U.S. patent application number 16/053964 was filed with the patent office on 2018-12-06 for tissue sample container and methods.
This patent application is currently assigned to Leica Biosystems Nussloch GmbH. The applicant listed for this patent is Leica Biosystems Nussloch GmbH. Invention is credited to David BERARDELLI, Charles E. CLEMENS, Jo FLEMING.
Application Number | 20180345282 16/053964 |
Document ID | / |
Family ID | 49769464 |
Filed Date | 2018-12-06 |
United States Patent
Application |
20180345282 |
Kind Code |
A1 |
FLEMING; Jo ; et
al. |
December 6, 2018 |
TISSUE SAMPLE CONTAINER AND METHODS
Abstract
A tissue sample container including a base having a plurality of
sample holding sections, which are configured to receive a
plurality of tissue samples in a given orientation and are
demarcated by section walls; and a lid configured to sealingly
engage the base. The sample holding sections are sized and shaped
to correspond to a specific tissue sample size and shape such that
the base in cooperation with the section walls, maintain the given
orientation and identity of the tissue samples within respective
sample holding sections.
Inventors: |
FLEMING; Jo; (Boulder,
CO) ; CLEMENS; Charles E.; (Encinitas, CA) ;
BERARDELLI; David; (San Diego, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Leica Biosystems Nussloch GmbH |
Nu loch |
|
DE |
|
|
Assignee: |
Leica Biosystems Nussloch
GmbH
Nu loch
DE
|
Family ID: |
49769464 |
Appl. No.: |
16/053964 |
Filed: |
August 3, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14406899 |
Dec 10, 2014 |
10092905 |
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PCT/US2013/047293 |
Jun 24, 2013 |
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16053964 |
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61792929 |
Mar 15, 2013 |
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61663326 |
Jun 22, 2012 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
F04C 2270/041 20130101;
B01L 3/502715 20130101; B01L 3/50853 20130101; G01N 2001/368
20130101; G01N 1/36 20130101; B01L 2300/04 20130101; A61B 10/0096
20130101; B01L 3/545 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00; A61B 10/00 20060101 A61B010/00; G01N 1/36 20060101
G01N001/36 |
Claims
1. A core biopsy tissue sample container comprising: a base having
a sample holding section, which is configured to receive a
plurality of biopsy core samples, and hold the plurality of biopsy
core samples such that each of the biopsy core samples is
substantially aligned with at least one adjacent biopsy core sample
in a planar orientation, such that the plurality of biopsy core
samples are non-overlapping when viewed from at least one angle;
and a lid configured to engage and substantially seal the base.
2. The core biopsy tissue sample container according to claim 1,
wherein the sample holding section comprises a plurality of
sections, each section configured to receive one of the plurality
of biopsy core samples.
3. The core biopsy tissue sample container according to claim 2,
wherein the sample holding sections are differently sized and
shaped to correspond to respective differently sized and shaped
tissue samples.
4. A tissue sample container, comprising: one or more inserts
having a plurality of sample holding sections, which are configured
to receive a plurality of tissue samples in a given orientation,
said sample holding sections being demarcated by section walls; a
base configured to receive the one or more inserts that can be
selectively placed in the base; and a lid configured to at least
partially cover the sample holding sections and, in cooperation
with the inserts, maintain the given orientation of the tissue
samples within the respective sample holding sections, and
sealingly engage the base herein the inserts are sized according to
the tissue specific samples and selectively placed in the base.
5. The tissue sample container according to claim 4, wherein the
inserts are removable such that the inserts are sized according to
one of the tissue specific examples and can be placed into the
tissue sample container to hold one of the tissue specific
examples.
6. The tissue sample container according to claim 4, further
comprising a fluid dispensing mechanism which is fluid
communication with the inside of the tissue sample container for
dispensing a fluid inside the tissue sample container while the lid
and the base are engaged.
7. The tissue sample container according to claim 4, further
comprising a label containing information identifying the tissue
sample container and being, attached to at least one of the lid,
the base, and one of the plurality of sample holding sections.
8. The tissue sample container according to claim 4, further
comprising an identifier containing information identifying one of
the plurality of tissue samples and being attached to at least one
of the plurality of sample holding sections.
9. The tissue sample container according to claim 4, wherein the
section walls prevent the plurality of tissue samples from passing
between respective sample holding sections.
10. The tissue sample container according to claim 4, wherein the
sample holding sections are differently sized and shaped to
correspond to respective differently sized and shaped tissue
samples.
11. A tissue sample container, comprising: a base having a
plurality of sample holding sections, which are configured to
receive a plurality of tissue samples in a given orientation, said
sample holding sections being demarcated by boundary ribs; a
retaining member configured to at least partially cover the sample
holding sections and, in cooperation with the boundary ribs,
maintain the given orientation of the tissue samples within the
respective sample holding sections; and a lid configured to
sealingly engage the base and in cooperation with the boundary
ribs, maintain the given orientation and identity of the tissue
samples within respective sample holding sections.
12. The tissue sample container according to claim 11, wherein a
least one of the retaining member and the base is configured to
urge against the plurality of tissue samples.
13. The tissue sample container according to claim 12, farther
comprising a biasing element, wherein the retaining element is
attached to the retaining member by the at least one biasing
element configured to provide relative movement of the retaining
element with respect to the retaining member.
14. The tissue sample container according to claim 13, wherein the
retaining member comprises a plurality of retaining elements, each
of the plurality of retaining elements configured to urge against
one of the plurality of tissue samples.
15. The tissue sample container according to claim 11, wherein the
sample holding sections are differently sized and shaped to
correspond to respective differently sized and shaped tissue
samples.
