Clamping device and methods for its manufacture and use

Abstract

A clamping device (10) for clamping and positioning a tissue sample, in particular a tissue section, is described, comprising a gripping pliers (5) with two pre-tensioned gripping jaws (5a, 5b), a first (1a) and a second spring leg (1b) connected thereto, wherein the gripping jaws (5a, 5b) are arranged at an angle to each spring leg (1a, 1b) and a spring element (3) formed by one of the spring legs (1a, 1b), wherein at least one spring leg (1a, 1b) is deflectable in order to move the gripping pliers (5) into an open position.

Description

[0001] The present invention relates to a clamping device for clamping and positioning a tissue sample over a flat surface, to a method for manufacturing the same, and to a method for clamping a tissue sample using the same and their use according to the preamble of the independent claims. State of the art

[0002] In modern cancer medicine, the goal is to tailor therapy as closely as possible to the needs of each individual patient. Efforts are made to address individual circumstances (personal characteristics and genetic predispositions). Based on molecular genetic analyses of, for example, tumor tissue, the aim is to target the pathologically altered cells as effectively as possible and, if possible, to avoid non-specific chemotherapy, which attacks all rapidly growing cells and with all its associated side effects. This approach seeks to protect healthy body cells as much as possible and to prevent the growth and spread of diseased tumor cells in a targeted manner.

[0003] For this purpose, it is necessary to cultivate tissue, especially tumor tissue, in order to test the effects of drugs on it ex vivo. This is possible, for example, using fluorescence microscopes with a cultivation unit, in which samples are cultured, stained, and treated with active substances to test their efficacy.

[0004] To obtain good optical access to biopsied tissue, the punched or otherwise obtained samples are cut into thin slices and placed in the culture medium. These tissue sections have, for example, dimensions of 5 mm laterally and a thickness of 200 µm. When placed in the receiving containers, they curl up undefinedly, clump together, or move uncontrollably when the culture vessels are moved, thus severely impairing the introduction of light and optical accessibility.

[0005] DE 4306310 A1 discloses a receiving block for a tissue sample with an opening into which the tissue sample is inserted. To prevent loss of the tissue sample, it is held by mesh filters or nonwovens arranged on both sides of the sample.

[0006] DE 102019101035 A1 discloses a sample holder for a tissue sample with two plates that are held together by means of magnetic elements and between which a tissue sample can be clamped. Disclosure of the invention

[0007] Against this background, a clamping device, a method for manufacturing the same, and a method for clamping a tissue sample into the same and their use with the characterizing features of the independent claims are provided according to the invention.

[0008] The clamping device according to the invention is designed for clamping and positioning a tissue sample, in particular a tissue section, over a flat area.

[0009] A tissue sample can refer, for example, to a biopsied tissue sample from plants, animals or humans, particularly with a thickness between 10µm and 10mm.

[0010] In the context of the present invention, "flat clamping" means that the tissue sample, for example the tissue section, is stretched across a flat surface and cannot curl up or clump together.

[0011] The clamping device comprises a gripping jaw formed from two pre-tensioned jaws. This means that the jaws are pre-tensioned, causing them to press against each other. Furthermore, the clamping device includes a first and a second spring arm, with each gripping jaw arranged at an angle to each spring arm. One of the spring arms forms a spring element. This spring element can be, for example, a tab-, wave-, or loop-shaped protrusion of the spring arm that is flexible or resilient, at least in the direction of the gripping jaw. At least one of the spring arms, and preferably both, can be reversibly deflected, for example, downwards or upwards, to move the gripping jaw into an open position. For this purpose, a compressive force F is applied to an upper and / or lower surface of the spring element, causing the spring arm to move into the open position.Moving the spring-loaded arms causes the gripping jaws to be pulled apart. In the open position, a tissue sample can be inserted into the gripping forceps, so that the forceps act as a frame in which the tissue sample is held.

[0012] The spring force of the gripping jaws can be adjusted to the thickness and width of the tissue sample, for example, by modifying the geometry, particularly the material thickness of the clamping device, the length of the spring element, and the length of the spring legs. The spring legs, for instance, have a length of 20–30 mm.

