Device and method for separating tissue sample for multiple diagnostic modes, and packages therefor

Abstract

Disclosed herein are devices and methods for recovering solid tissue and exfoliated cells ("D-cells") from biopsy. In an embodiment, a biopsy container device includes a sample collection container, a basket screen, and a buffer container. The sample collection container includes a reagent chamber. The basket screen is configured for at least partially removable attachment within the sample collection container, and the basket screen includes a screen surface configured to permit passage of exfoliated cells from the biopsy but not permit passage of solid tissue from the biopsy. The buffer container is configured for removable attachment to a sample collection container, and the buffer container includes a buffer chamber.

Description

[0001] priority This application claims priority to U.S. Application No. 18 / 468,416, filed September 15, 2023, entitled “Method and System for Recovering Evaluable Analytes from Core Needle Biopsy”; U.S. Application No. 18 / 514,870, filed November 20, 2023, entitled “Apparatus and Method for Separating Tissue Samples for Multiple Diagnostic Modalities”; U.S. Application No. 18 / 403,550, filed January 3, 2024, entitled “Apparatus and Method for Separating Tissue Samples for Multiple Diagnostic Modalities”; and U.S. Application No. 18 / 770,387, filed July 11, 2024, entitled “Medical Device Packaging Container”, the entire contents of which are incorporated herein by reference and form the basis of this application. Technical Field

[0002] This disclosure generally relates to apparatus and methods for separating tissue samples for various diagnostic modalities. More specifically, this disclosure relates to biopsy container apparatus for recovering solid tissue and exfoliated cells from biopsies, and corresponding methods of use and packaging thereof. This disclosure generally relates to packaging for such containers. Background Technology

[0003] Biopsies have been used in medical diagnosis for many years as a method to extract and analyze cell or tissue samples to better understand the nature and extent of a disease. Biopsies can aid in the diagnosis of a variety of conditions such as cancer, in which tiny fragments of suspicious growths or lesions are removed for microscopic examination. Through this examination, pathologists can attempt to detect the presence of abnormalities, malignant cells, infections, or other pathological conditions.

[0004] The procedure for performing a biopsy can vary depending on the location and nature of the tissue or cells being sampled. Some biopsies, such as those on the skin, are simple and can be performed using only a needle or scalpel, potentially with local anesthesia. However, those on deeper tissues, such as within organs or bones, may require more invasive techniques, including imaging guidance such as ultrasound, CT, or MRI.

[0005] Biopsies play a role in medical decision-making. While imaging and clinical evaluation can provide insights into a patient's condition, diagnosis may rely on the cellular and molecular details available only from a biopsy. It can help determine the presence of disease and provide information about its stage, potential invasiveness, and other characteristics crucial for tailoring effective treatment strategies.

[0006] The diagnostic process for solid tumors typically involves a tissue biopsy. Traditionally, a biopsy involves surgically removing a large amount of tissue from a patient's tumor or suspected affected tissue. Once removed from the patient, the tissue is processed and subsequently used for a variety of different types of diagnostic tests.

[0007] In recent years, biopsy tools and techniques have evolved to be less invasive, resulting in significantly smaller tissue samples. Surgical excision biopsies have been largely replaced by core needle biopsy (CNB) tools. Smaller biopsies are less invasive for patients, faster for clinicians, and generally cheaper for the healthcare system. Consequently, the standard biopsy tissue size has decreased significantly between the period before approximately 2010 and the years since. The disadvantage of smaller biopsies is that they provide less tissue for pathologists to examine and analyze in order to make a diagnostic opinion.

[0008] Meanwhile, diagnostic testing paradigms have expanded to include a greater number of tests designed to identify molecular variations. The reduction in biopsy tissue size and the increased number of tests required for biopsy tissue have created an imbalance between tissue supply and demand. As a result, in some cases, clinicians use less diagnostic information than they would like to make treatment decisions for patients. In other cases, patients undergo a second biopsy. The risk that biopsy samples will contain insufficient tissue to allow for the execution of clinically indicated tests is a problem large enough to have several unofficial names, with "tissue depletion" being the most common. Tissue depletion rates for core needle biopsies reported in the literature range from 22% to 82% of all biopsies.

[0009] Therefore, there is an imbalance between the typical amount of tissue produced by a core needle biopsy and the typical amount of tissue required for testing. The inadequacy of both the quality and quantity of sample material available for molecular testing impacts the quality of healthcare. This ultimately affects patient care, as many specimens received in pathology laboratories are unavailable for molecular testing, causing these patients to miss out on improved treatment options related to precision medicine (defined as using molecular testing to identify mutations to guide treatment).

[0010] Unfortunately, current standard tissue biopsy procedures result in some of the acquired cells being discarded along with medical waste. These cells, obtained from patients, are inevitably detached from the tissue due to the trauma associated with cutting the tissue with the sharp edge of the core needle and then retracting it into the metal core needle biopsy tube (hereinafter referred to as D-cells). These cells are invisible to the naked eye. They contain valuable genetic information, but clinicians or technicians who hold the core needle handle and place the tissue in a standard formalin-containing cup after acquisition, then discard the entire needle and any D-cells on it into the medical waste container, will not notice them at all. Current standard care includes fixing the tissue with formalin, a process called formalin-fixed paraffin embedding (FFPE), and is known to produce suboptimal results when any tissue treated with it is used as sample material in molecular testing. Invention Summary

[0011] This disclosure provides a biopsy container device that allows a clinician performing a core needle biopsy to place the acquired tissue in a manner that the biopsy container device recovers solid tissue (“D-cells”) from the needle, obtained during the biopsy process, or cells detached from the patient’s body tissue surrounding the path traveled by the needle. D-cells are an unused resource for diagnostic testing, primarily because the cells are below the visual acuity of the human eye. This valuable biological resource is typically discarded, but the device and method of this disclosure enable the recovery of this biological resource for diagnostic testing.

[0012] As discussed in more detail below, the biopsy container device disclosed herein allows clinicians performing core needle biopsies to place tissue in a manner in which the biopsy container device contains and preserves microscopic concomitant portions (D-cells) of the biopsy tissue, which would otherwise be inadvertently discarded. More specifically, the biopsy container device disclosed herein, by means of a dedicated removable sieve suspended within a multifunctional waterproof container, allows cells detached from tissue obtained during the biopsy process or from patient body tissue surrounding the path traversed by the needle to be preserved and separated from tissue to be sent to a standard pathology laboratory for processing. These recovered cells (D-cells) constitute an unused resource for diagnostic testing. This resource is typically discarded, but the device and method of this disclosure ensure that said resource is recovered for diagnostic testing.

[0013] A first aspect of this disclosure is to provide a biopsy container device for recovering solid tissue and D-cells from a biopsy. The biopsy container device 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 to be at least partially removably attached within the sample collection container, and the basket sieve includes a sieve surface configured to allow D-cells from the biopsy to pass through but not solid tissue from the biopsy. The buffer container is configured to be removably attached to the sample collection container and includes a buffer chamber.

[0014] A second aspect of this disclosure is to provide another biopsy container device for recovering solid tissue and D-cells from a biopsy. The biopsy container device includes a sample collection container, a basket sieve, and a buffer container. The sample collection container includes reagents. The basket sieve is configured to be at least partially removably attached within the sample collection container, and the basket sieve includes a sieve surface configured to allow D-cells from the biopsy to pass through but not solid tissue from the biopsy. The buffer container is configured to be removably attached to the sample collection container, and the buffer container includes a buffer solution.

[0015] A third aspect of this disclosure is to provide another biopsy container device for recovering solid tissue and D-cells from a biopsy. The biopsy container device 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 allow D-cells from the biopsy to pass through but not solid tissue from the biopsy. The solid surface is movably attached relative to the sieve surface, and is configured to translate between (i) a first configuration and (ii) a second configuration: in the first configuration, the solid surface overlaps with the sieve surface to prevent D-cells from passing through the sieve surface; in the second configuration, the solid surface is removed from the sieve surface to allow D-cells to pass from the upper chamber through the sieve surface to the lower chamber.