16. A tissue sample container, comprising: a base having a
plurality of sample holding sections, which are configured to
receive a plurality of tissue samples in a given orientation; a
retaining member configured to at least partially cover the sample
holding sections and, a lid configured to sealingly engage the
base, wherein at least one of the base or the retaining member is
configured, in cooperation with the other, to urge towards the
plurality of tissue samples to maintain the given orientation of
the tissue samples within the respective sample holding
sections.
17. The tissue sample container according to claim 16, wherein the
plurality of sample bolding sections of the base have a plurality
of second tissue engaging surfaces which are configured to receive
the plurality of tissue samples in the tissue sample container.
18. The tissue sample container according to claim 17, wherein the
retaining member includes a frame portion and a retaining element
attached to the frame portion by at least one biasing element
configured to provide relative movement of the retaining element
with respect to the frame portion, the retaining element having an
first tissue engaging surface that is urged against the plurality
of tissue samples such that the tissue samples are retained between
the first tissue engaging surface and the plurality of second
tissue receiving surfaces.
19. The tissue sample container according to claim 18, wherein the
retaining member comprises a plurality of said retaining elements
connected to the frame portion by respective biasing elements, each
of the plurality of retaining elements corresponding to one of the
plurality of tissue samples, wherein each of the plurality, of
retaining elements are movable with respect to the frame portion
independently of other retaining elements.
20. The tissue sample container according to claim 19, wherein the
biasing element is substantially S-shaped including first and
second end portions, one end portion being connected to the frame
portion and the other end portion being connected to the tissue
retaining element.
21. A tissue sample container according to claim 16, wherein the
base has at least one mold having a second tissue engaging surface,
which is configured to receive a plurality of tissue samples,
wherein the retaining member includes a frame portion and a tissue
retaining element attached to the frame portion by at least one
biasing element configured to provide relative movement of the
tissue retaining element with respect to the frame portion, the
tissue retaining element having a first tissue engaging surface
that is urged against the plurality of tissue samples such that the
tissue samples are retained between the first tissue engaging
surface and the second tissue engaging surface of the at least one
mold of the base.
22. The tissue sample container according to claim 16, further
comprising a fluid dispensing mechanism which is fluid
communication with the inside of the tissue sample container for
dispensing a fluid inside the tissue sample container while the lid
and the base are engaged.
23. The tissue sample container according to claim 22, wherein said
sample holding sections are in fluid communication with each
other.
24. The tissue sample container according to claim 16, further
comprising a label containing information identifying the tissue
sample container and being attached to at least one of the lid, the
base, and one of the plurality of sample holding sections.
25. The tissue sample container according to claim 16, further
comprising a label containing information identifying one of the
plurality of tissue samples and being attached to at least one of
the plurality of sample holding sections.
27. A tissue sample container, comprising: a base having a
plurality of sample holding sections, which are configured to
receive a plurality of tissue samples in a given orientation, said
sample holding sections being demarcated by boundary ribs; a
retaining member configured to at least partially cover the sample
holding sections and, in cooperation with the boundary ribs,
maintain the given orientation of the tissue samples within the
respective sample holding sections; and a lid configured to
sealingly engage the base and in cooperation with the boundary
ribs, maintain the given orientation and identity of the tissue
samples within respective sample holding sections, wherein the
retaining member further comprises a plurality of retaining
elements each having a section perimeter, wherein the section
perimeters are positioned over the boundary ribs to maintain the
given orientation of the tissue samples within the respective
sample holding sections.
28. The tissue sample container according to claim 27, further
comprising a fluid dispensing mechanism which is in fluid
communication with the inside of the tissue sample container for
dispensing a fluid inside the tissue sample container while the lid
and the base are engaged.
29. The tissue sample container according to claim 28, further
comprising an identifier containing information identifying one of
the plurality of tissue samples and being attached to at least one
of the plurality of sample holding sections.
30. The tissue sample container according to claim 27, wherein the
sample holding sections are differently sized and shaped to
correspond to respective differently sized and shaped tissue
samples.
Description
REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional application of pending U.S.
patent application Ser. No. 14/406,899, filed Dec. 10, 2014 (now
allowed), which is a 371 of PCT/US2013/047293, filed Jun. 24, 2013
and which claims benefit of U.S. Provisional Patent Application
Ser. No. 61/663,326, filed Jun. 22, 2012 and U.S. Provisional
Patent Application Ser. No. 61/792,929, filed Mar. 15, 2013, the
disclosures of which are hereby incorporated by reference and
priority of which is hereby claimed pursuant to 37 CFR 1.78(a)(4)
and (5)(i).
FIELD OF THE INVENTION
[0002] The present disclosure relates generally to a tissue sample
container, and in particular, to a tissue sample container
configured to maintain the given orientation and identity of a
tissue sample within the container.
BACKGROUND OF THE INVENTION
[0003] Biopsy is the removal of tissue to examine it for signs of
cancer or other disorders. Biopsies may be open (surgically
removing tissue) or percutaneous (e.g. by fine needle aspiration,
core needle biopsy or vacuum assisted biopsy). The biopsy site can
be located via palpation, ultrasound or mammography.
[0004] Biopsy samples are obtained in a variety of ways using
various medical procedures involving a variety of the sample
collection devices. Examples of collection devices include those
marketed under the tradenames MAMMOTOME (from DEVICOR MEDICAL
PRODUCTS, Cincinnati Ohio), CELERO, ATEC AND EVIVA (all from
HOLOGIC, Marlborough Mass.), and FINESSE and ENCOR (all from BARD
BIOPSY SYSTEMS, Tempe Ariz.).