[0013] The advantage here is that the tissue sample retains its flat shape when clamped in the device, thus ensuring optimal accessibility. This is particularly beneficial for microscopic, and especially fluorescence microscopic, examination of the tissue sample, as optical accessibility and the introduction of light for examination are crucial factors. Furthermore, the clamp prevents the tissue sample from moving uncontrollably in the sample liquid when a sample or culture vessel, into which the clamp is inserted, is moved, which could impair the optical examination.

[0014] The clamping device immobilizes the tissue sample in such a way as to ensure excellent conditions for its examination, particularly optical examination. The tissue sample is also thus easily accessible for culture media, test substances, drugs, intercalating dyes, antibodies, and the like.

[0015] Furthermore, the clamping device can be advantageously used for transporting the tissue sample. For this purpose, the tissue sample is first picked up or clamped by the device and then immersed in liquid nitrogen, so that the tissue sample can be transported frozen in a flat shape, either clamped in the device and together with it, or alternatively without it.

[0016] Further advantageous embodiments of the present invention are the subject of the dependent claims.

[0017] In an advantageous embodiment, the spring element is formed, for example, by the first, outer spring leg. This has the advantage that the spring element does not obstruct the view of the tissue sample clamped in the clamping device, allowing the operator to visually inspect it, for example, to verify whether the tissue sample is correctly clamped or whether the clamping device is properly inserted into a container. Furthermore, the center of gravity of the clamping device is shifted to the side of the spring element, so that the clamping device can be leaned against a container into which it is inserted on that side. Alternatively, the spring element is formed by the second, inner spring leg. This provides the operator with particularly good access to the clamping device, allowing for easy operation.

[0018] It is advantageous if the clamping device is made of a metal, in particular a corrosion-resistant stainless or spring steel and / or if the clamping device includes titanium.

[0019] Advantages of using corrosion-free spring steel include its corrosion resistance, long service life, easy formability, and high strength, which allows the spring steel to return to its initial position after pressure is released without permanent deformation. Furthermore, the strength properties can be specifically adjusted and thus adapted to the application.

[0020] The advantages of using titanium include its high strength, toughness, and hardness combined with low density, making it both stable and lightweight. Titanium is also corrosion-resistant, temperature-resistant, and biocompatible. Alternatively or additionally, it is advantageous if the clamping device comprises a thermoplastic material, in particular polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polyetheretherketone (PEK), polytetrafluoroethylene (PTFE), Teflon, and / or polytetrafluoroethylene (TPFE).

[0021] Compared to metallic materials, their lighter weight and lower modulus of elasticity (E-modulus) make them softer and more pliable, thus allowing for gentler clamping of the tissue sample. A clamping device made of thermoplastic material is also very cost-effective.

[0022] A further advantage of all the aforementioned materials is their biocompatibility and the fact that they are non-cytotoxic, meaning the clamping device does not affect the tissue sample. Furthermore, these materials can be sterilized or autoclaved, ensuring the clamping device is sterile for use and reusable, thus allowing for multiple uses.

[0023] Furthermore, a clamping device made of hybrid materials is also conceivable. For example, the spring arms could be made of a metal, particularly stainless steel, while the gripping forceps and / or jaws are made of a thermoplastic material, or vice versa. In this case, the jaws could be disposable. It is also conceivable that the jaws, for example, made of stainless steel as a reusable component, could be combined with a disposable component made of a thermoplastic material. This could be visualized, for example, as a kind of overshoe. Additionally, metal-made jaws could have a coating, for example, of silicone, heparin, and / or hyaluronic acid. This could, for example, prevent rejection reactions of the tissue sample.

[0024] In a further advantageous embodiment, the spring element is arranged orthogonally, i.e., at an angle of 90° to the main axis of the spring leg that forms the spring element. The advantage here is that optimal force transmission from the spring element to at least one, and advantageously to both, spring legs occurs, so that the gripping jaws are pulled apart and the clamping device is moved into an open position.

[0025] Alternatively, the spring element is arranged at an angle of less than 90° or greater than 90° to the main axis of the spring leg that forms the spring element. This can offer ergonomic advantages, such as good accessibility and ease of use.

