Patent Description:
Core biopsy is a routine procedure used to obtain a sample of a biological tissue from a live organ for a laboratory examination. <FIG> - ID depict schematically a core biopsy needle <NUM> used for taking core biopsy samples. Core biopsy needle <NUM> comprises a mandrel <NUM> and a Cannula <NUM>. Mandrel <NUM> is an elongated solid needle having a distal tip <NUM> at the end of needle <NUM> and a notch <NUM> adjacent to distal tip <NUM>. Notch <NUM> is an interior shaft recess, used for receiving the tissue sample. Cannula <NUM> is a sleeve exterior to mandrel <NUM> and is configured for sliding over mandrel <NUM>.

During a core biopsy procedure distal tip <NUM> of core biopsy needle <NUM> is brought up to a few millimeters from a region to be sampled in an organ (<FIG>). Mandrel <NUM> is advanced forward into the organ, typically at a high speed to reduce pain in an awakened patient, allowing organ tissue to fill in notch <NUM> (Figure IB). Cannula <NUM> is then advanced forward over the mandrel, thereby cutting off a sample tissue which is left in notch <NUM> (<FIG>). Core biopsy needle <NUM> is removed from the organ and Cannula <NUM> is pulled back in order to expose and remove the sample tissue from notch <NUM> (Figure ID). The sample tissue is typically removed from notch <NUM> into a vial filled with a preservative solution such as a solution including formaldehyde, usually by hand using a syringe or using a small sharp-end tool. Several sample tissues may be put in a single vial during such a core biopsy procedure, being left in the preservative solution until taken through a preparation process for laboratory examination.

A typical preparation process is detailed for example in <CIT>, and may include the following steps:.

In recent years there is continuous trend towards more localized diagnose for many diseases, e.g. local diagnose of prostate cancer. A more localized diagnose enables a more localized treatment, leading to reducing healing time and collateral damage during and after treatment, increasing healing likelihood, decreasing patient suffer and inconvenience and reducing overall treatment cost. Local diagnose procedures rely on the ability to gather accurate data regarding not only the disease histological characteristics but specifically the spatial location of the disease within the organ. Specifically, recent developments in the field of imaging and tracking techniques of treatment tools have led to improved ability of tracing a treatment tool, for example a biopsy needle, within the body. Devices and methods for increasing positioning accuracy of a medical instrument and recording positioning measurements during a medical procedure - e.g. core biopsy - are described for example in <CIT>, <CIT> or <CIT>. In particular, <CIT> discloses a biopsy apparatus including a biopsy probe having a biopsy cannula and a sample basket arranged coaxially about a longitudinal axis. The sample basket is movably disposed relative to the biopsy cannula along the longitudinal axis from a tissue harvesting position to a tissue sample retrieval region. The sample basket has a sample notch formed as an elongate recessed region for receiving a tissue sample. A tissue sample retrieval mechanism includes a sample collection tank configured for removable insertion into a sample tank receptacle. The sample tank receptacle permits movement of the sample collection tank in a direction perpendicular to the longitudinal axis and prohibits movement of the sample collection tank in a direction along the longitudinal axis. However, the current biopsy needles and tissue handling techniques are inherently limited by the shortage of devices and methods that may deliver the required spatial resolution, tissue harvesting efficiency and adequacy of post-biopsy tissue handling, for optimized histological review. Commonly, in the course of a diagnostic procedure involving obtaining core biopsy samples, several samples are taken from several locations in the inspected organ. For example, when core biopsy samples are taken from a prostate to confirm or refute a suspicion of prostate cancer, about six samples, typically, are taken from each half (left and right) of the prostate. The surgeon attempts to distribute the locations from where the samples are taken over the volume of each half, so as to decrease interdependency between samples and thereby increase detection likelihood. However, with current samples handling procedures, several samples, and often all six samples from one half of the prostate, are inserted into a same vial immediately after taking.

As a result, all information about the original location from where a particular sample was taken in the prostate is lost. It is only known that the samples in a certain vial were taken from a particular half (left or right) of the prostate.

Yet, even employing an ideal procedure with currently available devices and tools would still be deficient. Such an ideal procedure may comprise, for example, (<NUM>) a perfectly accurate spatial tracing of the biopsy needle while taking a core biopsy sample in the organ, (<NUM>) inserting each single sample to a separate vial, and (<NUM>) identifying on each such vial the sample that is inside, for example by marking a serial number of the sample on the vial, thereby allowing to correlate later on each sample with the location from where the sample was taken. Yet, with the current needles and tissue handling techniques, even such an ideal procedure may lead to a spatial location uncertainty of more than <NUM>. This spatial uncertainty corresponds to the core axis and is as large as the notch length.

When the biopsy needle axis is referred to as the Z axis and the perpendicular plane as the X-Y plane, it is noted that X or Y axis location estimation errors are only those of the needle spatial recognition through, e.g., an imaging modality and/or a tracking modality. It is assumed that tracing and imaging techniques are able to provide an error of no more than a few millimeters, and possibly less than one millimeter, in the X-Y plane. By using some imaging and tracking techniques, similar accuracy of a few millimeters or even less than one millimeter may be achieved for the location of the needle Distal tip. However, Z-axis inaccuracy of the sample original location is dominated not by the needle spatial recognition available through such techniques, but rather by inherent uncertainty resulting from the available biopsy needles designs and the tissue core handling as is explained below. As tissue cores are usually inserted into vials containing preservative solutions, the original orientation of the core sample within the organ is lost, leading to a Z axis inaccuracy of <NUM> or more, depending on the needle notch length. Free floating cores may break into smaller pieces, of which original orientation is unknown, leading again to a Z axis inaccuracy of <NUM> or more, depending on the core length. Moreover, such breaking of core samples often results in loss of pieces of a sample/specimen, resulting in turn in substantial reduction of detection probability. Further, an average tissue core length can occasionally be only <NUM>- <NUM>% of its full potential length (i.e. the length of the needle notch). This also results in an average Z axis inaccuracy of <NUM> for a <NUM> notch length. Further, fixation of a tissue core in preservative solution results in shrinkage that, depending on the tissue type and size as well as other variables, may decrease some <NUM>% of the specimen original size.

Herein the terms "notch" and "notch floor" are used interchangeably, referring to the shaft on which a sample tissue is supported, as well as to the volume taken by the sample above the notch floor. Thus, a sample may be referred to as being supported "in" the notch, or supported "on" the notch, or supported "on the notch floor", and so on. Accordingly, "the notch faces direction A" should be interpreted as meaning "the notch floor faces direction A", whereas the direction the notch floor faces is the direction of the normal to the notch floor.

Herein are provided devices that in some aspects improve techniques for collecting onto a sample holder a biological tissue carried on a shaft. Collecting a biological tissue from a shaft onto a sample holder reduces damage to the biological tissue, retains the tissue's integrity and preserves the tissue's orientation. Specifically, devices are provided that in some aspects improve techniques for handling biological tissues that are taken with a biopsy needle. Devices are provided herein that in some embodiments maintain sample tissue orientation and/or allow Z axis inaccuracy of not more than <NUM> millimeter and even Z axis accuracy better than <NUM> millimeter. Devices are provided that in some embodiments enable increased disease detection probability.

Thus, according to an aspect of some embodiments, there is provided a device for handling core biopsy tissues taken using a core biopsy needle having a notch. The device comprises a base, a lever and a needle bed physically associated with one of the base and the lever, and configured to support a core biopsy needle substantially in a pre-defined position. The other of the base and the lever is configured to attach to a sample holder so that the sample holder may be facing a core biopsy needle supported by the needle bed. The lever is physically associated with the base and is movable between settings relative the base. Thus, a sample holder attached to the device and a core biopsy needle, supported by the needle bed, are movable relative to one another. In a first setting of the lever relative to the base the sample holder may touch a core biopsy tissue initially attached to the notch of the core biopsy needle, thereby attaching the core biopsy tissue to the sample holder. In a second setting of the lever relative to the base, the sample holder and the notch of the biopsy needle are distant from one another.

In some embodiments the needle bed is physically associated with the base and the lever is configured to attach to a sample holder. In some embodiments the needle bed is physically associated with the lever and the base is configured to attach to a sample holder.

In some embodiments the lever is physically associated with the base by a pivot, thereby being movable between settings relative to the base substantially along an arc. In some embodiments the lever is physically associated with the base by a track, thereby being movable between settings relative to the base substantially along a linear trajectory. In some embodiments the track comprises rails. In some embodiments the track comprises grooves.

In some embodiments the notch of the core biopsy needle may comprise a notch floor and the sample holder is configured to touch the core biopsy tissue from a direction substantially across from the notch floor, thereby pressing the core biopsy tissue between the sample holder and the notch floor. In some embodiments the sample holder is configured to touch the core biopsy tissue from a direction substantially not across from the notch floor, thereby not pressing the core biopsy tissue between the sample holder and the notch floor.

In some embodiments the sample holder comprises a sample sheet, capable of adhering to a core biopsy tissue by touching the core biopsy tissue.

In some embodiments the sample holder comprises a cassette. In some embodiments the cassette is configured to hold a sample sheet, capable of adhering to a core biopsy tissue by touching the core biopsy tissue.

In some embodiments the core biopsy tissue is attached to the sample holder so that an orientation of the core biopsy tissue on the notch is substantially maintained on the sample holder.

In some embodiments the device further comprises a dying module configured for selectively colouring a core biopsy sample in a portion thereof by touching the portion. In some embodiments the sample holder may touch the dying module in a setting of the lever relative to the base, so that a core biopsy tissue attached to the sample holder is selectively coloured in a portion thereof that is associated with a pre-defined portion of the notch of the biopsy needle.

Aspects and embodiments of the invention are further described in the specification herein below.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of conflict, the patent specification, including definitions, takes precedence.

As used herein, the terms "comprising", "including", "having" and grammatical variants thereof are to be taken as specifying the stated features, integers, steps or components but do not preclude the addition of one or more additional features, integers, steps, components or groups thereof. These terms encompass the terms "consisting of and "consisting essentially of.

As used herein, the indefinite articles "a" and "an" mean "at least one" or "one or more" unless the context clearly dictates otherwise.

As used herein, the terms "sample tissue", "sample" and "specimen" may be used interchangeably.

Some embodiments of the invention are described herein with reference to the accompanying figures. The description, together with the figures, makes apparent to a person having ordinary skill in the art how some embodiments of the invention may be practiced. The figures are for the purpose of illustrative discussion and no attempt is made to show structural details of an embodiment in more detail than is necessary for a fundamental understanding of the invention. For the sake of clarity, some objects depicted in the figures are not to scale.

