Patent Application
20250160802
The present disclosure generally relates to apparatuses and methods for segregating tissue samples for multiple diagnostic modalities. More specifically, the present disclosure relates to biopsy container apparatuses for recovering solid tissue and dislodged cells from a biopsy and their corresponding methods of use.
The systems and methods of the present disclosure can be used in combination with the apparatuses and methods of U.S. patent application Ser. No. 18/468,416, filed Sep. 15, 2023, entitled “Methods and Systems for Recovering Assessable Analytes from Core Needle Biopsies,” the entire contents of which is incorporated herein by reference.
Solid tumor diagnostic procedures typically involve a tissue biopsy. Traditionally, a biopsy involves a substantial amount of tissue being surgically excised from a tumor or suspected affected tissue in a patient. The tissue, once removed from the patient's body, is processed and subsequently can be used for a number of different types of diagnostic tests.
In recent years, biopsy tools and techniques have advanced to be less invasive, with dramatically smaller tissue samples. Surgically-excised biopsies have largely been replaced by core needle biopsy (CNB) tools. Smaller biopsies are less traumatic for patients, quicker for the clinician to perform, and less expensive for the healthcare system in general. Hence, standard biopsy tissue size has declined significantly between the period before approximately 2010 and the years thereafter. The disadvantage of smaller biopsies is that they provide less tissue for pathologists to examine and analyze to render diagnostic opinions.
At the same time, diagnostic testing modalities have expanded to include an increased number of tests aimed at identifying molecular changes. The declining tissue biopsy size and the expanding quantity of testing required of the biopsied tissue has created an imbalance between tissue supply and demand. The result is that in some cases, clinicians make treatment decisions for patients with less diagnostic information than they would like. In other cases, patients are subjected to a second biopsy. The risk that a biopsy sample will have insufficient tissue to allow for the clinically-indicated tests to be performed is a big enough problem that it has several unofficial names, with “Tissue Exhaustion” being the most common. Tissue Exhaustion rates for core needle biopsies are reported in literature to be between 22-82% of all biopsies.
An imbalance therefore exists between the typical amount of tissue yielded from a CNB and the typical amount of tissue needed for testing. Healthcare quality is impacted by the shortfall in the quality and quantity of substrate available for molecular testing. This ultimately affects patient care, with many specimens received in the pathology laboratory not being available for molecular testing, resulting in these patients missing out on the improved treatment options associated with precision medicine (defined as using molecular testing to find a mutation to guide therapy).
It is unfortunate that standard tissue biopsy handling practices today result in some of the harvested cells being discarded along with medical waste. These cells come from the patient, unavoidably dislodged (referred to hereafter as D-cells) from the tissue due to the trauma associated with of the sharp edge of the CNB needle cutting through tissue and then pulling back into the metal CNB tube (e.g., as shown in
The present disclosure provides a biopsy container apparatus that allows a clinician who performs a core needle biopsy to deposit the harvested tissue in such a way that it recovers cells that are dislodged (“D-cells”) from the solid tissue that is procured during the biopsy procedure. D-Cells are an unrealized resource for diagnostic testing, mainly because cells are below the acuity of the human eye. This valuable biologic resource is typically discarded, but the apparatuses s and methods of the present disclosure enable its recovery for diagnostic testing.
As discussed in more detail below, the biopsy container apparatus disclosed herein enables a clinician who performs a core needle biopsy to deposit the tissue in such a way that it contains and preserves the microscopic accompanying portions (D-cells) of the biopsied tissue that would otherwise be inadvertently discarded. More specially, the biopsy container apparatus disclosed herein enables cells that are dislodged from tissue that is procured during a biopsy procedure to be kept and segregated from the tissue that will be sent for standard pathology laboratory processing, using a specialized removable sieve suspended within a multi-functional watertight container. These recovered cells (D-cells) constitute an unrealized resource for diagnostic testing. This resource is typically discarded, but the apparatuses and methods of the present disclosure ensure recovery for diagnostic testing.