[0026] The spring element is positioned in the upper half of the spring leg that forms it. This allows for easy and convenient operation of the clamping device, and it also allows the device to extend beyond a sample container, particularly a culture vessel, into which it is inserted, and to be supported by it. This ensures stable positioning of the clamping device within the container. Alternatively, the spring element can be positioned at any desired location on the spring leg.

[0027] In a particularly advantageous first embodiment, the first spring leg has a central recess in an overlapping spring leg area, and the second spring leg tapers and has a bending area, so that the spring legs can be positioned interlocking, similar to the interlocking of an inverted pair of tweezers.

[0028] For this purpose, the slendered spring leg is bent or folded multiple times and passed through the recess of the other spring leg, so that the spring leg initially located on a front side is now on a back side in the area of ​​the gripping jaws. Here, "front side" refers, for example, to the side of the spring leg towards which the gripping jaws point, and "back side" refers to the side of the spring leg away from which the gripping jaws point. In an alternative advantageous embodiment, for example, both spring legs are slendered in the overlapping area, particularly asymmetrically, so that they can be positioned interlocking. At the point freed by the slendering of one spring leg, the other spring leg crosses it, so that the spring leg initially located on a front side is then moved to a back side, and vice versa.The advantage here is that the interlocking spring arms position them very precisely relative to each other, resulting in the gripping jaws lying very accurately on top of each other and, after the gripping forceps are opened, precisely aligning again when they close. This ensures precise, defined, and secure clamping of the tissue sample between the gripping jaws and prevents slippage or sliding of the jaws against each other, thus also guaranteeing that no loss of preload occurs. Furthermore, the tissue sample is simply clamped during clamping and is not subjected to any additional shear stress.

[0029] At least one end of the gripping jaw of the gripping pliers is, for example, round, square, grid-shaped, or forked. A forked gripping jaw can have two or more prongs. Each of the above-mentioned shapes of the gripping jaw ends can have rounded or square edges.

[0030] Advantageously, at least one gripping jaw of the gripping pliers has a recess which has a round, oval, angular and / or grid-like, in particular net-like, shape.

[0031] Alternatively, the gripping jaw can also have several such recesses. The advantage of one or more recesses in the gripping jaw, and especially in both gripping jaws, is that the tissue sample is held firmly and securely and cannot buckle, slip out, or curl up on one side, thus ensuring a flat grip and positioning of the tissue sample held by the gripping forceps.

[0032] In one embodiment, for example, the gripping jaws of the gripping pliers are designed to be analogous to each other.

[0033] The advantage here is that the entire surface of the gripping jaws is used to hold the tissue sample, so there is no additional material to obstruct the visual view of the sample. Furthermore, this ensures that the gripping jaws exert even, uniform pressure on the tissue sample.

[0034] A benefit of gripping jaws with a grid-like design is that even small tissue samples can be held very securely.

[0035] Alternatively, the gripping jaws of the gripping forceps can have different shapes. An advantage here is, for example, a good compromise between visual accessibility, ease of handling, and secure gripping of the tissue sample. A grid-like lower gripping jaw or a fork-shaped lower gripping jaw with an additional continuous crossbar connecting the tines of the fork facilitates the picking up of a tissue sample because the tissue can then be gripped across its entire surface, similar to a cake server. If an upper fork-shaped gripping jaw does not have this crossbar, or if material of the upper gripping jaw is omitted elsewhere, then a larger area of ​​the tissue sample is advantageously visible, thus facilitating visual analysis. This example can also be applied to other gripping forceps geometries with different gripping jaws.

[0036] In a particularly advantageous embodiment, the gripping pliers are arranged on the spring legs at an angle α of 45°-175°, and preferably of 125°.

[0037] Depending on the circumstances and conditions, this angle can easily be changed.

[0038] In a further advantageous embodiment, the clamping device comprises a holding element which is formed from an extension of the spring legs.

[0039] The clamping device can be held by the holding element and inserted, for example, into a sample container, particularly a culture vessel containing culture medium, without affecting the tension of the clamped tissue sample. The advantage of this is that there is no risk of the tissue clamped in the forceps becoming dislodged when holding the clamping device by the handle.

[0040] The shape of the clamping device is, for example, tailored to the shape of the sample container, particularly the cultivation vessel, and is positioned within it. The holding element can optionally be omitted if the clamp is held in place by other means. In this case, the manufacturing process for the clamping device, such as the sheet metal cutting and bending, is modified accordingly.

