Sectionable cassette and embedding frame with tissue-securing separable lid, and method of preparing biopsy tissue samples

Abstract

A histological tissue sample support device (200) includes a tissue cassette (112), a frame (14), and a lid (118 ''). The tissue cassette (112) has a recess (112b) comprising a body having a bottom wall (112c) and at least one side wall (112a), and is formed from a material capable of smooth slicing in a microtome and capable of resisting degradation of solvents and chemicals used to secure, treat and stain tissue. A tissue cassette (112) is movably coupled to the frame (14). The lid (118 '') is separably coupled to the peripheral portion (16) of the frame (14). When the lid (118'') is separated from the peripheral portion (16), the lid (118 '') and the tissue cartridge (112) are movable relative to the frame (14) from a first position to a second position, and in the second position, at least a portion of the side walls and the bottom wall (112c) extend beyond a bottom edge of the frame (14) for slicing in the microtome.

Description

[0001] This application is a divisional application of the invention patent application with application number 201680055724.3 (international application number PCT / US2016 / 044379) filed on July 28, 2016 and invention name “Sliceable box and embedding frame with a tissue-fixing detachable cover, and method for preparing biopsy tissue samples”. Technical Field

[0002] The present invention relates generally to supports for processing and embedding tissue samples for pathological analysis, and more particularly to a microtome-sectionable support and a support frame having a tissue-securing detachable cover that can accommodate one or more tissue samples. Background Art

[0003] In order to accurately diagnose various tissue diseases and conditions, medical personnel must remove one or more tissue samples from the patient's body. This process of collecting tissue from the body is called a biopsy. Once the one or more tissue samples are removed and sent to the pathology laboratory, the tissue will undergo a series of procedures performed by a histopathologist and ultimately a pathologist in order to diagnose one or more conditions associated with the tissue. The present invention generally relates to those procedures typically performed by a histopathologist to prepare one or more tissue samples into slides that can be analyzed under a microscope by a pathologist.

[0004] Although the singular term "sample" is used throughout the specification, it should be understood that the term also includes multiple "samples". Once the tissue sample is taken out from the patient's body, it is usually placed in a sample container containing a tissue fixative solution, and the container is then transported to the pathology laboratory. The tissue will experience the process known as "specimen removal" in the pathology laboratory, during which the pathology technician will retrieve the tissue sample from the container, usually cut the tissue into a suitable size for tissue processing, place each sample in a small plastic tissue box of suitable size, and assign a tracking number to each box. Then, these tracking numbers will be recorded in the tracking system used by the laboratory. For the smallest tissue sample that may only be the scraping debris, the box includes a fine grid opening located at the side and bottom. In other cases involving very small tissue samples, the sample is placed in a bag similar to a tea bag, which prevents the smallest tissue sample from escaping. Larger tissue samples are placed in boxes with larger slotted openings, but these openings are still smaller than the tissue sample in the box.

[0005] The box is then placed in a stainless steel perforated basket and passed through a tissue processing machine, usually overnight. The machine uses a combination of vacuum, heat and chemicals to remove the interstitial fluid in the tissue. Once the fluid has been removed from the tissue sample, the processing machine immerses the tissue sample in a bath of a hardenable material such as molten paraffin (that is, the form of wax) so that the space in the tissue is replaced by paraffin. The pathological tissue technician then removes the basket from the machine and takes out each tissue box. In the routine procedures of many years of practice, the pathological tissue technician takes out the tissue sample individually from each box. The pathological tissue technician must be based on the careful orientation of the tissue sample to the stainless steel base mold, which is roughly the size of the tissue box and is partially filled with molten paraffin. The tissue sample must usually be manually held against the bottom of the mold using tweezers. If not, this may impair the ability to perform appropriate slice cutting of the tissue sample in a microtome later. Then, the molten paraffin is rapidly cooled on a freezing plate that may be a thermoelectric cooler (TEC) to partially solidify the paraffin, thereby keeping the tissue sample against the bottom of the mold along a suitable orientation.

[0006] Then, box is placed on the top of base mould and the embedding material that is also usually paraffin is poured into the base mould through the open top of box.At this moment, the function of box at this point in the program changes into fixed type device for being installed in microtome and for making shavings or thin slices by solidified paraffin in microtome from the tissue holding component.Cooling base mould, until all molten paraffins harden, and pathological tissue technician removes stainless steel base mould from embedding paraffin block.Therefore, tissue sample is embedded in the hard paraffin rectangular block with plastic tissue cassette on opposite side.As mentioned above, box can be used as holder or holder in microtome chuck then.The same as tissue processing machine, embedding process is completed in batches, and in this process, common pathological tissue technician can embed about 40 to 60 boxes per hour.

[0007] Then, the hardened paraffin block preparation sheet containing the embedded tissue sample is cut into extremely thin sections to be placed on a microscope slide. The embedded tissue block is mounted in a chuck on a microtome by a pathological tissue technician, and the chuck is sized to accept the side of the block with an embedded plastic box. Then the pathological tissue technician can begin to slice the paraffin block sheet into thin slices, and the paraffin block has the tissue sample embedded relative to the plastic box surface. This produces the band of each thin slice of the tissue embedded in the hardened paraffin. The action of the microtome makes each thin slice stick together when correctly completed, and subsequently makes these very thin slice bands float in a water bath, and slides are carefully placed below the thin slice. Then, the thin slice in which the thin-section tissue sample is embedded is adhered to the top of the slide.

[0008] When the pathologist has enough slides from the tissue sample, they are placed in an automated staining machine. The staining machine goes through a series of infiltration steps to stain different tissues and cells on the slide with different colors. This helps the pathologist identify different structures and makes it easier to spot any abnormalities in the tissue. Once the staining process is complete, the slide is covered with a coverslip and is ready for the pathologist to place under a microscope for analysis.

[0009] Based on the summary of the procedures provided above, it should be understood that conventional tissue sample handling and processing is a very labor-intensive process involving several manual steps performed by a pathological tissue technician. Therefore, repetitive stress injuries such as carpal tunnel syndrome are common. This is especially true for tissue sample embedding processing. These multiple manual operations and repeated tissue processing increase the possibility of human error. In addition, a well-trained and skilled pathological tissue technician is required to ensure that the tissue sample finally adhered to the slide for analysis by the pathologist is in the best condition and orientation in order to make an accurate diagnosis.

