Patent Publication Number: US-2023134295-A1

Title: Method and apparatus for dislodging core tissue biopsy samples from core collectors and for storing and preparing samples for pathology

Description:
FIELD 
     This patent specification relates to dislodging core tissue biopsy samples from a core collector and to cassettes for core tissue samples and methods of loading tissue samples therein, preparing the samples for delivery to a pathology laboratory, and to kits for handling and shipping core tissue biopsy samples. 
     BACKGROUND 
     Core biopsy is a well-known medical procedure. FIG. A shows one example of steps in collecting a tissue sample with a core biopsy instrument. The instrument initially houses a core collector A 1  of a core biopsy needle, sometimes called only a core collector or a coring needle or stylet, in a sheath A 2 . Core collector A 1  is spring loaded and fired out of sheath A 2  and into tissue A 3 . A sample of tissue protrudes into a slot or cutout A 4  near the distal end of core collector Al, and then the instrument fires sheath A 2  over core collector Al. The sharp distal end of sheath A 2  cuts the tissue A 5  that has protruded in slot A 4  from surrounding tissue to thereby separate a core tissue sample A 5 . The physician withdraws core collector A 1  together with sheath A 2  from the patient and hands the instrument to an assistant. The assistant pulls back sheath A 2  to expose the core tissue sample A 5  and wipes, sometimes repeatedly, the open side of slot A 4  on a foam pad, GAUZE, Tefla pad or similar material to thereby deposit the tissue sample A 5  thereon. The assistant then cocks the spring-loaded instrument to prepare it for taking another sample and hands it back to the physician if additional samples need to be taken. FIG. B illustrates two known foam pads B 1  in cassettes B 2 , with several tissue samples on the pads (only one of the samples is labeled A 5 ). The assistant covers the tissue sample on foam pad B 1  with another foam pad (not shown|) or a membrane permeable to tissue fixative and places the sealed cassette B 2  in a bottle of tissue fixative for delivery to pathology. In the example of prostate core biopsy, a typical transrectal systematic biopsy involves samples from the parasagittal plane on the right and left sides of the base, midzone, and apex, with each site arbitrarily assigned by the operator. Known current procedures typically involve extracting  12  to  16  or more cores per biopsy, often from the standard sextant and other areas of the peripheral, transition, or anterior zones. The optimal number and location of core samples are not standardized and vary based on individual preferences and experience. In the example of breast biopsy, typically tissue samples are taken from lesion locations that have been previously found through imaging modalities such as x-ray, ultrasound, and MRI. Core biopsies also are used for other organs and tissue such as liver, kidneys and breasts. 
     In known current practice, the assistant typically wipes the distal portion of the core collector on the foam pad to dislodge the sample from the core collector and might use tweezers to help remove the sample from the core collector or to reposition the sample on the foam pad. The tissue sample fits snugly in the core collector and can be slightly compressed therein, making it difficult in some cases to remove and requiring manipulations that may deform it. The tissue sample may not simply fall out of the core collector by shaking and thus removal in the standard process involves swiping on a foam pad or filter paper or the like and possibly using forceps or another tool to remove the sample from the core collector and straighten it on the foam pad or the like. FIG. B illustrates two foam pad cassettes with core tissue samples. In this figure, three core samples are in each cassette although in typical practice each cassette would hold only a single core sample. Dislodging a tissue sample from a core collector needle onto a foam pad may not preserve sample integrity and may result in artifacts such as compression, tearing, and twisting that may interfere with subsequent examination. Dipping and swishing to dislodge a tissue sample from a core collector also have been used or proposed. 