[0005] Some of these systems collect the tissue sample in a closed
container. U.S. Pat. No. 8,118,775 describes a closed tissue sample
storage container that is designed to spatially segregate biopsy
samples during the collection procedure. U.S. Pat. No. 7,572,236
describes a biopsy device with a closed container for collecting
one or more samples. The container includes a basket for flushing
away blood and other tissue debris from the specimens.
[0006] After the samples are removed from the patient, a tissue
marker can be inserted into the tissue site to later relocate the
site, if needed. For example, U.S. Pat. Nos. 6,270,464, 6,356,782,
6,699,205, 7,229,417 and 7,625,397 all describe tissue markers and
methods for marking a biopsy site. It is desirable to be able to
later relocate the position that the sample was taken from the
tissue site by correlating information retained with the sample
against the tissue marker.
[0007] After a tissue sample is collected, the sample is analyzed
at a lab (e.g. a pathology lab, biomedical lab, etc.) that is set
up to perform the appropriate tests (such as histological
analysis). Often, collection of the sample, and analysis of the
sample are performed at different locations and the sample must be
transported from the collection location (e.g. hospital, clinic,
etc.) to the lab (e.g. a pathology lab, biomedical lab, etc.) for
analysis.
[0008] Thus, after collection, the tissue samples are typically
removed from the collection container and placed into another
container for transport to a lab. Currently, the sample may simply
be placed loosely in a specimen jar filled with the fixing agent or
chemical (e.g., a solution of formaldehyde in water such as
Formalin), which preserves the tissue sample for analysis and the
specimen jar sealed for shipping. If: multiple samples are
collected, multiple samples from the same patient may be placed in
the same jar for transportation. It is desirable to retain
information collected during the tissue with each sample.
[0009] Once the tissue sample arrives in the lab, a series of steps
may be performed for processing the tissue sample including:
[0010] 1. Fixation of the sample to immobilize molecular components
and/or prevent degradation. This is typically done with a fixing
agent or chemical (e.g., a solution of formaldehyde in water such
as formalin) shortly after sample collection.
[0011] 2. Transferring the sample from the transportation jar to a
processing cassette.
[0012] 3. Infiltrating the sample with an embedding material, such
as the paraffin wax.
[0013] 4. Embedding the sample in the paraffin wax.
[0014] 5. Sectioning using for example a microtome by slicing the
sample into a plurality of thin sections (e.g., 2 to 25.mu. thick
sections), prior to performing any staining analysis.
[0015] Fixation is a process by means of which cell proteins are
stabilized, and the process is normally performed using chemical
fixatives. A good fixative is usually a fluid that will neither
shrink nor swell the tissue, and more particularly will not
dissolve its constituent parts, but will kill bacteria and render
enzymes inactive. In addition, the solution should modify tissue
constituents in such a way that they retain their form when
subjected to treatment that would have damaged them in their
initial state. The most commonly used fixative is formalin. In more
recent years, alternatives to formalin (formaldehyde) have been
proposed. WO 2004/093541 A1 teaches a formaldehyde-free,
non-alcoholic tissue preservative composition comprised of
ethanedial and a polar aprotic solvent in aqueous solution. Other
non-formalin based fixatives include glutaraldehyde, alcoholic
solvents, or acetic acid.
[0016] Typically after fixation, the sample is often removed from
the container, placed in a cassette, and embedded in preparation
for sectioning. Such sectioning of the sample often helps a medical
professional properly assess the sample under a microscope (e.g.
diagnose relationships between cells and other constituents of the
sample, or perform other assessments). In order to properly section
the sample, several steps are typically performed to embed the
sample within a solid substrate. A commonly used solid substrate
may include, for example, paraffin wax, which is used to hold the
sample in position while also providing a uniform consistency to
further facilitate sectioning with the microtome.
[0017] Under existing practices, this fixing, transferring,
infiltrating, and embedding must all be done manually, and such
manual handling of the sample can increase the likelihood of
misidentifying the sample, cross contaminating the samples, or
losing part or all of the sample. Further, as multiple samples may
be placed in the same jar, and each sample is merely loosely
floating in the fixing agent, information about each sample, such
as the orientation of the sample with respect to collection and,
which sample was collected from which area of the patient (i.e., 2
mm from mass, 4 mm from mass, 6 mm from mass etc.) may be lost and
unavailable to the medical professional when assessing the sample.
Additionally, the numerous steps of manual manipulation can often
increase the time that it takes to provide a proper assessment for
each sample, once the sample is collected from the patient.
[0018] In the practice of histopathology and the preparation of
cellular tissue materials for examination with the microscope,
preparatory steps have an important impact on the availability of
microscopic details that form the basis of proof for a diagnosis.
For example, it may be critical to maintain orientation of the
tissue sample during the preparatory phases. In addition, movement
of the sample during preparation, either during collection and
transfer to the lab or during laboratory processing in a tissue
processing cassette, may damage the sample.
[0019] When tissue materials are collected, as with a tissue, there
are specific criteria or judgments made of what might be suspicious
of showing a disease process. The suspect area of the tissue is
sampled with the intention of revealing a tissue diagnosis as the
basis of a treatment method or approach. Contemporary methods of
tissue biopsy and means for providing imaging of hidden suspect
tumor targets deep within body cavities or organs, include, in the
most modern approach, use of image guidance techniques, direct
vision for surface lesions where a biopsy of tissue surfaces are
harvested, needle through cut biopsies, aspiration biopsies of
fluid, incision biopsies of surface lesions, remote skinny needle
biopsies with ultrasound, or MRI, direct video or radio-graphic
guidance to an imaging system. The resultant captured tissue may be
solid, semi-solid, or liquid, as with cavity fluids containing
traces of surface cells, to be determined benign, malignant, or
inflammatory. In some instances, core needle biopsies are
preferred.