[0016] A fourth aspect of this disclosure is to provide a method for recovering solid tissue and D-cells from a biopsy using a buffer container device, the buffer container device comprising a buffer container, a basket sieve, and a sample collection container. The method includes: releasing solid tissue and D-cells from a 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 containing the solid tissue from the sample collection container; placing the basket sieve containing the solid tissue into a sealed container for tissue processing; and sealing a mixture comprising the D-cells, the buffer solution, and the reagents for diagnostic testing.

[0017] A fifth aspect of this 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 to be at least partially removably attached within the sample collection container, and the basket sieve includes a sieve surface configured to allow D-cells from the biopsy to pass through but not solid tissue from the biopsy. The buffer container is configured to be removably attached to the sample collection container, and the buffer container includes a buffer chamber.

[0018] A sixth aspect of this disclosure is to provide another biopsy container device for recovering solid tissue and D-cells from a biopsy. The biopsy container device includes a sample collection container, a basket sieve, and a buffer container. The sample collection container includes reagents. The basket sieve is configured to be at least partially removably attached within the sample collection container, and the basket sieve includes a sieve surface configured to allow D-cells from the biopsy to pass through but not solid tissue from the biopsy. The buffer container is configured to be removably attached to the sample collection container, and the buffer container includes a buffer solution.

[0019] A seventh aspect of this disclosure is to provide a method for recovering solid tissue and D-cells from a biopsy using a buffer container device, the buffer container device comprising a buffer container, a basket sieve, and a sample collection container. The method includes: releasing solid tissue and 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 containing the solid tissue from the sample collection container; placing the basket sieve containing the solid tissue into a sealed container for tissue processing; and sealing a mixture comprising the D-cells, the buffer solution, and the reagents for use in a diagnostic test.

[0020] This disclosure also describes a novel packaging for medical devices. More specifically, this disclosure provides a novel packaging for a novel medical device that allows a clinician performing a core needle biopsy to place the acquired tissue in such a manner that the novel medical device recovers solid tissue (“D-cells”) detached from the needle during the biopsy or from the patient’s body tissue surrounding the path traveled by the needle. The packaging can also be used for other medical devices, such as those requiring upright components, liquids, or tissue samples that are prone to spillage during transport and / or medical procedures.

[0021] As discussed in more detail below, the medical device and its packaging container disclosed herein allow clinicians performing core needle biopsies to place tissue in a manner in which the medical device and its packaging container contain and preserve microscopic concomitant portions (D-cells) of the biopsy tissue, which would otherwise be inadvertently discarded. The medical device disclosed herein enables the preservation of tissue obtained during the biopsy process or cells detached from patient body tissue surrounding the path taken by the needle, separate from tissue to be sent for standard pathology laboratory processing. The packaging container disclosed herein secures the medical device or other medical device during transport and also facilitates medical procedures involving the medical device.

[0022] An eighth aspect of this disclosure is to provide a packaging container for one or more medical devices. The packaging container includes an inner component and an outer component. The inner component includes a support surface having at least one cutout configured to hold the one or more medical devices during transport and to hold the one or more medical devices upright during use. The outer component surrounds the inner component and includes a tear line allowing a user to remove a portion of the outer component and expose the support surface of the inner component, enabling the user to use the one or more medical devices while they are held upright by the inner component.

[0023] A ninth aspect of this disclosure is to provide another packaging container for one or more medical devices. The packaging container includes an inner component and an outer component. The inner component is formed from a first sheet of cardboard folded along a plurality of fold lines to form at least a support surface configured to hold the one or more medical devices during transport and to hold the one or more medical devices upright during use. The outer component is formed from a second sheet of cardboard folded along a plurality of fold lines to form a housing for the inner component. The outer component includes an upper portion and a lower portion. The upper portion is configured to be separated from the lower portion to expose the inner component.

[0024] A tenth aspect of this disclosure is to provide a medical packaging. The medical packaging includes one or more medical devices and a packaging container. The packaging container contains the one or more medical devices therein. The packaging container has at least one slit configured to hold the one or more medical devices during transport and to hold the one or more medical devices upright during use.

[0025] The eleventh aspect of this disclosure is to provide a method for using a packaging container for one or more medical devices before, during, and / or after a medical procedure such as a core needle biopsy.

[0026] Other objects, features, aspects, and advantages of the apparatus and methods disclosed herein will become apparent to those skilled in the art from the following detailed description, which, in conjunction with the accompanying drawings, discloses exemplary embodiments of the disclosed apparatus and methods. Attached Figure Description

[0027] Now refer to the accompanying drawings that form part of the original disclosure: Figures 1A-1C illustrate the routine procedure for performing a core needle biopsy (CNB) on a patient to analyze tissue obtained from a suspicious area according to the standard core needle biopsy method; Figure 2 illustrates a process for recovering an evaluable analyte from a tissue sample obtained via a core needle biopsy without exposing the evaluable analyte to formalin, according to one or more embodiments of this document. Figure 3 illustrates a core needle biopsy device according to one or more embodiments of this document; Figures 4A-4C illustrate the collection of tissue samples, including tissue cores and exfoliated cells, according to one or more embodiments of this document; Figure 5 illustrates a system for recovering evaluable analytes from tissue samples obtained via core needle biopsy without exposing the evaluable analytes to formalin, according to one or more embodiments of this document. Figure 6 is a flowchart illustrating an example method for recovering an evaluable analyte from a tissue sample obtained via a core needle biopsy according to one or more embodiments of this document; Figures 7A-7C are respectively magnified views of tissue cores, tissue specimens processed according to one or more embodiments of this document, and example cell abundance images of group tissue specimens processed with formalin using conventional methods; Figures 8A-8C are respectively magnified views of tissue cores, tissue specimens processed according to one or more embodiments of this document, and example cell abundance images of tissue specimens processed with formalin using conventional methods; Figures 9A-9C are respectively magnified views of a tissue core, a tissue specimen processed according to one or more embodiments of this document, and an example cell abundance image of a tissue specimen processed with formalin using conventional methods; Figures 10A and 10B are example cell abundance images, respectively, magnified views of tissue cores and tissue specimens processed according to one or more embodiments of this document; Figures 11A and 11B are exemplary cell abundance images, respectively, magnified views of tissue cores and tissue specimens processed according to one or more embodiments of this document; Figures 12A-12F are Figures 7A-7C and 10A-10F according to one or more embodiments of this document. Figure 10B Comparison of examples of immunohistochemical antibody-stained tissue specimens at different processing stages; Figure 13 shows an electrophoresis diagram of DNA degradation pre-sequencing assessment extracted from a representative sample of washed / recovered exfoliated cells according to one or more embodiments of this document, showing a bell-shaped curve with minimal signs of degradation. Figure 14 illustrates post-sequencing qualitative data from all washed specimens in assessing Phred scores according to one or more embodiments of this document; Figure 15 shows post-sequencing qualitative data from all washed specimens in assessing the N content per base, according to one or more embodiments of this document; Figure 16 shows a perspective view of a first exemplary embodiment of the biopsy container device according to the present disclosure; Figure 17 shows an exploded view of the biopsy container device of Figure 16; Figure 18 shows a cross-sectional view of the biopsy container device of Figure 16; Figure 19 shows a cross-sectional view of a second exemplary embodiment of the biopsy container device according to the present disclosure; Figure 20 shows an exploded view of a third exemplary embodiment of the biopsy container device according to the present disclosure; Figure 21 illustrates an example embodiment of a method for using a biopsy container device according to the present disclosure; Figures 22 to 27 show example embodiments of the steps of the method of Figure 21; Figure 28 shows a perspective view of a fourth exemplary embodiment of the biopsy container device according to the present disclosure; Figure 29 shows an exploded view of the biopsy container device of Figure 16; Figures 30 and 31 illustrate a fifth example embodiment of the biopsy container device according to the present disclosure; Figure 32 shows a perspective view of an example embodiment of a biopsy container device according to the present disclosure; Figure 33 shows a side view of the biopsy container device of Figure 32; Figure 34 shows a cross-sectional view of the biopsy container device of Figure 1 taken along section line III-III in Figure 33; Figure 35 shows an exploded view of the biopsy container device of Figure 32; Figure 36 shows an exploded cross-sectional view of the biopsy container device of Figure 32, taken along line VV in Figure 35; Figure 37 shows an informational view of the biopsy container device of Figure 32; Figure 38 illustrates an example embodiment of a method using the biopsy container device of Figure 32; Figures 39 to 48 show example embodiments of the steps of the method in Figure 38; Figure 49 shows a graphical summary of the method in Figure 38; Figure 50 shows a side view of a second exemplary embodiment of the biopsy container device according to the present disclosure; Figure 51 shows a cross-sectional view of the biopsy container device of Figure 50 taken along section line XX-XX in Figure 50; Figure 52 shows a perspective view of an example embodiment of a packaging container according to the present disclosure; Figure 53 shows the outer components of the packaging container of Figure 52 before the outer components are fully constructed and combined with the inner components shown in Figure 54; Figure 54 shows the internal components of the packaging container of Figure 52 before the internal components are constructed and combined with the external components shown in Figure 53; Figure 55 shows a top perspective view of the internal components of the packaging container of Figure 52, in which the internal components are constructed. Figure 56 shows a bottom perspective view of the internal components of the packaging container of Figure 52, in which the internal components are constructed. Figure 57 shows a top perspective view of the packaging container as described in Figure 52 below, after a portion of it has been removed. Figure 58 shows another top perspective view of the packaging container as described in Figure 52, after a portion of it has been removed; Figure 59 shows another top perspective view of the packaging container of Figure 52, which includes multiple individually packaged medical devices according to the present disclosure; Figure 60 shows a side plan view of an example embodiment of a medical device used with the packaging container of Figure 52; Figure 61 shows a cross-sectional view of the medical device taken along line XX in Figure 60; Figure 62 shows an exploded view of the cross-section of the medical device shown in Figure 61; Figure 63 illustrates an example embodiment of a method for using the medical devices of Figures 60 to 62 with the packaging containers of Figures 52 to 59 according to the present disclosure; Figure 64 shows the packaging containers of Figures 60 to 69 used in accordance with this disclosure. Figure 62 A top-view 3D view of the medical device; Figure 65 shows the packaging containers of Figures 52 to 59 used in accordance with this disclosure. Figure 62 A top-view 3D view of the medical device; Figure 66 shows the packaging containers of Figures 60 to 69 used in conjunction with the packaging containers of Figures 52 to 59 according to this disclosure. Figure 62 A top-view 3D view of the medical device; Figure 67 shows the packaging containers of Figures 60 to 69 used in conjunction with the packaging containers of Figures 52 to 59 according to this disclosure. Figure 62A top-view 3D view of the medical device; Figure 68 shows a top perspective view of a packaging container according to another exemplary embodiment of the present disclosure; Figure 69 shows another top perspective view of the packaging container of Figure 68; Figure 70 shows a top perspective view of the internal components of the packaging container of Figure 68, in which the internal components are constructed. Figure 71 shows a bottom perspective view of the internal components of the packaging container of Figure 68, in which the internal components are constructed; and Figure 72 shows a top perspective view of the structural components of the packaging container of Figure 52 and the packaging container of Figure 68. Detailed Implementation