The principles, uses and implementations of the teachings herein may be better understood with reference to the accompanying description and figures. Upon perusal of the description and figures present herein, one skilled in the art is able to implement the invention without undue effort or experimentation. In the figures, like reference numerals refer to like parts throughout.

An embodiment of a tissue collecting device <NUM> as described herein is schematically depicted in <FIG>. Tissue collecting device <NUM> comprises a base <NUM>, a needle bed <NUM> attached to base <NUM> and a lever <NUM>. Needle bed <NUM> is configured to support, substantially in a pre-defined position, a shaft <NUM> carrying a biological tissue <NUM>. A sample holder <NUM> is attached to lever <NUM>, substantially facing needle bed <NUM>. For use, shaft <NUM> is supported by needle bed <NUM> in a pre-defined position, thus having a substantially unique location and orientation relative to needle bed <NUM> and to base <NUM>. Further, shaft <NUM> is supported by needle bed <NUM> so that tissue <NUM> on shaft <NUM> faces sample holder <NUM>.

Tracks <NUM> are fixedly attached to base <NUM>, each comprising a pair of rails <NUM> and a groove <NUM> between the rails. Lever <NUM> is movable, substantially up and down along tracks <NUM>, between several settings. In a first setting schematically depicted in <FIG>, lever <NUM> is distant from needle bed <NUM>. Lever <NUM> may be moved down to a second setting (not shown), so that sample holder <NUM> is proximal to needle bed <NUM>, having a pre-defined arrangement relative to needle bed <NUM>. Tracks <NUM> confine movement of lever <NUM>, so that lever <NUM> may move substantially only up and down (e.g. between the first setting and the second setting), whereas sample holder <NUM> is maintained substantially parallel to needle bed <NUM>. When shaft <NUM>, carrying biological tissue <NUM> thereon, is suitably supported on needle bed <NUM>, sample holder <NUM> is also substantially parallel to shaft <NUM>, and sample holder <NUM> may touch biological tissue <NUM> when lever <NUM> is in the second setting. According to some embodiments, sample holder <NUM> may adhere to biological tissue <NUM> by touching. According to some embodiments sample holder <NUM> may adhere to biological tissue <NUM> by pressing. According to some embodiments, sample holder <NUM> may adhere to biological tissue <NUM> when lever <NUM> is in the second setting, and may further detach biological tissue <NUM> from shaft <NUM> when moved up to the first setting. Lever <NUM> is further detachable from base <NUM> and may be detached from base <NUM> by moving lever <NUM> up beyond the first setting and through openings <NUM> until lever <NUM> is not confined by tracks <NUM>.

A further embodiment of a tissue collecting device <NUM> as described herein is schematically depicted in <FIG>. Tissue collecting device <NUM> has similar functionality as tissue collecting device <NUM>, comprising lever <NUM> movable substantially up and down along tracks <NUM>, between settings, relative to base <NUM>. Tissue collecting device <NUM> is different from tissue collecting device <NUM> in that needle bed <NUM> is attached to lever <NUM> rather than being attached to base <NUM>, whereas base <NUM> is configured to support sample holder <NUM> attached thereto. Shaft <NUM> may be positioned in place and supported by needle bed <NUM> in a pre-defined position facing sample holder <NUM>, thereby being movable relative to sample holder <NUM> together with lever <NUM>. In a first setting, depicted schematically in <FIG>, lever <NUM> is distant from base <NUM> thereby needle bed <NUM> is distant from sample holder <NUM>. Lever <NUM> is may be moved down to a second setting (not shown) so that needle bed <NUM> is proximal to sample holder <NUM>, having a pre-defined arrangement relative to sample holder <NUM>. Tracks <NUM> confine movement of lever <NUM>, so that lever <NUM> may move substantially only up and down (e.g. between the first setting and the second setting), whereas needle bed <NUM> is maintained substantially parallel to sample holder <NUM>. When shaft <NUM>, carrying biological tissue <NUM> thereon, is suitably supported by needle bed <NUM>, shaft <NUM> is also substantially parallel to sample holder <NUM>, and biological tissue <NUM> may touch sample holder <NUM>, and thereby adhere to sample holder <NUM>, when lever <NUM> is in the second setting.

An embodiment of a tissue handling device <NUM> as described herein is schematically depicted in <FIG>. According to some embodiments, tissue handling device <NUM> is configured for collecting biopsy samples from a biopsy needle onto a sample sheet held by a cassette. Simple handling of biopsy samples (e.g. moving a sample from place to place, inserting a sample into a container or removing a sample from a container, and so on) is then enabled or at least facilitated by handling the sample sheet carrying the core biopsy sample or by handling the cassette.

Tissue handling device <NUM> comprises a base <NUM>, a gun house <NUM>, a needle bed <NUM> and a lever <NUM>. Base <NUM> comprises a front stopper <NUM>, a sliding groove <NUM> and a sliding table <NUM>, having a front end <NUM> (<FIG>), a back end <NUM> and a back stopper <NUM> proximal to back end <NUM>. Gun house <NUM> is configured to secure in a pre-defined position a biopsy gun <NUM>, having a gun handle <NUM> and a biopsy needle <NUM>, as is schematically depicted in <FIG>. The gun house is substantially formed between the front stopper <NUM> and the back stopper <NUM>, The sliding table is configured to slide back and forth inside the sliding groove of the base. When the sliding table is pulled backwards so as to increase the distance between the front stopper and the back stopper, gun house <NUM> is opened for receiving therein a gun handle <NUM>, as is depicted schematically in <FIG> and <FIG>. The gun house is configured for securing in a pre-defined position, a biopsy gun, by pushing the sliding table forward, so as to decrease the distance between the front stopper and the back stopper, until back stopper <NUM> presses onto handle <NUM> of biopsy gun <NUM>. Reference is now drawn to <FIG>, schematically depicting a cross-section of tissue handling device <NUM> in side view, with gun house <NUM> open and empty (<FIG>), with gun house open and comprising gun handle <NUM> therein (<FIG>), and with gun house <NUM> closed, securing gun handle <NUM> and biopsy gun <NUM> (<FIG>). Sliding table <NUM> further comprises a table magnet <NUM>, secured on front end <NUM> of the sliding table. Base <NUM> further comprises a locking member <NUM>, comprising a locking magnet <NUM>. Locking member is adjustably positioned proximal to or substantially inside sliding groove <NUM> in base <NUM>. When sliding table <NUM> is pushed forward, thereby securing a biopsy gun inside gun house <NUM>, table magnet <NUM> reaches proximal to locking magnet <NUM>. Magnetic attraction between locking magnet <NUM> and table magnet <NUM> generates a force on sliding table <NUM> in a forward direction, causing sliding table <NUM> to press gently on the biopsy gun and secure the biopsy gun inside gun house <NUM>. When a biopsy gun is secured inside gun house <NUM>, front stopper <NUM> and back stopper <NUM> prevent substantial displacements of the biopsy gun sideways, forward and backwards, whereas biopsy needle <NUM> may thereby be positioned in place, supported by needle bed <NUM>.

Needle bed <NUM> is depicted schematically in <FIG>. Needle bed <NUM> comprises two alignment shoulders <NUM> on top of a support surface <NUM>. Needle bed <NUM> further comprises a positioning sleeve <NUM>, aligned horizontally on top of support surface <NUM>. Needle bed <NUM> may be substantially exposed to body fluids due to contact with biopsy needle <NUM>, and therefore needs to be replaced after a last sample tissue is taken from the live organ in a biopsy session. Needle bed <NUM> is attached to base <NUM> by pins <NUM> on base <NUM> and slits <NUM> in needle bed <NUM> and can be detached from the base and attached to the base quickly by hand.

When it is desired to secure a biopsy gun in the gun house, sliding table <NUM> is pulled fully backwards so as to allow the handle of the biopsy gun to enter the gun house between front stopper <NUM> and back stopper <NUM> and leaving a space between the gun handle and the front stopper as is depicted schematically in <FIG>. The biopsy gun is placed on the sliding table, attached to the back stopper thereby being displaced backwards from the front stopper. Biopsy needle <NUM> is aligned between shoulders <NUM> of needle bed <NUM> so that the biopsy needle is aligned horizontally, in line with the symmetry axis of positioning sleeve <NUM> and the distal tip of the biopsy needle is outside the positioning sleeve.

For securing the biopsy gun in place, the sliding table is pushed forward, thereby pushing the biopsy gun so that biopsy needle <NUM> enters the positioning sleeve as is depicted schematically in <FIG>. When the handle of the biopsy gun contacts the front stopper, no further displacement forward is possible and biopsy needle <NUM> is thus secured in its pre-defined position. Magnetic attraction between locking magnet <NUM> and table magnet <NUM> generates a force on sliding table <NUM> forward, thereby securing the biopsy gun in place.

Lever <NUM> is pivotally connected to base <NUM>, thereby enabled to move substantially up and down relative to the base. Lever <NUM> comprises a handle <NUM> physically secured to the lever, for manually moving lever <NUM> by a user. Lever <NUM> further comprises a cassette holder <NUM>. <FIG> schematically depicts lever <NUM> without cassette holder <NUM>, from a bottom view, that is to say a view of the side of lever <NUM> facing the base. <FIG> schematically depict lever <NUM> with cassette holder <NUM>. Cassette holder <NUM> is movable with respect to lever <NUM>, and hence with respect to the base <NUM>, in a direction perpendicular to the long dimension of biopsy needle <NUM>. Cassette holder <NUM> is configured to move manually, e.g. by pressing with fingers, between two well-defined positions, for collecting two tissues from biopsy needle <NUM>, one tissue in each well-defined position. A protruding cap <NUM>, supported by a compression spring (not seen) is configured to apply pressure on cassette holder <NUM> when cassette holder <NUM> is assembled onto lever <NUM> and to hold the cassette holder in a well-defined position, when pressed into a respective depression on the side facing the lever of cassette holder <NUM>. Two round depressions on the side facing the lever of cassette holder <NUM> define the two positions, respectively, for accepting the two tissues.

Cassette holder <NUM> comprises a rectangular protrusion <NUM> and a curved tooth <NUM>, supported by a compression spring <NUM>, for attaching onto a cassette (<NUM> in <FIG>). Thereby cassette holder <NUM> is configured to attach to a cassette and hold it firmly, as is detailed further below. When a cassette is attached to cassette holder <NUM>, a pointer <NUM> identifies for a user where on the cassette a sample tissue will be attached to.