A first aspect of the present disclosure is to provide a biopsy container apparatus for recovering solid tissue and D-cells from a biopsy. The biopsy container apparatus includes a sample collection container, a basket sieve, and a buffer container. The sample collection container includes a reagent chamber. The basket sieve is configured for removable attachment at least partially within the sample collection container and includes a sieve surface configured to pass the D-cells from the biopsy but not the solid tissue from the biopsy. The buffer container is configured for removable attachment to the sample collection container and includes a buffer chamber.
A second aspect of the present disclosure is to provide another biopsy container apparatus for recovering solid tissue and D-cells from a biopsy. The biopsy container apparatus includes a sample collection container, a basket sieve, and a buffer container. The sample collection container includes a reagent. The basket sieve is configured for removable attachment at least partially within the sample collection container and includes a sieve surface configured to pass the D-cells from the biopsy but not the solid tissue from the biopsy. The buffer container is configured for removable attachment to the sample collection container and includes a buffer.
A third aspect of the present disclosure is to provide another biopsy container apparatus for recovering solid tissue and D-cells from a biopsy. The biopsy container apparatus includes an upper chamber, a lower chamber, a sieve surface and a solid surface. The sieve surface is located between the upper chamber and the lower chamber and is configured to pass the D-cells from the biopsy but not the solid tissue from the biopsy. The solid surface is movably attached with respect to the sieve surface and configured to translate between (i) a first configuration in which the solid surface overlaps the sieve surface to prevent the D-cells from passing through the sieve surface and (ii) a second configuration in which the solid surface is moved away from the sieve surface to permit the D-cells to pass though the sieve surface from the upper chamber to the lower chamber.
A fourth aspect of the present disclosure is to provide a method of recovering solid tissue and D-cells from a biopsy using a buffer container apparatus including a buffer container, a basket sieve and a sample collection container. The method includes depositing the solid tissue and the D-cells from the biopsy into a buffer solution within the buffer container, removing the buffer container from the basket sieve and the sample collection container, pouring the solid tissue, the D-cells and the buffer solution into the basket sieve while the basket sieve is located within the sample collection container, removing the basket sieve with the solid tissue from the sample collection container, placing the basket sieve with the solid tissue into a sealed container for tissue processing, and sealing a mixture including the D-cells, the buffer solution and the reagent for diagnostic testing.
Other objects, features, aspects and advantages of the apparatuses and methods disclosed herein will become apparent to those skilled in the art from the following detailed description, which, taken in conjunction with the annexed drawings, discloses exemplary embodiments of the disclosed apparatuses and methods.
Referring now to the attached drawings which form a part of this original disclosure.
Selected embodiments will now be explained with reference to the drawings. It will be apparent to those skilled in the art from this disclosure that the following descriptions of the embodiments are provided for illustration only and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.
The buffer container 12 includes a buffer chamber 20 for storing or receiving buffer solution 21. The bottom edge 23 of the buffer chamber 20 is sealed and watertight so that the inner space 22 of buffer chamber 20 retains the buffer solution 21. In an embodiment, the buffer chamber 20 is pre-filled with the buffer solution 21 within the inner space 22. In an embodiment, the buffer solution 21 is a sterile phosphate-buffered saline (PBS) buffer solution. In an embodiment, the buffer chamber 20 includes between 1 and 2 mL of buffer solution. In an embodiment, the buffer chamber 20 is pre-filled with approximately 1-2 ml of buffer solution. While PBS is the most likely choice of buffer, any similar buffer solution, such as Buffer Roswell Park Memorial Institute (“RPMI 1640 Media”) Buffer Solution, would serve the same purpose.