[0028] Selected embodiments will now be described with reference to the accompanying drawings. It will be apparent to those skilled in the art from this disclosure that the following description of the embodiments is for illustrative purposes only and is not intended to limit the invention as defined by the appended claims and their equivalents.

[0029] A biopsy is a diagnostic procedure in which a sample of tissue is removed from the body and examined under a microscope to determine the presence, cause, or extent of a disease. Routine biopsy techniques are used to diagnose a variety of conditions, including cancer.

[0030] Routine excisional biopsies and incisional biopsies can involve the surgical removal of tissue. In an excisional biopsy, the entire mass or suspicious area is removed, usually with a margin of surrounding normal tissue. An incisional biopsy, on the other hand, removes only a portion of the suspicious area. These techniques are useful for larger masses or lesions that cannot be easily accessed with a needle. The removed tissue is then examined under a microscope by a pathologist to determine its nature.

[0031] Another common technique includes endoscopic biopsy. Endoscopic biopsy is performed using an endoscope, a flexible tube with a light source and camera attached to its end. Miniature instruments can be inserted through the endoscope to obtain tissue samples from the region of interest.

[0032] Another less invasive and routine technique is needle biopsy, which uses a sharp, hollow needle to extract a core of tissue from a suspicious area. Depending on the size and location of the lesion, different types of needle biopsies can be used, such as fine-needle aspiration (FNA) and core needle biopsy (CNB). FNA uses a thin needle to aspirate cells or fluid, while CNB uses a slightly larger needle to remove the core. These methods can be guided by imaging techniques such as ultrasound, CT scans, or MRI to ensure proper needle placement and accurate sampling of the target tissue.

[0033] FNA is a diagnostic procedure that involves using a thin, hollow needle to extract cells or fluid from a mass or lump inside the body for microscopic examination. This minimally invasive technique is routinely used to study and diagnose a variety of conditions, particularly in the case of tumors or cysts.

[0034] During a femoral neck examination (FNA), the clinician inserts a thin needle, typically attached to a syringe, into the suspected area. Needle placement can be guided by palpation, especially if the mass is just beneath the skin. For deeper or less palpable masses, imaging modalities such as ultrasound, computed tomography (CT) scans, or magnetic resonance imaging (MRI) can be used to ensure accurate needle placement.

[0035] Once the needle is in the desired position, a syringe can be used to create a slight vacuum, helping to draw cells or fluid into the needle. The collected sample is then spread onto a microscope slide and sent to a pathology laboratory. There, it can be stained by a pathologist and examined under a microscope to determine the nature of the cells, whether they are benign, malignant, inflammatory, or related to other conditions.

[0036] A drawback of FNA is that the small sample size can sometimes limit a pathologist's ability to make a definitive diagnosis. The procedure may not always yield a sufficient number of cells, leading to indeterminate or uncertain results. This limitation often necessitates repeating the procedure or using alternative tests, making it less efficient in some cases. Furthermore, while FNA can identify malignancies, it may not be sufficient to determine the specific type or subtype of cancer, a crucial aspect of personalized treatment. Therefore, if the results from FNA are indeterminate or contradict other clinical evidence, a wider range of biopsy methods may be needed for further evaluation.

[0037] Furthermore, the accuracy of FNA is highly dependent on the operator's skill. Inexperienced operators may increase the risk of uncertain or inaccurate results. There is also a small but present risk of complications such as bleeding, infection, or unintentional damage to nearby structures, especially when aspirating from deep organs. Another concern with FNA is the theoretical risk that the procedure may unintentionally spread cancer cells due to the need to aspirate target cells. Additionally, FNA provides only a cellular sample, unlike a biopsy which provides a larger tissue sample. This difference means that FNA cannot assess the structural composition of the tissue, which is necessary for some diagnoses. Moreover, FNA is purely diagnostic and lacks the therapeutic benefits such as drainage or lesion removal. Therefore, while FNA is a valuable tool, its limitations need to be carefully considered by healthcare professionals.

[0038] A standard alternative to FNA is to perform a core needle biopsy (CNB). CNB is a medical procedure used to extract a small tissue sample from a suspicious area within the body, typically from a mass or lump that a healthcare provider suspects may be cancerous.

[0039] Figures 1A-1C illustrate a routine method for performing CNB on patient 110 to analyze tissue obtained from suspicious region 120 according to conventional CNB methods.

[0040] To perform CNB, at 100a, a clinician may use a hollow needle 130 to obtain a slender (e.g., cylindrical or other shaped) tissue sample—a tissue core—from the suspicious area 120. The procedure may involve the use of imaging guidance, such as ultrasound, mammography, or MRI, to help precisely locate the needle. After anesthetizing the area with a local anesthetic, the clinician may insert the hollow needle 130 through the skin into the suspicious area 120. At 100b, the hollow needle 130 may be withdrawn from the patient 110, with the tissue sample contained within it. Then, at 100c, the tissue sample may be withdrawn from the needle 130 and placed in a cassette 140 for processing. Once the tissue sample has been obtained and fixed in the cassette 140, it may subsequently be sent to a pathology laboratory for microscopic examination.

[0041] Once the sample arrives at the pathology laboratory, the pathologist can examine it to determine the nature of the cells and the type of disease present, if any. Results are typically expected within a few days to a week, depending on the complexity of the case and the specific protocols of the medical facility.