     The submission of a high-quality core sample to a pathologist is a crucial component for a successful pathologic evaluation. It is important to preserve core sample integrity and orientation to ensure that the diagnostic sample delivered to a pathologist accurately represents the patient&#39;s tissue in situ with respect to the position, size, shape, and orientation of a lesion and the cells therein. It is desirable for the core tissue sample to remain intact, as close as practicable to the way it was while in its anatomical origin. However, the known process described above for depositing core samples on foam pads is a delicate operation that is difficult to perform with good or consistent results and may not preserve core sample integrity. The current gold-standard process of depositing a core tissue sample on a foam pad or the like tends to introduce artifacts in the sample due to stretching, folding, tearing, or compression of the tissue during sample processing. For example, the tissue samples in FIG. B show tortuosity and poor integrity, which can make pathology interpretation difficult and less reliable. Core volume and integrity are important particularly where tissue architecture in the sample is paramount, such as in samples of non-malignant liver (e.g., cirrhosis) and non-malignant kidney (e.g., glomerulonephritis). Proposals for a cassette that accepts a plurality of tissue samples are discussed in U.S. Pat. Nos. 5,002,377, 5,127,537 and 10,670,593 and in published applications US 201/067338 A1 and US 2019/0060893A1. To applicant&#39;s knowledge, they have not been translated into commercial products and put into practical use. U.S. Pat. No. 10,670,593 discusses a protein matrix for receiving multiple tissue samples and one example is a matrix hydrated to make it flexible and driven over a roller such that channel openings widen and an adhesive at the channel bottoms would hold sample in place despite the widened openings. 
     SUMMARY OF DISCLOSURE 
     This patent specification describes a new system and method for retrieving biopsy tissue samples or specimens from a biopsy core collector, submerging them in a fixative solution, and storing them for transport to a pathology lab for analysis in a manner which preserves tissue integrity and improves the diagnostic value of core tissue samples such as from core biopsies of the prostate. In the new system and method, a cassette is made of a material such as polymer or an injection molded plastic and has one or more liquid-lined channels, each sized and shaped to accept a core tissue sample from a core collector. This new approach can standardize and reduce variability of retrieval methods as well as accelerate sample processing at the point of collection (clinic) and in the pathology laboratory. 
     Notably, a special liquid in the channel has the requisite chemical and physical properties to sufficiently attract and retrieve the tissue sample on contact, enabling facile removal from the sample collection device (core collector) while preserving tissue integrity and orientation. The term special liquid is used in this patent specification to refer to a substance that is hydrophilic and can be a liquid, colloidal, or hydrogel solution, suspension, or dispersion that has the properties of being hydrous and hydrophilic and further has the special properties that are described below and result in the ability to attract a tissue sample from a core collector in a touch-and-go motion and to easily release the tissue sample when needed. The physician or assistant gently contacts the exposed axis of a core tissue sample that is contained within a core collector (needle) to the liquid-lined channel. The special liquid is designed to exert cohesive forces on the exposed surface of the tissue sample in the core collector, resulting in the tissue dislodging from the core collector and attaching preferentially to the special liquid in the liquid-lined channel. Moreover, the attraction of the tissue to the liquid-lined inside wall of the channel ensures retention of the special liquid in the channel and thus retention of the tissue sample in the channel. Importantly, the attachment of the tissue sample to the channel is a non-covalent and non-permanent, driven primarily by gentle and transient surface tension and hydrostatic forces, such that the tissue sample can detach easily from the liquid-lined channel as required for secondary tissue processing. Simply lining up the core collector to the channel and lightly touching the tissue sample to the liquid in the channel transfers an intact and undamaged core sample to the channel, and the sample can be easily taken out of the channel for further processing and assessment in a pathology lab. An important advantage of this new approach is the ability to easily capture the tissue from the core collector at the collection point (clinic) and subsequently release it easily at the processing point (pathology lab) without requiring further processes to uncouple the tissue sample from the channel using mechanical, enzymatic, or other special means. The coherence of the special fluid lining the channel to the channel wall is greater than the coherence of this special fluid to the tissue sample and is greater than the coherence of the tissue sample to the inside wall of the core collector. The new approach leverages differences in sources of cohesion and adherence among the tissue sample, the inner wall of the core collector, a special liquid, and the inner wall of a channel in a cassette. Preferably, the material forming the inner wall of the channel is sufficiently hydrophilic to allow the special liquid to line it. 
     As noted, the term special liquid as used in this patent specification differentiates from solid material and refers to substances that at room temperature are more viscous than water and encompasses suspensions or solutions of solid materials such as gels and hydrogels and liquids that are so viscous that they stay in a channel when smeared thereon. The special liquids referred to this this patent specification have the important properties described above that result in attracting a tissue sample from a core collector and holding the sample in the channel but easily releasing the tissue sample from the channel when needed rather than acting as an adhesive that makes release from the channel so difficult that the sample would be damaged or distorted by the release. 