[0041] Another object of the invention relates to a method for manufacturing the clamping device according to the invention for clamping and positioning a tissue sample over a flat surface, comprising the following steps: a) Provision of a metal sheet, in particular made of stainless or spring steel and / or titanium b) Cutting out, in particular laser cutting, milling, punching and / or etching of the metal sheet, so that a one-piece, two-dimensionally contoured metal sheet is obtained c) The metal sheet is bent multiple times so that the gripping jaws of the gripping pliers are subjected to preload, which presses the gripping jaws against each other. If, for example, one of the spring legs has a notch in an overlapping section and the other spring leg has a tapered section and a bend, the spring legs can be positioned interlocking. For this purpose, the tapered spring leg is bent or creased multiple times and passed through the notch of the other spring leg, so that the spring leg, initially located on a front side, is moved to a back side in the area of ​​the gripping pliers. Here, "front side" refers, for example, to the side of the spring leg towards which the gripping pliers point, and "back side" refers to the side of the spring leg away from which the gripping pliers point.

[0042] In an optional step d), heat treatment is carried out, in particular stress-relieving annealing, to improve the material structure and to reduce or eliminate any residual stress unintentionally introduced by bending (cold forming) and to prevent unwanted distortion.

[0043] Alternatively, the clamping device according to the invention is manufactured using an injection molding process with the following steps: a') Providing a thermoplastic material, in particular PP, PE, PET, PEK, PTFE and / or TPFE for an injection molding process b') Injection molding of at least two molded parts which are each formed from at least one spring leg with a gripping jaw and wherein each molded part has a joining area c') Bonding and / or joining the molded parts together in the joining area. The joining area is located above the spring element, in particular in the upper third of the clamping device.

[0044] Alternatively, the clamping device according to the invention is manufactured using an additive process with the following steps: a'') Providing a metal and / or a plastic b'') Additive manufacturing of the clamping device

[0045] Each of the aforementioned methods for manufacturing the clamping device yields a clamping device comprising two spring legs, a spring element formed by one of the spring legs and a gripping pliers arranged at an angle to the spring legs with two gripping jaws pre-tensioned against each other.

[0046] The invention further relates to a method (100) for clamping a tissue sample, in particular a tissue section, comprising the steps: k) Providing a clamping device according to the invention l) Applying a compressive force F, in particular one applied manually, to an upper and / or lower surface of the spring element, such that at least one spring leg is deflected upwards or downwards. m) Inserting a tissue sample between the gripping jaws of the gripping forceps n) Relieving the spring element so that the compressive force F is eliminated and the spring element and at least one deflected spring leg are returned to their respective original positions and the tissue sample is clamped between the gripping jaws of the gripping forceps with a predefined force, and o) optional positioning of the clamped tissue sample, especially in a culture container

[0047] The clamping device according to the invention is advantageously used, for example, for clamping a tissue sample, in particular a tissue section, over a flat surface, and for positioning it, in particular, in a sample container, for example, a cultivation vessel of a microscope, for example, a fluorescence microscope. In the cultivation vessel, the tissue sample can, for example, be cultured, stained, and treated with active substances to test their efficacy.

[0048] Furthermore, the clamping device can also be used to transport a tissue sample clamped into it, so that the tissue sample is already available in a flat, stretched form at the place of use and can be inserted directly into a sample container, for example a cultivation vessel, using the clamping device. Brief description of the drawing

[0049] The drawing illustrates advantageous embodiments of the present invention, which are explained in more detail in the following description. It shows: Fig. 1: a schematic representation of a clamping device according to a first embodiment of the present invention, Fig. 2: a schematic representation of a clamping device according to a second embodiment of the present invention, Fig. 3: a schematic 3D view of the clamping device according to Fig. 2, Fig. 4: a schematic representation of an overlapping spring leg area of ​​a clamping device according to the invention in an alternative embodiment, Fig. 5a-e: each a schematic representation of a variant of a gripping jaw of the gripping pliers of the clamping device according to the invention, Fig. 6: the schematic representation of a flowchart of an embodiment of the inventive method for clamping a tissue sample.