[0010] U.S. Patent Nos. 5,817,032 (the '032 patent), 7,156,814, 7,179,424, 7,722,810, 7,776,274, and 8,383,067 disclose various improvements in the art, including novel ways to hold tissue samples during the sampling, embedding, and sectioning or slice cutting procedures. The disclosures of U.S. Patent Nos. 5,817,032 (the '032 patent), 7,156,814, 7,179,424, 7,722,810, 7,776,274, and 8,383,067 are incorporated herein by reference in their entirety. For example, the '032 patent relates to a tissue restraint and support device that may be a cassette and that may be smoothly sectioned using a microtome. When such a cassette is used, the tissue sample is secured within the cassette and subjected to a process in which paraffin replaces the tissue fluid. Then, the tissue sample and the box are sliced ​​at the same time for subsequent installation on a microscope slide. Since the tissue sample is not taken out from the box during the time from the time when the tissue sample is processed in the tissue processing machine to the time when the tissue sample is cut or sliced ​​using a microtome, a large amount of processing time is saved. In addition, due to the elimination of the separate tissue processing steps, the chance of human error or tissue loss is significantly reduced. The '032 patent and the above-mentioned incorporated published applications generally also disclose further improvements that help to automate the entire process and cooperate with novel tissue supports (e.g., box) to even further reduce the processing steps during the entire procedure and make the procedure more reliable.

[0011] There are various drawbacks of current procedures and restrictions on innovation. For example, improvements to the external form of boxes and frames are bound by existing limitations of tissue pathology laboratory equipment, such as tissue processing distiller and "input devices" for tissue processors, embedding stations and slicers. Many of these processes are integrated with systems and machines for automation of steps and for robotized processing between these steps, which further limits the potential for innovation. In addition, material costs have been rising in recent years, especially fluoropolymer (FEP / PFA) sliceable plastics for sliceable boxes. Each box is basically consumed by the slice procedure, which increases the cost of pathology procedures. In addition, since sliceable FEP / PFA materials are not rigid, it is challenging to manufacture reliable lids that will not be deformed in size during transportation and storage with this material. At present, frames and box baskets are shipped to consumers in separate boxes and must be assembled by users. Due to the increasing scrutiny of government and competitive forces on health care costs, low-cost devices and methods are needed to reduce labor.

[0012] Despite various advances in this area, there is an increasing need for further improvements involving increased throughput and more consistent quality of embedded tissue samples and the resulting slices or strips of embedded tissue to be used for diagnosis. This may be particularly important when dealing with smaller tissue sample sizes, although the improvements disclosed herein are applicable to all tissue sample sizes. Summary of the invention

[0013] According to one embodiment, histological tissue sample support device comprises a tissue cassette with a recess, and this recess comprises a bottom wall and at least one side wall, and the tissue cassette is made of a material that can smoothly slice in a microtome and resist the solvent and chemical degradation for fixing, handling and dyeing tissue. Device also comprises a framework and a lid, and this framework comprises a peripheral portion and a bottom edge, and the tissue cassette is movably connected to the framework, and this lid is detachably connected to the peripheral portion of the framework. It should be understood that the lid can be connected to the peripheral portion in a fragile manner or in any other separable manner. When the lid separates from the peripheral portion, the lid and the tissue cassette can be moved to the second position from a first position relative to the framework, and in the second position, at least a portion of the sidewall and the bottom wall extend beyond the bottom edge of the framework for slicing in the microtome.

[0014] According to another embodiment, a histological tissue sample support device includes a tissue cassette having a recess, the recess including a bottom wall and at least one side wall, the tissue cassette being made of a material that can be smoothly sliced ​​in a microtome and resists degradation by solvents and chemicals used to fix, process and stain tissues. The device also includes a frame and a cover, the frame including a peripheral portion and a bottom edge, the tissue cassette being movably connected to the frame, an elastic structure that can be sliced ​​by the microtome being configured to engage and hold the tissue in place during processing and embedding, and the cover being detachably connected to the peripheral portion of the frame and to the elastic structure, the cover being used to press the elastic structure against the tissue. The elastic structure is able to be smoothly sliced ​​in the microtome and is porous to allow penetration of solvents and chemicals used to fix, process and stain tissues and embedding materials used to embed tissues when the tissue is held in the recess by the elastic structure. When the cover is separated from the peripheral portion, the cover and the tissue cassette are able to move from a first position to a second position relative to the frame, and in the second position, at least a portion of the bottom wall, the side wall and at least a portion of the elastic structure extend beyond the bottom edge of the frame for slicing in the microtome.

[0015] In use, a method of preparing one or more biopsy tissue samples for histological examination using a histological tissue sample support device includes positioning a tissue sample in a tissue cassette, closing a peripheral edge portion and a cover of the frame when the tissue cassette is in a first position relative to the frame, separating the cover from the peripheral edge portion of the frame, and moving the cover and tissue cassette relative to the frame to a second position, the support device including a microtome-slicable tissue cassette, a frame including a peripheral edge portion, and a cover detachably coupled to the peripheral edge portion of the frame, wherein in the second position a portion of the tissue cassette extends beyond an edge of the frame for slicing in the microtome.

[0016] According to another embodiment, an apparatus for holding a histological tissue sample while slicing the tissue sample in a microtome includes a tissue cassette having a recess, the recess including a bottom wall and at least one side wall, the tissue cassette being configured to hold the tissue sample, being made of a first material that can be smoothly sliced ​​in the microtome, and being resistant to degradation by solvents and chemicals used to fix and process the tissue sample during a histological procedure. The apparatus also includes a frame having a peripheral portion and a cover, the frame being made of a second material different from the first material and being integrally formed with the tissue cassette, and the cover being detachably coupled to the peripheral portion.

[0017] In use, a method of making an apparatus for holding a histological tissue sample while slicing the tissue sample in a microtome includes molding a tissue cassette having a recess including a bottom wall and at least one side wall, and molding a frame such that the frame is integrally coupled to the tissue cassette, the recess including a bottom wall and at least one side wall, the tissue cassette being made of a first material that can be successfully sliced ​​in the microtome, the tissue cassette further resisting degradation by solvents and chemicals used to fix and process the tissue sample during a histological procedure, the frame having a peripheral edge, being made of a second material different from the first material and including a cover detachably coupled to the peripheral edge.

[0018] Embodiments of the present invention also provide a kind of histological tissue sample support device, and this support device comprises a tissue box with a recess, and this recess comprises a bottom wall and at least one side wall.The tissue box is made of the material that can be sliced ​​smoothly in a microtome and resists the degradation of solvents and chemicals used to fix, process and dye tissue.The framework comprises a bottom edge, and the tissue box is movably connected to the framework.The lid is connected to the framework, wherein the lid and the tissue box can be moved to a second position from a first position relative to the framework, and in the second position, at least a part of the side wall and the bottom wall extend beyond the bottom edge of the framework for slicing in the microtome.

[0019] In an additional or alternative aspect, the cover is coupled to the frame by a hinge. The box is coupled to the frame using at least one breakaway connection. The cover can be moved from a closed position to an open position and can be locked to the tissue box in the closed position. The box, cover and frame can be molded from a single material. The box and frame can alternatively be formed using other techniques, such as by co-molding or insert molding with different materials.