     Significant advantages of the new approach described in this patent specification include: (1) improved tissue sample integrity (compared to known current standard devices/methods), with fewer collection-related and processing-related tissue sample artifacts that interfere with diagnostic use such as tearing, folding, and compression; (2) acceleration of sample processing, both primary (point of collection—tissue to channel in cassette) and secondary (pathology lab) tissue sample processing (cassette to slide); and (3) improved diagnostic value, with preservation of tissue integrity and orientation so that samples can be easily and unambiguously associated with their anatomical origin, with improved usability (e.g., in the current known gold standard methods typically a certain percentage of the samples are unusable due to loss or to collection-related artifacts but the new approach yields a much higher percentage of usable samples, thereby offering substantial improvement in the pathological diagnostic value to the patient and physician). 
     According to some embodiments, a system comprises: a tissue core sample cassette having a base with a channel configured to hold a tissue sample and filled with a special liquid that comprises a hydrogel; said cassette further comprises a removable membrane covering the channel that keeps the liquid therein and a lid hinged to the base and configured to pivot between open and closed positions; wherein: said lid has an array of through holes that are over said channel when the lid is closed and further has a bottom surface that surrounds the array of holes and when the lid is closed is flush with an upper surface of the base that surrounds the channel therein; said lid is configured to snap-fit to the base when closed over said membrane and to open and expose the membrane when manually pushed from the base; said liquid is exposed when the lid is moved from being closed over the membrane to being open and the membrane is peeled off; and said liquid has the property of attracting a tissue sample touched thereto and keeping a tissue sample in the channel, being soluble in tissue fixative, and free of substances adversely affecting sample characteristics; said lid is transparent and has a pattern of visible markings along said array of through holes that are spaced by selected distance, to facilitate grossing a tissue sample in the channel while the lid is closed; and said lid when closed over a tissue sample in the channel is configured for flow of tissue fixative through said holes to the sample. Gross processing or “grossing” is the process by which pathology specimens undergo examination with the bare eye to obtain diagnostic information, prior to cutting and tissue sampling to prepare material for subsequent microscopic examination. 
     According to some embodiments, the system can further include one or more of the following: (a) a plurality of said tissue sample cassettes forming a set of cassettes and a vessel having an internal cross-section matching an outside shape of said cassettes and configured to hold said set of cassettes stacked on each other and sealed while immersed in tissue fixative: (b) each of one or more of said cassettes is permanently pre-labeled with an identification of an anatomical and regional origin of a tissue sample according to a medical labeling convention.; (c) the base of each of one or more of the cassettes in the set includes a hinge pin and the lid includes a rounded channel with that tightly fits over the hinge pin and has an opening configured to snap over the pin, wherein the lid and base are separately molded of respective polymeric materials and the lid is snapped over said pin to pivot about the pin between being open and closed; (d) the lid of each of one or more of the cassettes in the set includes an upward peripheral lip configured to pool formalin; (e) the lid of each of at least some of the cassettes in the set includes a downward peripheral lip configured to tightly fit over a periphery of the base; (f) the base of each of one or more some of the cassettes in the set includes a central opening that the lid clears, which central opening facilitates flow of tissue fixative such as formalin or other liquids bathing tissue samples in said cassettes when in said vessel; (g) the base of each of one or more of the cassettes in the set is generally round and is scalloped with two diametrically opposed finger-hold indentation to facilitate handling the cassette; (h) said upper surface of the base surrounding the channel is flat and said base has a generally hollow underside in each of one or more of the cassettes in the set; (i) the lid of each of one or more of the cassettes in the set has a flat underside surface surrounding said array of through holes; and (j) the lid may not be hinged to the base. 
     According to some embodiments, a tissue core sample cassette comprises: a base with an open channel configured to hold a tissue sample and configured to hold a special liquid that comprises a hydrogel; a lid hinged to the base and configured to pivot between being open and being closed; wherein: said lid has an array of through holes that are over said channel when the lid is closed and further has a bottom surface that surrounds the array of holes and when the lid is closed is flush with an upper surface of the base that surrounds the channel therein; said lid is configured to snap-fit to the base when closed and cover said channel with at least some of the holes over the channel and to open and expose the channel when manually pushed from the base; said lid is transparent and has a pattern of visible markings along said array of holes that are spaced by selected distance, to facilitate grossing of a tissue sample in the channel while the lid is closed; and said lid when closed over a tissue sample in the channel is configured for flow of tissue fixative through said holes to the sample. 