[0042] One of the main advantages of core needle biopsies (CNBs) is their less invasive nature compared to surgical biopsies, which typically require larger incisions and longer recovery times. This biopsy method offers faster recovery, less scarring, and is generally safer than surgical alternatives. However, core needle biopsies also have limitations, including the possibility that the needle may not capture the tissue most representative of the entire abnormality. Therefore, the results may be indeterminate or not entirely accurate, potentially leading to the need for further testing or surgical biopsy.

[0043] While conventional CNB techniques may be valuable for diagnosing many conditions, they may not provide sufficient tissue for certain molecular or genetic tests that can be used for modern targeted therapies. One reason for this limitation is the conventional way in which tissue derived from CNB is preserved.

[0044] Tissue samples obtained using CNB are routinely preserved in formalin (e.g., formaldehyde-containing) solutions. Formalin serves as a fixative for preserving CNB-derived tissue samples, acting by creating cross-links between proteins. These cross-links stabilize cellular structures and preserve the morphology and cellular details of the tissue. When performing CNB, tissue samples are routinely and immediately immersed in formalin to prevent autolysis and degradation of cellular components. The preserved tissue can then be processed, embedded in paraffin, and sectioned for microscopic examination, such as staining with hematoxylin and eosin. The use of formalin has been routinely proven to ensure the preservation of the histopathological characteristics of the tissue core, allowing pathologists to make accurate diagnostic interpretations.

[0045] However, the routine use of formalin in tissue sample preservation is also one of the reasons for the drawbacks of conventional CNB techniques, as it can easily destroy certain analytes, such as nucleic acids. Therefore, any remaining analytes derived from tissue samples may not be usable to provide reliable diagnostic or molecular testing data due to their exposure to formalin.

[0046] In addition to the tissue core obtained during a biopsy, extra diagnostic material can be released from the tissue in the form of exfoliated cells. Because these exfoliated cells are not visible to the naked eye, they are usually discarded, or remain attached to the needle itself, or to the gauze pad used by the physician to place the visible tissue mass.

[0047] The embodiment described herein preserves both the tissue core and exfoliated cells, which are separated from the needle by vortexing in a buffer solution. The solution can then be filtered to separate the tissue core from the exfoliated cells. The visible tissue core can then be separated (e.g., extracted) and placed in a container such as a cassette for routine processing. Reagents can be added to the exfoliated cells to lyse the cells and stabilize their nucleic acids.

[0048] The embodiments relate to methods and systems for the efficient and effective recovery of evaluable analytes from tissue samples obtained via CNB, the evaluable analytes potentially including, but not limited to, DNA, RNA, exosomes, or proteins. The process may include providing a hollow needle embedded with a tissue sample, immersing the needle in a buffer solution (such as a sterile phosphate-buffered saline solution), and vortexing to detach the tissue and cells, thereby forming an intermediate mixture. The mixture may be filtered into a sample tube using a specialized filter to separate the tissue core and generate a second intermediate mixture containing detached cells in the buffer solution.

[0049] A certain volume of cell lysis and nucleic acid stabilizing reagent (e.g., equal in volume to the second intermediate mixture) can be mixed with the second intermediate mixture, resulting in cell lysis and the formation of a third mixture. The analyte can then be extracted from this mixture. Unlike conventional CNB techniques and sample preparation, this implementation operates without exposing the analyte to formalin. The method can be aided by a system including a core needle and containers for buffer solutions, sample tubes, filters, and containers for removing tissue cores, all or some of which are available as kits. The method may also optionally involve tube centrifugation (i.e., rotation) to separate the mixture, thereby facilitating the removal of the supernatant from the sample tubes and the storage of the sample tubes at a temperature of approximately 4 degrees Celsius, thereby reducing the need for deep freezing of the analyte.

[0050] The implementation method thus enables the recovery of detached cells for analysis of analytes contained therein (e.g., DNA, RNA, exosomes, proteins) without exposure to formalin.

[0051] The implementation method can provide a simpler CNB and sample preparation process, reduce skill requirements and the impact of their variation, and reduce the time required to bring samples to the laboratory for diagnostic or molecular research (such as nucleic acid sequencing).

[0052] Creating two specimens from one means that the likelihood of exhausting the parent tissue is reduced, allowing pathologists to comply with regulatory and accreditation requirements and providing an improved patient experience.

[0053] The shortened pre-analysis process also reduces the risk of encountering false negatives or false positives from the specimen. The inventors maintained a pre-analysis process of 15 minutes in their proof-of-concept study. While regulations for pre-analysis are inconsistent or unavailable for most types of specimens—molecular degradation and other issues can begin as early as one hour when using conventional methods—this is significant.

[0054] Figure 2 illustrates a process 200 according to one or more embodiments herein for recovering an evaluable analyte from a tissue sample obtained via CNB without exposing the evaluable analyte to formalin. The evaluable analyte may be, for example, DNA, RNA, exosomes, or proteins.

[0055] At 200a, a core needle 230 may be provided, having a tissue sample obtained via CNB disposed therein. The tissue sample may include a tissue core 242 and exfoliated cells 272.

[0056] At position 200b, the portion of the core needle 230 containing the tissue sample may be immersed in a buffer solution in container 250 and vortexed until the tissue core 242 and exfoliated cells 272 detach from the core needle, forming a first intermediate mixture in container 250, the first intermediate mixture comprising the buffer solution, the tissue core 242, and the exfoliated cells. The buffer solution may comprise an aqueous phosphate-buffered saline solution. The buffer solution may be sterilized prior to immersion of the core needle 230 therein.

[0057] The first intermediate mixture in container 250 can be filtered through a filter into sample tube 270 (e.g., a container) to separate tissue core 242 from the first intermediate mixture, resulting in tissue core 242—which can be placed at 200°C in a container such as cassette 240—and a second intermediate mixture comprising a buffer solution and exfoliated cells 272. The filter may be at least partially disposed in sample tube 270.

[0058] A cell lysis and stabilizing agent may be added to a second intermediate mixture in sample tube 270 to obtain a third mixture comprising lysed exfoliated cells 272, from which analytes can be evaluated for recovery. The volume of the cell lysis and stabilizing agent may be equal to the volume of the second intermediate mixture. In some embodiments, the cell lysis and stabilizing agent may comprise 2 mL to 5 mL of the agent. The cell lysis and stabilizing agent may be a concentrated dual-action cell lysis and nucleic acid stabilizing agent.

[0059] The evaluable analytes can then be separated from the third mixture contained in sample tube 270, and analyses (e.g., DNA / RNA / protein / gene analysis) can be performed using the evaluable analytes.

[0060] The sample tube 270, in which the third mixture is disposed, can be stored in a freezing device, for example at an internal temperature of 4 degrees Celsius. Therefore, the embodiments described herein eliminate the need for storage in a deep-freezing device.

[0061] Figure 3 illustrates a core needle biopsy device 300 according to one or more embodiments herein. The core needle biopsy device 300 may include a core needle, a handle, a sheath, and other components necessary to cover the core needle with the sheath, and may be configured for performing a core needle biopsy on a patient and / or specifying a particular core needle biopsy to be performed.

[0062] Figures 4A-4C illustrate the acquisition of a tissue sample 414 according to one or more embodiments herein, the tissue sample 414 comprising a tissue core and exfoliated cells. Specifically, Figures 4A-4C, in addition to the tissue core, illustrate the capture of exfoliated cells in a target tissue region 412 using a core needle 430 and the retraction of the core needle 430 into a core needle sheath 432, similar to the capture of the tissue sample at 200a. The basis for the acquisition of exfoliated cells in the CNB can occur when the core needle sheath 432 is released and covers the biopsy needle. The tissue sample 414, including the tissue core and exfoliated cells (e.g., exfoliated tumor cells), remains in the space between the core needle 430 and the core needle sheath 432.

[0063] Since individual cells and small cell clusters are not visible to the naked eye, they are typically not considered when processing transferred specimens. However, according to the embodiments described herein, placing a core needle 430 and a core needle sheath 432 in a buffer solution produces a liquid biopsy specimen from which tissue can be separated and sent for routine processing, and exfoliated cells are preserved and retained for subsequent use. The filtration, subsequent lysis, and stabilization of the embodiments described herein provide long-term, economical storage of exfoliated cells.