[0020] A method for preparing one or more biopsy tissue samples for histological examination using a histological tissue sample support device is provided, the support device comprising a tissue cassette that can be sliced ​​by a microtome, a frame, and a cover coupled to the frame. The method comprises positioning the tissue sample in the tissue cassette, closing the cover when the tissue cassette is in a first position relative to the frame, and moving the cover and the tissue cassette relative to the frame to a second position in which a portion of the tissue cassette extends beyond an edge of the frame for slicing in the microtome.

[0021] The method may further include subjecting the tissue cassette and tissue sample to a process of replacing the fluid in the tissue sample with a hardenable material before or after moving the cover and tissue cassette to the second position, embedding the tissue cassette and tissue sample in the embedding material, hardening the embedding material into a block, and using a microtome to slice the block into slices of the embedding material, tissue cassette, and tissue sample. The method may further include positioning the histological tissue sample support device in the microtome and locking the cover to the tissue cassette after hardening the embedding material into a block.

[0022] Various additional features and advantages of the present invention will become more apparent to those of ordinary skill in the art upon reading the following detailed description of exemplary embodiments in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is a perspective view of an assembly according to one embodiment.

[0024] Figure 2 yes Figure 1 , showing a top view of an assembly of the tissue cassette and frame in an open position, ready to receive tissue in the tissue cassette.

[0025] Figure 3A It is roughly along Figure 2 The line 3A-3A intercepts Figure 1 , showing a tissue cassette and frame in an open position ready to receive tissue in the tissue cassette.

[0026] Figure 3B It is roughly along Figure 2 The line 3A-3A intercepts Figure 1 A cross-sectional view of the assembly showing the peripheral portion of the frame in a closed position.

[0027] Figure 3C is a diagram showing the approximate direction of the assembly in the transition position. Figure 2 The line 3A-3A intercepts Figure 1 A cross-sectional view of a portion of an assembly of a microtome in which the cover is separated from the periphery of the frame in a transitional position and a portion of the tissue and tissue cassette is ready for sectioning in a microtome.

[0028] Figure 3D The diagram shows the approximate edges of a tissue cassette embedded in paraffin. Figure 2 The line 3A-3A intercepts Figure 1 A cross-sectional view of a portion of an assembly.

[0029] Figure 4 is a perspective view of an assembly according to one embodiment positioned in a slicer.

[0030] Figure 5 is a plan view of a sample wax sheet prepared using a method according to one embodiment.

[0031] Figure 6 is a plan view of a sample wax sheet prepared using a method according to one embodiment.

[0032] Figure 7 is a perspective view showing another embodiment of an integrally formed box and frame structure.

[0033] Figure 8is a cross-section taken generally along the central longitudinal axis with the lid in the closed position Figure 7 A perspective view of the structure shown in FIG.

[0034] Fig. 9 The lid is in the open position Figure 7 A top view of the structure shown in FIG.

[0035] Fig. 10A and Fig. 10B yes Fig. 9 The corresponding cross-sectional view of the structure shown (along Fig. 9 10A-10A), Fig. 10A The lid is shown in the open position, while Fig. 10B The lid is shown in a closed position.

[0036] Fig. 10C is similar to Fig. 10B However, a cross-sectional view of the box portion transitioning downward into the mold is shown.

[0037] Fig. 10D is similar to Fig. 10C However, a cross-sectional view of an integrated transition structure with a microtome sectionable cassette portion and a tissue sample embedded in a block of embedding material, such as paraffin, is shown.

[0038] Fig.11A is a perspective view that has been cross-sectioned to show additional detail of the integrated structure of the box and frame of this embodiment.

[0039] Fig. 11B is similar to Fig.11A However, a cross-sectional view of the lid is shown with the structure in the closed position.

[0040] Fig. 11C is similar to Fig. 11B However, a cross-sectional view of the cassette is shown in the transition position.

[0041] Fig. 12A is another cross-sectional view of the integrated box and frame structure of this embodiment showing additional detail.

[0042] Fig. 12B is similar to Fig. 12A However, a cross-sectional view of the cassette is shown in the transition position.

[0043] Fig.13 is a perspective view of another embodiment of the integrated structure of the box and frame showing the cover of the box portion in an open position.

[0044] Fig.14 The lid is shown in the closed position Fig.13 Cross-sectional view of the box and frame integrated structure (along the Fig.13 14-14 of FIG. 14).

[0045] Fig.15 is a perspective view showing another embodiment of the integrated structure of the box and the frame with the cover of the box portion in an open position.

[0046] Fig.16A The lid is shown in the closed position. Fig.15 Cross-sectional view of the box and frame integrated structure (along the Fig.15 16-16 of FIG. 1 ).

[0047] Fig. 16B is similar to Fig.16A However, a cross-sectional view of the tissue sample with the cover structure engaged within the cassette portion is shown.

[0048] Fig.17 is a perspective view of another embodiment showing the integrated structure of the box and frame with the cover portion shown in an open position.

[0049] Fig.18 The cover is shown in the open position. Fig.17 A top view of a box and frame integrated structure.

[0050] Fig.19A It is roughly along Fig.18 A cross-sectional view taken along line 19A-19A.

[0051] Fig.19B is similar to Fig.19A However, a cross-sectional view of the cover portion is shown in the closed position.

[0052] Fig.19C is similar to Fig.19B However, a cross-sectional view is shown of the cover portion pressing or moving downwardly against the tissue sample within the cartridge body and showing the cartridge transitioning downwardly relative to the frame and into the mold.

[0053] Fig. 20A Additional details are shown Fig.17 A perspective enlarged view of the box and frame integrated structure.

[0054] Fig. 20B is similar to Fig. 20A However, a perspective view of the cover portion is shown in the closed position.

[0055] Fig. 20C is similar to Fig. 20B However, a perspective view of the cassette is shown transitioning or moving downwardly relative to the frame to a second transition position.

[0056] Fig.21is a top view showing another embodiment of an assembly consisting of a box and frame integral structure.

[0057] Fig.22A yes Fig.21 A partially exploded cross-sectional view of the structure shown in .

[0058] Fig. 22B yes Fig.22A The structure shown but showing a cross-sectional view of the lid in the closed position.

[0059] Fig. 22C is similar to Fig. 22B However, a perspective view of the box is shown transitioning to the second position within the frame.

[0060] Fig.23A and 23B Alternative embodiments of resilient tissue engaging structures or fingers for retaining tissue to the bottom wall of the cassette are shown respectively.

[0061] Fig.24A is a cross-sectional view of the structure showing the cassette during movement or transition between a first position and a second position, the cross section being taken transverse to the longitudinal dimension of the frame and cassette.