In the illustrated embodiment, the buffer container 12 has a funnel shape to assist a user in depositing a biopsy sample from a core needle into the buffer solution 21 within the buffer chamber 20. More specifically, the buffer container 12 includes a funnel portion 24. The funnel portion 24 flares outwardly from bottom to top, while the buffer chamber 20 has a generally cylindrical shape for insertion into the basket sieve 14 and/or the sample collection container 16 as shown in
In the illustrated embodiment, the buffer container 12 includes a top opening 26 and a lid 28. The lid 28 attaches to the top of the funnel portion 24 to cover the top opening 26 and enclose the inner space 22 so that the buffer solution 21 does not spill if the biopsy container apparatus 10 is inverted. The lid 28 can be attached by being screwed onto the top of the funnel portion 24, or by another suitable attachment mechanism. In an embodiment, the lid 28 is configured to attach to both the buffer container 12 and the sample collection container 16, so that a user can remove the lid 28 form the buffer container 12 when beginning use of the biopsy collection apparatus 10 and then later place the lid 28 on the sample collection container 16 to seal its contents, as discussed in more detail below.
In the illustrated embodiment, the buffer container 12 also includes a first attachment mechanism 30 to enable attachment to a second attachment mechanism 32 of the sample collection container 16. More specifically, the outer surface of the buffer chamber 20 includes the first attachment mechanism 30. In the illustrated embodiment, the second attachment mechanism 32 is located on the inner surface of the sample collection container 16. The first attachment mechanism 30 and the second attachment mechanism 32 enable removable attachment of the buffer container 12 to the sample collection container 16, with the buffer container 12 located at least partially within the sample collection container 16. As shown in
The sample collection container 16 includes a reagent chamber 38 for storing or receiving a reagent 39. In
In the illustrated embodiment, both the upper portion 40 and the lower portion 42 of the sample collection container are generally cylindrical, with the lower portion 42 having a smaller inner diameter than the upper portion 40, as shown in
The basket sieve 14 includes a sieve surface 54 configured to pass the D-cells from a biopsy but not solid tissue from the biopsy. The pore size of the sieve is approximately 40-100 microns in diameter per pore (the pore aperture size) to allow D-cells 62 to fall through. In the illustrated embodiment, the sieve surface 54 is the lower surface of the basket sieve 14. As seen in
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In the illustrated embodiment, the biopsy container apparatus 10c includes a buffer container 12c, a basket sieve 14c and a sample collection container 16c. As with the biopsy container apparatus 10, the buffer container 12c and basket sieve 14c are configured for removable attachment to the sample collection container 16c.
In the illustrated embodiment, the buffer container 12c is generally similar to the buffer container 12 discussed herein. The buffer container 12c includes a buffer chamber 20c, a funnel portion 24c, a top opening 26c and a lid 28c. As seen in
In the illustrated embodiment, the buffer container 12c also includes a skirt 74c with threads 76c on its inner surface. The threads 76c on the inner surface on the skirt 74c are configured to mate with the threads 72c of the sample collection 16b. So the threads 76c on the inner surface on the skirt 74c attach to the threads 72c of the sample collection 16c when the lid 28c is threaded onto the threads 70c at the top of the funnel portion 24c, and the lid 28c is then threaded onto the threads 72c of the sample collection container 16c once the threads 76c on the inner surface on the skirt 74c are unthreaded from the threads 72c of the sample collection 16c.
In the illustrated embodiment, the buffer container 12c also includes a handle 78c protruding from skirt 74c. The handle 78c enables the user to (i) hold the biopsy container apparatus 10c with one hand while the other hand unscrews the lid 28c, (ii) hold the biopsy container apparatus 10c steady with one hand while the other hand operates a core needle 60 containing a tissue sample, maneuvering it into the funnel portion 24c and depositing its contents therein, (3) unscrew the buffer container 12bc from the sample collection container 16c, and (4) lift and pour the contents of the buffer container 12c (e.g., the solid tissue 62, the D-cells 64 and the buffer solution 21) into the basket sieve 14c and sample collection container 16c.