[0064] Figure 5 illustrates system 500, which is used to recover an evaluable analyte from a tissue sample obtained via core needle biopsy without exposing the evaluable analyte to formalin, according to one or more embodiments herein. All or part of system 500 may be provided as a kit. The evaluable analyte may be, for example, DNA, RNA, exosomes, or proteins.

[0065] System 500 may include a core needle (e.g., the core needle of core needle biopsy device 300), which may be configured to collect tissue samples obtained via core needle biopsy, wherein the tissue samples include tissue cores and exfoliated cells.

[0066] System 500 may include a buffer container 502 configured to contain a buffer solution and receive a core needle in which a tissue sample is disposed, such that a portion of the core needle containing the tissue sample may be immersed in the buffer solution and swirled until the tissue core and exfoliated cells detach from the core needle to form a first intermediate mixture within the buffer container, the first intermediate mixture comprising the buffer solution, the tissue core, and the exfoliated cells.

[0067] System 500 may include sample tube 504. The sample tube may be further configured to add a cell lysis and stabilizing reagent, in a volume equal to that of the second intermediate mixture, to the second intermediate mixture to obtain a third mixture comprising lysed exfoliated cells, from which an analyte can be evaluated for recovery.

[0068] System 500 may include a filter 506 (e.g., a filter of 40 pm to 100 pm) configured to be at least partially disposed within sample tube 504 such that a first intermediate mixture can be filtered into sample tube 504 using filter 506 to separate tissue core from the first intermediate mixture, resulting in a tissue core and a second intermediate mixture comprising a buffer solution and exfoliated cells.

[0069] System 500 may include container 508, which is configured for organizing the storage of the core.

[0070] System 500 may include container 510, which is used to provide cell lysis and stabilizing reagents.

[0071] Figure 6 is a flowchart illustrating an example method 600 according to one or more embodiments herein, for recovering an evaluable analyte from a tissue sample obtained via a core needle biopsy. In some embodiments, one or more process blocks of Figure 6 may be performed by components similar to one or more devices or components of Figures 3-5 or other components or devices. The evaluable analyte may be, for example, DNA, RNA, exosomes, or proteins.

[0072] Operation 602 may include providing a core needle having a tissue sample obtained via core needle biopsy disposed therein, and may be performed alone or in combination with one or more other operations shown in FIG. 6. The tissue sample may include a tissue core and exfoliated cells.

[0073] Operation 604 may include providing a buffer solution and may be performed alone or in combination with one or more other operations shown in FIG. 6. The buffer solution may be sterilized and does not contain formalin.

[0074] Operation 606 may include immersing a portion of the hollow needle containing a tissue sample in a buffer solution, and may be performed alone or in combination with one or more other operations shown in FIG. 6.

[0075] Operation 608 may include vortexing the core needle in a buffer solution until the tissue core and exfoliated cells detach from the core needle to form a first intermediate mixture comprising the buffer solution, the tissue core, and the exfoliated cells, and may be performed alone or in combination with one or more other operations shown in FIG. 6.

[0076] Operation 610 may include filtering a first intermediate mixture into a sample tube using a filter at least partially disposed in the sample tube to separate the tissue core from the first intermediate mixture, resulting in a tissue core and a second intermediate mixture comprising a buffer solution and exfoliated cells, and may be performed alone or in combination with one or more other operations shown in FIG. 6. The tissue core may be extracted and disposed within a container configured for conventional tissue processing of the tissue core.

[0077] Operation 612 may include adding a cell lysis and stabilizing reagent, in a volume equal to that of the second intermediate mixture, to the second intermediate mixture to obtain a third mixture comprising lysed exfoliated cells, from which evaluable analytes not exposed to formalin can be recovered, and may be performed alone or in combination with one or more other operations shown in Figure 6. The cell lysis and stabilizing reagent may be a concentrated dual-action cell lysis and nucleic acid stabilizing reagent.

[0078] Operation 614 may include separating an evaluable analyte that has not been exposed to formalin from a third mixture, and may be performed alone or in combination with one or more other operations shown in Figure 6.

[0079] Operation 616 may include evaluating an evaluable analyte that has not been exposed to formalin, and may be performed alone or in combination with one or more other operations shown in Figure 6.

[0080] Although Figure 6 illustrates example method 600 and its operations, in some embodiments, the methods shown herein may include additional operations, fewer operations, operations with different arrangements, or operations different from those shown in Figure 6. Furthermore, or alternatively, the two or more operations shown in Figure 6 may be performed at least partially in parallel.

[0081] experiment method During the procedure, the interventional radiologist was provided with a container of phosphate-buffered saline (PBS) for each of the five cases. For the first three cases, the radiologist performed one or two punctures to obtain tissue, and then transferred the tissue to an empty container by scraping it onto a saline-soaked gauze pad with a scalpel blade. This gauze pad was subsequently filled with formalin. For the final puncture, the tissue in the needle was immersed in the container with PBS and gently agitated to separate the tissue from the needle and any exfoliated cells that might have been loosened during the procedure.

[0082] By placing and agitating the needle tip into a container with fluid after the procedure, both the target tissue and invisible cells can be recovered and processed separately according to their different needs, as shown in Figure 2. In the first three cases of this experiment, the washing step was performed as the final puncture by the interventional radiologist to avoid re-entering the patient with a potentially contaminated needle. For the last two cases, the PBS solution and container were sterilized prior to the procedure. This allowed the interventional radiologist to release tissue and any exfoliated cells from all punctures into the PBS solution.

[0083] The initial methods in the first three cases inadvertently allowed testing of washed tissue specimens—which were processed slightly differently from the initial puncture and therefore may have undergone some pre-analytical changes—to determine whether they resulted in any downstream differences in assessment, such as in morphology and immunohistochemistry, compared to unwashed tissue processed in a routine manner.

[0084] Antibodies against proteins known to be expressed on the cell membrane, cytoplasm, and nucleus in tumor biopsies that were part of the first three cases were evaluated to determine whether the pretreatment washing step altered protein expression compared to the conventional unwashed method.

[0085] Once the final puncture is complete, formalin is added to the container holding the unwashed tissue. All tissue cores—washed and unwashed—are placed in separate boxes for subsequent embedding and sectioning.

[0086] Washed specimens—those released from PBS in the interventional radiology department—were filtered through a disposable 100 pm sieve. Tissue cores recovered from the sieve were then placed in a box, placed in formalin, and processed using a formalin-fixed paraffin-embedded (FFPE) procedure. The filtered solution was transferred to microcentrifuge tubes and centrifuged until all fluid was processed. At this point, 500 pl of lysis and preservation reagent was added to the microcentrifuge tubes and repeatedly pipetted to lyse the cells. This mixture, comprising only exfoliated cells from the parent tissue and excluding tissue debris, was then placed in a 20°C freezer and held there until all cases in this study cohort were collected. The following timestamps were recorded: time of tissue acquisition from the interventional radiologist, time of transport to the laboratory, and time of addition of preservation reagent to the precipitated exfoliated cells, and compiled into a pre-stabilization time (Table 1).

[0087] Table 1: Tumor type, cell abundance, and quantitative and qualitative nucleic acid indicators associated with each specimen.

[0088] Table 1 (continued) The maternal tissue core was examined using open-field microscopy to assess its cell abundance, while also considering the presence of normal tissue and / or necrotic areas in the specimen to determine its impact on nucleic acid recovery.

[0089] After all cases were collected, DNA extraction was performed. Quantitative analysis was conducted in duplicate, using both a fluorometer and a spectrophotometer. The latter was used to obtain the A260 / 280 absorbance ratio to assess DNA purity. The amount of recovered DNA was calculated by multiplying the concentration measured by the fluorometer by the elution volume. Qualitative parameters were obtained using a fragment analyzer and included specimen size and genomic quality number (GQN). The latter was calculated with a threshold of 500 base pairs, a length previously used to evaluate DNA derived from formalin-fixed paraffin-embedded (FFPE) tissue blocks: 10 points is optimal, while 1 point indicates high degradation. Subsequently, libraries were constructed from the DNA of each case, with 200 ng of each sample added, for a total volume not exceeding 30 μL.