Cassette <NUM> is schematically illustrated in <FIG>. Cassette <NUM> comprises a cassette base <NUM> and a cassette cover <NUM>, and configured to hold firmly a sample sheet <NUM> in between, when attached together by pressing. Cassette base <NUM> is a substantially rectangular slab of firm plastic material, comprising a shallow depression <NUM> on its upper surface for accepting sample sheet <NUM> thereon. The cassette base further comprises a rectangular through hole <NUM> on one end of the slab, and a circular through hole <NUM> on the other end of the slab, both together identify a left-right direction, allowing a discrimination between a first sample and a last sample taken onto the cassette. Because of circular through hole <NUM> and rectangular through hole <NUM>, cassette <NUM> has an unsymmetrical external outline, substantially precluding rotational symmetry of the cassette, except for the trivial rotational symmetry of <NUM> degrees. When attached to cassette holder <NUM>, rectangular protrusion <NUM> is inserted into rectangular through hole <NUM>, and curved tooth <NUM> is inserted into circular through hole <NUM>, thereby attaching the cassette to the cassette holder.

Cassette base <NUM> further comprises four sample-edge depressions <NUM> on the edge of shallow depression <NUM>. Sample-edge depressions <NUM> enable attachment of a long and narrow biological tissue to its full length, from biopsy needle <NUM>, minimizing risk of losing sample ends, as is further explained below. Cassette base <NUM> further comprises four protrusions <NUM> on the sides of cassette base <NUM> for attaching into associated depressions <NUM> on the inner face of cassette cover <NUM>, thereby attaching cassette base <NUM> and cassette cover <NUM> together.

Cassette cover <NUM> is a substantially rectangular slab of firm plastic material, curved to have a U shape profile. Depressions <NUM> on the inner side of the legs of the U are configured to attach to protrusions <NUM> on cassette base <NUM>, enabling thereby attachment of cassette base <NUM> and cassette cover <NUM> together. Four corner depressions <NUM> facilitate detaching the cassette base from the cassette cover, e.g. for removing the sample sheet with sample tissues on it.

Cassette cover <NUM> comprises two rectangular windows <NUM> on the flat portion of the U. Rectangular windows <NUM> are through-openings on cassette cover <NUM>, and when cassette <NUM> is assembled with sample sheet <NUM> held in place between cassette base <NUM> and cassette cover <NUM>, windows <NUM> allow view and access to a portion of sample sheet <NUM> from the cassette cover side. The flat portions of the U maintains sample sheet <NUM> between cassette base <NUM> and cassette cover <NUM> flat and prevent the sample sheet from folding or bending.

Sample sheet <NUM> is a substantially rectangular film, folded in two rims to fit between cassette base <NUM> and cassette cover <NUM>. As is schematically depicted in <FIG>, when cassette <NUM> is assembled with a sample sheet, the folded rims of the sample sheet is pressed tight between cassette base <NUM> and cassette cover <NUM>, thereby preventing sample sheet from folding or bending spontaneously.

Sample sheet <NUM> may adhere to a biological tissue upon manually pressing on, or forming contact between the biological tissue and the sample sheet. Sample sheet <NUM> can further maintain such adherence, and the biological tissue remains stuck to the sample sheet following immersion in water-based solutions such as formaldehyde and during a chemical process that the sample tissue goes through in preparation to examination, as described above. Sample sheet <NUM> is optionally permeable to fluids, so that a fluid can permeate through sample sheet <NUM> from side to side. Sample sheet <NUM> may further be biocompatible. If a same needle is used repeatedly for obtaining several samples from the same organ, sample sheet <NUM> is further sterile, since during pressing the cassette with the sample sheet to the sample tissue, the biopsy needle may touch the sample sheet, and then be inserted again to the live organ to take a next sample. In some embodiments, sample sheet <NUM> can survive sterilization process without being damaged. In some embodiments sample sheet <NUM> is made of a mesh film of cellulose esters such as Immobilon-NC Transfer Membrane by Millipore™. In some embodiments sample sheet <NUM> is made of a film such as Mixed Cellulose Esters Membrane ME <NUM> or WME by Whatman Ltd. In some embodiments sample sheet <NUM> is made of a film such as Supor® <NUM> PES Membrane Disc Filter by Pall Corporation. In some embodiments sample sheet <NUM> is made of a film such as Cellulose Filters, for example grade <NUM> or grade <NUM> or grade <NUM>, by Whatman Ltd. In some embodiments sample sheet <NUM> is a mesh film of cellulose esters covered with glue or another adhesive material so that sample tissues adhere to it. Thus, sample sheet <NUM> substantially comprises an adhering surface, capable of adhering to a biological tissue as described above, at least on the surface of the sample sheet that faces the sample tissue prior to collecting the tissue.

For attaching a sample tissue to the sample sheet, the lever with a cassette and a sample sheet inside, is lowered onto the needle notch, as is schematically depicted in <FIG>. To ensure attachment of the sample tissue to the sample sheet it is required to apply some degree of pressure or sufficient contact. The pressure applied is regulated by an adjustable pin <NUM>. Pin <NUM> is adjustable to control the height of lever <NUM> above base <NUM> when fully lowered, thereby defining the pressure applied by the sample sheet on the sample tissue. <FIG> schematically depicts sample sheet <NUM> inside cassette <NUM> touching mandrel <NUM> above notch <NUM>. Sample-edge depressions <NUM> enable sample sheet <NUM> to yield as the cassette is pressed to the mandrel, thereby enabling better attachment of the sample tissue to its full length, and minimizing risk of losing sample ends as is schematically depicted in <FIG>.

In some embodiments, sample sheet <NUM> includes a mark <NUM>, e.g. a perforated hole, chamfer edge etc, identifying one corner of the sample sheet and thus precluding the sample sheet from rotational symmetry (except for the trivial rotational symmetry of <NUM> degrees). When placing a new sample sheet in a cassette, the sample sheet is placed so that the mark is adjacent to a particular end of the cassette, for example adjacent to rectangular through hole <NUM>. Mark <NUM> facilitates preserving the orientation of the sample tissues throughout the preparation process prior to examination, so that during examination it is known what end of the sample tissue is from far end of the notch (closest to the distal tip) and what end of the sample tissue is from near end of the notch (closest to the handle of the biopsy gun), as is further detailed and explained below regarding <FIG>.

It is noted that mark <NUM> (a truncated corner in <FIG>) on the sample sheet preserves the orientation of the sample tissues up to and including step (j) in the method described above, that is as long as the sample tissues are adhered to the sample sheet, and before a slicing step.

Orientation of the sample tissues may be preserved in the slicing step (k) and paraffin melting step (<NUM>), by adequately marking the slices in step (k) and adequately marking the glass plates in step (<NUM>), so as to preserve sample tissues orientation.

The end of each sample tissue closest to mark <NUM> may be dyed in step (j), thereby identifying orientation after slicing and paraffin melting.

A photograph of the sample tissue on the notch of the needle may be taken using a photographing device such as a camera. The camera is placed e.g. at a location displaced from the mandrel perpendicularly to the axis of the biopsy needle and having line of sight with the mandrel. A photograph is taken when the biopsy gun is secured in the tissue handling device <NUM>, in step (c) in the method above.

A picture may be taken of the sample tissue on the sample sheet, thereby preserving the information on the position of the sample sheet relative to the sample sheet subsequent to slicing.

By recording the position of the distal tip of the needle inside the live organ while taking the sample tissue, for example by using techniques as is explained in the introduction above, the position of the distal tip of the needle at the moment of taking the sample tissue is known. By measuring, on the photograph, the distance between an end of the sample tissue and the needle distal tip, or between an end of the sample tissue and an end of the sample sheet, the position of any point on the sample tissue relative to the distal tip is known. By preserving tissue orientation until examination step (<NUM>) as explained above, any disease or tumor detected in examination is correlated to an identified end of the sample tissue. By considering the above mentioned pieces of information, a tumor or disease detected in examination can be correlated to an identified location inside the live organ from which the sample tissue was taken.

According to some embodiments a dummy sample is attached to the sample sheet at a well defined position on sample sheet <NUM>. Consequently, in slicing step (k) above, the slices contain slices of the sample tissue (or sample tissues) and slices of the dummy sample, thus preserving orientation and position information in steps (k) and (<NUM>) in the method above. In some embodiments the dummy sample is colored or shaped so as to identify the close side to the distal tip and to identify left / right orientation of the sample sheet. In some embodiments the cassette holder of the tissue handling device is rotatable on an axis perpendicular to the plane of the sample sheet. When taking sample tissues from the biopsy needle onto the sample sheet using such a tissue handling device with a rotatable cassette holder, two tissue samples are adhered to the sample sheet in an angle. In some embodiments, two sample tissues adhered so in an angle, facilitate preserving sample orientation throughout the process until and including step (<NUM>) above.

In some embodiments the cassette holder of the tissue handling device is configured to displace linearly between well-defined positions, as cassette holder <NUM> above, and also to rotate on an axis perpendicular to the plane of the sample sheet. When taking sample tissues from the biopsy needle onto the sample sheet using such a tissue handling device with a linearly displaceable and rotatable cassette holder, three tissue samples may be adhered to the sample sheet in a pattern. In some embodiments, three sample tissues adhered so in a pattern, facilitate preserving sample planar orientation (rotation of the sample pattern in the plane of the sample pattern) and also up-side-down rotation, throughout the process until and including step (<NUM>) above.

An embodiment of a tissue handling device <NUM> as described herein is schematically depicted in <FIG>. Tissue handling device <NUM> comprises a base <NUM>, a gun house <NUM>, a needle bed <NUM> and a lever <NUM>.

Gun house <NUM> comprises a gun frame <NUM> configured for receiving therein a biopsy gun <NUM>, having a gun handle <NUM> and a biopsy needle <NUM>, as depicted schematically in <FIG>. Gun frame <NUM> has a shape and internal dimensions that fit a shape and external dimensions of gun handle <NUM>, so that when gun handle <NUM> is suitably placed inside gun frame <NUM>, biopsy gun <NUM> is secured in gun house <NUM>. When biopsy gun <NUM> is secured in gun house <NUM>, gun frame <NUM> prevents substantial movements of biopsy gun <NUM> sideways, forward and backwards. When biopsy gun <NUM> is suitably placed and secured in gun house <NUM>, biopsy needle is supported on needle bed <NUM> in a substantially pre-defined position. Biopsy gun <NUM> suitable to be secured in gun house <NUM> is, generally, of a particular model and having gun handle <NUM> of particular dimensions and shape that fit gun frame <NUM>. When it is desired to use a tissue handling device such as tissue handling device <NUM> with a biopsy gun of a different model than biopsy gun <NUM>, having a gun handle with different shape and external dimensions, a gun frame different from gun frame <NUM> must appropriately be used. Gun house <NUM> is physically secured to base <NUM> by two nuts <NUM> secured to base <NUM>, as is schematically depicted in <FIG>. Thereby, when desired, gun house <NUM> may be replaced by another gun house having a gun frame that fits a biopsy gun different from biopsy gun <NUM>.

