Tool for collecting a sample of formalin-fixed and paraffin-embedded tissues, associated sampling method and sampling device

Abstract

The invention relates to a tool (1) for collecting a sample, suitable for molecular analysis, comprising a tube (2), a rod (3) comprising a rod body (3-1), an ejection end and a gripping end (3-2) extending out of the first end of the tube (2), so as to allow a movement of the rod (3) along a longitudinal axis of the tube (2), the sampling tool (1) being arranged so as to pass from a sampling configuration in which the ejection end of the rod body (3-1) partially occupies the second end (2-2), to an ejection configuration in which the ejection end of the rod body (3-1) extends out from the second end (2-2) of the tube (2). The invention further relates to a device (6) and a method for collecting an associated sample, suitable for molecular analysis.

Description

Tool for collecting a sample of formalin-fixed, paraffin-embedded tissues, collection method and associated collection device

[0001] The technical sector of the present invention relates to devices for the collection of samples and in particular biological samples intended to undergo molecular analysis.

[0002] Below, we describe the known prior art from which the invention was developed.

[0003] The tissue microarray (TMA) technique is well-known; it involves mounting sections of biological tissue on a microscope slide for visual or electronic analysis. Unlike the traditional technique used in pathology laboratories, which typically mounts only one to three sections at a time, TMA allows for mounting a large number of tissue sections on a single slide.

[0004] The TMA technique involves taking one or more patties or cores from several dozen, or even several hundred, different blocks containing biological samples either embedded in paraffin or frozen. All the patties or cores are then assembled in a frozen or paraffin-embedded embedding medium in which cavities have been made.

[0005] One can refer, for example, to US patent 7572410, which describes a coring device comprising a coring punch, a sample core removal punch, and an ejection means for removing the cores into one or more receiving blocks of paraffin or any frozen or unfrozen medium, the coring punch being mounted substantially coaxially in the sample punch, the sample punch being in an external position, the two punches being movable in translation and / or rotation relative to each other, and the ejection means being arranged to eject the cores from each punch.

[0006] This device only allows sampling across the entire thickness of the sample block. Since areas of interest are identified by a zenithal image, it is then possible to extract the desired tissue from a core sample, mixed with other elements that were impossible to see before sampling.

[0007] The aim of the present invention is to provide means for taking samples of controlled depth in a simple and easy-to-implement manner for the user for the purpose of molecular analysis.

[0008] Controlled depth sampling allows for the creation of biological activity profiles or localized expression profiles in three dimensions.

[0009] The applications are numerous in the field of medical diagnostics and medical research. Examples include the precise determination of tumor vascularization or brain mapping for rare diseases.

[0010] The invention aims to overcome these drawbacks. The following presents a simplified summary of selected aspects, embodiments, and examples of the present invention in order to provide a basic understanding of the invention. However, this summary does not constitute an exhaustive overview of all aspects, embodiments, and examples of the invention. Its sole purpose is to present selected aspects, embodiments, and examples of the invention in a concise form as an introduction to the more detailed description of the aspects, embodiments, and examples of the invention that follows the summary.

[0011] According to a first aspect, the invention relates to a sample collection tool, adapted for molecular analysis, of a block of formalin-fixed, paraffin-embedded tissue for a sample collection device, characterized in that the collection tool comprises: a tube having a recess opening onto a first and a second end of the tube, a rod comprising a rod body, an ejection end and a gripping end extending out of the first end of the tube, so as to allow movement of the rod along a longitudinal axis of the tube, in which: the first end of the tube is arranged to form a reversible mechanical link with a gripping means of a collection unit of a sample collection device so as to allow rotational and / or translational movement of the tube along the longitudinal axis of said tube,The second end of the tube is adapted to take a sample from the paraffin-embedded tissue block; the gripping end of the rod is arranged to form a reversible mechanical link with a gripping means of a sampling unit of a sampling device so as to allow translational movement of the rod along the longitudinal axis of the tube; the sampling tool is further arranged to transition from a sampling configuration in which the ejection end of the rod body partially occupies the recess of the second end of the tube, to a sample ejection configuration in which the ejection end of the rod body is deployed out of the second end of the tube.

[0012] According to other optional features of a sampling tool according to the invention, the latter may optionally include one or more of the following features, alone or in combination: the second end of the tube is pointed and has a surface, intended to come into contact with the formalin-fixed and paraffin-embedded tissue block, which includes an adhesive substance; the stem is made of brass; the internal diameter of the tube is between 50 µm and 200 µm; the first end of the tube and the gripping end are arranged to allow detachment with a gripping means from a sampling unit of a sampling device when the sampling tool is in the ejection configuration.

[0013] According to a second aspect, the invention relates to a device for taking a sample, suitable for molecular analysis, from a block of formalin-fixed, paraffin-embedded tissue, said device comprising: a sample-taking unit, mounted on a central base, in at least one block of formalin-fixed, paraffin-embedded tissue, said sample-taking unit being movable in translation along a first X-axis, a second Z-axis, and a third Y-axis of the central base, the second Z-axis being perpendicular to the first X-axis and the third Y-axis; a tray comprising one or more blocks of formalin-fixed, paraffin-embedded tissue, said tray being movable in translation along the third Y-axis of the central base, in which the sample-taking unit comprises: a sample-taking tool, suitable for molecular analysis,of the formalin-fixed, paraffin-embedded tissue block comprising: a tube having a recess opening onto a first and a second end of the tube, the second end of the tube being adapted for taking a sample of the formalin-fixed, paraffin-embedded tissue block; a rod comprising a rod body, an ejection end and a grasping end extending out of the first end of the tube, so as to permit movement of the rod along a longitudinal axis of the tube; a grasping means arranged to form a reversible mechanical link with the first end of the tube, so as to permit rotational and / or translational movement of the tube along a longitudinal axis of said tube, the grasping means being further arranged to form a reversible mechanical link with the grasping end of the rod so as to permit translational movement of the rod along the longitudinal axis of the tube.the sampling unit being further configured to allow the sampling tool to transition from a sampling configuration in which the ejection end of the rod body partially occupies the recess in the second end of the tube, to a sample ejection configuration in which the ejection end of the rod body is deployed out of the second end of the tube.

[0014] According to other optional features of the sampling device according to the invention, the latter may optionally include one or more of the following features, alone or in combination: a processor configured to control the sampling unit so as to position the second end of the sampling tool tube in contact with a predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block and to control the switching of the sampling tool to the sampling configuration; when the sampling tool is in sampling configuration, the processor is configured to control the sampling unit so that the second end of the sampling tool tube penetrates the predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block by a predetermined distance.When the sampling tool is in sampling configuration, the processor is configured to: command the sampling unit so that the end of the sampling tool's stem makes contact with the predetermined area of ​​the formalin-fixed, paraffin-embedded tissue block from a predetermined distance; command a movement of the sampling unit along the first X-axis and / or the third Y-axis so that the end of the sampling tool's stem scrapes the predetermined area of ​​the formalin-fixed, paraffin-embedded tissue block; the processor is configured to command the sampling unit to position the second end of the sampling tool's tube above an analysis tube on the tray and to command the sampling tool to switch to sample ejection configuration.It further comprises one or more means of identification for identifying at least one block of formalin-fixed, paraffin-embedded tissue. It also comprises at least one camera arranged to record the passage of the sampling tool from a sampling configuration to a sample ejection configuration. It further comprises a probing unit configured to determine the distance between the second end of the tube and a surface of the block of formalin-fixed, paraffin-embedded tissue. It further comprises a movable ejection unit for the sampling tool, the movable ejection unit being arranged to allow the sampling tool to be detached from the gripping means when said tool is in the ejection configuration.