[0062] Fig. 24B is similar to Fig.24A , but showing the box fully transitioning into the second position. DETAILED DESCRIPTION

[0063] First reference Figure 1 and 2 , shows an assembly 10 constructed in accordance with an illustrative embodiment of the present invention. Assembly 10 includes a tissue sample box 12 carried within a frame 14, the frame 14 including a peripheral rim portion 16. A cover 18 is detachably coupled to the peripheral rim portion 16. The peripheral rim portion 16 generally includes an interior defined between peripheral walls 16a, 16b, 16c, 16d, and the cover 18 is sized and configured to fit within the interior and detachably couple to at least one of the peripheral walls 16a, 16b, 16c, 16d. The frame 14 generally includes an interior defined between peripheral outer walls 14a, 14b, 14c, 14d, and also as generally discussed in the patents and patent applications incorporated above and for the same purposes, the box 12 is sized and configured to frictionally or "snap-fit" fit within the interior and move within the interior between at least a first position and a second position. The first position is Figure 3B , and the second position is Figure 3C It is shown in Figure 3C 1 , a lower portion of cassette 12 is exposed below the bottom of frame 14 for allowing cassette 12 and tissue sample to be sectioned in a microtome when frame 14 is retained in the microtome chuck.

[0064] The connection of tissue cassette 12 to framework 14 can be completed in many different ways, such as any way described in the patents and patent applications incorporated above. In an illustrative embodiment, box 12 includes a box that maintains lugs 20, which are frictionally fixed in the maintenance grooves 40 of framework 14. The friction assembly between lugs 20 and grooves 40 prevents box 12 from moving undesirably between the first position and the second position. Groove 40 is tapered so that groove 40 is narrower at the bottom than at the top. In this regard, the box is maintained to move the lug 20 to the second position required force less than the lug 20 is moved to the first position required force. It should be understood that box 12 can be configured as a tissue support in any suitable manner, and framework 14 can be configured in any suitable manner. Any one of the disclosed constructions, features, characteristics and materials for tissue support (e.g., box) and framework in the patents and patent applications incorporated above can be used for box 12 and framework 14. In the illustrated embodiment, the cartridge 12 is porous and releasably secured in a frame 14, and the frame 14 is further configured to be releasably secured to a microtome chuck ( Figure 4 The general procedures for processing, embedding, and sectioning are discussed in the patents and patent applications incorporated above.

[0065] Reference now Figure 2 and Figure 3A , showing in more detail the connection between the frame 14, the peripheral portion 16 and the cover 18. The peripheral portion 16 is coupled to the wall 14a of the frame 14 by a frangible hinge 22. Figure 3B As shown, the peripheral portion 16 is snap-fitted into the closed position by engagement of latches 24, 26, 28 with the frame 14. The latches 24, 26 are located on the outer wall 16a of the peripheral portion 16 and engage with openings 30, 32 in the wall 14a of the frame 14, respectively. The latch 28 is located on the wall 16c of the peripheral portion 16 and engages with an outer flange 34 of the wall 14c of the frame 14. The cover 18 is detachably coupled to the peripheral portion 16 by a breakaway connection 36 on the peripheral walls 16a, 16b, 16c, 16d. As shown in FIG. Figure 3B and Figure 3C As best shown, the cover 18 is sized and configured to frictionally or "snap-fit" within the interior of the frame 14 and to move between at least a first position and a second position within the interior. More particularly, the cover 18 includes a cover retention tab 38 on each of the four corners of the cover 18. The retention tab 38 is configured to engage with a retention groove 40 of the frame 14, which is located on each of the four corners of the frame 14. The cover 18 carries a resilient structure 42 on a central portion of the cover 18, which can serve as a breakaway transition central section of the cover 18 to which the resilient structure 42 is attached.

[0066] The resilient structure 42 is a compliant structure that holds the tissue in a desired orientation without creating artifactual indentations on the tissue sample 44 during processing. Figure 3A As shown, one or more tissue samples 44 can be placed in the box 12, which defines a recess or interior area surrounded by at least one side wall 12a and including a bottom wall 12b. Although a rectangular recess is shown, it will be understood that any other shape, such as a cylindrical shape or a shape with a slot or alignment feature for the tissue sample 44, can be used.

[0067] The porosity of the elastic structure 42 allows the solvents and chemicals used for fixing, processing and dyeing tissues and the embedding materials used for embedding tissues to be infiltrated when the tissue is maintained by the elastic structure 42. The elastic structure 42 has a compressible and configurable thickness that the tissue is joined and held in place during processing and embedding. In addition, the elastic structure 42 can be sliced ​​smoothly in a microtome after the void or hole is filled with the liquefied embedding material that hardens subsequently. The elastic structure 42 can be, for example, an open-cell foam material, for example, a foam comprising at least one of polyether or polyurethane, and can be a full-net foam. Here, "full-net" means that at least substantially all cells of the foam are open. The open cells help to ensure that the fluid used during processing and embedding procedures is fully infiltrated and finally discharged. The elastic structure 42 can also be a gel, a slicable plastic, polyester, alginate or other material, which can be infiltrated with the embedding material and sliced ​​smoothly in a microtome without adversely affecting the resulting tissue and the band of the embedding material.

[0068] Reference now Figure 3B , the assembly 10 is shown with the rim 16 in the closed position and the box 12 and lid 18 in the first position. Once tissue is loaded in the interior or recess of the box 12, the rim 16 can be rotated to the closed position. As the rim 16 moves from the open position to the closed position, the frangible hinge 22 breaks. Once the hinge 22 breaks, the rim 16 can continue to rotate until the latches 24, 26, 28 engage the openings 30, 32 and the outer flange 34 of the frame 14, thereby securely locking the rim 16 to the frame 14. When the rim 16 is in the closed position, the resilient structure 42 biases the tissue sample 44 toward the bottom wall 12b of the box 12. When the rim 16 is securely closed on the frame 14, the box 12 is trapped inside the retaining groove 40 and cannot be removed from the frame 14. The lid retaining tab 38 is aligned with the wider top of the retaining groove 40 of the frame 14. Alternatively, in this position, the lid retention tabs 38 may be located within the tops of the retention grooves 40 and aligned with the corresponding box retention tabs 20 when the lid 18 is closed.