Lever <NUM> is pivotally connected to a pedestal <NUM>, pedestal <NUM> being firmly attached to base <NUM>. Pedestal <NUM> is configured to support needle bed <NUM> at an elevated position relative to base <NUM>, so that, when biopsy gun <NUM> is secured in gun house <NUM>, biopsy needle <NUM> is positioned just above needle bed <NUM>, to be supported thereon. Lever <NUM> is configured to be pivotally moved up and down relative to base <NUM>, between an open position, depicted in <FIG>, and a closed position, depicted in <FIG>.

<FIG> schematically depict pedestal <NUM>. On top of pedestal <NUM>, a needle bed holder <NUM> comprises four rubber pins <NUM> to be supported on. Rubber pins <NUM> are attached in a top portion thereof to needle bed holder <NUM> in four blind holes (not shown) on a bottom surface of needle bed holder <NUM>. Bottom portions of rubber pins <NUM> extend downwards from the bottom surface of needle bed holder <NUM> and are fixed inside pedestal <NUM>. By flexibly squeezing, rubber pins <NUM> allow needle bed holder <NUM> to arrange parallel to lever <NUM> when lever <NUM> is pivotally moved downwards to a closed position, as is detailed and explained further below.

Needle bed holder <NUM> is a substantially rectangular slab, having two swallowtail- shaped grooves <NUM> and a round recess <NUM> on a top surface, configured to allow needle bed holder <NUM> to hold needle bed <NUM> attached thereto. <FIG> schematically depicts a cross- section of pedestal <NUM> in a plane passing through two rubber pins <NUM>. In <FIG> a top surface of needle bed holder <NUM> is not shown, exposing the top portion of rubber pins <NUM> and an internal configuration of needle bed holder <NUM>.

<FIG> schematically depicts a cross-section of pedestal <NUM> in a vertical plane passing through the center of needle bed holder <NUM>. Needle bed holder <NUM> comprises a top magnet <NUM> inside an internal hollow compartment, and pedestal <NUM> comprises a bottom magnet <NUM> in an internal hollow compartment thereof. When needle bed holder <NUM> is arranged in place, supported by rubber pins <NUM>, top magnet <NUM> and bottom magnet <NUM> generate a mutual magnetic attraction force, that attracts needle bed holder <NUM> onto pedestal <NUM>, thereby assisting in stabilizing needle bed holder <NUM> on rubber pins <NUM>.

Needle bed holder <NUM> further comprises rigid pins <NUM> fixed inside needle bed holder <NUM> and having a bottom part thereof projecting downwards from needle bed holder <NUM>. Pedestal <NUM> comprises two through holes <NUM>, arranged to fit rigid pins <NUM>. Through holes <NUM> have a diameter larger than the diameter of rigid pins <NUM>, so that rigid pins <NUM> do not substantially restrict needle bed holder <NUM> from tilting on top of rubber pins <NUM>, yet rigid pins <NUM> restrict needle bed holder <NUM> from substantially displacing horizontally, thereby assisting stabilizing needle bed holder <NUM> on rubber pins <NUM> against horizontal displacements. In some embodiments through holes <NUM> may have a diameter larger than the diameter of rigid pins <NUM> by about <NUM>- <NUM>, for example by about <NUM>, by about <NUM> and even by about <NUM>. In some embodiments, rigid pins <NUM> may have different diameters from one another, and through holes <NUM> may have different diameters from one another respectively, thereby compelling assembly of needle bed holder <NUM> onto pedestal <NUM> in a single orientation.

Pedestal <NUM> further comprises a stopper pillar <NUM> extending upwards towards lever <NUM>. Lever <NUM> may be lowered towards a closed position until lever <NUM> is stopped by stopper pillar <NUM>, stopper pillar <NUM> thereby sets the position of lever <NUM> above pedestal <NUM> in a closed position. Some embodiments of pedestal <NUM> may not comprise stopper pillar <NUM>, in which embodiments pressing lever <NUM> downwards to a closed position may apply pressure on rubber pins <NUM>, but nevertheless may not apply pressure on a sample tissue or flatten a sample tissue, as is further explained below.

<FIG> schematically depict needle bed <NUM> from a top perspective view. Needle bed <NUM> comprises two alignment shoulders <NUM> and a support platform <NUM>, aligned along the center line of needle bed <NUM>, on a top surface <NUM>. A descended step <NUM> on the near end (that is to say the end closer to gun house <NUM>) of support platform <NUM> is descendent relative to support platform <NUM> thereby being configured to support the cannula <NUM> of a biopsy needle <NUM>, whereas support platform <NUM> supports the mandrel <NUM>, having a smaller diameter than the cannula. <FIG> schematically depicts needle bed <NUM> from a bottom view. Needle bed <NUM> comprises bed slides <NUM> along the two rims of a bottom surface thereof and further comprises bulges <NUM> on bed slides <NUM>. Needle bed <NUM> further comprises a flexible leaf <NUM> having a round protrusion <NUM> at the free end of the leaf.

In use, needle bed <NUM> may be exposed to body fluids due to contact with the biopsy needle, and therefore may need to be replaced after a last sample tissue is taken from the live organ in a biopsy session. Needle bed <NUM> is therefore configured to be quickly assembled to, and disassembled from, needle bed holder <NUM>, by hand. Needle bed <NUM> is assembled onto needle bed holder <NUM> by inserting bed slides <NUM> to swallowtail grooves <NUM> and sliding needle bed <NUM> horizontally until stopper <NUM> on the bottom surface of needle bed <NUM> touches a respective portion of swallowtail grooves <NUM> and stops further displacement of needle bed <NUM>. While sliding needle bed <NUM> onto needle bed holder <NUM>, rigid pins <NUM> restrict horizontal displacement of needle bed holder <NUM>, as described above, thereby facilitating assembly. When needle bed <NUM> is so assembled onto needle bed holder <NUM>, bulges <NUM> are configured to chafe against swallowtail grooves <NUM> of needle bed holder <NUM>, thereby assisting in stabilizing needle bed <NUM> in place. Further, when needle bed <NUM> is assembled onto needle bed holder <NUM> by sliding all the way through and stopper <NUM> stops further displacement of needle bed <NUM>, round protrusion <NUM> on leaf <NUM> enters round recess <NUM> on needle bed holder <NUM>, thereby assisting in fixing needle bed <NUM> on needle bed holder <NUM>.

<FIG> schematically depicts a cross section of needle bed <NUM> in a vertical plane through biopsy needle <NUM>. When needle bed <NUM> is assembled in tissue handling device <NUM> and biopsy gun <NUM> is placed in gun house <NUM>, biopsy needle <NUM> is arranged on top of support platform <NUM>, and support platform <NUM> supports biopsy needle <NUM> in a position pre-defined by gun house <NUM> and by alignment shoulders <NUM>.

Lever <NUM> is depicted schematically in <FIG> in a perspective view, depicting the side that faces base <NUM> when lever <NUM> is moved down to a closed position. <FIG> schematically depicts lever <NUM> pivotally connected to pedestal <NUM>, thereby enabled to move substantially up and down relative to base <NUM>. Lever <NUM> comprises a handle <NUM> physically associated with lever <NUM>, for manually moving lever <NUM> by a user. Lever <NUM> is further configured to attach to a cassette <NUM>, cassette <NUM> being used for receiving sample tissues from biopsy needle <NUM> and for facilitating handling such sample tissues.

<FIG> schematically depict lever <NUM> without cassette <NUM>. Lever <NUM> comprises a cassette house <NUM> configured to attach to cassette <NUM> as is explained below. Cassette house <NUM> comprises a cassette surface <NUM> descended between a first elevated rim <NUM> and a second elevated rim <NUM> depicted in cross-sectional view 5D. A first protrusion <NUM> and a second protrusion <NUM> protrude from the first elevated rim and from the second elevated rim, respectively, towards cassette surface <NUM>, thereby forming a first groove <NUM> and second groove <NUM> configured for cassette attachment as is explained further below. First protrusion <NUM> is wider than second protrusion <NUM>, namely first protrusion <NUM> protrudes more, respectively, than second protrusion <NUM>, thereby forming left-right asymmetry of cassette house <NUM>, due to a deeper first groove <NUM> relative to second groove <NUM>. An asymmetry of cassette house <NUM>, together with a respective asymmetry of cassette <NUM>, compels a single orientation of attachment of cassette <NUM> in cassette house <NUM>, thereby retaining orientation of a sample tissue taken for inspection and attached to cassette <NUM>, as is further detailed below.

Lever <NUM> further comprises a cassette back stopper <NUM>, comprising a depressable pin <NUM> physically associated with a compression spring <NUM> and with a back stopper pin <NUM>. Figure IOC schematically depicts lever <NUM> in cross-sectional view through cassette back stopper <NUM>. For inserting cassette <NUM> to cassette house <NUM> for attachment therein, depressable pin <NUM> is depressed, e.g. by fingers, thereby pushing back stopper pin <NUM> into second groove <NUM>, and allowing sliding cassette <NUM> into second groove <NUM> and first groove <NUM>. Cassette <NUM> may be so slid into cassette house <NUM> until cassette <NUM> is stopped by front stoppers <NUM>. When depressable pin <NUM> is released, compression spring <NUM> restores back stopper pin <NUM> (and depressable pin <NUM>) to the former protruding position, thereby securing cassette <NUM> in cassette house <NUM>. When cassette <NUM> is attached to lever <NUM> in cassette house <NUM>, cassette <NUM> is allowed to slide in cassette house <NUM> back and forth between front stoppers <NUM> and back stopper pin <NUM>, thereby allowing collecting more than one sample tissue onto cassette <NUM>, as is explained further below.