[0015] According to a third aspect, the invention relates to a method for taking a sample, suitable for molecular analysis, from a block of formalin-fixed, paraffin-embedded tissue, said method being implemented by a sampling device according to the invention, the method comprising the following steps: receiving a digitized image of a colored section of a block of formalin-fixed, paraffin-embedded tissue, the digitized image comprising at least one predetermined annotated area; identifying the block of formalin-fixed, paraffin-embedded tissue from which the digitized image of the colored section of formalin-fixed, paraffin-embedded tissue originates; capturing a second digitized image of the identified block of formalin-fixed, paraffin-embedded tissue; superimposing the first digitized image onto the second digitized image; and transferring the predetermined annotated area onto the second digitized image.command of the sampling unit in such a way as to take a sample from the formalin-fixed, paraffin-embedded tissue block according to the markings in the second digitized image.

[0016] According to other optional features of the sampling method according to the invention, the latter may optionally include one or more of the following features, alone or in combination: the predetermined annotated area includes sampling coordinates, a tissue typology, and an associated pathology; said method further includes a step of determining, prior to the sampling unit ordering step, a sampling length based on the sampling coordinates, tissue typology, and associated pathology of the predetermined annotated area; a sampling preparation step, the preparation step comprising: a determination, based on the sampling coordinates and tissue typology, of the number of sections to be made from the formalin-fixed, paraffin-embedded tissue block; at least one section with a thickness between 10 µm and 600 µm from the formalin-fixed, paraffin-embedded tissue block.fixing each section to a support, each section forming a subblock of formalin-fixed, paraffin-embedded tissue to be extracted, implementation of the capture, layering, and ordering steps from each subblock of formalin-fixed, paraffin-embedded tissue. The support is a blank paraffin block, and the preparation step further includes the following steps: soaking a paraffin plastic film in liquid paraffin; initial positioning of the paraffin plastic film on a contact surface of the formalin-fixed, paraffin-embedded tissue block; initial heat treatment at the melting temperature of the paraffin plastic film; at least one section with a thickness between 10 µm and 600 µm, including maintaining the fused paraffin plastic film on the contact surface of the formalin-fixed, paraffin-embedded tissue block.and wherein the fixation step comprises: a second heat treatment at the melting temperature of the virgin paraffin block and the section of the formalin-fixed, paraffin-embedded tissue block fused to the paraffin plastic film; a second positioning of the section of the formalin-fixed, paraffin-embedded tissue block and the paraffin plastic film onto the virgin paraffin block.

[0017] A primary advantage of the present invention lies in the ease of extracting a sample cake or core while controlling the sampling depth.

[0018] Another advantage of the present invention lies in the ease of analysis of the sample taken since it is not necessary to deparaffinize the sample.

[0019] Another advantage of the present invention lies in the ease of verifying that the sampling process is carried out correctly.

[0020] Another further advantage of the present invention lies in the reduction or even the annihilation of contamination between different samples since the sampling tool is for single use only.

[0021] Another advantage of the present invention lies in the regularity and homogeneity of the samples taken.

[0022] Another advantage lies in the fact that this invention makes it possible to link and ensure traceability between the diagnosis made on a stained microscope slide by a pathologist and the molecular analysis of a targeted area taken from the formalin-fixed and paraffin-embedded tissue block corresponding to the sampling device of the invention.

[0023] Another further advantage of the present invention lies in the complete automation of the device allowing for the recovery of precise samples at a high rate without the need for a replacement, by a user of the sampling tool, after each sample.

[0024] Other features, advantages, and details of the invention will be better understood upon reading the supplementary description that follows, in relation to the drawings in which:

[0025] Lare represents a sampling tool according to the invention in sampling configuration.

[0026] Lare represents a sampling tool according to the invention in an ejection configuration.

[0027] The diagram represents an overview of a sampling device according to the invention.

[0028] Lare represents an embodiment of a guidance unit along the X axis of the central base of a sampling device according to the invention.

[0029] Lare represents an embodiment of a mobile functional unit of a sampling device according to the invention.

[0030] Lare represents an embodiment of a guidance unit along the Y axis of a sampling device according to the invention.

[0031] Lare represents an embodiment of a tray of a sampling device according to the invention.

[0032] Lare represents an embodiment of a guidance unit along the Z axis of the central base of the sampling device according to the invention.

[0033] The figure represents a front view of an embodiment of a functional unit that moves in translation along the Z axis of the sampling device according to the invention.

[0034] The figure represents a rear view of an embodiment of a functional unit that moves in translation along the Z axis of the sampling device according to the invention.

[0035] The figure represents a side view of an embodiment of a functional unit moving in translation along the Z axis of the sampling device according to the invention.

[0036] Lare represents an embodiment of a probing unit of the sampling device according to the invention.

[0037] Lare represents an embodiment of a sampling unit of the sampling device according to the invention.

[0038] Lare represents an embodiment of a mobile ejection unit of the sampling device according to the invention.

[0039] Lare represents a diagram of a cross-section of a mobile ejection unit of the sampling device according to the invention.

[0040] Figure 1 represents a diagram of an embodiment of a sampling process according to the invention. The steps indicated by dotted lines are optional.

[0041] Lare represents a superposition of an annotated digitized image of a colored section of a formalin-fixed, paraffin-embedded tissue block to a digitized image of the formalin-fixed, paraffin-embedded tissue block seen from above, from which the colored section is taken.

[0042] Larepresents a digitized image of the formalin-fixed, paraffin-embedded tissue block viewed from above after transfer of a predetermined annotated area from a digitized image of a colored section of a formalin-fixed, paraffin-embedded tissue block.

[0043] The figures do not necessarily respect scales, particularly in thickness, for illustrative purposes.

[0044] Aspects of the present invention are described with reference to flowcharts and / or functional diagrams of processes and systems according to embodiments of the invention.

[0045] In the figures, flowcharts and functional diagrams illustrate the architecture, functionality, and operation of possible implementations of systems and processes according to various embodiments of the present invention. In this regard, each block in the flowcharts or block diagrams can represent a system, device, module, or code, which comprises one or more executable instructions for implementing the specified logical function(s). In some implementations, the functions associated with the blocks may appear in a different order than that shown in the figures. For example, two blocks shown successively may, in fact, be executed substantially simultaneously, or the blocks may sometimes be executed in reverse order, depending on the functionality involved.Each block in the schematic diagrams and / or flowchart, and combinations of blocks in the schematic diagrams and / or flowchart, can be implemented by special hardware systems that perform the specified functions or actions or carry out combinations of special hardware and computer instructions.

[0046] Aspects of the present invention are described with reference to functional diagrams of devices (systems) according to embodiments of the invention.