     According to some embodiments, the cassette described in the immediately preceding paragraph further includes one or more of the following: (a) the cassette includes special liquid filling the channel and a removable membrane covering the channel and keeping the liquid therein until being removed to expose the channel and the liquid; (b) said liquid has the property of attracting a tissue sample touched thereto and keeping a tissue sample in the channel, being soluble in tissue fixative, and free of substances adversely affecting sample characteristics; (c) said base includes a central opening configured for flow of tissue fixative therethrough; (d) said base is molded as a single piece and includes a hinge pin and said lid is separately molded as a single piece and includes a tubular catch with an opening configured to snap-fit over said hinge pin for pivoting thereabout; (e) said base is made of a polymeric material colored to contrast with a tissue sample in said channel; (f) said base is permanently pre-labeled with an identification of an anatomical origin of a tissue sample according to a medical labeling convention; and (g) said base includes one or more finger-hold indentations to facilitate handling the cassette at least when depositing a tissue sample in said channel. 
     According to some embodiments, a method of preparing tissue samples for sending to pathology comprises: touching exposed portions of respective tissue samples in core collector needles to a special liquid comprising hydrogel filling a channel in respective bases of cassettes to thereby dislodge the samples from the core collector needles into the respective channels; snapping and releasably locking a transparent lid over the channel and the sample therein in the respective cassettes; and stacking the cassettes with the samples therein and the lids closed in a vessel of tissue fixative having an interior shape conforming to and closely fitting the exterior shape of the stacked cassettes but providing sufficient space around the stacked cassettes for flow of tissue fixative up and down the vessel; and further providing central holes in said cassette bases for flow of tissue fixative in the vessel through said central holes in the bases of the cassettes stacked in the vessel. 
     According to some embodiments, the method can further include separately molding or otherwise forming the cassette bases as single pieces of polymeric materials in a color contrasting the tissue samples and the lids as single pieces of a hard transparent plastic. According to some embodiments, the method can include molding the cassette as a single piece of polymeric material, with the base and lid connected to each other with a living hinge formed as a part of the molding process such that the cassette can be easily closed after a tissue sample has been placed in the channel and opened later for visual grossing with appropriate markings to facilitate the process or for other purposes. This embodiment using a live hinge can make the process or manufacturing the cassette significantly less expensive than the process of molding or otherwise forming the base and lids as separate pieces and connecting them by snapping the lid into the hinge pins. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       To further clarify the above and other advantages and features of the subject matter of this patent specification, specific examples of embodiments thereof are illustrated in the appended drawings. It should be appreciated that these drawings depict only illustrative embodiments and are therefore not to be considered limiting of the scope of this patent specification or the appended claims. The subject matter hereof will be described and explained with additional specificity and detail through use of the accompanying drawings in which: 
         FIG.  1    is a perspective view of a core tissue sample cassette with a partway open lid, according to some embodiments. 
         FIG.  2    is a perspective view of a core tissue sample cassette with a fully open lid, according to some embodiments. 
         FIG.  3    is a perspective view of a cassette with a closed lid, according to some embodiments. 
         FIG.  4    is a perspective view of a portion of a cassette sectioned in a plane perpendicular to the length of a tissue sample channel, according to some embodiments. 
         FIG.  4   a    is a partial sectional view of a portion of a cassette adjacent a channel and  FIG.  4   b    is an alternative sectional view. 
         FIG.  5    shows at left a bottom view of a lid, a side view in the center, and a top view at right, according to some embodiments. 
         FIG.  6    illustrates a vessel enclosing a stack of tissue cassettes in formalin, according to some embodiments. 
         FIG.  7    illustrates an alternative example of a tissue sample cassette, according to some embodiments. 
         FIG.  8    is a perspective view of another tissue holder according to some embodiments that is configured to fit in a known cassette. 
         FIG.  9    is a perspective view of the tissue holder of  FIG.  8    placed in a known cassette, according to some embodiments. 
         FIG.  10    is another perspective view of the tissue holder of  FIGS.  8  and  9   , according to some embodiments. 