<FIG> schematically depicts cassette <NUM> in an exploded view, <FIG> schematically depicts cassette <NUM> in a top view and <FIG> schematically depicts cassette <NUM> in a bottom view. Cassette <NUM> comprises a cassette base <NUM>, a sponge <NUM> and a cassette cover <NUM>. Cassette <NUM> is configured to further include and hold a sample sheet <NUM>. Cassette base <NUM> is a substantially rectangular slab e.g. of firm plastic material, comprising a hollow compartment <NUM> on its surface facing cassette cover <NUM>, for including sponge <NUM> therein. Compartment <NUM> has a substantially rectangular periphery having a truncated corner <NUM>. Sponge <NUM> has periphery substantially similar to that of compartment <NUM>, having a rectangular shape with a truncated corner. Sponge <NUM> is made of a soft and flexible material, for suitably yielding and supporting sample sheet <NUM> when attaching a sample tissue thereon, as is further described below. Yielding herein means retreating flexibly in response to pressure, thereby enabling returning to a previous position when such pressure is stopped. Cassette cover <NUM> is a substantially rectangular slab e.g. of firm plastic material, curved to have a U shape profile. Cassette cover <NUM> comprises depressions <NUM> on the inner side of the legs of the U, configured to attach to protrusions <NUM> on cassette base <NUM>, enabling thereby attachment of cassette base <NUM> and cassette cover <NUM> by pressing. When cassette <NUM> is assembled with sample sheet <NUM>, sample sheet <NUM> is held pressed between cassette cover <NUM> and sponge <NUM> thereby being prevented from displacing, folding or bending spontaneously.

Cassette base <NUM> further comprises a protruding pin <NUM> extending upwards from the surface of cassette base <NUM> facing cassette cover <NUM>. Cassette cover <NUM> comprises an alignment hole <NUM>, arranged to fit to protruding pin <NUM>. For assembly of cassette <NUM>, protruding pin <NUM> must be inserted into alignment hole <NUM>. Protruding pin <NUM> and alignment hole <NUM> thus compel a single orientation of assembly of cassette cover <NUM> onto cassette base <NUM>.

Cassette cover <NUM> further comprises a first slide <NUM> on the outside of one leg of the U, and a second slide <NUM> on the other leg of the U, for allowing sliding cassette <NUM> into cassette house <NUM> for attachment therein. First slide <NUM> is wider than second slide <NUM>, thereby fitting first groove <NUM> and second groove <NUM>, respectively, and forming a left-right asymmetry in cassette <NUM> fitting to the left-right asymmetry of cassette house <NUM> described above.

Cassette base <NUM> comprises four flexible leafs <NUM>, each having a bulge <NUM> protruding outwards on the free end of the leaf. When cassette <NUM> is inserted into cassette house <NUM>, bulges <NUM> chafe on cassette surface <NUM>, thereby preventing free displacements of cassette <NUM> in cassette house <NUM>, and assisting stabilizing cassette <NUM> therein. Further, flexible leafs <NUM> enable cassette <NUM> to tilt in cassette house <NUM>, to an amount dictated by a gap between slides <NUM> and <NUM> and grooves <NUM> and <NUM>, respectively, thereby assisting in stabilizing cassette <NUM> parallel to a biopsy needle supported on support platform <NUM>, when cassette <NUM> is pressed towards the biopsy needle.

Cassette cover <NUM> comprises a window <NUM> for allowing view and access to a portion of sample sheet <NUM> inside cassette <NUM>. In use, sample tissues may be attached to sample sheet <NUM> on the area of window <NUM>. Window <NUM> has side edges <NUM>.

First slide <NUM> of cassette cover <NUM> is split by a gap <NUM> which is employed to discriminate first slide <NUM> from second slide <NUM> in subsequent process steps as is described further below.

Sample sheet <NUM> may be for example a film having a substantially rectangular shape with a sheet truncated corner <NUM>, fitting in shape and dimensions to compartment <NUM> in cassette base <NUM>. For assembly of cassette <NUM> with a sample sheet, sponge <NUM> is inserted to compartment <NUM> of cassette base <NUM>, sample sheet <NUM> is placed on top of sponge <NUM> and cassette cover <NUM> is pressed onto cassette base <NUM>, to form assembled cassette <NUM> as is schematically depicted in <FIG>. When assembled, cassette <NUM> holds sample sheet <NUM> pressed between sponge <NUM> and cassette cover <NUM>. Truncated corner <NUM> of compartment <NUM> and protruding pin <NUM> compel assembly of sample sheet <NUM> in a single orientation so that sheet truncated corner <NUM> of sample sheet <NUM> is adjacent truncated corner <NUM> of compartment <NUM>.

Thus, sample sheet <NUM> is precluded of rotation symmetry, except of the trivial rotational symmetry of <NUM> degrees, due to truncated corner <NUM>. Further, cassette <NUM> has an internal structure which is compatible with the unsymmetrical structure of sample sheet <NUM>, thus compelling assembly of sample sheet <NUM> in cassette <NUM> and holding sample sheet <NUM> therein, in a single orientation. The orientation of sample sheet <NUM> relative to cassette base <NUM> is unique because sheet truncated corner <NUM> of sample sheet <NUM> must fit truncated corner <NUM> of compartment <NUM>; the orientation of cassette base <NUM> relative to cassette cover <NUM> is unique due to protruding pin <NUM> and alignment hole <NUM>; and the orientation of cassette <NUM> relative to lever <NUM> and thereby to biopsy needle <NUM> (in <FIG>) is unique because of first slide <NUM> and second slide <NUM> on cassette cover <NUM>, and first groove <NUM> and second groove <NUM> on lever <NUM>, respectively. Consequently, the arrangement of cassette <NUM> relative to needle bed <NUM> is pre-defined and unique in the closed position of lever <NUM>. Hence, the orientation of sample sheet <NUM> relative to the notch of biopsy needle <NUM>, while attaching a sample tissue to sample sheet <NUM>, is unique, and the end of the sample tissue that is closer to sheet truncated corner <NUM> on sample sheet <NUM> is the end that was closer to the handle of the biopsy gun and distant from the distal tip of the biopsy needle. Therefore, the orientation of the sample tissue is known and maintained as long as the sample tissue is attached to sample sheet <NUM>.

Sample sheet <NUM> may adhere to a biological tissue upon manually pressing on, or forming contact between the biological tissue and the sample sheet. Sample sheet <NUM> can further maintain such adherence, and the biological tissue remains stuck to the sample sheet following immersion in water-based solutions such as formaldehyde and during a chemical process that the sample tissue goes through in preparation to examination, as described above. Sample sheet <NUM> is substantially similar to sample sheet <NUM> described above in all the characteristics involving adherence to a biological tissue and further in characteristics corresponding to affecting the sample tissue. Specifically, sample sheet <NUM> comprises an adhering surface capable of adhering to a biological tissue at least on the surface of the sample sheet that faces the sample tissue prior to collecting the sample tissue onto the sample sheet as described above.

In use of tissue handling device <NUM> and for attaching a sample tissue to sample sheet <NUM>, cassette <NUM> is assembled with sample sheet <NUM> and inserted to cassette house <NUM> in lever <NUM>, as is described above. A user may select a position on sample sheet <NUM> where a sample tissue would adhere, by selecting a position of cassette <NUM> relative to lever <NUM>, between back stopper pin <NUM> and front stoppers <NUM>. In some embodiments at least two such positions of cassette <NUM> are enabled, allowing attaching at least two sample tissues on a same sample sheet <NUM>. In some embodiments several such positions of cassette <NUM> are enabled, allowing attaching several sample tissues on a same sample sheet <NUM>.

Biopsy gun <NUM>, including a sample tissue in the notch of biopsy needle <NUM>, is placed in gun house <NUM> so that the notch of biopsy needle <NUM> is facing upwards, towards lever <NUM>. Biopsy needle <NUM> is positioned between alignment shoulders <NUM> and supported on support platform <NUM> of needle bed <NUM>, as is depicted in <FIG>. Top magnet <NUM> in needle bed holder <NUM> (<FIG>) may apply a magnetic force on biopsy needle <NUM>, attracting biopsy needle <NUM> downwards towards support platform <NUM> and assisting stabilizing biopsy needle <NUM> thereon. The position of the distal tip of biopsy needle <NUM> on support platform <NUM>, e.g. along the long dimension of biopsy needle <NUM>, may be adjusted by a user by releasing nuts <NUM> (<FIG>), adjusting the position and orientation of gun house <NUM> and tightening nuts <NUM> again.

Lever <NUM> is lowered, e.g. by hand, to a closed position as is schematically depicted in <FIG>. When sample sheet <NUM> is brought to contact with the sample tissue in the notch of biopsy needle <NUM>, the sample tissue adheres to sample sheet <NUM>. Lever <NUM> may then be lifted to an open position and the user may select to displace cassette <NUM> to a new position on lever <NUM> and take a next sample tissue thereon, or to disassemble cassette <NUM> from lever <NUM>, to disassemble sample sheet <NUM> from cassette <NUM> and take sample sheet <NUM> with the sample tissue thereon for further process.

<FIG> schematically depicts a cross-section of tissue handling device <NUM> in a closed position, in a vertical plane along biopsy needle <NUM>, depicting lever <NUM> and pedestal <NUM>. When lever <NUM> is lowered towards a closed position, the notch <NUM> of biopsy needle <NUM> is facing window <NUM> of cassette <NUM>, and cassette base <NUM>, near window edges <NUM> touch biopsy needle <NUM> preferably on both sides of the notch. Lever <NUM> may be lowered further until lever <NUM> is stopped by stopper pillar <NUM>. Lowering lever <NUM> beyond the point at which cassette base <NUM> touch biopsy needle <NUM> applies a downwards force on biopsy needle <NUM> and on needle bed <NUM> and needle bed holder <NUM> supporting biopsy needle <NUM>. Rubber pins <NUM> (not shown in this Figure) may thus yield by squeezing, allowing lever <NUM> to lower further until being stopped by stopper pillar <NUM>.

Yielding of rubber pins <NUM> and bulges <NUM> on cassette base <NUM> as described above assists in compensating possible deviation from parallelism between cassette <NUM> and biopsy needle <NUM>. Such deviation from parallelism may occur e.g. due to accumulation of mechanical tolerances between cassette <NUM> and lever <NUM>, lever <NUM> and pedestal <NUM>, pedestal <NUM> and needle bed holder <NUM> and needle bed holder <NUM> and needle bed <NUM>. Further, it may occur that biopsy needle <NUM> might be bent (particularly in a vertical plane) resulting in a deviation from parallelism between cassette <NUM> and biopsy needle <NUM> even in a hypothetical case of an ideal mechanical configuration of tissue handling device <NUM> and absolute parallelism between cassette <NUM> and needle bed <NUM>. By pressing biopsy needle <NUM> downward by applying a downward force by lever <NUM> on biopsy needle <NUM> as described above, and by rubber pins <NUM> yielding flexibly to such downward force, needle bed <NUM> and consequently biopsy needle may tilt and align parallel to cassette <NUM>, thereby allowing a suitable contact between the sample tissue on the notch and sample sheet <NUM> in cassette <NUM>. In some embodiments rubber pins <NUM> may yield by squeezing as described above over a distance in the range of <NUM>-<NUM>. In some embodiments such distance may be <NUM>, <NUM> and even <NUM>. In some embodiments a mechanism other than rubber pins <NUM> is contemplated that enables needle bed <NUM>, and consequently biopsy needle <NUM>, to tilt, and possibly to yield, so as to align in parallel to cassette <NUM>; for example a mechanism including a single spring, a multitude of springs, a single bulk of soft and flexible material such as a sponge, or a mechanism including a ball joint, or any other suitable mechanism as known in the art.