[0047] As mentioned previously, the invention relates to a tool for collecting samples from a formalin-fixed, paraffin-embedded tissue block. The samples collected are preferably biological samples intended for molecular analysis, for example, the search for mutations to characterize a tumor, or transcriptomic analyses, using micro-quantities of material, for example, a few dozen or hundred cells.

[0048] In the context of the present invention, "formalin-fixed, paraffin-embedded tissue block" means a block comprising biological material to be harvested.

[0049] Within the framework of the invention, a sample collection tool, adapted for molecular analysis, from a block of formalin-fixed and paraffin-embedded tissue for a sample collection device comprises a tube, a rod whose arrangement allows the transition from a sample collection configuration to a sample ejection configuration.

[0050] As illustrated in Figures 1A and 1B, the sampling tool 1 comprises a tube 2, preferably sterile and single-use, having a recess opening onto a first and a second end 2-1, 2-2 of the tube 2.

[0051] In the invention, the first end 2-1 of the tube 2 is arranged to form a reversible mechanical connection with a gripping means for a sampling unit of a sampling device 6, so as to allow rotational and / or translational movement of the tube 2 along a longitudinal axis of said tube. More particularly, the first end 2-1 of the tube 2 can be adapted to the gripping means so as to allow a reversible mechanical connection.

[0052] The second end 2-2 of tube 2 is adapted to take a sample from the formalin-fixed, paraffin-embedded tissue block 10.

[0053] As an example, the second end 2-2 of tube 2 may have a tubular shape suitable for taking a core sample from the formalin-fixed, paraffin-embedded tissue block 10.

[0054] To ensure optimal recovery of a sufficient sample quantity for molecular analysis while avoiding the presence of excessive paraffin that would prevent such analysis, the internal diameter of tube 2 can range from 50 µm to 200 µm. This also allows for sample collection from any type of paraffin block, whether thick (several mm) or thin (1 mm or less).

[0055] In the invention, the sampling tool 1 comprises a rod 3, preferably sterile and single-use, including a rod body 3-1, an ejection tip, and a gripping tip 3-2 extending from the first end 2-1 of the tube 2, so as to allow movement of the rod 3 along a longitudinal axis of the tube 2. Like the first end 2-1 of the tube 2, the gripping tip 3-2 can be adapted to the gripping means to allow a reversible mechanical connection. To allow optimal control of the sampling tool and thus facilitate switching between configurations, the gripping tip 3-2 of the rod 3 may have a diameter larger than the diameter of the rod body 3-1.In particular, the diameter of the gripping end 3-2 may be greater than or equal to the internal diameter of the tube 2 so that the gripping end 3-2 forms a stop at the first end 2-1 of the tube 2 when the sampling tool is in sample ejection configuration.

[0056] As mentioned previously, the sampling tool 1 according to the invention is arranged to move from a sampling configuration to a sample ejection configuration.

[0057] In the sample collection configuration, the ejection end of the rod body 3-1 partially occupies the recess of the second end 2-2 of the tube 2. This allows part of the recess of the second end 2-2 of the tube 2 to be left free to allow for the recovery of the sample by coring.

[0058] In addition, in the sample ejection configuration, the ejection end of the rod body 3-1 is deployed out of the second end 2-2 of the tube 2.

[0059] Alternatively or in addition, the first end 2-1 of tube 2 and the gripping end 3-2 can be arranged to allow detachment from a sampling unit of a sampling device 6 using a gripping means when the sampling tool is in the ejection configuration. In this way, not only the biological material present in the sample collected but also that remaining in the second end 2-2 of tube 2 can be recovered.

[0060] In one particular embodiment, the ejection tip may be pointed and may include a surface, intended to come into contact with the formalin-fixed, paraffin-embedded tissue block 10, which comprises an adhesive substance. This improves sample retrieval from the paraffin-embedded tissue block 10.

[0061] To allow for optimal sample collection, the rod 3 can be made of brass. Indeed, since the sampling tool according to the invention is also suitable for collecting small samples, in particular those with a diameter of less than 1 mm, preferably less than 500 µm and even more preferably less than 200 µm, the use of a brass rod avoids the phenomenon of static electricity which would prevent the collection of the sample.

[0062] Preferably, the sampling tool 1 can have a length L between 8 mm and 12 mm.

[0063] This configuration of sampling tool 1 allows for the definition of very shallow sampling depths, for example less than the size of a cell.

[0064] The sampling tool 1 can be made of a material with good mechanical strength capable of withstanding rotation and perforating a paraffin block, as explained below. For example, sampling tool 1 can be made of a rust-resistant material, such as stainless steel.

[0065] The sampling tool 1 is rotated by means of a sampling device and then inserted into a formalin-fixed, paraffin-embedded tissue block through the second end 2-2 of tube 2. The rotation of the sampling tool 1, combined with its insertion into the formalin-fixed, paraffin-embedded tissue block, allows for perforation of the block and sampling to a very shallow depth, for example, on the order of 20 µm, with a movement accuracy of the sampling tool on the order of 5 µm. The sample then remains in the recess of tube 2 at the second end 2-2. The presence or absence of the sample can thus be easily verified.

[0066] According to one embodiment of the invention, the sampling tool 1 allows samples to be taken with a diameter between 0.15 mm and 0.25 mm and / or a height between 0.1 mm and 0.35 mm, preferably between 0.1 mm and 1 mm.

[0067] As illustrated in Figures 1A and 1B, the second end 2-2 of the sampling tool 1 may be flat, i.e. that said end may not be beveled.

[0068] According to another object of the invention, it is provided that the sampling tool 1 described above is adapted to be inserted into a sampling device suitable for molecular analysis, from a block of tissue fixed in formalin and embedded in paraffin 10.

[0069] Thus the sampling device according to the invention comprises a sampling unit, a tray, a central base, a sampling tool 1 according to the invention and a gripping means.

[0070] The sampling device is designed so that it defines three axes of translation: an X axis, a Y axis perpendicular to the X axis, and a Z axis perpendicular to the X and Y axes. The X and Z axes lie in the same plane defined by the central base 9. The Z axis, however, lies in a plane perpendicular to the plane defined by the central base 9.

[0071] This particular architecture also allows the sampling device 6 to be mobile in three directions of space and to define a work zone located on the Z axis. Thus, all the elements of the platform 8 can be able to be found in the work zone.

[0072] The working area corresponds to the area where all actions are performed, such as sample collection, grasping, or releasing the sampling tool 1. According to the invention, the sampling unit is mounted on the central base and is movable in translation along a first X-axis, a second Z-axis, and a third Y-axis of the central base, the second Z-axis being perpendicular to the first X-axis and the third Y-axis. Thus, the sampling unit allows for the collection of samples from at least one block of formalin-fixed, paraffin-embedded tissue.

[0073] As mentioned previously, the sampling unit includes a sampling tool 1 for a sample according to the invention.

[0074] In addition, the sampling unit includes a gripping means arranged to form a reversible mechanical link with the first end of tube 2, so as to allow rotational and / or translational movement of tube 2 along a longitudinal axis of said tube.