[0090] Each sample was sequenced, and the quality metrics of the sequencing runs for each case were evaluated. Specifically, the Phred score (a metric for measuring the quality of nucleotide identification during automated DNA sequencing) and the percentage of unidentified nucleotides (i.e., "N per base") were assessed. Phred scores ranged from 4 to 60, with 20 points corresponding to a 99% probability of correct base identification, 30 points to 99.9% accuracy, and 40 points to 99.99% accuracy. For Phred scores, the scores at each nucleotide position for each sample were collected, and graphs were generated showing the score distribution of the lower quartile (Q1), middle quartile (Q2–Q3), and upper quartile (Q4). The average quality score generally showed a stable decreasing trend with increasing read length. The "N per base" analysis reflects the percentage of a specific base that is unclear and cannot be identified as an A, T, C, or G nucleotide. In this metric, the presence of a very low proportion of N bases in the sequence is not surprising, especially near the ends of the sequence.

[0091] However, when the proportion of N bases exceeds a few percentage points, concerns arise regarding sequencing quality. The variables mentioned above were used as an indirect assessment of the raw DNA quality, following the principle that poor raw template quality is the most common cause of any subsequent sequencing problems.

[0092] result The entire process, from obtaining tissue specimens from the interventional radiology department, transporting them to the pathology laboratory, separating exfoliated cells from the parent tissue core, and stabilizing the former in DNA / RNA preservation reagent, took less than twenty minutes in four out of five cases (Table 1).

[0093] For this anomalous case, the preliminary analysis time was still kept under sixty minutes, due to transportation-related issues. However, this delay did not result in a significant difference in the assessed qualitative indicators. The manual handling time required for specimen processing was less than five minutes and could be completed by a single person.

[0094] Four of the five biopsy sites were from the liver, and the fifth from bone. The diagnoses for each case are given in Table 1. Tissue cores washed in PBS as previously described were then placed in formalin and subjected to FFPE treatment along with the unwashed cores to generate tissue blocks. In cases 1–3, the length of the washed single tissue cores ranged from 0.5 to 1.3 cm; while in cases 4 and 5, the total lengths were 4.0 cm and 4.6 cm, respectively, since all tissues obtained by puncture were washed (Table 1). Morphological examination after hematoxylin-eosin staining revealed no significant differences in either histological structure or cytological characteristics between washed and unwashed tissue specimens (Fig. 7A11B). Cell abundance was also similar between washed and unwashed cores, with no significant decrease in cell abundance observed. No core cell depletion was observed in this study related to the preparation of invasive slides. This may be because gentle shaking of the core was sufficient to recover loose cells, but not enough to cause a significant decrease in core cell abundance. Cell abundance in all specimens was rated as moderate or high (Table 1). Immunohistochemical staining for proteins expressed in the cell membrane (e.g., CD-56), cytoplasm (e.g., PSA), and nucleus (e.g., NKX3.1) showed no significant differences in staining intensity (Figures 12A–12F). A degree of heterogeneity in staining within the tumor tissue was observed in both paired core groups.

[0095] Nuclear material from exfoliated cells from the tissue core and corresponding needle was recovered from each case. No cell precipitate was identified in any of the supernatant washes from any specimen. These two observations suggest that cellular material was present in the supernatant washes, but in too small a quantity to form a visible precipitate. This was also true for cases 4 and 5, where all tissue from the puncture was contained in a single wash container. The amount of DNA present in the supernatant was variable, with the lowest amount in non-tumor liver tissue (cases 2 and 5) and higher in tumor tissue (Table 1). This is consistent with previous observations that fewer exfoliated cells are present as a process byproduct in normal tissue. The limited timeframe and unknown underlying diagnosis in each case prevented investigators from selecting only biopsied tumor tissue for testing. The largest amount of DNA recovered came from tumors from which all puncture tissues were washed (case 4). DNA purity assessed by A260 / 280 was above 1.8 in only two of the five cases, suggesting the possible presence of some residual contaminants in three specimens. No further purification was performed before library generation because the GQN in each case was equal to or close to 10. The extracted DNA sizes ranged from 15,000 to slightly less than 24,000 base pairs (Figure 13). Typical features of fragmentation, such as tailing at the lower end of each electrophoresis pattern, were absent or minimal in all cases. Higher molecular weight DNA (>50 kbp) was not attempted to be recovered because the recovered DNA was suitable for the purpose (e.g., the sequencing platform used was suited to short reads). Sufficient DNA was recovered for sequencing using a sequencer with a 200 ng total DNA input requirement. The resulting sequencing metrics indicated high-confidence data, with Phred scores consistently equal to or greater than 35 and not decreasing at the read ends (Figure 14). Furthermore, the N per base content never reached 1% in any read in any sample (Figure 14). Figure 15 ).

[0096] Figures 7A-7C are respectively magnified views of tissue cores, tissue specimens processed according to one or more embodiments of this document, and example cell abundance images of tissue specimens processed using formalin with conventional methods.

[0097] Figures 8A-8C are respectively magnified views of tissue cores, tissue specimens processed according to one or more embodiments of this document, and example cell abundance images of tissue specimens processed with formalin using conventional methods.

[0098] Figures 9A-9C are respectively magnified views of tissue cores, tissue specimens processed according to one or more embodiments of this document, and example cell abundance images of tissue specimens processed using formalin with conventional methods.

[0099] Figures 10A and 10B are example cell abundance images, respectively, magnified views of tissue cores and tissue specimens processed according to one or more embodiments of this document.

[0100] Figures 11A and 11B are example cell abundance images, respectively, magnified views of tissue cores and tissue specimens processed according to one or more embodiments of this document.

[0101] Figures 12A-12F are Figures 7A-7C and 10A-10F according to one or more embodiments of this document. Figure 10B A comparison of examples of immunohistochemical antibody-stained tissue specimens at different processing stages.

[0102] Figures 12A and 12B show the immunohistochemical staining results of antibodies against membrane-bound (e.g., CD-56) proteins in the tissue core. Figures 12C and 12D show the immunohistochemical staining results of antibodies against nuclear (e.g., NKX3.1) proteins in the tissue core. Figures 12E and 12F show the immunohistochemical staining results of antibodies against cytoplasmic (e.g., PSA) proteins in the tissue core.

[0103] Figures 12A, 12C, and 12E show unfinished processing (e.g., washing). Figures 12B, 12D, and 12F show completed processing (e.g., washing).

[0104] Figure 13 shows an electrophoresis plot for pre-sequencing assessment of DNA degradation extracted from a representative sample of washed / recovered exfoliated cells according to one or more embodiments of this document, showing a bell-shaped curve with minimal signs of degradation.

[0105] Figure 14 illustrates post-sequencing qualitative data from all washed specimens in assessing Phred scores according to one or more embodiments of this document.

[0106] Figure 15 shows post-sequencing qualitative data from all washed specimens in assessing the N content per base, according to one or more embodiments of this document.

[0107] Figures 16 through 18 illustrate example embodiments of a biopsy container device 1010 for recovering solid tissue and D-cells from a biopsy according to the present disclosure. In the illustrated embodiment, the biopsy container device 1010 includes a buffer container 1012, a basket sieve 1014, and a sample collection container 1016, which are three separable elements that can be attached prior to a biopsy and then separated during the method of use disclosed herein. As shown, the buffer container 1012 and the basket sieve 1014 are configured for removable attachment to the sample collection container 1016. Figure 16 shows the buffer container 1012, the basket sieve 1014, and the sample collection container 1016 attached together, while Figure 17 shows the buffer container 1012, the basket sieve 1014, and the sample collection container 1016 separated from each other.

[0108] Buffer container 1012 includes a buffer chamber 1020 for storing or receiving buffer solution 1021. The bottom edge 1023 of the buffer chamber 1020 is sealed and waterproof, such that the internal space 1022 of the buffer chamber 1020 retains the buffer solution 1021. In an embodiment, the buffer chamber 1020 is pre-filled with buffer solution 1021 within the internal space 1022. In an embodiment, the buffer solution 1021 is a sterile phosphate-buffered saline (PBS) buffer solution. In an embodiment, the buffer chamber 1020 contains 1 to 2 mL of buffer solution. In an embodiment, the buffer chamber 1020 is pre-filled with approximately 1-2 mL of buffer solution. While PBS is the most likely choice for the buffer, any similar buffer solution, such as the Roswell Park Memorial Institute (“RPMI 1640 medium”) buffer solution, will serve the same purpose.