[0020] It is of vital importance to orient the tissue in a fixed
and precise way that will demonstrate anatomical relationship of
importance to adjacent organ tissues or surfaces; all in
relationship to the disease process. For instances, if a
gastroenterologist or any other specialologist visualized a
suspicious area to biopsy, the ologist alone knows what was up or
down, right or left, adjacent the stomach or other anatomical
landmark.
[0021] WO 00/19897 teaches that typically prior to the fixation
stage, a lab technician will place the tissue samples into the
tissue cassette for processing. When the tissue samples are placed
in the tissue cassette, the tissue samples are oriented with a
specific surface facing up. Generally, the person retrieving the
tissue sample after processing and before embedding the tissue
sample, will place the surface facing up in the tissue cassette
face down in the wax mold for embedding. Thus, maintaining the
orientation of the tissue sample after the fixation stage is
critical to ensuring that the tissue sample is oriented properly in
the wax mold for sectioning.
[0022] For example, as taught in WO 00/19897 maintaining
orientation is especially critical for vessel tissue samples where
the section needs to be transverse, core biopsy tissue samples
where the tissues should lie flat in the same plane, and gall
bladder tissue samples where the tissue samples should be embedded
on the edge. Critical to maintaining the orientation of a tissue
sample may be maintaining proper position of all sides of a tissue
sample, for example, face-up/face-down; left/right; or
north/south.
[0023] Using a single container to maintain orientation of tissue
samples from different locations sites may be difficult as tissue
samples from different location sites are different shapes and
sizes. That is, tissue samples are different shapes and sizes
depending on the location from where the tissue sample was removed.
For example, fine need aspiration biopsy tends to be very small
pieces of tissue taken from the core of a fine needle, whereas, GI
biopsy samples are characterized by a few small tissue pieces.
[0024] Consequently, it is desired to produce a container to
retain, orient, and prevent cross contamination of a different
types of tissue samples during the preparatory phases of a
histological examination.
[0025] Also in consideration is the ischemic time for pathology
samples. That is, it is desirable to quickly preserve the tissue
because the faster the tissue is preserved, the better the tissue
is for IHC testing. It is further desirable to have a tissue
container that allows for time, temperature, and PH monitoring.
Also, it is desirable to have a container with an identifier or
label that can be tracked and traced during transportation, such as
a smart container.
SUMMARY OF THE INVENTION
[0026] This invention provides a container which can address some
of the problems described above. Example embodiments of this
invention may address one or more of the above identified issues.
However, an embodiment of this application need not solve, address,
or otherwise improve on existing technologies.
[0027] One or more embodiments of the invention may include a
tissue sample container, including a base having a plurality of
sample holding sections, which are configured to receive a
plurality of tissue samples in a given orientation, said sample
holding sections being shaped and sized to receive a tissue
specific tissue sample; a lid configured to sealingly engage the
base and in cooperation with the sample holding sections, maintain
the given orientation and identity of the tissue samples within the
respective sample holding sections.
[0028] Use of the container of the invention allows tissue
processing, including fixation, after orientating the tissue. After
the tissue sample is orientated, the tissue sample is ready for
tissue processing, such as such as fixation. The fixing step may
comprise applying a solution of fixative such that cross-links are
formed in the orientating composition thereby rendering the
orientating composition substantially insoluble during subsequent
steps of the tissue handling procedure and thereby ensuring the
tissue sample remains affixed to the surface of the tissue handling
device during the subsequent steps of the tissue handling procedure
but remains permeable to all the processing solutions. During
fixative, it is desirable that the fixative be contacted with the
tissue in a manner that allows for penetration of the fixative into
the tissue. Ideally, the tissue remains substantially uncompressed
during the fixation to allow adequate penetration of the fixative
and to preserve cellular morphology and structure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1A illustrates a top view of a tissue sample container
for according to a first example embodiment of the present
application;
[0030] FIG. 1B illustrates a cross-section view of the tissue
sample container for according to the first embodiment of the
present application;
[0031] FIGS. 2A-2C show a base of the tissue sample container
according to certain embodiments in a non-assembled state;
[0032] FIG. 3A is a cross-sectional view of one embodiment of the
tissue sample container in an unassembled stated;
[0033] FIG. 3B is a cross-sectional view of the tissue sample
container in FIG. 3A in an assembled state;
[0034] FIG. 4 is a planar view of the tissue sample container
according to one embodiment;
[0035] FIG. 5A is an exploded view of a tissue sample container
according to a first embodiment in a non-assembled state;
[0036] FIG. 5B shows the tissue sample container of FIG. 1A in an
assembled state;
[0037] FIG. 6 is an exploded view of a tissue sample container
according to another embodiment in a non-assembled state;
[0038] FIG. 7 is an exploded view of the tissue sample container
according to one embodiment in a non-assembled state;
[0039] FIG. 8 is an exploded view of the tissue sample container
according to one embodiment in a non-assembled state;
[0040] FIG. 9 shows a close-up view of the biasing element in a
non-exemplary embodiment of the invention;
[0041] FIG. 10 is an exploded view of the tissue sample container
according to one embodiment in a non-assembled state;
[0042] FIG. 11A is an exploded view of the tissue sample container
according to one embodiment in a non-assembled state; and
[0043] FIG. 11B is a close-up view of the embodiment shown in 11A
in an open state and a closed state.
DETAILED DESCRIPTION OF THE DRAWINGS
[0044] In the following detailed description, reference will be
made to the accompanying drawing(s), in which similar elements are
designated with similar numerals. The aforementioned accompanying
drawings show by way of illustration and not by way of limitation,
specific example embodiments and implementations consistent with
principles of an example embodiment. These implementations are
described in sufficient detail to enable those skilled in the art
to practice an example embodiment and it is to be understood that
other implementations may be utilized and that structural changes
and/or substitutions of various elements may be made without
departing from the scope and spirit of an example embodiment. The
following detailed description is, therefore, not to be construed
in a limited sense.