[0075] The gripping means is further arranged to form a reversible mechanical link with the gripping end 3-2 of the rod 3 so as to allow a translational movement of the rod 3 along the longitudinal axis of the tube 2. For this purpose, the gripping means can be traversed by an actuable ejector, cooperating mechanically with the gripping end 3-2 so as to allow a longitudinal movement of the rod 3 independently of the tube 2.

[0076] By way of illustration, the sampling device may include a mobile ejection unit for the sampling tool 1. The mobile ejection unit may be arranged to allow the sampling tool 1 to be detached from the gripping means when said tool is in the ejection configuration. Specifically, in the ejection configuration, the mobile ejection unit may be arranged to allow the gripping means to be detached from the first end 2-1 of the tube 2 and from the gripping end 3-2 of the rod 3.

[0077] The sampling device according to the invention further comprises a tray comprising one or more formalin-fixed tissue blocks embedded in paraffin 10, the tray 8 being movable in translation along the third axis Y of the central base.

[0078] Finally, the sampling unit of the sampling device according to the invention is configured to allow the passage of the sampling tool 1 from a sampling configuration in which the ejection end of the rod body 3-1 partially occupies the recess of the second end 2-2 of the tube 2, to a sample ejection configuration in which the ejection end of the rod body 3-1 is deployed out of the second end 2-2 of the tube 2.

[0079] In one embodiment of the sampling device according to the invention, the latter may include a processor configured to control the sampling unit so as to position the second end of the tube 2 of the sampling tool 1 in contact with a predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block 10 and to control the switching of the sampling tool 1 to the sampling configuration. By way of example, the predetermined area may correspond to a digitized image of the formalin-fixed and paraffin-embedded tissue block 10 on which image coordinates describe an area to be sampled.

[0080] Furthermore, in one embodiment of the sampling device according to the invention, when the sampling tool 1 is in sampling configuration, the processor can be configured to control the sampling unit so that the second end of the tube 2 of the sampling tool 1 penetrates the predetermined area of ​​the formalin-fixed, paraffin-embedded tissue block 10 by a predetermined distance. By way of illustration, the predetermined area can be annotated with information relating to the tissue type of said area, and the processor can thus determine a sampling distance based on the tissue type.

[0081] Alternatively, when the sampling tool 1 is in sampling configuration, the processor can be configured to: command the sampling unit so that the end of the rod 3 of the sampling tool 1 comes into contact with the predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block 10 from a predetermined distance; command a displacement of the sampling unit along the first X axis and / or the third Y axis so that the end of the rod 3 of the sampling tool 1 scrapes the predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block 10. This embodiment is particularly suitable in connection with the embodiment of the sampling tool for which the second end 2-2 of the tube 2 is pointed and includes an adhesive substance.

[0082] To enable the determination and identification of a formalin-fixed, paraffin-embedded tissue block, the sampling device may include one or more means of identification. Specifically, each block or set of blocks may be identified by a unique identifier, inscribed, for example, on an RFID tag positioned beneath the block, which can be read by the identification means, or by a barcode that can be read by a camera, if the sampling device includes one.

[0083] According to any one of the embodiments mentioned above, the processor of the device according to the invention can further be configured to control the sampling unit so as to position the second end of the tube 2 of the sampling tool 1 above an analysis tube 21 of the tray 8 and to control the switching of the sampling tool 1 to the sample ejection configuration. The sample can then be expelled from the tube 2 towards the analysis tube 21 or the entire sampling tool can detach from the sampling unit towards the analysis tube 21.

[0084] To ensure the monitoring and traceability of the sampling process, from the formalin-fixed, paraffin-embedded tissue block 10 to its analysis, the sampling device according to the invention may include one or more identification means for identifying the formalin-fixed, paraffin-embedded tissue block 10 from which a sample is taken. By way of non-limiting example, the sampling device may include a data memory in which are associated an identifier for a formalin-fixed, paraffin-embedded tissue block and an identifier for an analysis tube 21 into which the sample is expelled. In addition, the identifiers of the block and the analysis tube may be associated with an identifier for the sampling tool, thus enabling the tracking and control of samples when they are used to perform molecular analyses.

[0085] To improve the control and monitoring of a sample, the sampling device may further include a camera arranged to record the passage of the sampling tool 1 from a sampling configuration to a sample ejection configuration.

[0086] In one embodiment of the sampling device, the latter may include a probing unit configured to determine a distance between the second end of the tube 2 and a surface of the formalin-fixed, paraffin-embedded tissue block 10. By way of illustrative examples, the probing unit may be mechanical or take the form of a distance determination system including a known type of laser.

[0087] An illustrative and non-limiting example of such a sampling device 6 is presented in connection with figures 2 to 9.

[0088] As illustrated in, the sampling device 6 includes a tray 8 comprising at least one block of formalin-fixed, paraffin-embedded tissue 10 and a sampling unit 7 which rest on a central base 9 which also allows them to be fixed and stabilized.

[0089] To allow the movement of the various elements of the sampling device 6 along each axis X, Y, and / or Z, a guide unit can be used to move these elements. Thus, we can distinguish: a guide unit along the X axis, a guide unit along the Y axis, and a guide unit along the Z axis.

[0090] The sampling unit 7 can be moved in translation along the X and Z axes. The platform 8 can, on the other hand, be moved in translation along the Y axis.

[0091] The illustration shows a guide unit enabling the movement of the sample collection unit 7 along the X axis. The guide unit may further include a first rail 11 on which rests a first ball carriage 12.

[0092] The first rail 11 can be fixed to the central base (not shown in the figure) and constitutes the reference for the guide unit along the X axis. Its size and load capacity provide the rigidity and geometric qualities useful to the sampling device 6.

[0093] The first ball carriage 12 can be mobile in translation on the first rail 11 and thus defines the X axis on which the sampling unit 7 can move.

[0094] The guide unit, along the X-axis, may also include a first motorized ball screw 13 fixed to the central base (not shown in the figure) and allowing the sampling unit 7 to be moved along the X-axis. The first motorized ball screw 13 may be parallel to the first rail 11 and allow movement along the X-axis with a resolution of less than 0.005 mm and a repeatability of less than 0.02 mm.

[0095] A second carriage 14 is also shown, which can be connected on one side to the first ball carriage 12 and on the other side to the first motorized ball screw 13 via a connecting member 15. The second carriage 14 can therefore be moved in translation along the X axis via the first rail 11 and the first motorized ball screw 13. The second carriage 14 is also adapted to accommodate the sampling unit 7.

[0096] A connecting element 15, consisting of a plate and a nut, can be mounted on the guide unit along the X-axis to provide translational rigidity and relative flexibility in other directions. This also allows for the acceptance and compensation of any potential parallelism between the first rail 11 and the first motorized ball screw 13.

[0097] A support area 16, or anvil, may be present on the second trolley 14 directly above the first rail 11 and the working area defined by the Z axis. This support area 16 also allows the connection with the platform 8 in translation along the Y axis by stabilizing it in rotation.

[0098] Larepresents optional identification means 17 configured to scan and identify all objects present on tray 8, for example formalin-fixed and paraffin-embedded tissue blocks 10 but also analysis tubes 21 and the sampling device 1. The identification means 17 can be on the second trolley 14 so as to allow identification of objects on tray 8 from below.