[0069] like Figure 3BAs further shown, when the lid 18 is closed, the resilient structure 42 presses against the tissue sample 44 and deforms three-dimensionally around the tissue sample 44, thereby creating a three-dimensional space around the tissue sample 44 and substantially fixing the tissue sample 44 during the tissue processing and embedding procedures. This also ensures that the tissue sample 44 remains flat against the bottom wall 12b of the cassette 12, so that when microtome slices are made, a complete and continuous section of the tissue sample 44 can be substantially as shown. Figure 5 As shown. Figure 6 As shown, once all samples 44 have been sliced, the next slice will contain only the elastic structure 42 and the wax 50. One particular type of foam structure suitable for the elastic structure 42 has a pore size of 50-60 ppi (pores / inch), wherein each pore has a diameter between about 0.017 inches and 0.20 inches. The foam structure is fully reticulated and has a 20% deflection of 0.55 lbs / in 2 of compression force deflection and 1.4lbs / ft 3 The foam material can be obtained from the foam of Crest Foam of Mnazi, New Jersey under the name of T-50. This is a polyether / polyurethane foam and works well when the thickness is 0.06 inch to 0.10 inch, wherein the thickness is 0.075 inch for the actual manufacturing example. The foam should be constructed to make the treatment fluid flow out or release after each reagent cycle of the tissue processing machine. If the foam is too dense or too thick or not fully reticulated, then because each fluid bath must be completely cleared and replaced from one fluid bath to the next, the reagents may cross-contaminate or the tissue may not be fully penetrated by the fluid.

[0070] Now refer to Figure 3C and Figure 3D , shows the assembly 10 of the cassette 12 and lid 18 in the second position. Pressing the center of the lid 18 causes the breakaway connection 36 to separate, thereby allowing the lid 18 to move from the first position to the second position. When the connection 36 breaks, continued pressure on the center of the lid 18 causes the retaining tab 38 to abut against the tab 20 and slide through the retaining groove 40 of the frame 14. The downward movement of the lid 18 and the tabs 20, 38 causes the tissue cassette 12 to move from the first position toward the second position. More specifically, because the cassette retaining tab 20 and the lid retaining tab 38 are aligned in the groove 40, the downward movement of the lid retaining tab 38 causes the downward movement of the cassette retaining tab 20. Because the groove 40 is tapered, the friction fit between the groove 40 and the tabs 20, 38 in the second position secures the cassette 12 in the second position during the embedding and sectioning process. As shown in FIG. Figure 3B and Figure 3CAs best shown, the maintenance groove 40 includes a bottom edge 46. When the box 12 reaches the second position, the edge 46 will prevent the box from further moving the lug 20, thereby preventing the lid from moving the lug 38 through the groove 40. In the second position, the tissue sample 44, a portion of the box 12 and a portion of the elastic structure 42 transition to slice in a microtome. Even though the box 12 is shown as having a rectangular configuration, it will be appreciated that the box 12 can have an alternative configuration. For example, the box can have a circular configuration. Since the edge 46 limits the box 12 from traveling into the second position, the edge 46 ensures that the box 12 transitions to a predetermined depth that is independent of the configuration of the box 12. The illustrated configuration of the box 12, frame 14 and lid 18 is an improvement over current assemblies that require complex lid adjustment procedures, whereby the user must select from a limited number of specific engagement distances between the lid and the box. The specific engagement distances are determined by preset lugs inside the box basket that engage and maintain the lid. According to one aspect of the present invention, the complex adjustment process for the lid is eliminated by utilizing a disengaged rigid central transition lid that is coupled to the elastic structure. It should be understood that other configurations and designs may be used to achieve similar purposes.

[0071] Since millions of procedures are performed each year using assemblies like these, embodiments of the present invention are designed for high throughput and therefore for automated histopathology procedures. One such procedure is automated embedding. An exemplary automated embedding machine (not shown) uses a motorized transition device 48, such as Figure 3B and 3C As shown, the motorized transition device 48 pushes the cassette through the frame into the embedding mold 52. The transition device 48 may incorporate spring-loaded cylindrical fingers or legs that push the cassette through the frame. The transition device 48 may be modified so that it can cleanly break the breakaway connection 36 between the rim 16 and the lid 18 during the transition procedure. For example, a tubular cutter may be axially positioned around the cylindrical fingers that align with the connection 36 to cut the connection 36 more easily than simply breaking the connection 36 using shear forces.

[0072] In use, such as Figure 3A As shown, one or more tissue samples 44 are placed in the interior space or recess, specifically, on the bottom wall 12b of the box 12. The tissue samples 44 are sized and oriented in the box 12 according to the required cross-sectional planes desired by the pathologist for each tissue sample 44. The peripheral edge 16 is then closed and snapped into place so that the elastic structure 42 (e.g., foam) is formed as shown in FIG. Figure 3BAs shown, against tissue sample 44 and against bottom wall 12b along the desired directional constraint tissue sample 44. Elastic structure 42 can be deformed to produce the three-dimensional space that receives tissue sample 44. Elastic structure 42 should be enough to fix tissue sample 44 against the power of tissue sample 44, but is not enough to induce the artifact in tissue sample 44. At this moment, the assembly 10 with constrained tissue sample 44 can carry out conventional tissue treatment operation, and this tissue treatment operation uses vacuum, heat and chemicals to remove the interstitial fluid in the tissue and utilizes hardenable materials such as molten paraffin to replace those fluids. As mentioned above, during these processing steps, the porous characteristics of foam or other elastic structures 42 allow fluid to arrive and penetrate into the tissue sample 44 completely. In addition, elastic structure 42 constrains tissue sample 44 flatly against bottom wall 12b, and can not leave artifacts or marks that may interfere with the subsequent analysis under the microscope on tissue. It should be understood that different types of elastic cellular materials can be selected, for example, based on the type of tissue to be processed and analyzed. For example, small mucosal tissue samples can be successfully held and handled using the T-50 foam discussed above, while other types of tissues such as adipose tissue can be better provided by another type of elastic cellular material. As another example, larger tissue samples may require a holding structure that operates well over a large surface area.

[0073] It should also be understood that the processing steps can be performed before assembling the tissue cassette 12 with the frame 14. After tissue processing is completed, the cover 18 can be separated from the peripheral edge portion 16 so that the cassette 12 can be moved to a storage container such as a storage container. Figure 3C The second position is shown, which exposes a portion of the cassette 12 below the bottom edge 46 of the frame 14. The cassette 12 and frame 14 are then placed in a suitable mold 52 and embedded in paraffin 50. The cassette 12 and / or frame 14 may include machine-readable indicia that allow the machine to determine the type and size of cassette 12 being used and make an appropriate decision as to which mold to place the cassette 12 in for embedding. Figure 3D As shown, the entire assembly 10, including the exposed portion of the box 12, is embedded in a hardened block of paraffin wax 50. The mold 52 can generally follow the contour of the bottom 12b of the box 12, although the portion of the mold surrounding the box 12 is preferably square rather than circular. Figure 4 As shown, this facilitates the subsequent production of the thin film strip. Therefore, this part of the process can be similar to the process disclosed in the above-mentioned incorporated patents and patent applications. As discussed therein and with reference to Figure 4 The frame 14 then serves as a fixture for mounting the embedded component 10 in the microtome 54. The necessary number of slices 56 are removed from the exposed bottom side until a similar Figure 5Sufficient sections were collected as indicated in the table and appropriately mounted on microscope slides, stained, and coverslipped.