         FIG.  11    a is a top view and  FIG.  11    b is a bottom view of the tissue sample of  FIGS.  8 - 10   . 
       FIG. A illustrates a known method of taking a tissue sample with a core collector needle. 
       FIG. B illustrates tissue samples deposited on known foam pads. 
     
    
    
     DETAILED DESRIPTION 
     A detailed description of examples of preferred embodiments is provided below. While several embodiments are described, the new subject matter described in this patent specification is not limited to any one embodiment or combination of embodiments described herein, but instead encompasses numerous alternatives, modifications, and equivalents. In addition, while numerous specific details are set forth in the following description to provide a thorough understanding, some embodiments can be practiced without some or all these details. Moreover, for the purpose of clarity, certain technical material that is known in the related art has not been described in detail, to avoid unnecessarily obscuring the new subject matter described herein. It should be clear that individual features of one or several of the specific embodiments described herein can be used in combination with features of other described embodiments or with other features. Further, like reference numbers and designations in the various drawings indicate like elements. 
     Referring to  FIGS.  1 - 5   , a core tissue sample cassette  100  comprises a base  102  and a lid  104  that is hinged to the base at a hinge  106  and is shown in a partway open position, extending up from the base. Base  102  includes an elongated channel  108  that is shaped and sized to accept a core tissue sample. For example, channel  108  is shaped and sized to accept a tissue sample from an 18-gauge core collector needle. In use, channel  108  is filled with a special liquid that is discussed in more detail further below. The liquid can be placed in channel  108  at a time suited to the intended use of cassette  100 . For example, the liquid can be put in channel  108  when cassette  100  is manufactured and can be sealed in place, for example with adhesive or sticky tape or membrane over channel  108 . Or the liquid can be put in channel  108  by a distributor when filling an order for cassettes by an end user and likewise sealed in place. Or the liquid can be put in channel  108  at a medical office that performs biopsies, and this can be done just before a biopsy procedure or more likely from time to time to prepare a supply of cassettes that are expected to be used in the foreseeable future and again sealed. 
     Base  102  is generally circular and can be roughly 1.75 inches in diameter. Two finger-hold indents  116 ,  118  at diametrically opposite locations facilitate holding cassette  100 . Base  102  has a perimeter wall  120  that is generally smooth outside and is configured to accept labeling or to allow writing, for example information about a tissue sample or the patient. An upper surface of base  102  near channel  108  preferably has notation  120  that identifies the tissue sample that would be put in channel  108 . This notation preferably is permanent and can be laser etched or formed in some other way. An example is the notation LMB in  FIG.  1   , which identifies an anatomical location of a tissue sample according to a common medical convention. As discussed further below, cassettes  100  can be provided in a set, for example  12  or more cassettes, suited for a specific medical procedure, with each cassette pre-labeled with notation  120  identifying respective anatomical locations from which samples are expected to be taken. This notation can be placed in the process of manufacturing the cassettes, for example by molding, or hot-stamping, or screen printing, or can be placed later, for example using stick-on labels when cassettes are prepared for use in a specific medical procedure. Some cassettes in the set may be left unlabeled to allow for a custom label to be placed for tissue samples taken from less common anatomical locations or targeted locations. Alternative or additional labels may be placed at the bottom or base  102 . Base  102  preferably is a medium dark color, such as blue, to provide a contrasting background that facilitates visualizing a tissue sample. 