A typical biopsy sample tissue taken by a biopsy needle and positioned on the needle's notch may have an uneven thickness, that is to say the sample tissue's profile along the notch may deviate significantly from a straight line, having typical "hills" and "valleys". To ensure continuous adherence of the sample tissue to sample sheet <NUM> along the length of the sample tissue, continuous contact should be formed, possibly necessitating pressing down protruding portions of the sample tissue, to reach thin, or low-profile portions thereof. However pressing down thick portions of sample tissue, resulting in flattening the sample tissue, is generally undesired, because flat and thin sample tissues on the sample sheet may provide a small number of slices or sections for a later inspection e.g. under a microscope.

Sponge <NUM> in cassette <NUM> flexibly supports sample sheet <NUM>, so as to enable contact with thin portions of the sample sheet and reduce the amount of pressing down thicker portions of the sample. When cassette base <NUM> near window edges <NUM> of cassette <NUM> touch biopsy needle <NUM>, sample sheet <NUM>, supported by sponge <NUM>, is configured to enter into the notch to increase sample tissue collection efficiency. In some embodiments sample sheet <NUM>, supported by sponge <NUM>, is configured to enter into the notch a distance in the range of <NUM> - <NUM>, for example enter into the notch by about <NUM>. In some embodiments sample sheet <NUM>, supported by sponge <NUM>, is configured to enter into the notch and reach a distance in the range of <NUM>-<NUM> above the notch floor, for example reach a distance of about <NUM> above the notch floor. Sample sheet <NUM> reaching such a small distance above the notch floor may ensure adherence of sample tissue portions that are thicker than <NUM>, thereby minimizing amount of sample tissue left on the notch and increasing considerably sample tissue collection efficiency. Flexible support of sample sheet <NUM> by sponge <NUM> allows sample sheet <NUM> to yield at regions where thick portions of the sample tissue contact sample sheet <NUM>, thereby reducing amount of pressing and flattening such thicker portions of the sample tissue. Further, Flexible support of sample sheet <NUM> by sponge <NUM> allows sample sheet <NUM> to yield at the ends of the notch, thereby allowing sample sheet <NUM> to enter into the notch in the vicinity of notch ends, thereby allowing collection of sample tissue from the regions of the notch ends. Thus, flexible support of sample sheet <NUM> by sponge <NUM> allows maximizing collection efficiency of sample tissue from the notch by reaching sample tissue near notch ends and by reaching thin portions of sample tissue, while flattening thick portions of sample tissue is restricted, thereby retaining thickness of thick sample tissue portions for subsequent inspecting steps.

It is noted that in some embodiments the orientation of a biopsy gun relative to base <NUM> may be different from that which is described above in <FIG>, for example the biopsy gun may be oriented so that the notch faces sideways rather than upwards. Three embodiments comprising three different mutual orientations, respectively, of notch <NUM>, supporting a sample tissue, relative to sample sheet <NUM>, are schematically depicted in <FIG>. When lever <NUM> is lowered to a closed position, sample sheet <NUM> is substantially perpendicular to the notch floor, and consequently the sample tissue is not pressed between sample sheet <NUM> and the notch floor.

<FIG> depict schematically an embodiment of a cassette <NUM> configured to be used with tissue handling device <NUM>, in a semi exploded view (A) and in a closed state (B). In addition to being usable in conjunction with tissue handling device <NUM>, e.g. according to the description and methods described above, cassette <NUM> is further usable as a sample box, for holding a sample tissue within during a preparation process prior to sectioning, e.g. washing the sample with a preservative solution, drying the sample, and subsequent steps.

Cassette <NUM> is different from cassette <NUM> in having a box cover <NUM>, configured to cover the sample tissue held in the cassette, thereby rendering cassette <NUM> a closed sample box configured to be used in the sample preparation steps as described above. Box cover <NUM> has a dimension and shape fitting to window <NUM> in cassette cover <NUM>. Further, box cover <NUM> comprises two cover pins <NUM> for attaching box cover <NUM> to cassette cover <NUM>. Cassette cover <NUM> comprises two holes <NUM> on edges <NUM> of window <NUM>, substantially fitting in dimensions to cover pins <NUM>. Thus, attaching box cover <NUM> to cassette cover <NUM> is achieved by inserting cover pins <NUM> to holes <NUM> and pressing onto box cover <NUM>.

Box cover <NUM> and cassette cover <NUM> comprise rinsing holes <NUM>, for allowing a washing fluid such as a preservative solution to penetrate easily the cassette and wash the sample tissue. Thus cassette <NUM> is rendered highly permeable to fluids even when closed by box cover <NUM>.

Cassette base <NUM> of cassette <NUM> comprises a labeling surface <NUM>, configured for attaching a label comprising a string for identifying the sample tissue held in the cassette, as well known and is routinely done in the art.

<FIG> depict schematically yet another embodiment of a cassette <NUM> configured to be used with tissue handling device <NUM>. Cassette <NUM> is depicted in <FIG> when installed on lever <NUM> of tissue handling device <NUM>. Cassette <NUM> may be employed in conjunction with tissue handling device <NUM> e.g. as is described above, to collect a sample tissue e.g. from a biopsy needle, and may further be employed as a sample box in subsequent steps in the preparation process prior to sectioning.

Cassette <NUM> comprises a cassette base <NUM> comprising a compartment <NUM> confined within base walls <NUM>. A cassette cover <NUM>, comprising a frame <NUM>, is configured to be attached to cassette base <NUM> inside compartment <NUM>, thereby holding firmly a sample sheet <NUM> on top of a sponge <NUM>, by pressing the sample sheet and the sponge between the frame and the caste base <NUM>. Frame <NUM> comprises an open window <NUM> allowing view and access to sample sheet <NUM>.

Each of the two opposing base walls <NUM> of cassette base <NUM> which are perpendicular to the axis of the biopsy needle <NUM>, comprises a depression <NUM>. Depressions <NUM> are positioned adjacent to the sample sheet and substantially where a biopsy needle, secured in place in tissue handling device <NUM>, touches cassette <NUM> when lever <NUM> is moved to a closed potion. Cassette <NUM> further comprises a box cover <NUM>, pivotally associated with cassette base <NUM>. Box cover may be open, as is schematically depicted in <FIG>, thereby allowing access to sample sheet <NUM> for attaching e.g. a biopsy sample thereon. By displacing box cover <NUM> around the pivot and attaching box cover <NUM> to cassette base <NUM>, box cover <NUM> may be closed, as is depicted in <FIG>. Box cover <NUM> is attached to cassette base <NUM> by tongue <NUM> whereas extensions <NUM> fit into wall depressions <NUM> to close them.

Box cover <NUM> and cassette base <NUM> further comprise rinsing holes <NUM>, for allowing a washing fluid such as a preservative solution to penetrate easily the cassette and wash the sample tissue. Thus cassette <NUM> is rendered highly permeable to fluids even when closed by box cover <NUM>.

When a sample tissue adhered to a sample sheet is processed as described above in preparation for section, and particularly during process steps that involve washing, the sample tissue may spontaneously detach from the sample sheet. Moreover, during such process steps the sample tissue may spontaneously tear, and portions of the sample may then detach from the sample sheet. Accordingly, when box cover <NUM> is closed, (and, likewise, when box cover <NUM> in cassette <NUM> is closed), escape of sample tissues from the cassette to the outside is substantially prevented. Furthermore when box cover <NUM> is closed, (and when box cover <NUM> in cassette <NUM> is closed), access to the sample sheet inside the cassette, for attaching a biological tissue thereon, is prevented.

Cassette base <NUM> of cassette <NUM> further comprises a labeling surface <NUM>, configured for attaching a label comprising a string for identifying the sample tissue held in the cassette, as well known and is routinely done in the art.

<FIG> schematically depicts a dyeing device <NUM> for dyeing sample tissues adhered to a sample sheet, e.g. for preserving orientation of the sample tissues during subsequent process steps including inspection under a microscope. Dyeing device <NUM> comprises a dyeing cassette house <NUM> configured to house cassette <NUM>. Dyeing cassette house <NUM> comprises a cassette house floor <NUM> descended between a first elevated wall <NUM> and a second elevated wall <NUM>. First elevated wall <NUM> comprises a protruding tooth <NUM>, arranged to fit to gap <NUM> in slide <NUM> of cassette cover <NUM>, thereby allowing to insert cassette <NUM> to cassette house <NUM> in a single orientation so that first slide <NUM> is adjacent first elevated wall <NUM>, and second slide <NUM> adjacent second elevated wall <NUM>.

Cassette house floor <NUM> further comprises three dyeing sponges 462a-462c, partially protruding upwards from cassette house floor <NUM>, for dyeing sample sheet <NUM> in cassette <NUM> attached thereto, possibly with sample tissues thereon. <FIG> schematically depicts a cross-section of dyeing device <NUM> in a vertical plane comprising dyeing sponges 462a-462c. Dyeing sponges 462a-462c may comprise a permeable and flexible material, capable of sucking liquid spontaneously from a bottom portion to a top portion thereof e.g. by capillarity, thus maintaining the sponges with dye for multiple dyeing sessions. Dyeing device <NUM> comprises three separated chambers 464a-464c, each configured to contain a dye in a liquid form and a dyeing sponge 462a-462c, respectively. Chambers 464a-464c are substantially rectangular, and arranged tilted diagonally at an angle relative to the vertical, inside cassette house floor <NUM>. Rectangular dyeing sponges 462a-462c that are inserted into chambers 464a-464c are thus consequently tilted, edges <NUM> forming dying tips, facing upwards towards a sample sheet and a sample tissue to be dyed. In some embodiments sponges 462a-462c are made of regular sponge. Dye can be applied to the sponges e.g. by pouring or dripping dye onto each from above. In some embodiments sponges 462a-462c may be used for multiple dyeing sessions. In some embodiments sponges 462a-462c may be used for a single dyeing event. In some embodiments dyeing device <NUM> is exposed to body fluids e.g. of marked sample tissue. In some embodiments sponges 462a-462c are disposable. In some embodiments cassette house floor <NUM> is disposable. In some embodiments dyeing device <NUM> is disposable.