[0045] FIGS. 1A and 1B illustrate a first exemplary embodiment of
the instant application. The tissue sample container 1 retains a
tissue sample 2 in proper orientation to allow for the automation
of the processing and a reduction of human error. As shown in FIG.
1B, a tissue sample container 1, according to one embodiment of the
invention, has a base 4, a lid 8, and a sample holding portion 10
which cooperate to retain the tissue sample 2 in a particular
orientation, as discussed below.
[0046] The base 4 has a bottom surface which may include a sample
holding portion 10 and may be divided into a plurality of sample
holding sections 11 demarcated by section walls 12 for holding the
tissue samples 2 after they are obtained. The sample holding
sections 11 may receive an individual sample (i.e. one sample in
each section) or a plurality of samples in each section.
[0047] The tissue sample container 1 is configured to hold one or
more samples 2. In the embodiment shown in FIGS. 1A and 1B, the
tissue samples 2 are preferably core biopsy samples. In such
instances, the tissue samples 2 may be elongated or otherwise
shaped, such that the tissue samples 2 are unable to rotate in the
sample holding sections 11 due to the engagement of the lid 8 in
cooperation with the section walls 12. Thus, the sample holding
sections 11 are configured in shape and size to receive a tissue
sample and to maintain its orientation.
[0048] Further, when the lid 8 is placed on top of the base 4 the
tissue sample container 1 is sealed as discussed in more detail
below. Once the tissue sample container 1 is sealed, the section
walls 12 in cooperation with the lid 8 sufficiently secures the
tissue samples 2 (as shown in FIG. 1B) such that they maintain
their orientation within the sample holding sections 11. Once
sealed, the tissue sample container 1 can be transported without
the tissue samples 2 losing their orientation.
[0049] The tissue sample holding sections are not limited to the
elongated shape as shown in FIG. 1A. In fact, the size and shape of
the tissue holding sections may be tissue specific. For example,
the tissue holding sections 11 for core biopsy sample might be long
and narrow, while the tissue holding sections 11 for skin tissue
might be shorter and wider. FIGS. 2A-2C illustrate some additional
shapes and sizes contemplated for the tissue sample holding
sections 11 depending on the specific tissue contained in the
tissue container 1. The shapes and sizes of the tissue sample
sections 11 are not limited to these configurations. Also, the
tissue sample container 1 may have one or more sample holding
sections 11 each differently sized and shaped to receive a tissue
sample 2 and retain the tissue sample 2 in a fixed orientation
while the tissue sample 2 is in the container as shown in FIG.
2B.
[0050] For transport, the tissue sample container 1 is sufficiently
sealed to secure the tissue samples 2 in a non-limiting embodiment.
As shown in FIG. 1B the tissue sample container 1 may have a
sealing gasket 16 (also illustrated in FIG. 5A). The sealing gasket
16 is not particularly limited and may be a rubber gasket, a
plastic gasket, an O-ring, or any other sealing member as would be
apparent to a person of ordinary skill in the art. In addition, the
connection between the base 4 and the lid 8 is not particularly
limited and may include one or more of a tongue and groove
configuration, a threaded configuration, a snap fitting
configuration, a pressure fitting configuration or any other
configuration as would be apparent to a person of ordinary skill in
the art.
[0051] An example of a sealing mechanism is shown in FIG. 1B. In
this embodiment, the connection between the base 4 and the lid 8
may have a two-part closing system with a temporary closed position
and a permanently closed position. FIG. 1B shows the permanently
closed position. In the temporary closed position, the base 4 has a
first lock 22 and second lock 24 and the lid 8 has a first snap 26
and a second snap 28. The first lock 22 and the first snap 26
engage to form the temporary closed position such that the samples
may be held in a temporary locked position. In addition, the lid 8
can be further pressed onto the base 4 to a completely locked
position such that the first lock 22 engages with the second snap
28 on the base 4 and the second lock 24 engages with the first snap
26 to form the permanently closed position. This permanently closed
position forms a fixed closing and further creates a seal at the
seal gasket 16. In a non-exemplary embodiment the lid 8 and the
base 4 can only be removed by peeling away a part of the lid 8 to
release the permanently closed position.
[0052] Alternatively, the lid 8 may be sealed to the base 8 as the
lid 8 is made out of heat sealable film 29 (illustrated in FIG. 8).
In this instance the heat sealable film 29 is attached to the base
4 in a heat sealable manner.
[0053] Once the tissue sample container 1 is sealed, it is ready
for processing. As described above, a tissue sample 2 is processed
with a fixing agent to fix and preserve the sample before analysis.
The tissue sample container 1 may have fluid dispensing mechanism
30 or a means for processing the tissue samples 2 without
disengaging the lid 8 from the base 4. Thus, formalin can be
inserted at the top or bottom of the tissue sample container I and
can penetrate around the tissue samples 2 even with the lid 8 and
base 4 closed. This reduces the human exposure to formalin. The
following is a description of different fluid dispending mechanisms
30 with reference to FIGS. 3A, 3B and 4.
[0054] As shown in FIG. 3A, with the fluid dispensing mechanism may
include a pouch 34 containing a fluid 35 that is released into the
tissue sample container 1 upon attachment of the lid 8 to the base
4. The fluid 35 in the pouch 34 may be any fluid to preserve and
store any tissue samples during transportation, such as formalin.
In the embodiment shown in FIGS. 3A-B, the pouch 34 is attached to
the inside of the lid 8. The pouch 34 has a frangible portion 36
configured to be broken or ruptured to allow the fluid 35 be
released into the tissue sample container 1. The pouch 34 and the
frangible portion 36 are designed such that fluid 35 is released
when the lid 8 becomes engaged with base 4.