     Lid  104  has an array of through holes  110  that are over channel  108  when the lid is closed ( FIG.  3   ) and allow tissue fixative to bathe a tissue sample in channel  8  when the closed cassette  100  is immersed in tissue fixative. The bottom surface of lid  104  that surrounds holes  110  is generally flat and is configured to lie substantially flush against the top surface of base  102  surrounding channel  108 . Lid  104  is transparent so that a tissue sample in channel  108  can be observed when lid  104  is closed ( FIG.  3   ). Lid  104  has markers  112  along the array of holes  110 , in two rows along the long dimension of channel  108 . For example, markers  112  that are short lines are spaced  5  mm apart and markers  112  that are dots can be spaced halfway between adjacent lines so that there is a marker, either a short line or a dot, every 2.5 mm ( FIG.  5   ). Markers  112  can be molded or otherwise formed and can assist in “grossing” a tissue sample under lid  104  while keeping the lid closed. “Grossing” refers here to a known pathology practice of visually assessing a tissue sample. Preferably, through holes 110  and markers  112  are to the side of a clear and transparent portion of lid  104  that is directly over channel  108  that allows a clear view of a tissue sample in channel  108  to facilitate grossing. A raised perimeter lip  114  around the top of lid  104  pools tissue fixative when cassette  100  is flat to keep a tissue sample in cassette  100  in fixative, for example when cassette  100  is temporarily placed on a flat surface after removal from a vessel in which it had been immersed in the fixative. Lid  104  has a snap-catch  122  protruding down and base  102  has a snap-hold  124  that releasably engage each other to hold lid  104  in a closed position for handling but to easily release and allow lid  104  to open by slight upward pressure on lid  104 . When closed, lid  104  partly encircles the sidewall of base  102  with a downwardly protruding lip  126  ( FIG.  4   ). Lid  104  preferably is transparent, but as an alternative can be made of a non-transparent material that is the same or like the material of base  102 . Preferably, lid  104  and base  102  are formed (molded) separately and the lid is hinged as described below, but if as an alternative lid  104  and base  102  are formed (molded) as a single unit, the hinge arrangement described below can be replaced by a living hinge. 
     Base  102  preferably is molded as a single piece of a polymeric material and includes hinge pins  128 . Lid  104  also is preferably molded as a single piece, of a transparent material, and has tubular snap-on extensions with a slot  130 a ( FIG.  5   ) at the bottom of the lid that snap on hinge pins  128  to thereby secure lid  104  to base  102  and allow the lid to pivot between open and closed positions. The bottom side of base  102  is generally hollow so the base is shaped as an upside-down shallow cup but may have some strengthening ribs at its underside. The sidewall of base  102  may be somewhat flared to assist in stacking cassettes  100  on top of each other. 
       FIG.  6    illustrates a vessel  132  releasably sealed with a lid  134  that can contain tissue fixative covering a stack  136  of cassettes  100 . Vessel  132  preferably is transparent and has an internal dimension that closely matches the outline of stack  136  of cassettes  100  but leaves space around the stack for flow of tissue fixative up and down the stack. Tissue fixative flow around the cassettes in the stack is further helped by providing a central opening  138  ( FIG.  2   ) in  base  102  of a cassette  100  and leaving some space around hinge  106  so that tissue fixative can flow in vessel  132  around stack  136  as well as through central openings  138  and spaces around hinge 106  and bathe the tissue samples in channels  108  though holes  110 . 
     As noted, channel  108  is filled with special liquid schematically shown as liquid  140  in  FIGS.  1  and  4     a - 4   b  and can be releasably sealed in place with a membrane  142  such as sticky tape over channel  108 . Liquid  140  is preferably viscous, highly hydrophilic and attracts and holds a tissue sample touched to it. The mechanism of attracting and holding a tissue sample can be observed in prototype systems and is believed to involve multiple concurrent forces, not all of which are entirely understood. Applicant&#39;s current theory is that the forces of attraction and coherence between the hydrophilic surface of the liquid-lined channel and the special liquid are greater than the forces of coherence between the special liquid and the tissue sample allowing the tissue sample to be easily removed from the liquid-lined channel when needed. Likewise, the forces of attraction and cohesion between the tissue sample in the channel and the special liquid lining the channel are greater than those between the tissue sample and the inner wall of the core collector holding the sample, allowing the tissue sample to be easily transferred from the core collector to the liquid-lined channel using a simple touch-and-go process without the need for mechanical tools that can damage the sample. Applicant&#39;s current theory is that this mechanism is driven primarily by from surface tension and the forces of attraction between the hydrophilic liquid  140  and the naturally hydrous/hydrophilic properties of tissue samples comprising of cells, extracellular matrix, and interstitial liquid. The surface tension between