[0099] The identification means 17 may be of the optical reader type. They are preferably installed with an optical axis of 45 degrees and may include a vertical protection (not shown in the figure) to protect them from possible contamination.

[0100] The means of identification 17 can, for example, be cameras, with or without integrated lighting.

[0101] The illustration shows an optional guide unit along the Y axis allowing the movement of the plate 8 along the Y axis. The guide unit along the Y axis may further include a second motorized ball screw 18 and a slide 19.

[0102] The second motorized ball screw 18 can be fixed on the central base 9 and allow movement of the drawer 19 along the Y axis with a resolution of less than 0.005 mm and a repeatability of less than 0.02 mm.

[0103] The second motorized ball screw 18 can form the main axis of the guide unit along the Y axis. It can ensure the perpendicularity of the Y axis with the X axis. It is therefore preferably perpendicular to the first rail 11 and parallel to the second carriage 14.

[0104] Drawer 19 can be the central element on which the loading and unloading operations necessary for the operation of the sampling device 6 are carried out. The drawer can also be intended to receive the tray 8 (not shown in the figure).

[0105] The drawer 19 can be connected on the one hand to the second motorized ball screw 18 by means of a nut 48 and on the other hand to the central base 9 by means of a support point 20 provided with a means for rolling the drawer 19 on the central base 9. Thus, the drawer 19 can define the work surface on which the operations of the sampling device 6 are carried out.

[0106] The travel of drawer 19 along the Y axis can define three distinct zones: a loading and unloading zone allowing loading and unloading of tray 8 and / or objects on tray 8, a working zone, and an intermediate zone between the loading / unloading zone and the working zone.

[0107] The support zone 16 on the second carriage 14 can thus stabilize the drawer 19 when it is in the intermediate zone. Indeed, the intermediate zone can correspond to the point where a transfer of support occurs for the drawer 19, which is therefore subject to oscillations.

[0108] Laillustre a method of embodiment of a tray 8, which includes blocks of fabric fixed with formaldehyde and embedded in paraffin 10, mounted on a drawer 19 in translation along the Y axis.

[0109] According to the optional embodiment of the invention shown in the figure, the tray 8 may also include at least one analysis tube 21 suitable for receiving the sampling tool 1 containing the sample. This also allows the sampling tool 1 containing the sample to be released directly after sampling. The sampling tool 1 is therefore preferably single-use, which prevents any contamination between two samplings.

[0110] According to the embodiment of the invention shown in the figure, the platform 8 can also include a support 22 comprising at least one sampling tool 1. This also allows a sampling tool 1 to be available for taking a sample.

[0111] Thus, the tray 8 can be attached to the drawer 19 in a removable manner. The underside of the tray 8 can rest on the support area 16, which stabilizes it during the various operations performed by the picking device 6.

[0112] The formalin-fixed, paraffin-embedded tissue blocks 10 can be individually and removably attached to the tray 8 by means of a lock. This individual lock is designed to ensure that there is no contact that could compromise the integrity of the blocks.

[0113] Tray 8 can accommodate at least one block of formalin-fixed, paraffin-embedded tissue 10. Preferably, tray 8 comprises sixteen formalin-fixed, paraffin-embedded tissue blocks 10.

[0114] The tray 8 can also include a bar 23 for aligning the formalin-fixed and paraffin-embedded tissue blocks 10. The bar 23 allows for precise positioning of the formalin-fixed and paraffin-embedded tissue blocks 10 and for stabilizing them during operations performed by the sampling device 6. In particular, the bar 23 allows for rotational stabilization of the formalin-fixed and paraffin-embedded tissue block 10, especially when the sampling tool 1 is rotating during sample collection.

[0115] The illustration shows a guidance unit along the Z axis. This guidance unit can be directly installed on the second carriage 14 of the guidance unit along the X axis.

[0116] The guidance unit along the Z axis may further include a second rail 24 connected to the second carriage 14 and to a third and fourth ball carriage 25.

[0117] On the third and fourth ball carriages 25, a first support 27 and a second support 28 can be fixed, intended to receive the various moving elements in translation along the Z axis.

[0118] A third motorized ball screw 26 can be connected to the first support 27 and allow the first and second supports 27 and 28 to move along the second rail 24 of the guide unit along the Z-axis. The third motorized ball screw 26 can also allow movement along the Z-axis with a resolution of less than 0.005 mm and a repeatability of less than 0.2 mm.

[0119] The Z-axis guide unit and the Z-axis moving elements can be fixed on the second carriage 14. Thus, the Z-axis moving elements can be translationally mobile along the Z-axis but also along the X-axis.

[0120] Figures 5B to 5D illustrate non-limiting examples of moving elements translating along the Z-axis, which may also include:

[0121] A camera 29 for image capture. The camera 29, possibly equipped with lighting, is capable of recording images of platform 8 and of the sampling tool 1.

[0122] A sampling unit 7. The sampling unit 7 is intended to receive the sampling tool 1 (not shown in figures 5A to 5D) and is capable of being rotated by means of a mechanical means such as a motor.

[0123] Thus, the sampling unit 7 is mobile in translation along the X axis and along the Z axis.

[0124] A mobile ejection unit 30 of the sampling tool 1 of the sampling unit 7.

[0125] A motorization unit 31 for clamping the sampling unit 7. The motorization unit 31 also enables the gripping and release of the sampling tool 1 from the sampling unit 7.

[0126] A retractable mechanical probing unit 32, in the sense that it is able to be coupled or decoupled from the guide unit along the Z axis. The mechanical probing unit 32 also allows probing the height of the formalin-fixed and paraffin-embedded tissue blocks 10 (not shown) so as to allow defining the zero point for calculating the length of the core or the pancake.

[0127] Lare represents a non-limiting example of a mechanical probing unit 32. It further comprises two units: A locking mobile 33 which allows the mechanical probing unit 32 to be locked in position, thus allowing it to be retractable and to be coupled or uncoupled from translational movements along the Z axis. A detecting mobile composed of a probe 34 and a pressure switch 35.

[0128] The mechanical probing unit 32 is held by means of the compression spring 36. It allows probing, with an effort of less than 1 Newton, of the height of a block of tissue fixed in formalin and embedded in paraffin given.

[0129] Overall, the formalin-fixed, paraffin-embedded tissue block is modeled from at least three measurement points. Locally, the working area is directly palpated.

[0130] The pressure switch 35, associated or not with the digital control of the guidance unit along the Z axis, ensures a measurement of the height of the formalin-fixed and paraffin-embedded tissue block 10 palpated with an accuracy of less than 0.01 mm.

[0131] When the blocking mobile 33 is in the clear position, the mechanical probing unit 32 is linked to the guidance unit along the Z axis and is able to take measurement points of the height of the formalin-fixed and paraffin-embedded tissue block 10. In addition, the mechanical probing unit 32 is activated before the sampling unit 7.

[0132] When the locking mobile 33 is in the engaged position, the probing unit 32 is detached from the guiding unit along the Z axis and remains in the raised position without interfering with the action of the sampling unit 7 which remains mobile in translation along the Z axis.