[0074] Another method (not shown) of loading tissue sample 44 into assembly 10 is possible. First, peripheral portion 16 is removed from frame 14 set aside. Tissue sample 44 is placed on elastic structure 42, and then frame 14 is installed on the top of lid 18. When frame 14 is installed on the top of peripheral portion 16, the locking 24, 26, 28 of peripheral portion 16 engages with opening 30, 32 and flange 34 of frame 14 respectively. In this way, peripheral portion 16 is fixed to frame 14. Then, assembly 10 can be positioned in its common upright position, while elastic cover 18 keeps being connected to frame 14 and structure 42 fixes tissue sample 44 to bottom wall 12b of box 12. Due to being easy to approach elastic structure 42, this technology is particularly useful for processing arrays of small tissue samples. In addition, elastic structure 42 can have tissue specific orientation or keep alignment feature to help the orientation of very specific type of tissue sample. For example, the elastic structure 42 can be made of a gel material with specific cavities or grooves that receive small, difficult to orient tissue samples. Such small tissue samples can be, for example, an optic nerve from a mouse or a thin arterial structure that must stand up at one end perpendicular to the slice plane.

[0075] In accordance with the above-incorporated patents and patent applications, the box 12 can be made of a sliceable plastic, such as perfluoroalkoxyethylene (PFA). The material forming the box 12 can be at least translucent so as not to be cluttered during tissue analysis. The frame 14 including the peripheral edge 16 and the cover 18 can be made of a more rigid, lower cost plastic, such as acetal. Acetal is easier to mold in large quantities or in multi-cavity injection molds. Unlike previous boxes used during tissue analysis, the cover 18 can be made of a more cost-effective plastic that is different from the plastic used to form the box 12. For example, the cover 18 can be made of acetal. In this regard, the volume of FEP / PFA used in the assembly 10 is minimized, which is beneficial for cost reasons. From Figure 2 It can be seen that the box 12 can be molded separately from the frame 14 and then inserted into the frame 14 using an appropriate friction or "snap" fit. In addition, when the box 12 and the frame 14 are made of materials with significantly different melting temperatures, they can be co-molded or insert molded in an injection molding machine. In this case, a separate connection (not shown) similar to the connection 36 will be formed between the peripheral edge portion 16 and the cover 18.

[0076] In the co-molding or insert molding process, the box 12 can be first molded using a material with a higher melting temperature. Then, the frame 14 and the lid 18 can be molded around the box 12, thereby linking them together in a single unit. Since the frame 14 and the lid 18 are made of plastics with a melting temperature lower than the plastics forming the box 12, this step of the process will not melt the box 12. In that way, by robot assembly, the box 12 can be molded together with the frame 14 around the box 12, thereby producing a processing container that the consumer does not need to assemble from parts. In addition, this molding process is used to produce a safe one-piece assembly for transportation and processing. By combining the box and the frame into a single piece before the customer receives the box and the frame, the assembly as a single piece is ready to load the tissue. This is advantageous compared to the previous assembly of the parts that the user needs to assemble before loading the tissue. In addition, by surrounding the box with the frame material of stable size, the integrity and shape of the box are maintained during transportation.

[0077] Now refer to Figure 7 , Figure 8 and 9 , an assembly 100 according to another illustrative embodiment of the present invention is shown and constructed. Similar structural and functional elements in the embodiments hereinafter are represented by the same reference numerals as previously shown and described. Assembly 100 includes a tissue sample box 112, which includes a body 112a carried in a frame 114, the body 112a having an interior or recess 112b, and the frame 114 includes a peripheral portion 116. A lid 118 is detachably coupled to the peripheral portion 116, and the peripheral portion 116 generally includes an interior 116a defined between surrounding walls 116b. The lid 118 is sized and configured to fit in the interior 116a and detachably coupled to at least one of the surrounding walls 116b. As discussed in the patents and patent applications incorporated above and for the same purposes, the frame 114 generally includes an interior 114a defined between surrounding outer walls 114b and the box 112 is sized to fit within the interior 114a of the frame 114 and to move between at least first and second "transition" positions within the interior 114a of the frame 114 after the box 112 is removed from the frame 114.

[0078] More specifically, in this embodiment, the entire box and frame assembly can be formed by a single material in a single molding process. For example, the material can be a polyethylene-polypropylene blend or any other suitable material, and these any other suitable materials have enough rigidity to provide necessary support and resist warping during storage and transportation, but allow the box body 112a to be sliced ​​as disclosed in the patents and patent applications incorporated above. Alternatively, according to factors such as cost and function, the lid 118, frame 114, box 112 and / or the parts of the box 12 can be made of different materials. Of course, the molding process may have separate molding steps. However, compared with the previous embodiment, the single material embodiment has various advantages, such as the cost advantage associated with a simpler molding process and the use of a single, cost-effective and functional material. As will be discussed below, this embodiment also shows the use of a flexible finger 120 as a resilient biasing structure extending from the inner surface of the lid 118 for use with one or more tissue samples 112 ( Fig. 10A ) is joined. The peripheral frame portion 116 is coupled to the remainder of the frame 114 via a hinge 122. Fig. 9 As best shown, the cover 118 is coupled to the peripheral portion 116 using a material "bridge" or breakaway connection 126 that breaks as the user presses on the cover 118 during the transition process as will be discussed below. Fig. 9 As shown, the cover 118 also includes "cutters" 130 that align with the bridges or breakaway connections 132 that secure the box body 112a to the frame 114. When the user presses the cover 118 and breaks the cover 118 from the peripheral portion 116 at the connection 126, these cutters 130 cut or break the bridges or connections 132 that maintain the box body 112a to the frame 114. It will be understood that the cutters 130 do not need to be sharp, but at least are meant to concentrate the force on the thin connection 132. Fig. 10A and Fig. 10B The respective open and closed positions of the cartridge cover 118 and the peripheral rim 116 are shown. Fig. 10B Resilient fingers 120 are shown for maintaining one or more tissue samples 124 against the bottom wall 112c of the cartridge 112 . Fig. 10C The transitional movement of the cassette 112 between an upper position (not shown) and a lower position within the mold 140 is shown.