special liquid  140  and a tissue surface that typically is hydrous and hydrophilic is believed to act as an attractant to drive contact and cohesion. As a result, these forces of attraction and cohesion drive combine to pull the tissue sample from a core collector needle into liquid  140  in channel  108  in a touch-and-go operation of touching an exposed surface of a tissue sample to liquid  140 . The following references, which are incorporated herein by reference, discuss hydrogels; (1) Ahmed EM, Hydrogel: Preparagion, characterization, and applications: A review, Journal of Advanced Research, Cairo University, 2090-1232, 2013 Elsevier B.V, http://dx.doi.org/10.1016/j.jar.2013.07.006, and (2) Jakab K., Marga F., Norotte C., Murphy, Vunjak-Novakovic, Forgacs G., Tissue engineering by self-assembly and bio-printing of living cells, Biofabrication. 2010 Jun; 2(2):022001. Doi:10.1088/1758-5085/2/2/022001. Applicant has found that a viscous liquid that currently is commercially available from Alcon Inc. of Forth Worth, Tex., USA under the designation Systane Ultra Lubricant works well as special liquid  140 . When special liquid  140  fills a channel  108 , the top level of the liquid can be to the top edge of the channel or below the top edge so long as there is sufficient liquid in the channel to help attract and hold a tissue sample in a touch-and-go motion. Another exemplary substance suitable for the special liquid  140  is commercially available from Medline Industries, LP of Northfield, IL under the designation Medline Skintegrity Hydrogel. The special liquid has viscosity higher than that of water at room temperature (1 centipoise (cps) according to https://www.smooth-on.com/page/viscosity-scale/) but less than that of peanut butter or tomato sauce (100,000-150,000 according to the same website). Preferably, the viscosity at room temperature (20 degrees Centigrade) is in the range 3-25,000 cps, more preferably in the 3-10,000 cps range, still more preferably in the 3-3,000 cps range, still more preferably in the 3-300 cps range, and still more preferably in the 3-15 cps range. The viscosity of Systane is reported to be in the 3.09-11.64 cps (see https://www.aaopt.org/detail/knowledge-base-article/ph-osmolality-and-viscosity-artificial-tears). 
       FIG.  4   a    illustrates in dotted lines several possible levels of special liquid  140  lining channel  108 , to the top or to lower levels to only partly fill channel  108 .  FIG.  4   b    is like  FIG.  4   a    but shows an alternative in which an upwardly extending rim surrounds channel  108  such that when lid  104  is closed over a tissue sample in channel  108  it would not crush or compress the tissue sample. 
     In typical use of cassette  100 , a physician uses a biopsy instrument to capture a tissue sample as known, withdraws the core collector from the patient and hands the instrument to an assistant. The assistant retracts the cutting sheath to expose the tissue sample that is in a notch in the core collector needle and touches an exposed surface of the tissue sample to liquid  140  in channel  108 . Typically, this involves a touch-and-go motion that does not require forceful wiping the tissue sample against the cassette and simply lets the tissue sample separate from the core collector needle and rest in channel  108 . Of course, at that time lid  104  is open, any membrane or tape  142  over channel  108  has been removed beforehand, and there is sufficient liquid  140  present in channel  108 . Once the tissue sample is in channel  108 , the assistant pivots and snaps lid  104  closed and hands the biopsy instrument back to the physician if additional samples are to be taken. As noted, this touch-and-go action preserves tissue sample integrity much better than a known method of wiping a tissue sample on a foam pad or using devices such as forceps to remove a tissue sample from a core needle collector and placing it on a foam pad or to rearrange a sample on a foam pad. In addition, applicant has found that the touch-and-go action speeds the process compared with the known method of wiping a sample on a foam pad and preparing it for sending to pathology. The assistant stacks the cassettes in a tissue fixative vessel ( FIG.  6   ), seals the vessel and prepares it for sending to pathology. A physician may perform initial grossing before the cassettes are put in the vessel. In a pathology lab, the cassettes are processed to treat the tissue samples as needed, and that process too is speeded up compared to treating tissue samples on foam pads, as the lab personnel receive samples the integrity of which has been preserved and orientation of which is apparent from the way they are in cassettes  100 . Practitioners have informed applicant that grossing samples on foam can take as much as  5  minutes per sample and typically includes having to straighten and rearrange the sample but grossing the already straight and integral sample in a cassette  100  saves 2-3 minutes per sample or as much as half-hour for a complete set of tissue samples. The sample can be processed in the usual manner in a standard tissue processor while remaining in cassette  100 , and the processed sample can be removed from cassette  100  and embedded in paraffin much more efficiently than a processed sample taken from a foam pad or filter paper that may require straightening and rearranging. Experience has shown applicant that the processing and paraffin embedding step using cassettes  100  can save an additional  2 - 3  minutes per sample in the lab. 