[0133] Figure 1 represents a non-limiting example of a sampling unit 7 according to an embodiment of the invention. The sampling unit is represented here by a spindle comprising: A rotating gear 37. A main sleeve 38. A gripper 39 for gripping and releasing the sampling tool 1. The gripping is further ensured by elastic deformation. A main bearing 40, which may be a double-row angular contact bearing. A secondary bearing 41. A locking means 42 for locking the gripper 39. A locking spring 43.

[0134] The toothed wheel 37 is preferably connected to a drive motor (not shown) of the sampling device 6. This enables the rotation of the sampling unit 7 and the sampling tool 1.

[0135] Bearings 40 and 41 facilitate the rotation of the sampling unit 7.

[0136] The locking means 42 is thus raised to the upper position by means of the motorization unit 31 for clamping the sampling unit 7. This allows the clamp 39 to open so as to allow the sampling tool 1 to be gripped. The opposite action of the locking spring 43 allows the clamp 39 to close and lock the sampling tool 1 in the sampling unit 7. The sampling tool 1 then becomes an integral part of the sampling unit 7 and the locking means 42 is in the lower position.

[0137] Lare represents a non-limiting example of a mobile ejection unit 30 of the sampling tool 1 which further comprises: A motor 44 including a rod. An ejector 45 passing through the entire sampling unit 7. A drive 46 fixed on one side to the motor 44 and, on the other side, to the ejector 45. A return spring 47 surrounding the ejector 45 and located between the drive 46 and the top of the sampling unit 7.

[0138] Thus, ejection of the sampling tool 1 is possible when the locking means 42 of the sampling unit 7 is in the high position and the gripping means is open.

[0139] When the motor 44 is deactivated, the return spring 47 locks the ejector 45 in the raised position via the drive 46.

[0140] When the motor 44 is activated, the rod moves downwards and thus drives downwards the driver 46 which in turn drives the ejector 45. The end of the ejector 45 being in the sampling unit 7 then pushes the sampling tool 1 out of the sampling unit 7.

[0141] To ensure that the sampling tool 1 is gripped by the clamp 39 and more generally by the gripping means, said sampling tool can be integrated into a tool holder 22-1 embedded in the support 22, as shown in Figure 1. The tool holder 22-1 advantageously has a beveled edge suitable for the gripping means, thus facilitating the gripping of the gripping end 3-2 of the sampling tool 1 and its positioning in the sampling unit 7.

[0142] In one particular embodiment, the sampling device 6 according to the invention may include a detection system, such as a dedicated sensor or a camera, configured to indicate whether or not the sampling tool 1 is connected to the gripping means. This information is advantageously processed by the sampling device 6 so as to automatically ensure the acquisition of a new sampling tool 1, present in the tool holder 22-1, when the detection system indicates that the gripping means does not already include a sampling tool 1. Otherwise, the sampling device 6 according to the invention may malfunction and stop the automated sampling.

[0143] According to a third aspect, as illustrated in Figures 10, 11 and 12, the invention relates to a method for taking 100 of a sample, suitable for molecular analysis, from a block of tissue fixed in formalin and embedded in paraffin 10, said method being implemented by a sampling device 6 according to the invention, said method comprising a receiving step 110 of a digitized image 101 of a colored section of a block of tissue fixed in formalin and embedded in paraffin 10, an identification step 120 of the block of tissue fixed in formalin and embedded in paraffin 10, a capture step 140 of a second digitized image 102, a superposition step 150 and transfer and a control step 170 of the sampling unit 7.

[0144] Thus, the sampling method 100 according to the invention includes a receiving step 110 of a digitized image 101 of a colored section of a formalin-fixed, paraffin-embedded tissue block 10, the digitized image comprising at least one predetermined annotated area 101-1. Indeed, as mentioned previously, the sampling device 6 is intended to include at least one formalin-fixed, paraffin-embedded tissue block 10; a digitized image 101 of a colored section of each of these blocks is generated and then annotated. By way of illustrative examples, the image can encode information relating to a tissue type described by image coordinates or by an RGB value or range of values ​​associated with the pixels of the digitized image and relating to a tissue component or, more generally, to a tissue type.Such a digitized image 101 of a colored section may for example be derived from a colored histological section of the corresponding formalin-fixed, paraffin-embedded tissue block 10 from which an anatomopathological examination was carried out.

[0145] The sampling method 100 according to the invention further includes an identification step 120 of the formalin-fixed, paraffin-embedded tissue block 10 from which the digitized image 101 of the colored section of formalin-fixed, paraffin-embedded tissue is derived. To enable identification of the corresponding formalin-fixed, paraffin-embedded tissue block, the digitized image 101 of the colored section may include an identifier relating to the formalin-fixed, paraffin-embedded tissue block 10 from which it is derived. The identifier of the digitized image may be compared to an identifier of each block, read via the identification means 17 of the sampling device 6, if so provided, or via a dedicated camera, in order to determine which block corresponds to the digitized image.To facilitate such determination, the sampling device 6 may include a data memory in which are listed the identifiers of each block of tissue fixed in formalin and embedded in paraffin 10.

[0146] Once the formalin-fixed, paraffin-embedded tissue block 10 has been identified, the sampling process 100 according to the invention includes a step of capturing 140 a second digitized image 102 of the identified formalin-fixed, paraffin-embedded tissue block 10 followed by a step of superimposing 150 the first digitized image 101 onto the second digitized image 102. The superimposing step 150 may include an adjustment of the resolution of the first digitized image 101 relative to the second digitized image 102.

[0147] The sampling method 100 according to the invention then includes a step of transferring the predetermined annotated area 101-1 onto the second digitized image 102. More particularly, a correspondence between the coordinates, in a two-dimensional plane X, Y, of the pixels relating to the predetermined annotated area 101-1 and the pixels of the second digitized image 102 can allow the predetermined annotated area 101-1 to be transferred.

[0148] The sampling process 100 finally includes a control step 170 of the sampling unit 7 of the sampling device 6 so as to take a sample of the formalin-fixed, paraffin-embedded tissue block 10 according to the marking, i.e., the transfer of the predetermined annotated area 101-1, from the second digitized image 102. Indeed, all the elements of the tray 8, or more generally of the drawer 19, are identified and their position is known. For example, the formalin-fixed, paraffin-embedded tissue blocks 10 are placed on a dedicated section of the tray 8. Furthermore, the identification means 17 are designed to be configured to allow the position of each element of the tray 8 to be determined.As an alternative or complement, the sampling unit 7 may include a camera arranged to generate digital images of the tray 8 and the processor of the sampling unit 7 may be configured to determine the position of each element of the tray in real time.

[0149] To optimize the collection of a sample suitable for molecular analysis, the predetermined annotated area 101-1 may include sampling coordinates, tissue typology, and associated pathology. Furthermore, the sampling method 100 according to the invention may include a determination step 160, prior to the control step 170 of the sampling unit 7, of a sampling length based on the sampling coordinates, tissue typology, and associated pathology of the predetermined annotated area.For this purpose, the sampling device 6 according to the invention may include a data memory in which is recorded a reference database indicating a predetermined sampling length based on a tissue typology, for example this may include epithelial tissues and their subgroups (surface epithelia, glandular epithelia, sensory epithelia), connective and supporting tissues and their subgroups (collagenous and reticular connective tissues, adipose tissues, supporting tissues which are divided between cartilage and bone), muscular tissues and their subgroups (striated muscle, cardiac muscle, smooth muscle) or nervous tissues and their subgroups (neurons, glial cells) and an associated pathology.