[0050] In Fig. Figure 1 shows a first embodiment of a clamping device 10 according to the invention. The clamping device 10 comprises a first spring arm 1a with a first gripping jaw 5a and a second spring arm 1b with a second gripping jaw 5b. The gripping jaws 5a, 5b are arranged at an angle on their respective spring arms 1a, 1b, pointing towards the second spring arm 1b, in particular at an angle α of 45°–175°, and preferably 125°. The gripping jaws 5a, 5b together form a gripping pliers 5. The gripping jaws 5a, 5b of the gripping pliers 5 are subjected to a preload V, which presses them against each other with a predefined force. The preload results from the manufacturing of the clamping device 10, for example, a corresponding bending process in combination with a suitable material for the clamping device 10.The clamping device 10 is made, for example, of corrosion-free stainless or spring steel, titanium and / or a thermoplastic material such as PP, PE, PET, PEK, PTFE and / or TPFE.

[0051] The spring legs 1a, 1b together form a first spring leg section 1. The second spring leg 1b forms a loop-shaped spring element 3, which has a top side 3a and a bottom side 3b. The spring element 3 is formed by the second spring leg 1b in an upper half of the first spring leg section 1 and is arranged orthogonally to the main axis of the spring legs 1a, 1b. Alternatively, and not in Fig. Figure 1 shows that the spring element 3 is arranged at an angle less than or greater than 90° to the main axis of the spring legs 1a, 1b.

[0052] In Fig. 1 the spring element 3 and the gripping pliers 5 point to the same side of the clamping device 10.

[0053] Furthermore, the clamping device 10 has a retaining element 7, which is formed by the sections of the spring legs 1a, 1b located above the spring element 3. Alternatively, the retaining element 7 can be omitted and the clamping device 10 can be held on the spring element 3 or another section of the spring legs 1a, 1b.

[0054] If a compressive force F is exerted on the upper 3a and lower 3b of the spring element 3, the first spring leg 1a, and with it the first gripping jaw 5a, is deflected downwards and the second spring leg 1b, and with it the second gripping jaw 5b, is deflected upwards, so that the gripping jaw 5 opens.

[0055] In Fig. Figure 1 shows the position of the upper surface 3a' and the lower surface 3b' of the spring element 3 in a state subjected to a compressive force F. The direction of movement of the spring arms 1a, 1b is indicated by the arrow S. The position of the first gripping jaw 5a in an open state 5a' and the position of the second gripping jaw 5b in an open state 5b' are also shown by the dashed lines. The arrows V indicate the preload V acting on the two gripping jaws 5a, 5b. In the open state, a tissue sample can be inserted into the gripping forceps 5.

[0056] When the spring element 3 is released, no pressure force F acts on the upper 3a and lower 3b of the spring element 3, so that it returns to its original position. This also returns the first spring leg 1a, and with it the first gripping jaw 5a, and the second spring leg 1b, and with it the second gripping jaw 5b, to their respective original positions, in which the gripping jaws 5a, 5b press against each other with a predefined force V, or, if a tissue sample is located between the gripping jaws 5a, 5b, it is clamped and held firmly by the predefined force V of the opposing gripping jaws 5a, 5b.

[0057] In the Fig. 2 and Fig. 3 is (in Fig. 2 in a side view and in Fig. Figure 3 (in a 3D view) shows a second embodiment of the clamping device 10 according to the invention. In contrast to Fig. 1. The spring element 3 is placed in the Fig. 2 and Fig. 3 formed by the first spring leg 1a. The spring element 3 is arranged orthogonally to the main axis of the spring legs 1a, 1b on the first spring leg 1a and points in the direction of the first spring leg 1a. Thus, the spring element 3 and the gripping jaw 5 point towards opposite sides of the clamping device 10.

[0058] Another difference to Fig. 1 is that the spring legs 1a, 1b are positioned interlocking. For this purpose, the first spring leg 1a has an overlapping spring leg area 4 (see figure). Fig. 3) a central first recess 11a and the second spring leg 1b narrows and has a bending area 11b with several bends.

[0059] The second spring leg 1b, which is tapered and bent in the spring leg area 4, is guided through the first recess 11a of the first spring leg 1a, so that it is initially located on a front side of the clamping device 10 and then, in the area of ​​the gripping jaws 5, on a rear side of the clamping device 10. In the Fig. 2, Fig. 3 and Fig. 4 is the front side of the clamping device 10 towards which the gripping pliers 5 point, and the back side is the side of the clamping device 10 away from which the gripping pliers 5 point.