[0079] exist Fig. 10C In the second or lower position, the previously discussed bridge or connection 126 has been broken and, therefore, the cover 118 is maintained against the upper peripheral surface of the cartridge body 112a. In the second or lower position, as previously described, the cartridge body 112a is exposed below the bottom of the frame 114 to allow the cartridge body 112a and tissue sample 124 to be sliced ​​in the microtome 54 ( Figure 4 ), while frame 114 remains in the slicer chuck. Fig. 10C As further shown, the frame 114 is frictionally retained within the mold 140 by being maintained against a resilient sealing member 142 coupled to the mold 140 . Fig. 10D The process is shown following the steps of filling the mold 140 with an embedding material such as paraffin wax 150 and allowing the paraffin wax 150 to solidify into a block encapsulating the sectionable cassette 112 and the tissue sample 124 held within the recess or interior 112b of the cassette 112. This solidified block 150 is then sectioned in a microtome 140 as described in the patents and patent applications incorporated herein by reference and fully above. Figure 4 ), and the thin ribbon sections 56 are placed on a microscope slide (not shown) for pathological diagnosis.

[0080] Fig.11A , Fig. 11B and Fig. 11C The construction and use of the separation connection 126, 132 and the cutter 130 associated with the box 112 and the frame 114 are better shown. Specifically, the cutter 130 is aligned with the bridge 132 that connects the box body 112a to the frame 114, and as shown in FIG. Fig. 11B As shown, when these cutters 130 are pressed downward, they will cut or help break or shear the frangible bridge or connection 132 to separate the box 112 from the frame 114. Almost simultaneously, the frangible bridge 126 of material holding the box cover 118 to the peripheral edge 116 breaks and the cover 118 then moves with the box body 112a from the first position (not shown) to the peripheral edge 116. Fig. 11C The second transition position is shown. Fig. 12A and Fig. 12B Another perspective view is shown, which shows the bridge 132 and the use of the cutter 130 to break the bridge 132 and allow the box 112 and the box cover 118 to be separated from each other. Fig. 12A The first position shown moves to Fig. 12B The second position is shown in FIG.

[0081] Fig.13 and Fig.14 Another illustrative embodiment of an apparatus 100' is shown, which is very similar to the embodiment described with reference to Figures 7 to 12A and 12B , shown and described. Fig.13 and Fig.14Like reference numerals in the drawings refer to like structures shown and described in the previous embodiments. Therefore, further explanation of the previously described structures is unnecessary. In this embodiment, the resilient fingers 120 depicted in the previous embodiments have been replaced by gaskets 160, which are connected to the underside of the cover 118 by resilient legs 162. Again, the entire box and frame structure including the gasket members 160 and legs 162 can be molded from a single material and in a single mold, greatly simplifying the manufacturing process. Alternatively, two or more of these components can be co-molded or insert molded. As Fig.14 As shown, the resilient gasket member 160 is used to maintain one or more tissue samples 124 against the bottom surface 112c of the box 112, thereby maintaining the one or more tissue samples 124 in a desired orientation and flat against the inner bottom surface 112c of the box interior 112b. When the gasket 160 engages the tissue sample 124 when the box lid 118 is closed, the legs 162 connecting the gasket 160 to the underside of the box lid 118 can rotate and bend slightly. This stabilizes and holds the one or more tissue samples 124 during tissue processing and embedding.

[0082] Fig.15 , Fig.16A and Fig. 16B Another illustrative embodiment of the device 10" is shown, which is very similar to Fig.13 and Fig.14 The same reference numerals again refer to the same elements in structure and function as previously described, and therefore do not need to be described again. Fig.13 and Fig.14 The only differences in the embodiment of FIG. 1 are that the resilient spacer member 160' has been reshaped and slightly more rounded in structure, and the leg members 162' are resilient and twistable similar to springs to better engage and retain the one or more tissue samples 124 within the cartridge interior 112b and as described above. Fig. 16B As shown abutting the interior bottom surface 112c of the box 112.

[0083] Now refer to Fig.17 , Fig.18 , Fig.19A and Fig.19B , another exemplary embodiment of the device 100'' is shown and as will be understood from the following description, this embodiment can also be formed from a single material and in a single mold. Again, in this embodiment, the same reference numerals refer to the same elements of the previous embodiments. In this embodiment, as with respect to Figures 7 to 12BIn the illustrated and described embodiment, the cassette body 112a is connected to the inner peripheral surface of the frame 114 by a breakaway material bridge or connection 132. However, the cover 118' of the cassette 112 is designed to fit and lock within the cassette body 112a and be pressed downwardly into the interior 112b of the cassette body 112a and against the one or more tissue samples 124 in the interior 112b to maintain the one or more tissue samples 124 against the inner bottom surface 112c of the sectionable cassette 112. The "locking" may simply be a friction fit. Fig.19C As shown, the material bridge 132 between the box body 112a and the frame 114 is designed to be thin and fragile when the box 112 transitions from the first position to the second position. Fig.19C As shown, a user or machine can press the box cover 118' into the box body 112a, and the box cover 118' can also be as shown. Fig.19C The hinge 176 connects the lid 118' to the frame 114 and has such a length that when the box body 112a is removed from the Fig.19B The first position shown transitions to Fig.19C In the second position shown, the box cover 118' can extend downwardly into the box body 112a. Fig. 20A , Fig. 20B and Fig. 20C The structure and function of this illustrative flexible and elongated hinge structure 176 is better shown in FIG.

[0084] Figures 21 to 24B Another embodiment of device 200 is shown. Again, the device 200 can be formed by a single material and in a single mold as will be understood from the accompanying drawings and subsequent description, or can be formed by different materials using other molding techniques such as co-molding or overmolding as any of the embodiments described above. Again, the same reference numerals in this embodiment refer to the same elements of the structure and corresponding functions described in the previous embodiment. Therefore, further description of such elements is no longer repeated here. As will be described, the elements marked with one or more symbols (') are slightly modified from the previous corresponding elements. In this embodiment, as previously shown and described embodiments, the box body 112a is connected to the inner peripheral surface of the frame 114 by disengaging the material bridge or connecting portion 132. The cover 118 "of the box 112 includes a cutter 130 but is also designed to be locked to the box body 112a using multiple locking 202. As in the previous embodiment, the cover 118 "can be separated from the peripheral portion 16 of the frame 14. Another difference between this embodiment and the previous embodiment having a "spring structure" for engaging the tissue sample within the cartridge 112 is that the spring structure includes a plurality of linear fingers 204 that may be straight and as shown in FIG. Fig.23A As best shown in FIG. Fig. 23B As alternatively shown in , the distal end 204a of the finger 204 can instead be curved to provide more surface area engagement with one or more tissue samples and a "softer" engagement that is less likely to damage the tissue samples. Another difference between this embodiment and the previously described embodiments relates to the method and structure for positioning the box 112 and the cover 118" within the frame 114. In this regard, as shown in Fig.24A and Fig. 24B As best shown, each corner of the box cover 118" engages with a box positioning element 210 formed as part of the inner corner of the frame 114. The box positioning element 210 is flexible and hollow so that when the corner of the cover 118" passes the box positioning element 210, the corner of the cover 118" deforms the box positioning element 210 and ultimately, for example Fig. 22B and Fig. 24B 14. As shown in FIG. 14, the cassette 112 and lid 118 are "snapped" below the cassette retaining element 210. As described above, this maintains the cassette 112 and lid 118" in the second position and ready for embedding and subsequent microtome sectioning.