[0150] In one embodiment of a sampling method 100 according to the invention, this method may include a sampling preparation step 130 comprising: A determination 131, based on the sampling coordinates and tissue type, of the number of sections to be prepared from the formalin-fixed, paraffin-embedded tissue block 10. Preparing these sections preserves the formalin-fixed, paraffin-embedded tissue block 10, since the sampling will be performed on these sections and not directly from the original formalin-fixed, paraffin-embedded tissue block 10. At least one section 135 with a thickness between 10 µm and 600 µm from the formalin-fixed, paraffin-embedded tissue block 10.In addition, step 131 of the determination process may include a verification of the cell typology. This verification involves preparing an additional reference section at the same sampling coordinates but at a different depth, and fixing it to a histological slide and staining it to verify that the section contains the tissue typology of interest related to the pathology. If the tissue typology identified in the histological slide differs from the cell typology of the additional reference section from the predetermined area labeled 101-1, then the sampling is invalidated and the procedure is stopped. Each section is fixed to a support, forming a subblock of formalin-fixed, paraffin-embedded tissue to be sampled.From each section, it is possible to form a sub-block fixed to a support adapted to the section, i.e., a flexible support allowing sampling by the sampling device 6 according to the invention; in particular, a flexible support may correspond to a block composed of paraffin. Implementation of the capture steps 140, the layering step 150, and the control step 170 from each sub-block of formalin-fixed tissue embedded in paraffin 10. The implementation of these steps from sections of a formalin-fixed tissue block embedded in paraffin 10 thus makes it possible to further limit the recovery of unwanted components, mainly paraffin but also unwanted biological material, in the sample, which often poses a problem in the context of the desired molecular analysis.

[0151] The 100 sampling process allows for precise control of the sampling of a portion of biological material from each section and control of the thickness of the "tissue pancake" sampled, thus defining a desired cell volume of a tissue type of interest, without being "contaminated" by other tissue types, in order to perform a more precise quantitative analysis in molecular biology.

[0152] In one embodiment of a sampling method according to the invention, the support can be a virgin paraffin block. The virgin paraffin block can have a predetermined thickness, thus allowing control of the quantities of paraffin and biological material to be sampled from the section of the formalin-fixed, paraffin-embedded tissue block, thereby ensuring optimal reproducibility of the sampling.

[0153] Furthermore, in order to further improve the reproducibility of the sampling and to allow for precision in the quantity of biological material collected, the sampling process 100 according to the invention may include the following steps: Soaking 132 a paraffin plastic film in liquid paraffin. The soaking step 132 is preferably carried out before the cutting step 135. The paraffin plastic film may be cut to the dimensions of the blank paraffin block and then soaked in liquid paraffin, for example at 62°C, so that the paraffin plastic film becomes transparent. Initial positioning 133 of the paraffin plastic film on a contact surface of the formalin-fixed, paraffin-embedded tissue block 10. The contact surface of the formalin-fixed, paraffin-embedded tissue block 10 may correspond to a face from which a section is intended to be made.The contact surface can thus be roughed out with a microtome in order to remove the excess paraffin in which the biological material is embedded.

[0154] Advantageously, the paraffin-embedded plastic film can have dimensions substantially similar to, or even larger than, those of the contact surface of the paraffin-fixed tissue block 10, for example, along the length and / or width of said block. A first heat treatment 134 is carried out at the melting temperature of the paraffin-embedded plastic film. At least one section 135 with a thickness between 10 µm and 600 µm, as previously mentioned, the section comprising securing the fused plastic film to the contact surface of the paraffin-embedded tissue block 10, for example, by means of a fastening device such as clips. The fastening device can, for example, be arranged to hold two longitudinally opposite ends of the fused plastic film. This prevents the section from curling up on itself and the paraffin from cracking and disintegrating.

[0155] In this embodiment, the fixation step 136 comprises: A second heat treatment 137 at the melting temperature of a virgin paraffin block and of the section of the formalin-fixed, paraffin-embedded tissue block 10 fused to the paraffin plastic film. The heat treatments 134 and 137 can be carried out using a heating plate. A second positioning 138 of the section of the formalin-fixed, paraffin-embedded tissue block 10 and of the paraffin plastic film on the virgin paraffin block. This second heat treatment 137 thus allows the section / paraffin plastic film assembly to adhere to the virgin paraffin block. The paraffin plastic film is oriented to form a protective layer, so the section is placed between the paraffin plastic film and the virgin paraffin block. Of course, the paraffin plastic film can also be removed mechanically, for example with tweezers, if necessary.

[0156] Thus, this allows the section of the formalin-fixed, paraffin-embedded tissue block to be transferred onto the blank paraffin block and to preserve the topography, maintaining its flatness and without any artifacts such as folds or tears, biological material and thus ensures an optimal comparison with a digitized image 101 of a colored section of a reference formalin-fixed, paraffin-embedded tissue block 10.