[0055] More specifically, as shown in FIG. 3B, the pouch 34 is
disposed directly above the tissue samples 2 and when the lid 8 is
lowered onto the base 4, a squeezing force is applied to the pouch
34 as the lid 8 is forced downward. This motion increases the
pressure of the fluid within the pouch 34 so that the frangible
portion 36 ruptures when the pressure of the fluid 35 exceeds the
strength of the frangible portion 36.
[0056] Thus, upon engagement of the lid 8 to the base 4, the
frangible portion 36 breaks and releases the fluid 35 into the
inside of the tissue sample container 1 as shown in FIG. 3B. The
fluid 35 is then released into the sample holding sections 11 of
the base 4, submerging the tissue samples 2 in the tissue sample
container 1.
[0057] The frangible portion 36 may be a perforated region or a
region formed of a material different from the remainder of the
pouch 34, such that the frangible portion 36 of the pouch can be
caused to break in a predictable manner. As an example, the lid 8
may be placed upside down to rest on top of the base 4 during
transport to prevent inadvertent busting of the pouch 34. The
volume of fluid 35 provided is chosen to be sufficient to fill the
tissue sample container 1 such that the tissue samples 2 are
submerged. Further, in some non-limiting embodiments, a breaking
member having, for example, a needle shape and oriented to engage
the frangible portion 36 of the pouch 34 and rupture the frangible
portion 36 may be provided within the tissue sample container
1.
[0058] Alternatively, as shown in FIG. 4, in one embodiment of the
invention, the fluid dispensing mechanism 30 may be a porthole 38
on the lid 8 of the tissue sample container 1. In this instance the
porthole 38 may be attached to an external formalin reservoir (not
shown in the figures) such that the formalin can be dispensed in
the inside of the tissue sample container 1 through the porthole
38. While the porthole 38 is shown in the center of the lid 8, this
location is not limiting and the porthole 38 could be located
anywhere on the lid 8.
[0059] Further, the fluid 35 can pass in between the sample holding
sections 10 depending on their size and height. For example in the
embodiment shown in FIG. 2B, the section walls 12 are solid and
high such that fluid 35 may not be able to pass through the section
walls 12. However, in FIGS. 2A and 2C, the section walls are
perforated such that fluid 35 may pass through the section walls
12.
[0060] Further, in some embodiments, a label 7 or ID tag, may be
attached to each tissue sample container 1 as shown in FIG. 1A.
Also an identifier 9 may be attached to one or more tissue holding
sections 11 configured to receive the tissue sample 2. An important
aspect of tissue transportation is properly keeping track of tissue
samples. This includes not only tracking the tissue sample
containers 1, but also easily identifying the samples 2 within a
container.
[0061] In FIG. 1A, the label 7 is shown disposed on the base 4;
however, the label 7 can be located anywhere on the tissue sample
container 1. (An example of the label 7 on the lid 8 is shown in
FIG. 7.)
[0062] In the embodiment shown in FIG. 1A, a single label 7 is
present; however more than one label 7 may be present and the
labels can be physically separated or located together. There also
can be a label 7 for each tissue sample container 1 as well as for
each tissue sample 2 in the tissue sample container 1. Thus, one or
multiple labels 7 can be placed in the sample holding sections 11,
the lid 8, the base 4, or another area of the tissue container
2.
[0063] In the embodiment shown in FIG. 1A, an identifier 9 is
associated with each tissue holding section 11 to more easily
identify the samples within the tissue container. Also, the
identifiers 9 may help identify the orientation of the tissue
sample 2. For example, the identifiers 9 as shown in FIG. 1A may
provide guidance as to the north/south or left/right orientation of
the tissue sample with respect to the identifier 9.
[0064] The label 7 or the identifier 9 may be a computer readable
tag including, but not limited to, labels having an incorporated
RFID, labels having an incorporated one-dimensional barcode (1-D
barcode), labels having an incorporated two-dimensional barcode
(2-D barcode), and labels having an incorporated three-dimensional
barcode (3-D barcode). However, the computer readable label is not
limited to RFID, 1-D barcode, 2-D barcode, or 3-D barcode labels
and may include any type of label readable by a computer as would
be apparent to a person of ordinary skill in the art.
[0065] In some embodiments, a label 7 or identifier 9 is present
that may be sensitive to changes to the sample or to the tray
itself. For example, the label 7 or identifier 9 may be present
that changes physical (i.e. color) or chemical (i.e. redox,
conjugation, etc.) properties during fixation of the sample.
Similarly, a label 7 may be present that is sensitive to the
processing steps which precede embedding (i.e. dehydration).
Alternatively, the label 7 or identifier 9 present that is
sensitive to the embedding step (i.e. infiltration of wax). The
label 7 or identifier 9 may have a property that changes
incrementally or switches when the step is complete. In this way,
the technician, or an automated system, will be able to determine
when the sample has finished one step before another is
started.
[0066] The tissue sample container 1 of any embodiment of the
present application may be formed from a variety of materials and
their construction is not particularly limited. Further, an
embodiment of this tissue sample container 1 may be constructed
from a material having one or more of the following features:
transparent on imaging or with minimal interference (i.e. radio
transparent), resistant to chemical fixatives (such as formalin),
resistant to degradation from chemicals used in tissue processing
(such as alcohol, xylene or acids), and resistant to temperatures
used in tissue embedding.
[0067] In addition, the lid 8 may include a coating on a surface
which faces the tissues. The coating is such that is reduces the
adhesion between the tissue sample and the tissue facing surface.