[0060] All other features of the in the Fig. 2 and Fig. The second embodiment of the clamping device 10 shown in Figure 3 corresponds to the first embodiment as shown in Figure 3. Fig. 1 shown and described in relation to this.

[0061] In Fig. Figure 3 also shows that the first gripping jaw 5a is fork-shaped with two outer prongs, between which there is a recessed area, and that the second gripping jaw 5b has a circular second recess 9. Due to the interlocking of the spring arms 1a, 1b, the prongs of the first gripping jaw 5a and the boundary of the circular second recess 9 of the second gripping jaw 5b are positioned precisely one above the other, and the recess 9 and the recessed area 11a between the prongs of the first gripping jaw 5a are aligned. A tissue sample clamped between the gripping jaws 5a, 5b is thus held by the prongs of the first gripping jaw 1a and the boundary of the second recess 9 of the second gripping jaw 1b. The tissue sample is directly visible and accessible in the area of ​​the second recess 9.

[0062] In Fig. 4 is the overlapping spring leg area 4 in a way that relates to the Fig. 2 and Fig. Figure 3 shows an alternative embodiment. Both spring legs 1a, 1b are asymmetrically tapered and interlocked in the overlapping spring leg area 4. The first spring leg 1a is initially located on a rear side of the clamping device 10 and is guided to the front side of the clamping device 10 in the overlapping spring leg area 4 at the point freed by the second tapered spring leg area 1b' of the second spring leg 1b, so that it is located in the area of ​​the gripping jaw (not in Fig. 4 shown) is located on the front of the clamping device 10. The second spring leg 1b is initially located on the front of the clamping device 10 and is guided backwards to the rear of the clamping device 10 in the overlapping spring leg area 4 at the point that is free through the first tapered spring leg area 1a' of the first spring leg 1a, so that it is located in the area of ​​the gripping jaw (not in Fig. (as shown in Figure 4) is located on the rear side of the clamping device 10. In this way, the spring legs 1a, 1b cross each other.

[0063] In Fig. Figures 5 and 5 show different variants a) - e) of a gripping jaw 5a, 5b of the gripping pliers 5 of the clamping device 10. The gripping jaws 5a, 5b can, for example, be configured as shown in Fig. They have 3 different shapes. Alternatively, and not shown in the figures, the gripping jaws 5a, 5b can also be designed analogously to each other and have the same shape.

[0064] The end region of the gripping jaw 5a, 5b of the gripping tongs 5 ​​can, for example, be rounded, angular, grid-shaped, or forked. The gripping jaw 5a, 5b includes, for example, a second recess 9 which has a round, oval, angular, and / or grid-shaped form.

[0065] In Fig. 5a) The gripping jaw 5a, 5b has a square recess 9. The end region of the gripping jaw 5a, 5b is also square.

[0066] In Fig. 5b) The gripping jaw 5a, 5b has a round recess 9. The end area of ​​the gripping jaw 5a, 5b is square.

[0067] In Fig. 5c) the gripping jaw 5a, 5b is fork-shaped with two lateral prongs that define the gripping jaw 5a, 5b.

[0068] In Fig. 5d) The gripper jaw 5a, 5b has a round recess 9. The end area of ​​the gripper jaw 5a, 5b is also rounded.

[0069] In Fig. 5e) The gripper jaw 5a, 5b has a recess 9 which has a grid-like structure. The end region of the gripper jaw 5a, 5b is angular. Other shapes for the recess and the end regions of the respective gripper jaw 5a, 5b are also possible.

[0070] Fig.Figure 6 shows an embodiment of a method 100 for clamping the tissue sample, in particular a tissue section, into the clamping device 10 according to the invention.

[0071] After the clamping device 10 is provided in step k), a compressive force F is applied to the upper and / or lower surface of the spring element 3 in step I), such that at least one spring leg 1a, 1b is deflected upwards or downwards. Next, in step m), the tissue sample is inserted between the gripping jaws 5a, 5b of the gripping forceps 5. Subsequently, in step n), the compressive force F is released, so that the spring element 3 is relieved of the force and both the spring element 3 and the at least one deflected spring leg 1a, 1b are returned to their respective original positions, and the tissue sample is clamped between the gripping jaws 5a, 5b of the gripping forceps 5 with a predefined force.