[0109] In the illustrated embodiment, the buffer container 1012 has a funnel shape to assist the user in releasing biopsy samples from the core needle into the buffer solution 1021 within the buffer chamber 1020. More specifically, the buffer container 1012 includes a funnel portion 1024. The funnel portion 1024 expands outward from bottom to top, while the buffer chamber 1020 has a generally cylindrical shape for insertion into the basket sieve 1014 and / or sample collection container 1016, as shown in FIG18. The funnel portion 1024 is configured to guide solid tissue and D-cells from the biopsy into the buffer chamber 1020 when ejected from the core needle, as discussed in more detail below.

[0110] In the illustrated embodiment, the buffer solution container 1012 includes a top opening 1026 and a cap 1028. The cap 1028 is attached to the top of the funnel portion 1024 to cover the top opening 1026 and seal the internal space 1022, such that the buffer solution 1021 will not overflow if the biopsy container device 1010 is inverted. The cap 1028 can be attached by screwing it onto the top of the funnel portion 1024 or by another suitable attachment mechanism. In this embodiment, the cap 1028 is configured to attach to both the buffer solution container 1012 and the sample collection container 1016, such that the user can remove the cap 1028 from the buffer solution container 1012 when beginning to use the biopsy collection device 1010, and then later place the cap 1028 on the sample collection container 1016 to seal its contents, as discussed in more detail below.

[0111] In the illustrated embodiment, the buffer container 1012 further includes a first attachment mechanism 1030 for attaching to a second attachment mechanism 1032 of the sample collection container 1016. More specifically, the outer surface of the buffer chamber 1020 includes the first attachment mechanism 1030. In the illustrated embodiment, the second attachment mechanism 1032 is located on the inner surface of the sample collection container 1016. The first attachment mechanism 1030 and the second attachment mechanism 1032 enable removable attachment of the buffer container 1012 to the sample collection container 1016, wherein the buffer container 1012 is at least partially located within the sample collection container 1016. Figure 18 As shown, the first attachment mechanism 1030 and the second attachment mechanism 1032 create a waterproof seal between the outer surface of the buffer container 1012 and the inner surface of the sample collection container 1016, ensuring that liquid will not leak from the sample collection container 1016 if the biopsy container device 1010 is inverted. In the embodiments shown in Figures 16 to 18, the first attachment mechanism 1030 and the second attachment mechanism 1032 are corresponding threads that allow the buffer container 1012 to be screwed into the sample collection container 1016. In an alternative example embodiment of the biopsy container device 1010b shown in Figure 20, the first attachment mechanism 1030b includes a rubber sleeve on the outer surface of the buffer chamber 1020b of the buffer container 1012b, and the second attachment mechanism 1032b includes a rubber sleeve on the inner surface of the sample collection container 1016b.

[0112] Sample collection container 1016 includes a reagent chamber 1038 for storing or receiving reagent 1039. In Figure 18, sample collection container 1016 includes an upper portion 1040 and a lower portion 1042, wherein the reagent chamber 1038 is located within and / or formed by the lower portion 1042. The bottom edge 1044 of sample collection container 1016 is sealed and waterproof, such that the reagent chamber 1038 retains the reagent 1039. In the illustrated embodiment, the reagent chamber 1038 is pre-filled with reagent 1039 within an internal space 1046. In this embodiment, reagent 1039 is a solution for lysing cells and preserving nucleic acids at approximately twice the normal concentration of readily available cell lysis reagents. In this embodiment, reagent 1039 is Zymo DNA / RNAShield™ reagent, or an equivalent for lysing cells and preserving nucleic acids, at twice the normal concentration defined and provided by Zymo. In one embodiment, reagent chamber 1038 includes 1 to 2 mL of reagent 1039. In another embodiment, reagent chamber 1038 is pre-filled with 1-2 mL of double-concentration cell lysis / nucleic acid stabilizing reagent 1039. In yet another embodiment, reagent chamber 1038 includes a first amount of reagent 1039, and buffer chamber 1020 includes a second amount of buffer solution 1021, the volume of which is approximately equal to the volume of the first amount of reagent.

[0113] In the illustrated embodiment, both the upper portion 1040 and the lower portion 1042 of the sample collection container are generally cylindrical, with the lower portion 1042 having a smaller inner diameter than the upper portion 1040, as shown in FIG18. As shown in FIG18, the sample collection container 1016 may include an internal boss 1050 between the upper portion 1040 and the lower portion 1042, the internal boss 1050 being configured to support the basket sieve 1014. In an alternative embodiment, the upper portion 1040 and the lower portion 1042 may have approximately the same diameter, and the sample collection container 1016 may include an internal ridge between the upper portion 1040 and the lower portion 1042, the internal ridge being configured to support the basket sieve 1014.

[0114] The basket sieve 1014 includes a sieve surface 1054 configured to allow D-cells from a biopsy to pass through but not solid tissue from a biopsy. The sieve has an aperture of approximately 40-100 micrometers in diameter (aperture size) per pore to allow D-cells 1062 to fall through. In the illustrated embodiment, the sieve surface 1054 is the lower surface of the basket sieve 1014. As shown in Figure 3, the basket sieve 1014 also includes a lip 1056 resting on a boss 1050 or ridge of the sample collection container 1016, such that the basket sieve 1014 is suspended above the reagent chamber 1038 and below the buffer container 1012 within the sample collection container 1016. As shown in an alternative example embodiment of the biopsy container device 1010a in Figure 19, the basket sieve 1014a may also include annular or hook-shaped vertical members 1058 to help the user lift the basket sieve 1014a upwards during use to remove the basket sieve 1014a (and the tissue it carries) from the sample collection container 1016.

[0115] As shown in Figure 18, when the buffer solution container 1012, basket sieve 1014, and sample collection container 1016 are attached, the basket sieve 1014 is suspended above the reagent chamber 1038 of the sample collection container 1016, and the buffer solution container 1012 is suspended above the basket sieve 1014 via attachment of a first attachment mechanism 1030 to a second attachment mechanism 1032. Those skilled in the art will recognize from this disclosure that other ways of attaching the elements exist, such that they are substantially as follows: Figure 18 The arrangement is shown.

[0116] As shown in Figure 18, when the basket sieve 1014 is attached to the sample collection container 1016, the basket sieve 1014 is at least partially located within the sample collection container 1016. In Figure 18, the basket sieve 1014 is completely located within the sample collection container 1016. Similarly, when the buffer container 1012 is attached to the sample collection container 1016, the buffer container 1012 may be at least partially or completely located within the sample collection container 1016. In Figure 18, the buffer container 1012 is partially located within the sample collection container 1016, with the reagent chamber 1020 located within the sample collection container 1016 and the funnel portion 1024 located outside the sample collection container 1016. More specifically, the buffer chamber 1020 of the buffer container 1012 is at least partially located within the sample collection container 1016, and the funnel portion 1024 of the buffer container 1012 is at least partially located outside the sample collection container 1016. Those skilled in the art will recognize from this disclosure that various arrangements of the buffer container 1012, the basket sieve 1014, and the sample collection container 1016 exist without departing from the spirit and scope of this disclosure. In other embodiments, the buffer container 1012 and / or the basket sieve 1014 may be removably attached to the outside of the sample collection container 1016.

[0117] Figure 21 illustrates an example embodiment of a method 1100 for recovering solid tissue and D-cells from a biopsy using a biopsy container device 1010 according to the present disclosure. Figures 22 through 27 illustrate the various steps of method 1100. Those skilled in the art will recognize from the present disclosure that certain steps may be added, removed, or modified without departing from the spirit and scope of the present disclosure.

[0118] In step 1102 (Figures 22 and 23), a user (e.g., an interventional radiologist or other clinical user) uses a core needle 1060 to obtain an image-guided biopsy from a patient with a suspected mass lesion in the body (e.g., liver, lung, kidney, etc.). The core needle 1060 removes both solid tissue 1062 and exfoliated cells 1064 (D-cells) from the patient. The funnel portion 1024 facilitates spatial alignment of the CNB needle tip with the target area and provides a convenient way for the user to place the needle tip (and therefore the tissue sample) into the buffer solution 1021. Manipulating the needle tip into small targets is not easy because the user's hand is approximately eight (8) inches from the needle tip (gripping the handle; not the tip), and the other hand is either holding the buffer container or a conventional tray or holder for placing the container (not shown) or otherwise unavailable and not typically used to guide the needle tip. The larger funnel shape 24 of this disclosure makes it easier to hit the target.