In non-limiting embodiments, the coating can be a Teflon coating,
including Polytetrafluoroethylene (PTFE) coating or the coating can
be Polypropylene (PP).
[0068] In a second embodiment of the instant Application, the same
base 4 may be used for a variety of differently sized and shaped
sample holding sections 11. As such, the section walls 12 may be
removable from the base 4 and the tissue sample container 1 may be
used to retain the orientation of a variety of different tissue
specific tissue samples.
[0069] In this embodiment an insert 13 (having the same shape as
the outline of the section walls 12) is contemplated that may be
inserted into the base 4 to form tissue specific, tissue sample
holding sections 11. In this embodiment, a kit may be provided
which has multiple inserts 13 with a variety of sized and shaped
tissue specific sample holding sections 11. Each, tissue specific
sample holding section 11 of the insert 13 may be shaped and sized
to sufficiently maintain the orientation of the tissue specific
tissue sample 2 in the tissue container 1. That is, the inserts 13
in cooperation with the lid 8 maintain the orientation of the
tissue specific sample since they are shaped and sized according or
the sample size of the tissue sample.
[0070] FIGS. 5A and 5B illustrate a tissue sample container 1
according to a second embodiment of the present application. The
second embodiment mirrors the first embodiment with a few
differences. First, a tissue sample container 1 according to a
second embodiment of the application, includes a retaining member 6
which cooperates with the base 4 and the lid 8 to retain the tissue
sample 2 in a particular orientation, as discussed above. Second,
the tissue sample holding sections 11 are demarcated by boundary
ribs 40 as opposed to section walls 12 in the above example. The
boundary ribs 40, in an exemplary embodiment, are shorter in height
than the section walls 12. As such, the boundary ribs 40 in
cooperation with the retaining member 6 maintain the orientation of
the tissue samples 2. In all other aspects the second embodiment is
similar to the first embodiment.
[0071] The retaining member 6 is configured to be inserted over the
base 4 as shown in FIG. 5A such that the retaining member 6 at
least partially covers the sample holding sections 11. The
retaining member 6 may have a single retaining element 14, as shown
in FIG. 5A or a plurality of retaining elements 14, as shown in
FIG. 6. In the example shown in FIG. 6, the retaining member 6
includes a plurality of retaining elements 14 corresponding in
number and in alignment with the sample holding sections 11.
[0072] In an non-exemplary embodiment, each retaining element 14
has a mesh structure and is moveably attached to retaining member 6
by a biasing element 15. In this embodiment, there is a biasing
element 15 on opposite sides of each retaining element 14. When the
retaining member 6 is secured to the base 4, the biasing element 15
urges the retaining element 14 downwardly towards the sample
holding sections 10. In one embodiment, the biasing element 15
urges the retaining elements 14 downwardly--against the tissue
samples 2 so that the tissue samples 2 are retained between the
retaining member 6 and the base 4 to maintain the proper
orientation of the tissue samples 2.
[0073] Alternatively, the retaining elements 14 may urge against
the boundary ribs 40 to provide a slight space between the tissue
sample 2 and the retaining element 14 so that the retaining element
14 and the boundary ribs 40 cooperate to hold the tissue samples 2
in place. In such instances, the tissue samples 2 may be elongated
or otherwise shaped, such that the tissue samples 2 are unable to
rotate in the sample holding sections 10 due to the engagement of
the boundary ribs 40 and the retaining element or elements 14.
[0074] Similar to the embodiment described above, the lid 8 is
placed on top of the base 4 to seal the tissue sample container 1.
Once the tissue sample container 1 is sealed, boundary ribs 2 in
cooperation with the retaining element 14 sufficiently secures the
tissue samples 2 such that they maintain their orientation within
the sample holding sections 11, and the tissue sample container 1
can be transported without the tissue samples 2 losing their
orientation.
[0075] FIG. 5A shows four sample holding sections 11; however, the
sample holding sections are not limited to this number. Also, as an
alternative to the above, the base 4 may incorporate the biasing
element to bias a portion of the base against the tissue samples 2
to sufficiently hold the tissue samples' given orientation
depending on the shape and size of the tissue sample 2. Further,
the boundary ribs 40 are shown in FIG. 5A to extend in both the
longitudinal and latitudinal direction of the base 4 such that the
boundary ribs 40 cross to form substantially rectangular sample
holding sections 11. The sample holding sections 11 are not limited
to this shape and the boundary ribs 40 may extend in only one
direction.
[0076] Similar to the embodiment above, the fluid 35 may be
dispersed inside the container. The retaining member 6 may have a
plurality of perforations 32 to allow the fixing agent to flow
freely in the container 1. Thus, the fluid 35 released into the
tissue sample container 1 can pass through the retaining member 6
to the tissue samples 2 in the sample holding sections 11. In the
instances, where a porthole 38 is used for administering the fluid
35 the porthole 38 may also be connected through the retaining
member 6, specifically in instances where the lid is a heat
sealable film 29 as discussed above (illustrated in FIG. 7).
[0077] As an alternative example, the boundary ribs 40 may have
perforated walls to further allow fluid to communicate between the
sample holding sections 11. That is, in some instances the boundary
ribs 40 may have a height great enough such that they partially or
wholly contact the retaining member 6 or retaining elements 14 such
that fluid 35 may be prevented from passing from one sample holding
section 11 to another. Or, the boundary ribs 40 may have a very
small height or have perforations to allow fluid flow between the
sample holding sections 11.
[0078] Further, FIG. 7 illustrates another example of this
embodiment where the boundary ribs have a small height such that
they do not contact the retaining member 12 and the sample holding
sections 10. In this instance, the retaining member 14 maintains
the tissue samples fixed orientation and identity within the tissue
sample container 1.