For use, each dyeing sponge 462a-462c is soaked with a particular dye, for example dyeing sponge 462a may be soaked with a red dye, dyeing sponge 462b may be soaked with a yellow dye and dyeing sponge 462c may be soaked with a blue dye. Three dots 468a-468c, arranged on cassette house floor <NUM> adjacent dyeing sponges 462a-462c, respectively, are colored each by the dye used with the respective dyeing sponge, for informing a user what color each dyeing sponge may mark a sample tissue with. Dye materials used for soaking sponges 462a-462c and consequently for marking sample tissues are such that endure subsequent process steps of the sample tissue and remain adhered to the sample tissue, such as TMD™ Tissue Marking Dyes by Triangle Biomedical Sciences or such as Tissue Marking Dyes® (for example model numbers <NUM>-x) by Cancer Diagnostics, Inc. , or any other suitable dye as is known in the art.

In use, cassette <NUM> is suitably placed inside dyeing cassette house <NUM> aligned as described above and with a sample sheet <NUM> including at least one sample tissue facing downwards towards cassette house floor <NUM>. It is noted that a sample tissue attached to sample sheet <NUM> is generally aligned having its long dimension crossing all three dyeing sponges. <FIG> schematically depicts a cross section, along a vertical plane as in <FIG>, of dyeing device <NUM>, having a cassette <NUM> suitably assembled in dyeing cassette house <NUM>. It is noted that in <FIG>, a sample tissue attached to sample sheet <NUM> is generally aligned having its long axis parallel to the plane of the Figure. Edges <NUM> are substantially at a height above cassette house floor <NUM> that ensures contact of edges <NUM> with sample sheet <NUM>, and consequently with sample tissues attached thereto. A sample tissue attached to sample sheet <NUM> typically protrudes from sample sheet <NUM> downwards towards dyeing sponges 462a-462c, thereby sinking slightly into the sponges when pressed towards the sponges. Sponges 462a-462c thus yield to the pressure of the sample tissue, thereby marking the sample tissue along a substantial portion of the tissues' cross-section perimeter. Marking the sample tissue around the perimeter of the sample tissue and at least around a substantial portion thereof allows for colored markings on sequential slices of the sample tissue rather than only on the first slice.

Not part of the invention, a dyeing device comprising a cassette house floor such as cassette house floor <NUM> of dyeing device <NUM>, may be configured to be attached, permanently or temporarily, to a base such as base <NUM> of tissue handling device <NUM>. According to some such embodiments, a cassette house floor such as cassette house floor <NUM> may comprise two pins extending downwards from a bottom surface thereof and arranged to fit into through holes <NUM> in pedestal <NUM>. According to some such embodiments, needle bed <NUM> and needle bed holder <NUM> may be disassembled from pedestal <NUM> by lifting upwards, e.g. by hand. A cassette house floor, comprising two pins extending downwards as described above and further comprising dyeing sponges on a top surface thereof such as in cassette house floor <NUM>, may then be attached onto pedestal <NUM> instead of needle bed holder <NUM>, as is schematically depicted in <FIG>. It is noted that a replacement of needle bed holder <NUM> with a cassette house floor for dyeing a sample tissue as described above may thus be accomplished easily and quickly, by hand.

Not part of the invention, a method of dyeing a sample sheet, possibly carrying one or more sample tissues thereon, and using a tissue handling device such as tissue handling device <NUM> also is dicslosed. Cassette <NUM> comprising sample sheet <NUM> is assembled to lever <NUM>, and a biopsy gun comprising a biopsy sample tissue in the notch thereof is positioned in gun house <NUM>. The biopsy needle is suitably arranged on needle bed <NUM> and the sample tissue is collected to cassette <NUM>, by lowering lever <NUM> to a closed position as described and explained above. After collecting the sample tissue onto sample sheet <NUM> in cassette <NUM> and lifting lever <NUM> to an open position, the biopsy gun is removed from gun house <NUM>. Needle bed holder <NUM> together with needle bed <NUM> thereon are disassembled from pedestal <NUM>, and a cassette house floor comprising pins for attachment to pedestal <NUM> and fitting to through holes <NUM> therein is attached to pedestal <NUM> as explained above. Lever <NUM>, comprising cassette <NUM> with a sample tissue <NUM> adhered thereto, is lowered again to a closed position bringing sample sheet <NUM> and the sample tissue thereon substantially into contact with the sponges on the cassette house floor on pedestal <NUM>. Then lever <NUM> is lifted, sample sheet <NUM> and the sample tissue in cassette <NUM> being marked.

The method described above is particularly advantageous because the two steps of collecting a sample tissue onto the sample sheet and marking the sample sheet are employed using a single device. Consequently, disassembling the cassette from a first device and then assembling the cassette in a second device between the two steps is avoided, leading to a substantial reduction in risk to the cassette and the samples thereon. Further, a higher accuracy associated with the location of the marks on the sample sheet may be attained, because substantially fewer mechanical tolerances are accumulated in carrying out the method.

<FIG> schematically depicts an exemplary sample sheet <NUM> with a long sample tissues 480a and short sample tissue 480b, following coloring using e.g. dyeing device <NUM> as described above. The truncated corner of sample sheet identifies the orientation of the sample tissues relative to the biopsy needle and the distal tip as described above. Consequently, employing the example provided above of the order of the three dyes in dyeing device <NUM>, the end of the sample tissues closer to the truncated corner is colored red, the other end is colored blue and the middle is yellow.

By coloring sample tissues with a mark as described above, and possibly with more than one mark as described above, information of original orientation and location of the sample tissue is preserved as is detailed below:.

The location of the notch of the biopsy needle - and the location of the notch ends - relative to sample sheet <NUM>, when a sample tissue is attached to sample sheet.

When, during processing a sample tissue prior to inspection, the sample tissue or a portion thereof is removed from the sample sheet - e.g. slices of the sample tissue are taken for inspection under a microscope - the marks still identify on the sample portion both orientation and location of that portion relative to the biopsy needle notch.

It is noted that by using several marks side by side as is described above, and preferably by using several marks with different colors, such orientation and location information is retained also on short or partial sample tissues such as short sample tissue 170b: if a short sample tissue is marked with only two marks (of different colors), full information of orientation and location is maintained on the sample tissue; if a very short sample tissue is marked with only a single mark, the original location of very short sample tissue is still known (although orientation information might be lost).

Not part of the invention, a method for handling biological tissues obtained with a core biopsy needle could be carried out as follows.

It is noted that when cassette <NUM> or cassette <NUM> is used rather than cassette <NUM>, the steps of disassembling the cassette (in step <NUM> above), removing the sample sheet from the cassette and placing the sample sheet in a sample box as is illustrated in <FIG> become redundant. Thus, when a cassette such as cassette <NUM> or cassette <NUM> is used, the following steps may be employed following dyeing the sample tissue in step <NUM> above: 6a. A box cover such as box cover <NUM> in cassette <NUM> or box cover <NUM> in cassette.

<NUM> is attached to the cassette thereby closing the window of the cassette.

The closed cassette with the sample tissues on the sample sheet inside is taken through a suitable chemical preparation process prior to examination, as is described in step <NUM> above.

The next steps are substantially similar to the steps <NUM> - <NUM> above. For example, following step 7a, the box cover is removed and the cassette (such as <NUM> or <NUM>) is disassembled, the sample sheet is removed and placed, face down, in a metal mold as described in step <NUM> above and illustrated in <FIG>. Subsequently, the cassette, rather than a sample box, is placed on top of the metal mold, and labeling surface such as labeling surface <NUM> in cassette <NUM> is used for labeling the resulting paraffin block with the sample tissue therein. Thus, by employing a cassette such as cassette <NUM> or cassette <NUM>, direct handling with the sample sheet with the sample tissues adhered thereon is minimized, thereby reducing risk of damage to sample tissue or loss of sample tissues, and further reducing the complexity of the process and hence reduces the time of the process.

An image of the sample tissue on the sample sheet may be taken, immediately after collecting the sample tissue from the notch, using an imaging modality such as a camera. <FIG> schematically depicts tissue handling device <NUM> comprising tissue handling device <NUM> and further comprising a camera <NUM> fixedly installed on base <NUM> and configured to obtain an image of sample sheet <NUM> in cassette <NUM>, when lever <NUM> is in an open position as is depicted in <FIG>.

Camera <NUM> is employed to obtain an image of the location of the sample tissue relative to the sample sheet and particularly relative to a mark on the sample sheet such as truncated corner <NUM> or relative to an edge of the sample sheet.

To maintain knowledge of sample orientation, the sample itself must be marked, e.g. a colored dot may be marked on the sample tissue. The sample tissue may be marked at any arbitrary location on the sample if marking is done prior to obtaining an image using camera <NUM>. Alternatively the sample should be marked at a known point such as the end of the sample closest to the distal tip of the needle, thereby identifying that end of the sample. Following slicing of the sample and during an inspection under a microscope, the pathologist may indicate e.g. a tumor at a distance from the marked dot on the sample tissue. The location of the marked dot on the sample is known from the image taken by camera <NUM> (either the dot appears in the image or the location of the dot is the location of the end the sample, which always appears in the image). Hence, the exact location of the tumor may be traced back to a particular location along the biopsy needle at the moment the biopsy sample was taken.

By recording the position of the distal tip of the needle inside the live organ while taking the sample tissue, for example by using techniques as is explained in the introduction above, the position of the distal tip of the needle at the moment of taking the sample tissue is known. By measuring, using the marks on the sample tissue, the distance between an end of the sample tissue and the needle distal tip, or between an end of the sample tissue and an end of the sample sheet, the position of any point on the sample tissue relative to the distal tip is known. By preserving tissue orientation until examination, any disease or tumor detected in examination is correlated to an identified end of the sample tissue. By considering the above mentioned pieces of information, a tumor or disease detected in examination can be correlated to an identified location inside the live organ from which the sample tissue was taken.

Herein are provided devices and methods that in some aspects improve techniques for handling biological tissues that are taken with a biopsy needle. Specifically, devices and methods are provided herein that maintain sample tissue orientation and/or allow Z axis accuracy of not more than <NUM> millimeter and even Z axis accuracy better than <NUM> millimeter.