In the illustrated embodiment, the basket sieve 14c is generally similar to the basket sieve 14 discussed herein. The basket sieve includes a sieve surface 54c and a lip 56c. The sieve surface 54c is configured to pass the D-cells 64 from a biopsy but not solid tissue 62 from the biopsy. The lip 56c is configured to rest on a corresponding ledge or ridge line of the sample collection container 16c. As illustrated, the lip 56c can be wider on one side of the basket sieve 14c than another. As seen in
In the illustrated embodiment, the biopsy container apparatus 200 includes an upper chamber 202 and a lower chamber 204 which are separated by a sieve surface 206 and a solid surface 208. The sieve surface 206 is located between the upper chamber 202 and the lower chamber 204 and is configured to pass the dislodged cells 64 from a biopsy but not the solid tissue 62 from the biopsy. The solid surface 208 is movably attached with respect to the sieve surface 206 and configured to translate between (i) a first configuration in which the solid surface 208 overlaps the sieve surface 206 to prevent the D-cells 64 from passing through the sieve surface 206 and (ii) a second configuration in which the solid surface 208 is moved away from the sieve surface 206 to permit the D-cells 64 to pass though the sieve surface 206 from the upper chamber 202 to the lower chamber 204.
In the illustrated embodiment, the biopsy container apparatus 200 includes a handle 210 attached to the solid surface 208. The handle 210 enables a user to translate the solid surface 208 in a perpendicular direction with respect to the height of the biopsy container apparatus 200 as shown in
In use, a radiologist user who takes a needle biopsy unscrews the lid 228 from the upper chamber 202, places the core needle 60 including solid tissue 62 and D-cells 64 into upper chamber 202, and swirls the core needle 60 to dislodge the solid tissue 62 and D-cells 64. The user then pulls the handle 210 to pull the solid surface 208 from between the upper chamber 202 and the lower chamber 204 and away from the sieve surface 206, releasing the D-cells 64 into buffer solution into the lower chamber 204, where they mix with a reagent (e.g. Zymo DNA/RNA Shield™ reagent) in the lower chamber 204. The user then pushes handle 210 back to its original position, sealing the D-cells 64 in solution in the lower chamber 204, then tilts the biopsy container apparatus 200 upside down to release the solid tissue 62 from the upper chamber 202 into a standard formalin-containing vial for transport to paraffin preparation lab. The user the screws the lid 228 back on, and sends the biopsy container apparatus 200 containing the D-cells 64 in solution for molecular testing. As seen in
The embodiments described herein provide improved apparatuses and methods for segregating tissue samples for multiple diagnostic modalities. An advantage of the disclosed apparatuses and methods is that D-cells can be collected at the site of the procedure, in an easy to perform process that almost completely eliminates pre-analytic variation and more importantly, before exposure to formalin fixation. This front-end approach, where the collection and stabilization occurs before fixation, is in contrast to other proposed biopsy substrate shortage solutions that seek to improve the substrate after it has already been fixed in formalin and damaged (back-end approaches). Prototype testing has shown that the specimen collected as D-cells by using this method result in more than sufficient amounts of nucleic acids, that are also of high quality, for molecular studies.
It should be understood that various changes and modifications to the apparatuses and methods described herein will be apparent to those skilled in the art and can be made without diminishing the intended advantages.
In understanding the scope of the present invention, the term “comprising” and its derivatives, as used herein, are intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, and/or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and/or steps. The foregoing also applies to words having similar meanings such as the terms, “including”. “having” and their derivatives. Also, the terms “part,” “section,” or “element” when used in the singular can have the dual meaning of a single part or a plurality of parts.
The term “configured” as used herein to describe a component, section or part of a device includes hardware that is constructed to carry out the desired function.
While only selected embodiments have been chosen to illustrate the present invention, it will be apparent to those skilled in the art from this disclosure that various changes and modifications can be made herein without departing from the scope of the invention as defined in the appended claims. For example, the size, shape, location or orientation of the various components can be changed as needed and/or desired. Components that are shown directly connected or contacting each other can have intermediate structures disposed between them. The functions of one element can be performed by two, and vice versa. The structures and functions of one embodiment can be adopted in another embodiment. It is not necessary for all advantages to be present in a particular embodiment at the same time. Every feature which is unique from the prior art, alone or in combination with other features, also should be considered a separate description of further inventions by the applicant, including the structural and/or functional concepts embodied by such features. Thus, the foregoing descriptions of the embodiments according to the present invention are provided for illustration only, and not for the purpose of limiting the invention as defined by the appended claims and their equivalents.