[0085] Although the present invention has been described by the description of specific embodiments of the present invention, and although the embodiments have been described in considerable detail, it is not intended that the scope of the appended claims be limited or in any way restricted to such details. The various features discussed herein may be used alone or in any combination within and between the various embodiments. Other advantages and modifications will be apparent to those skilled in the art. Therefore, the broader aspects of the present invention are not limited to the specific details, representative devices and methods, and illustrative examples shown and described. Therefore, modifications may be made from these details without departing from the scope or spirit of the general concept of the present invention.

Claims

1. A histological tissue sample support device, comprising: a tissue cassette having a recess including a bottom wall and at least one side wall, the tissue cassette being formed of a material that can be smoothly sectioned in a microtome and resists degradation by solvents and chemicals used to fix, process and stain tissue; a frame including a peripheral portion and a remainder, the remainder of the frame including a bottom edge, the tissue cassette being movably coupled to the remainder of the frame; a retaining groove integrally formed with the frame; a tissue cassette retaining tab formed integrally with the tissue cassette; a cover detachably coupled to the peripheral portion of the frame, the cover being sized and configured so that it fits within an interior of the peripheral portion defined between surrounding walls of the peripheral portion; and a cover retaining tab formed integrally with the cover; wherein the peripheral portion and the cover are movable from an open position, wherein the tissue cassette and the frame are ready to receive tissue in the recess of the tissue cassette, to a closed position on the remainder of the frame and the tissue cassette, wherein the peripheral portion is locked to the remainder of the frame; wherein, after the peripheral portion and the cover are in the closed position, the cover is separated from the peripheral portion, the cover and the tissue cassette are movable from a first position relative to the frame to a second position relative to the frame, and in the second position, at least a portion of the side wall of the tissue cassette and the bottom wall of the tissue cassette extend beyond the bottom edge of the remainder of the frame for sectioning in the microtome; When the cover and the tissue cassette move between the first position and the second position, the tissue cassette retaining tab and the cover retaining tab slide within the retaining groove between the first position and the second position, thereby preventing the cover and the tissue cassette from moving unexpectedly.

2. The support device according to claim 1, wherein: The peripheral edge portion is coupled to the remainder of the frame with a frangible hinge.

3. The support device according to claim 1, wherein: The cover is coupled to the peripheral portion using at least one breakaway connection.

4. A histological tissue sample support device, comprising: a tissue cassette having a recess including a bottom wall and at least one side wall, the tissue cassette being formed of a material that can be successfully sectioned in a microtome and resists degradation by solvents and chemicals used to fix, process and stain tissue; a frame including a peripheral portion and a remainder, the remainder of the frame including a bottom edge, the tissue cassette being movably coupled to the remainder of the frame; a retaining groove integrally formed with the frame; a tissue cassette retaining tab formed integrally with the tissue cassette; a microtome-slicable resilient structure configured to engage and maintain tissue in place within the recess during processing and embedding; as well as a cover retaining tab formed integrally with the cover; a cover detachably coupled to the peripheral portion of the frame and to the elastic structure, the cover being fitted within an interior of the peripheral portion defined between surrounding walls of the peripheral portion, the cover being used to press the elastic structure against the tissue, and the elastic structure also enabling smooth sectioning in the microtome and being porous to allow penetration of the solvent and the chemicals used for fixing, processing and staining the tissue and the embedding material used for embedding the tissue when the tissue is maintained in the recess by the elastic structure, wherein the rim and the cover are movable from an open position, in which the tissue cassette and the frame are ready to receive tissue in the recess of the tissue cassette, to a closed position, in which the rim is locked to the remainder of the frame; wherein, after the peripheral portion and the cover are in the closed position, the cover is separated from the peripheral portion, the cover and the tissue cassette are movable from a first position relative to the frame to a second position relative to the frame, and in the second position relative to the frame, the bottom wall of the tissue cassette, at least a portion of the side wall of the tissue cassette, and at least a portion of the resilient structure extend beyond the bottom edge of the remainder of the frame for slicing in the microtome; When the cover and the tissue cassette move between the first position and the second position, the tissue cassette retaining tab and the cover retaining tab slide within the retaining groove between the first position and the second position, thereby preventing the cover and the tissue cassette from moving unexpectedly.

5. The support device according to claim 4, wherein: The cover is coupled to the peripheral portion using at least one breakaway connection.

6. The support device according to claim 4, wherein: The tissue cassette is coupled to the frame using at least one breakaway connection.

7. A method of preparing one or more biopsy tissue samples for histological examination using a histological tissue sample support device, the support device comprising a microtome-slicable tissue cassette including a recessed portion, a frame including a peripheral portion and a remaining portion, and a cover detachably coupled to the peripheral portion of the frame, the tissue cassette being located within an interior of the remaining portion of the frame, the cover being mounted within an interior of the peripheral portion defined between surrounding walls of the peripheral portion, and the frame further comprising a retaining groove formed integrally with the frame, the tissue cassette further comprising a cassette retaining tab formed integrally with the tissue cassette, and the cover further comprising a cover retaining tab formed integrally with the cover, the method comprising: positioning a tissue sample in the recess of the tissue cassette when the peripheral edge and the cover are in an open position; closing the peripheral edge portion of the frame and the cover to the remaining portion of the frame and the tissue cassette when the tissue cassette is in a first position relative to the frame, and where the peripheral edge portion is locked to the remaining portion of the frame; separating the cover from the peripheral portion of the frame; as well as Moving the cover and the tissue cassette from the first position relative to the frame to a second position relative to the frame includes sliding the cassette retention tab and the cover retention tab within the retention groove such that a portion of the tissue cassette extends beyond an edge of the frame for sectioning in the microtome.

8. The method of claim 7, further comprising: before or after moving the cover and the tissue cassette to the second position, subjecting the tissue cassette and the tissue sample to a process of replacing fluid in the tissue sample with a hardenable material; embedding the tissue cassette and the tissue sample in an embedding material; allowing the embedding material to harden into a block; as well as The block is sliced ​​into thin slices of the embedding material, the tissue cassette, and the tissue sample using a microtome.

9. The method of claim 7, further comprising: After the embedding material has hardened into a block, the histological tissue sample support device is positioned in a microtome.

10. The method of claim 7, further comprising securing the tissue sample by contacting the tissue sample with a microtome-slicable resilient structure, the resilient structure coupled to the cover.

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