Devices and methods are provided that enable increased disease detection probability. Straight sample tissues on the sample sheet enable increased disease detection probability.

Thus, according to an aspect of some embodiment, there is provided a device for collecting onto a sample holder a biological tissue carried on a shaft. The device comprises a base, a lever and a needle bed. The needle bed is attached to one of the base and the lever and is configured to support, substantially in a pre-defined position, a shaft carrying a biological tissue. The other one of the base and the lever is configured to support a sample holder attached thereto. The lever is movable between settings relative to the base, thereby a sample holder suitably attached to the device is movable relative to the needle bed, so that:.

According to some embodiments the lever is detachable from the base. According to some embodiments the lever is not detachable from the base.

According to some embodiments the lever is pivotally associated with the base thereby being movable between the settings relative to the base substantially along a curve. According to some embodiments the lever is mechanically associated with the base by a track, thereby being movable between the settings relative to the base substantially along the track. According to some embodiments the track comprises one or more rails. According to some embodiments the track comprises one or more grooves.

According to some embodiments the needle bed is detachable from the device.

According to some embodiments the needle bed is a disposable part.

According to some embodiments the sample holder and the needle bed face one another in the second setting.

According to some embodiments the sample holder may contact a biological tissue carried by a shaft supported by the needle bed when the lever is in the second setting.

According to some embodiments the shaft is a core biopsy needle. According to some embodiments the shaft is a core biopsy needle having a notch. According to some embodiments the notch of the core biopsy needle comprises a notch floor configured to carry a biological tissue.

According to some embodiments the needle bed is configured to support a core biopsy needle so that the notch floor is substantially parallel to the sample holder when the lever is in the second setting. According to some embodiments a biological tissue carried on the notch is pressed between the sample holder and the notch floor when the lever is in the second setting.

According to some embodiments the needle bed is configured to support a core biopsy needle so that the notch floor is not parallel to the sample holder when the lever is in the second setting. According to some embodiments the needle bed is configured to support a core biopsy needle so that the notch floor is perpendicular to the sample holder when the lever is in the second setting. According to some embodiments a biological tissue carried on the notch is not pressed between the sample holder and the notch floor when the lever is in the second setting. According to some embodiments the tissue collecting device further comprises a gun house configured to secure to the device a biopsy gun having a biopsy needle so that the biopsy needle is supported by the needle bed in the pre-defined position.

According to some embodiments the gun house has an adjustable dimension and/or shape. According to some embodiments the gun house has fixed dimensions and shape.

According to some embodiments the sample holder is capable of adhering to a biological tissue by contacting the biological tissue. According to some embodiments the sample holder is configured to contact, in the second setting, a biological tissue carried on the shaft, thereby adhering to the biological tissue and detaching the biological tissue from the shaft when the lever is moved to the first setting.

According to some embodiments the sample holder is configured to hold a sample sheet capable of adhering to a biological tissue by contacting the biological tissue. According to some embodiments the sample holder comprises a sample sheet, capable of adhering to a biological tissue by contacting the biological tissue.

According to some embodiments the sample holder comprises a cassette configured to hold a biological tissue collected from a shaft by the device. According to some embodiments the cassette is detachable from the device by hand. According to some embodiments the cassette is configured to hold a sample sheet, capable of adhering to a biological tissue by contacting the biological tissue. According to some embodiments the sample sheet is configured to contact, in the second setting, a biological tissue carried on the shaft, thereby adhering to the biological tissue and detaching the biological tissue from the shaft when the lever is moved to the first setting. According to some embodiments the cassette has an unsymmetrical external outline precluding rotational symmetry of the cassette, except for the trivial rotational symmetry of <NUM> degrees. According to some embodiments the cassette may be attached to the device only in a single orientation of the cassette relative to the base of the device. According to some embodiments a biological tissue is attached to the sample holder so that an orientation of the biological tissue on the notch is substantially maintained on the sample holder.

According to some embodiments the sample holder is controllably displaceable relative to the device when attached to the device. According to some embodiments the sample holder is controllably displaceable between several well-defined positions, thereby allowing collecting sequentially onto several locations on the sample holder, several biological tissues, respectively. According to some embodiments the needle bed is flexibly attached to the device thereby being able to tilt relative to the device and align substantially parallel to the sample holder when the lever is in the second setting. According to some embodiments the needle bed is flexibly attached to the device thereby being able to yield relative to the device when the lever is in the second setting.

According to some embodiments the tissue collecting device further comprises an imaging modality fixedly attached to the base and aimed and configured to obtain an image of the sample holder when the lever is in the first setting. According to some embodiments the imaging modality is a CCD camera.

Not part of the invention, there is provided a cassette for collecting and holding a biological tissue on a sample holder, comprising: a cassette base comprising a base slab, and a cassette cover comprising a window and disposed, in an assembled cassette, above the cassette base. The cassette is configured to be assembled with a sample holder having an adhering surface configured to adhere to a biological tissue, the sample holder being held substantially between the cassette base and the cassette cover whereas at least a portion of the adhering surface is accessible through the window.

According to some embodiments the sample holder comprises a sample sheet. According to some embodiments the cassette further comprises the sample holder, disposed substantially between the cassette base and the cassette cover. According to some embodiments the sample holder is capable of adhering to a biological tissue by contacting the biological tissue on the adhering surface.

According to some embodiments the cassette has an unsymmetrical external outline precluding rotational symmetry of the cassette, except for the trivial rotational symmetry of <NUM> degrees. According to some embodiments the sample holder is held by being pressed along a portion thereof between the cassette base and the cassette cover. According to some embodiments the sample holder comprises a mark, the mark precludes rotational symmetry of the sample holder except for the trivial rotational symmetry of <NUM> degrees. According to some embodiments the mark is a visual mark. According to some embodiments the mark is a structural. According to some embodiments the mark is a hole in the sample holder. According to some embodiments the hole is a through-hole. According to some embodiments the adhering surface has a substantially rectangular shape and the mark is a truncated corner of the rectangle.

According to some embodiments the cassette is configured to hold the sample holder in a single orientation by comprising an internal structure compatible with the structural mark of the sample holder. According to some embodiments the internal structure comprises a pillar. According to some embodiments the internal structure comprises a protrusion. According to some embodiments the internal structure comprises an unsymmetrical compartment. According to some embodiments the compartment has a substantially rectangular shape with a truncated corner.

According to some embodiments the cassette further comprises a flexible layer disposed between the cassette base and the cassette cover so that a sample sheet is held in the assembled cassette between the flexible layer and the cassette cover. According to some embodiments the flexible layer comprises a sponge.

According to some embodiments the cassette further comprises a box cover configured to cover the window. According to some embodiments the box cover covers the window by attaching to the cassette base or to the cassette cover. According to some embodiments the box cover comprises through holes for rendering the cassette permeable to fluid. According to some embodiments the cassette further comprises a labeling surface configured for attaching thereon a label comprising an identification string.

According to an aspect of some embodiment, there is provided a dyeing device configured for dyeing a biological tissue adhered to a sample holder having a pre-defined external outline. The dyeing device comprises: a sample holder house having a shape compatible with the pre-defined external outline of the sample holder, thereby being configured to house the sample holder, and a protruding dyeing tip positioned in the sample holder house and configured to dye a biological tissue upon contacting the biological tissue. The protruding dyeing tip is configured to contact a biological tissue carried on a sample holder that is suitably positioned in the sample holder house, thereby dyeing the biological tissue.

According to some embodiments the sample holder comprises a cassette as described above.

According to some embodiments the dyeing device comprises at least two dyeing tips, wherein each dyeing tip is configured to dye a biological tissue with a different colour, respectively.

According to some embodiments the tissue handling device described above further comprises a dyeing module comprising a dyeing tip configured for selectively colouring a biological tissue in a portion thereof by contacting the portion with the dyeing tip. According to some embodiments a sample holder is attached to the lever and wherein in a setting of the lever relative to the base the sample holder may contact the dyeing module so that a biological tissue attached to the sample holder is selectively coloured in a portion thereof.

According to an aspect of some embodiment, there is provided a device for dyeing a biological tissue carried on a sample holder. The device comprises a base, a lever and a dyeing module comprising a dyeing tip. The dyeing module is attached to one of the base and the lever. The other of the base and the lever is configured to support a sample holder attached thereto. The lever is movable between settings relative to the base, thereby a sample holder attached to the device is movable relative to the dyeing module, so that in a first setting the sample holder and the dyeing module are distant from one another. In a second setting the sample holder and the dyeing module are situated proximal to one another having a predefined arrangement relative to one another.

According to some embodiments the dyeing module is attached to the base and the lever is configured to be attached to a sample holder. According to some embodiments the dyeing module is attached to the lever and the base is configured to be attached to a sample holder. According to some embodiments the dyeing tip contacts the sample holder when the lever is in the second setting. According to some embodiments the dyeing tip contacts a biological sample adhered to the sample holder when the lever is in the second setting.

Methods described herein facilitate maintaining order while handling sample tissues, thus minimizing mistakes as to patient's biopsy misplacement. Since the sample tissues are handled with the sample sheet through most steps in the preparation to examination process, from harvesting to the mold, misplacement of sample tissues and likelihood of errors is lowered.

The method described herein considerably reduces labor in handling sample tissues. Further, the method described herein minimizes damage to sample tissues and loss of sample tissues portions. As sample tissues are handled while adhered to a sample sheet.

Although the invention is described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. References to methods as disclosed herein are for illustration of use and do not form parts of the invention. The scope of the invention is defined by the appended set of claims.

Citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the invention.

Claim 1:
A device (<NUM>) for collecting onto a sample holder (<NUM>) a biological tissue carried on a shaft (<NUM>), characterised in that,
the device comprising a base (<NUM>), a lever (<NUM>) and a needle bed (<NUM>), wherein said needle bed is attached to one of said base and said lever and is configured to support, in a pre-defined position, a shaft configured for carrying a biological tissue, whereas the other one of said base and said lever is configured to support a sample holder attachable thereto, and wherein said lever is movable between settings relative to said base so that:
- in a first setting of said settings, a sample holder suitably attached to said device and said needle bed are distant from one another, and
- in a second setting of said settings said sample holder and said needle bed are situated proximal to one another having a predefined arrangement relative to one another,
and wherein, in said second setting, said sample holder is configured to contact a biological tissue carried on a shaft supported by said needle bed, thereby adhering to said biological tissue, and thereby detaching said biological tissue from said shaft when said lever is moved from said second setting to said first setting.