Claims

A sampling tool (1) for collecting a sample, adapted for molecular analysis, from a formalin-fixed, paraffin-embedded tissue block (10) for a sampling device (6), characterized in that the sampling tool (1) comprises: a tube (2) having a recess opening onto a first and a second end (2-1, 2-2) of the tube (2), a rod (3) comprising a rod body (3-1), an ejection end and a gripping end (3-2) extending out of the first end (2-1) of the tube (2), so as to allow movement of the rod (3) along a longitudinal axis of the tube (2), wherein: the first end (2-1) of the tube (2) is arranged to form a reversible mechanical connection with a gripping means of a sampling unit (7) of a sampling device (6) so as to allow rotational and / or in translation of the tube (2) along the longitudinal axis of said tube,the second end (2-2) of the tube (2) is adapted to take a sample from the formalin-fixed, paraffin-embedded tissue block (10), the gripping end (3-2) of the rod (3) is arranged to form a reversible mechanical link with a gripping means of a sampling unit (7) of a sampling device (6) so as to allow translational movement of the rod (3) along the longitudinal axis of the tube (2), the sampling tool (1) being further arranged to move from a sampling configuration in which the ejection end of the rod body (3-1) partially occupies the recess of the second end (2-2) of the tube (2), to a sample ejection configuration in which the ejection end of the rod body (3-1) is deployed out of the second end (2-2) of the tube (2). Sampling tool (1) according to claim 1, characterized in that the second end (2-2) of the tube (2) is pointed and has a surface, intended to come into contact with the formalin-fixed and paraffin-embedded tissue block (10), which includes an adhesive substance. sampling tool (1) according to one of claims 1 or 2, characterized in that the rod (3) is made of brass. sampling tool (1) according to any one of claims 1 to 3, characterized in that the internal diameter of the tube (2) is between 50 µm and 200 µm. Sampling tool (1) according to any one of claims 1 to 4, wherein the first end (2-1) of the tube (2) and the gripping end (3-2) are arranged to permit disengagement with a gripping means of a sampling unit (7) of a sampling device when the sampling tool (1) is in ejection configuration. A sampling device (6) for taking a sample, suitable for molecular analysis, from a formalin-fixed, paraffin-embedded tissue block (10), said sampling device (6) comprising: a sampling unit (7) mounted on a central base (9) for taking samples from at least one formalin-fixed, paraffin-embedded tissue block (10), said sampling unit (7) being translationally movable along a first X-axis, a second Z-axis, and a third Y-axis of the central base (9), the second Z-axis being perpendicular to the first X-axis and the third Y-axis; a tray (8) comprising one or more formalin-fixed, paraffin-embedded tissue blocks (10), said tray (8) being translationally movable along the third Y-axis of the central base (9), in which the sampling unit (7) comprises: a sampling tool (1) for taking a sample, suitable for molecular analysis,of the formalin-fixed, paraffin-embedded tissue block comprising: a tube (2) having a recess opening onto a first and a second end (2-1, 2-2) of the tube (2), the second end (2-2) of the tube (2) being adapted for taking a sample of the formalin-fixed, paraffin-embedded tissue block (10), a rod (3) comprising a rod body (3-1), an ejection end and a grasping end (3-2) extending out of the first end (2-1) of the tube (2), so as to permit movement of the rod (3) about a longitudinal axis of the tube (2), a grasping means arranged to form a reversible mechanical connection with the first end (2-1) of the tube (2), so as to permit rotational and / or translational movement of the tube (2) about a longitudinal axis of said tube,the gripping means being further arranged to form a reversible mechanical link with the gripping end (3-2) of the rod (3) so as to allow translational movement of the rod (3) along the longitudinal axis of the tube (2), the sampling unit (7) being further configured to allow the passage of the sampling tool (1) from a sampling configuration in which the ejection end of the rod body (3-1) partially occupies the recess of the second end (2-2) of the tube (2), to a sample ejection configuration in which the ejection end of the rod body (3-1) is deployed out of the second end (2-2) of the tube (2). Sampling device (6) according to claim 6, characterized in that it comprises a processor configured to control the sampling unit (7) so as to position the second end (2-2) of the tube (2) of the sampling tool (1) in contact with a predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block (10) and to control the switching of the sampling tool (1) to the sampling configuration. Sampling device (6) according to claim 7, wherein when the sampling tool (1) is in sampling configuration, the processor is configured to control the sampling unit (7) so that the second end (2-2) of the tube (2) of the sampling tool (1) penetrates the predetermined area of ​​the formalin-fixed, paraffin-embedded tissue block (10) from a predetermined distance. Sampling device (6) according to claim 7, wherein, when the sampling tool (1) is in sampling configuration, the processor is configured to: command the sampling unit so that the end of the shaft (3) of the sampling tool (1) comes into contact with the predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block (10) from a predetermined distance, command a displacement of the sampling unit along the first X axis and / or the third Y axis so that the end of the shaft (3) of the sampling tool (1) scrapes the predetermined area of ​​the formalin-fixed and paraffin-embedded tissue block (10). Sampling device (6) according to any one of claims 7 to 9, characterized in that the processor is configured to control the sampling unit (7) so as to position the second end of the tube (2) of the sampling tool (1) above an analysis tube (21) of the tray (8) and to control the switching of the sampling tool (1) to the sample ejection configuration. Sampling device (6) according to any one of claims 6 to 10, characterized in that it further comprises one or more means of identification (17) enabling identification of at least one block of formalin-fixed, paraffin-embedded tissue (10). Sampling device (6) according to any one of claims 6 to 11, characterized in that it also includes at least one camera (29) arranged to record the passage of the sampling tool (1) from a sampling configuration to a sample ejection configuration. Sampling device (6) according to any one of claims 6 to 12, characterized in that it further comprises a probing unit configured to determine a distance between the second end (2-2) of the tube (2) and a surface of the formalin-fixed, paraffin-embedded tissue block (10). Sampling device (6) according to any one of claims 6 to 13, characterized in that it further comprises a mobile ejection unit (30) of the sampling tool (1) of the sampling unit (7), the mobile ejection unit (30) being arranged to allow the sampling tool (1) to be detached from the gripping means when said tool is in ejection configuration. A method for taking (100) a sample, suitable for molecular analysis, from a formalin-fixed, paraffin-embedded tissue block (10), said method being carried out by a sampling device (6) according to any one of claims 6 to 14, the method comprising the following steps: receiving (110) a digitized image (101) of a colored section of a formalin-fixed, paraffin-embedded tissue block (10), the digitized image (101) of a colored section comprising at least one predetermined annotated area (101-1), identifying (120) the formalin-fixed, paraffin-embedded tissue block (10) from which the digitized image (101) of a colored section of the formalin-fixed, paraffin-embedded tissue block (10) is taken, capturing (140) a second digitized image (102) of the block of tissue fixed in formalin and embedded in paraffin (10) identified,superimposition (150) of the first digitized image (101) onto the second digitized image (102) and transfer of the predetermined annotated area (101-1) onto the second digitized image (102), command (170) of the sampling unit (7) so as to take a sample from the formalin-fixed, paraffin-embedded tissue block (10) according to the marking of the second digitized image (102). Sampling method (100) according to claim 15, wherein the predetermined annotated area (101-1) includes sampling coordinates, a tissue typology and an associated pathology, said method further comprising a determination step (160), prior to the control step (170) of the sampling unit (7), of a sampling length as a function of the sampling coordinates, the tissue typology and the associated pathology of the predetermined annotated area (101-1). A sampling method (100) according to any one of claims 15 or 16, said method comprising a sampling preparation step (130), the preparation step (130) comprising: a determination (131), based on the sampling coordinates and tissue typology, of a number of sections of the formalin-fixed, paraffin-embedded tissue block (10) to be made, at least one section (135) of a thickness between 10 µm and 600 µm of the formalin-fixed, paraffin-embedded tissue block (10), fixation (136) of each section on a support, each section forming a sub-block of formalin-fixed, paraffin-embedded tissue to be sampled, implementation of the capture (140), superposition (150) and ordering (170) steps from each sub-block of formalin-fixed, paraffin-embedded tissue (10). A sampling method (100) according to claim 17, wherein the support is a virgin paraffin block and wherein the preparation step (130) further comprises the following steps: soaking (132) a paraffin plastic film in liquid paraffin, first positioning (133) of the paraffin plastic film on a contact surface of the formalin-fixed, paraffin-embedded tissue block, first heat treatment (134) at the melting temperature of the paraffin plastic film (10), at least one cut (135) of a thickness between 10 µm and 600 µm comprising holding the fused paraffin plastic film on the contact surface of the formalin-fixed, paraffin-embedded tissue block (10),and wherein the fixation step (136) comprises: a second heat treatment (137) at a melting temperature of the virgin paraffin block and of the section of the formalin-fixed, paraffin-embedded tissue block fused to the paraffin plastic film, a second positioning (138) of the section of the formalin-fixed, paraffin-embedded tissue block and of the paraffin plastic film on the virgin paraffin block.

Images