[0079] FIG. 8 shows an additional embodiment of the tissue sample
container 1 of this application. This embodiment is the same as the
embodiments described with respect to FIGS. 5A, 5B, 6, and 7 except
in this embodiment, the base 4 or the retaining member 6 is
configured, to urge towards the tissue samples 2 to clamp or engage
the tissue samples. Similar to other embodiments, the retaining
member 6 can contact the boundary ribs 40 and not urge directly
against the tissue samples.
[0080] In the example shown in FIG. 8, the retaining member 6
includes a frame portion 48 and a plurality of retaining elements
14 corresponding in number and in alignment with the sample holding
sections 11. In an non-exemplary embodiment, the retaining elements
14 have a mesh structure and are moveably attached to the frame
portion 48 by a biasing element 15 respectively provided on
opposite sides of each of the retaining elements 14. When the
retaining member 6 is secured to the base 4, the biasing element 15
urges the retaining elements 14 downwardly away from the frame
portion 48 and toward the sample holding sections 10. The bottom
facing surfaces of the retaining elements 14 define a first tissue
engaging surface 54 for respectively engaging the tissue sample 2.
Further, the top surface of the base 4 defines a second tissue
engaging surface 56 for receiving the tissue samples 2. The biasing
element 15 urges the retaining elements 14 downwardly towards or
against the tissue samples 2 so that the tissue samples 2 are
retained between a first tissue engaging surface 54 of the
retaining elements 14 and the second tissue engaging surface 56 of
the base 4 to maintain the proper orientation of the tissue samples
2.
[0081] As shown in FIG. 8, according to this embodiment the
retaining member 6 includes a plurality of retaining elements 14.
However, the retaining member 6 may comprise only one retaining
element 14, similar to the retaining member 6 as described with
respect to FIG. 5A.
[0082] In addition, as shown in FIG. 8, the base 4 may comprise a
plurality of molds 58 which receive the tissue sample 2. In this
embodiment the sample 2 is retained between the surface of the mold
58 and the retaining elements 14.
[0083] As mentioned above, the retaining element 14 is attached to
the frame portion 48 by a biasing element 15. That is, the biasing
element 15 is attached at one end to the frame portion 48 and to
the retaining element 14 on the other end. The biasing element 15
is configured to provide relative movement of the retaining element
14 with respect to the frame portion 48. The biasing element 15
urges the retaining element 14 towards the base 4 to maintain the
tissue samples' orientation. Thus, the biasing element 15 can take
on any shape that performs this function. Also in certain
embodiments, the retaining elements 14 are movable with respect to
the frame portion independently of other retaining elements 14.
[0084] One example of the biasing element 15 is shown in FIG. 9
where each biasing element has a substantially S or Z shape. In
this example, each biasing element 15 has a first member 60 with a
first end 62 and a second end 66. The first end 62 is connected to
the tissue retaining element 14. Extending downward at an angle
from the second end 66 of the first member 60 is a first angled
member 64. A second angled member 68 is connected to the first
angled member 64 by a first curved hinged point 74. The second
angled member 68 extends upward from the first angled member 64 at
an angle; and in a non-limiting embodiment, the second angled
member 68 and the first angled member 64 form an angle less than
90.degree.. Extending downward from the second angled member 68 is
a third angled member 70. The second angled member 68 and the third
angled member 70 are connected by a second curved hinge point 76.
In a non-limiting embodiment, the third angled member 70 and the
second angled member 68 form an angle less than 90.degree..
Further, in a non-limiting embodiment, the third angled member 70
and the first angled member 64 form an angle less than 90.degree..
A second member 72 connects to the third angled member 70 and
extends substantially parallel to the tissue retaining element 14.
The second member 72 attaches to the retaining member 6 in a
non-limiting embodiment.
[0085] FIG. 10 shows an alternate embodiment to the embodiments
described with respect to FIGS. 1A, 1B and 2. This embodiment is
similar to the embodiments described above, except in this
embodiment, the retaining member 6 has retaining elements 14 which
extend towards the lid 8 instead of towards the base 4. In this
embodiment, the retaining elements 14 have section perimeters 44
which outline each retaining element 14. FIG. 11A illustrates an
example where in the section perimeters 44 have a long and narrow
shape.
[0086] As shown in FIG. 11A, the section perimeters 44 are
positioned to partially cover the tissue samples 2 and to align
over the boundary ribs 40 on the base 4. The section perimeters 44
can contact the boundary ribs 40 as shown in the close state of
FIG. 11B, but they are not limited by this feature. In this
example, the tissue sample 2 is sized according to the size of the
retaining elements 14, such that the retaining elements 14, in
combination with the boundary ribs 40, maintain the tissue sample's
orientation.
[0087] Although a few example embodiments have been shown and
described, these example embodiments are provided to convey the
subject matter described herein to people who are familiar with
this field. It should be understood that the subject matter
described herein may be embodied in various forms without being
limited to the described example embodiments. The subject matter
described herein can be practiced without those specifically
defined or described matters or with other or different elements or
matters not described. It will be appreciated by those familiar
with this field that changes may be made in these example
embodiments without departing from the subject matter described
herein as defined in the appended claims and their equivalents.
Further, any description of structural arrangement of components or
relationship there between is merely for explanation purposes and
should be used to limit an example embodiment.
[0088] Aspects related to the example embodiment have been set
forth in part in the description above, and in part should be
apparent from the description, or may be learned by practice of
embodiments of the application. Aspects of the example embodiment
may be realized and attained using the elements and combinations of
various elements and aspects particularly pointed out in the
following detailed description and the appended claims.
[0089] It is to be understood that both the foregoing descriptions
are an example and are explanatory only and are not intended to be
limiting.
* * * * *