized in that the polarizer (15) is breakable. 10. Dispositif selon l’une quelconque des revendications précédentes, caractérisé par le fait que la plaque de tubes (1) comporte des rebords (16) venant s’emboîter sur l’élévateur (7) afin de bloquer l’assemblage entre la plaque de tubes (1) et l’élévateur (7). 11. Dispositif selon la revendication 10 caractérisé par le fait que les rebords10. Device according to any one of the preceding claims, characterized in that the tube plate (1) comprises flanges (16) which fit onto the elevator (7) in order to block the assembly between the plate. tubes (1) and the elevator (7). 11. Device according to claim 10 characterized in that the edges (16) de la plaque de tubes (1) disposent d’une section centrale plus haute (17) afin d’y apposer un identifiant de type code-barres. (16) of the tube plate (1) have a higher central section (17) in order to affix a barcode type identifier. 12. Procédé pour analyser des prélèvements biologiques mettant en œuvre le dispositif selon l’une quelconque des revendications 1 à 11 et comprenant notamment les étapes ci-après : 12. A method for analyzing biological samples using the device according to any one of claims 1 to 11 and comprising in particular the following steps: - retirer le bouchon (8) d’un tube (3) d’une plaque de tubes (1) et déposer l’élément à analyser (5) dans ce tube (3) et fermer ledit tube (3) par ce même bouchon (8) ; - remove the stopper (8) from a tube (3) from a plate of tubes (1) and place the element to be analyzed (5) in this tube (3) and close said tube (3) with this same stopper (8); - introduire dans chaque puits profond (11) d’une plaque de puits profonds (6) une solution de lyse (13) ; - introduce into each deep well (11) of a deep well plate (6) a lysis solution (13); - emboîter la plaque de tubes (1 ) dans la plaque de puits profonds (6), la solution de lyse (13) pénétrant alors dans chaque tube (3) de la plaque de tubes (1) par leur extrémité inférieure perforée (2) ; - fit the tube plate (1) into the deep well plate (6), the lysis solution (13) then entering each tube (3) of the tube plate (1) through their perforated lower end (2) ; - incuber sous agitation l’ensemble constitué de la plaque de tubes (1) emboîtée dans la plaque de puits profonds (6) ; - incubate, with shaking, the assembly consisting of the tube plate (1) nested in the deep well plate (6); - insérer l’élévateur (7) entre la plaque de tubes (1) et la plaque de puits profonds (6) tout en les maintenant emboîtées pour essorer l’élément à analyser contenu dans chaque tube (3) ; - insert the elevator (7) between the tube plate (1) and the deep well plate (6) while keeping them nested to wring out the element to be analyzed contained in each tube (3); - retirer la plaque de tubes (1) de la plaque de puits profonds (3). - remove the tube plate (1) from the deep well plate (3).
EP21702660.8A 2020-01-31 2021-01-29 Device for analysing solid biological elements and device for implementing same Pending EP4096826A1 (en)

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FR3106764B1 (en) 2022-04-29
US20230069276A1 (en) 2023-03-02
FR3106764A1 (en) 2021-08-06

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