[0072] In an optional step o), the clamped tissue sample is positioned in a sample container, in particular in a culture vessel 17. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] DE 4306310 A1

[0005] DE 102019101035 A1

[0006]

Claims

[1] Clamping device (10) for clamping and positioning a tissue sample, in particular a tissue section, comprising a gripping pliers (5) with two pre-tensioned gripping jaws (5a, 5b), a first (1a) and a second spring leg (1b) connected thereto, wherein the gripping jaws (5a, 5b) are arranged at an angle to each spring leg (1a, 1b) and a spring element (3) formed by one of the spring legs (1a, 1b), wherein at least one spring leg (1a, 1b) is deflectable in order to move the gripping pliers (5) into an open position. [2] Clamping device (10) according to claim 1, wherein the clamping device (10) comprises a metal, in particular a corrosion-free stainless or spring steel and / or titanium and / or a thermoplastic polymer, in particular polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polyetheretherketone (PEK), polytetrafluoroethylene (PTFE), Teflon and / or polytetrafluoroethylene (TPFE). [3] Clamping device (10) according to one of the preceding claims, wherein the spring element (3) is arranged orthogonally to it, in particular in an upper half of the spring leg (1a, 1b) forming it. [4] Clamping device (10) according to one of the preceding claims, wherein in an overlapping spring leg area (4) the first spring leg (1a) has a central recess (11a) and the second spring leg (1b) tapers and has a bend area (11b) so that the spring legs (1a, 1b) can be positioned interlocking, or wherein both spring legs (1a, 1b) are tapered, in particular asymmetrically, so that the spring legs (1a, 1b) can be positioned interlocking. [5] Clamping device (10) according to one of the preceding claims, wherein the gripping jaws (5a, 5b) of the gripping pliers (5) are designed analogously to each other or have a different shape. [6] Clamping device (10) according to one of the preceding claims, wherein at least one end area of ​​the gripping jaw (5a, 5b) of the gripping pliers (5) is rounded, angular, grid-shaped or fork-shaped. [7] Clamping device (10) according to one of the preceding claims, wherein at least one gripping jaw (5a, 5b) of the gripping pliers (5) has a recess which has a round, oval, angular and / or grid-shaped form. [8] Clamping device (10) according to one of the preceding claims, wherein the gripping pliers (5) are arranged at an angle α of 45°- 175°, and preferably of 125°, on the spring legs (1a, 1b). [9] Method for manufacturing a clamping device (10) according to one of claims 1-8, for clamping and positioning a tissue sample over a surface, comprising the steps: a) Providing a sheet of metal b) Cutting out, in particular laser cutting, milling, punching and / or etching of the metal sheet, so that a one-piece, two-dimensionally contoured metal sheet is obtained c) Repeated bending of the metal sheet so that the gripping jaws (5a, 5b) of the gripping pliers (5) have a preload which presses the gripping jaws (5a, 5b) against each other d) Optional heat treatment, in particular stress-relieving annealing. [10] Method for clamping a tissue sample, in particular a tissue section, into a clamping device (10) according to one of claims 1-8 comprising the steps: k) Providing the clamping device (10) I) Applying a compressive force F to an upper (3b) and / or lower (3a) surface of the spring element (3) such that at least one spring leg (1a, 1b) is deflected upwards or downwards. m) Inserting a tissue sample between the gripping jaws (5a, 5b) of the gripping forceps (5) n) Relieving the spring element (3) so that the spring element (3) and the at least one deflected spring leg (1a, 1b) are returned to their respective original positions and the tissue sample is clamped between the gripping jaws (5a, 5b) of the gripping forceps (5) with a predefined force V, and o) optional positioning of the clamped tissue sample in a sample container, in particular in a culture container. [11] Use of a clamping device (10) according to one of claims 1-8 for clamping a tissue sample, in particular a tissue section, over a flat surface, for positioning the same in a sample container, in particular in a cultivation container and / or for transporting the clamped tissue sample.

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