       FIG.  7    illustrates an alternative cassette  200  that has a base  202  with a channel  208  that can be the same as channel  108  or can vary in depth from a shallow proximal end to a deeper distal end. Channel  208  can be filled completely or partly with liquid  140  (not shown) that can be releasably sealed in the channel with a membrane or tape (not shown) like tape  142  ( FIG.  1   ). Lid  204  is hinged at  206  to pivot between being open as seen in  FIG.  7    and closed and has an array of through holes  210  like holes  110 . At its underside, an area surrounding holes  210  is flat and is flush against a flat area surrounding channel  208  when lid  204  is closed. Lid  204  and base  202  have a snap-catch arrangement like that of cassette  100  so that lid  202  is securely but releasably held to base  202  when the lid is closed. 
       FIGS.  8 - 11     b  illustrate another alternative embodiment. In which a new tissue sample holder  800  is configured to fit in a known cassette  900 , such as a cassette available from Leica Biosystems Inc. of Buffalo Grove, Ill.  FIG.  8    shows in perspective tissue holder  800  and cassette  900  separate from each other and  FIG.  9    shows tissue sample holder  800  fitted in cassette  900 . Tissue cassette  800  comprises a base  802  with a channel  808  that is like channel  108  in  FIGS.  1 - 5    and serves like functions. Notably, channel  808  is configured to extend diagonally when in cassette  800 , thereby allowing channel  808  to accommodate tissue samples longer than the length of a side of known cassette  900 . Base  802  has finger holds  816 ,  818  that facilitate handling tissue holder  808  and are like finger holders  116  and  118  in the embodiments of  FIGS.  1 - 7   . 
     As best seen in  FIGS.  11   a   - b,  channel  808  has a row of through-holes  810  that allow for fixative flow through the bottom side of channel  808  and around a tissue sample in channel  808 . Preferably, the row of through-holes  810  extends along substantially the entire length of channel  808 . In typical use, a membrane  842   b  is taped at the bottom side of tissue holder, over the row of through-holes  810  to temporarily prevent liquid flow through holed  810 . Special liquid  840  is placed in channel  88  to line the channel, as in the case channel  108 . A membrane  842   a  can be placed over the top side of channel  808  to seal the top of the channel and keep special liquid  840  therein. Base  802  can be prepared in this manner at the manufacturing site or at a clinic where it would be used for a tissue sample. Alternatively, at the use site only a membrane  842   b  can be used, at the bottom side of base  802 , special liquid  840  can be placed in channel  808 , and to top side of channel  808  can be left uncovered, i.e., without a membrane  842   a  if a tissue sample is expected to be soon placed in holder  800 . As another alternative, if special liquid  840  is sufficiently viscous to continue lining channel  808  when smeared therein, one or both of membranes  842   a  and  142   b  would not be used at all. 
     As described for the embodiment in  FIGS.  1 - 7   , in typical use an assistant removes membrane  840 a (if that membrane is present) and touches an exposed side of a tissue sample to special liquid  840  lining channel  808  to thereby dislodge the sample from a tissue collector into channel  808  in the touch-and-go motion described above. The assistant places tissue holder  800 , with the tissue sample in channel  808 , in a cassette  900 , in the configuration seen in  FIG.  9   . The assistant places several such combinations of a tissue holder and a cassette, with respective tissue samples therein, in a vessel of a tissue fixative that is like vessel  132  but may be differently shaped, for shipment to a pathology lab. If a membrane  842   b  was used over the bottom side of channel  808 , it preferably is peeled off before placing the tissue holder and cassette in the tissue fixative vessel. 
     Although the foregoing has been described in some detail for purposes of clarity, it will be apparent that certain changes and modifications may be made without departing from the principles thereof. There can be many alternative ways of implementing both the processes and apparatuses described herein. Accordingly, the present embodiments are to be considered as illustrative and not restrictive, and the body of work described herein is not to be limited to the details given herein, which may be modified within the scope and equivalents of the appended claims or permissible revisions thereof.