[0119] In step 1104 (Figure 24), the user removes the cap 1028 and places the tip of the hollow needle 1060 into the funnel portion 1024 of the buffer container 1012. The user releases the contents of the hollow needle 1060 (including solid tissue 1062 and D-cells 1064) into the buffer solution 1021 within the closed end of the funnel shape 1024. The user can release the acquired tissue sample by vortexing the tip of the CNB needle in a generally circular motion at the closed distal end of the funnel shape 1024, an action somewhat similar to that used when using a hand whisk, if the whisk is a hollow needle.

[0120] In step 1106 (Figures 25 and 26), the user removes the buffer container 1012 from the sample collection container 1016. The user removes the buffer container 1012 from the sample collection container 1016 by disengaging the first attachment mechanism 1030 and the second attachment mechanism 1032. The user then pours the contents of the buffer container 1012 (solid tissue 1062, D-cells 1064, and buffer solution 1021) into a basket sieve 1014 located within the sample collection container 1016. As shown in Figure 26, the solid tissue 1062 is captured by the sieve surface 1054 and retained within the basket sieve 1014, while the buffer solution 1021 and D-cells 1064 fall through the sieve surface 1054 and mix with the reagent 1039 in the reagent chamber 1038 of the sample collection container 1016. Since reagent 1039 is 2-fold concentrated, the additional volumes of buffer solution 1021 and exfoliated cells 1064 restore the reagent concentration to normal.

[0121] In step 1108 (Figure 27), the user removes the basket sieve 1014 containing solid tissue 1062 from the sample collection container 1016. The user places the basket sieve 1014 containing solid tissue 1062 into a specimen cup 1066 containing formalin. The specimen cup 1066 is sealed and sent to a histopathology laboratory. The tissue core can then undergo conventional tissue processing, such as creating glass slide images for pathologists to diagnose.

[0122] In step 1110 (Figure 27), the user seals the sample collection container 1016, which includes exfoliated cells 1064, buffer solution 1021, and reagent 1039, for use in diagnostic testing. For example, the user may send the sealed sample collection container 1016 and its contents to a molecular laboratory for molecular diagnostic testing. At this point, the buffer container 1012 and basket sieve 1014 have been removed, and the sealed sample collection container 1016 contains the mixed buffer solution 1021, reagent 1039, and D-cells 1064.

[0123] Figures 28 and 29 illustrate alternative embodiments of the biopsy container device 1010c according to the present disclosure. Those skilled in the art will recognize that various elements of the biopsy container device 1010c can be modified with various elements of other biopsy container embodiments discussed herein, and vice versa. In Figures 28 and 29, the same reference numerals are used to describe the same elements as those of the biopsy container device 1010.

[0124] In the illustrated embodiment, the biopsy container device 1010c includes a buffer container 1012c, a basket sieve 1014c, and a sample collection container 1016c. Similar to the biopsy container device 1010, the buffer container 1012c and the basket sieve 1014c are configured for removable attachment to the sample collection container 1016c.

[0125] In the illustrated embodiment, the buffer container 1012c is generally similar to the buffer container 1012 discussed herein. The buffer container 1012c includes a buffer chamber 1020c, a funnel portion 1024c, a top opening 1026c, and a lid 1028c. As shown in FIG29, the lid 1028c is configured to fit both the buffer container 1012c and the sample collection container 1016c, such that a user can remove the lid 1028c from the buffer container 1012c when beginning to use the biopsy container device 1010c, and then later place the lid 1028c on the sample collection container 1016c to seal the D-cells 1064 within the sample collection container 1016c. More specifically, as shown in FIG29, the buffer container 1012c includes a thread 1070c at the top of the funnel portion 1024c, and the sample collection container 1016c includes a thread 1072c near its top edge. Threads 1070c and 1072c are the same size, such that cap 1028c is configured to screw onto both thread 1072c of buffer container 1012c and thread 1072c of sample collection container 1016c.

[0126] In the illustrated embodiment, the buffer solution container 1012c further includes a skirt 1074c having threads 1076c on its inner surface. The threads 1076c on the inner surface of the skirt 1074c are configured to mate with the threads 1072c of the sample collection container 1016b. Thus, when the cap 1028c is screwed onto the threads 1070c at the top of the funnel portion 1024c, the threads 1076c on the inner surface of the skirt 1074c are attached to the threads 1072c of the sample collection container 1016c, and once the threads 1076c on the inner surface of the skirt 1074c are unscrewed from the threads 1072c of the sample collection container 1016c, the cap 1028c is then screwed onto the threads 1072c of the sample collection container 1016c.

[0127] In the illustrated embodiment, the buffer container 1012c also includes a handle 1078c protruding from the skirt 1074c. The handle 1078c allows the user to (i) hold the biopsy container device 1010c with one hand while unscrewing the cap 1028c with the other hand, (ii) hold the biopsy container device 1010c steady with one hand while operating the hollow needle 1060 containing the tissue sample with the other hand, manipulating it into the funnel portion 1024c and releasing the contents therein, (iii) unscrew the buffer container 1012c from the sample collection container 1016c, and (iv) lift and pour the contents of the buffer container 1012c (e.g., solid tissue 1062, D-cells 1064, and buffer solution 1021) into the basket sieve 1014c and the sample collection container 1016c.

[0128] In the illustrated embodiment, the basket sieve 1014c is generally similar to the basket sieve 1014 discussed herein. The basket sieve 1014c includes a sieve surface 1054c and a lip 1056c. The sieve surface 1054c is configured to allow the passage of D-cells 1064 from a biopsy but not solid tissue 1062 from a biopsy. The lip 1056c is configured to rest on a corresponding boss or ridge of a sample collection container 1016c. As shown, the lip 1056c may be wider on one side of the basket sieve 1014c than on the other. As shown in Figure 29, the basket sieve 1014c is sized and shaped to be sealed together with the solid tissue 1016 within a corresponding specimen cup 1066 and delivered to a histopathology laboratory.

[0129] Figures 30 and 31 illustrate alternative example embodiments of the biopsy container device 1200. Those skilled in the art will recognize that various elements of the biopsy container device 1200 can be modified with various elements from other embodiments of the biopsy containers discussed herein, and vice versa.

[0130] In the illustrated embodiment, the biopsy container device 1200 includes an upper chamber 1202 and a lower chamber 1204, separated by a sieve surface 1206 and a solid surface 1208. The sieve surface 1206 is located between the upper chamber 1202 and the lower chamber 1204 and is configured to allow exfoliated cells 1064 from the biopsy to pass through but not solid tissue 1062 from the biopsy. The solid surface 1208 is movably attached relative to the sieve surface 1206 and is configured to translate between (i) a first configuration and (ii) a second configuration, in which the solid surface 1208 overlaps with the sieve surface 1206 to prevent D-cells 1064 from passing through the sieve surface 1206, and in the second configuration, the solid surface 1208 is removed from the sieve surface 1206 to allow D-cells 1064 to pass from the upper chamber 1202 through the sieve surface 1206 to the lower chamber 1204.

[0131] In the illustrated embodiment, the biopsy container device 1200 includes a handle 1210 attached to a solid surface 1208. The handle 1210 allows a user to translate the solid surface 1208 in a vertical direction relative to the height of the biopsy container device 1200, as shown in Figures 30 and 31. More specifically, the handle 1210 allows the user to pull the solid base 1208 out from between the upper chamber 1202 and the lower chamber 1204 and away from the sieve surface 1206, and then push the solid base 1208 back between the upper chamber 1202 and the lower chamber 1204, so that it overlaps with the sieve surface 1206 in the vertical direction of Figures 30 and 31. When the solid surface 1208 is pulled to one side, the sieve surface 1206 allows exfoliated cells 1064 to enter the lower chamber 1204, but retains solid tissue 1062 in the upper chamber 1202. As shown in the figure, the biopsy container device 1200 also includes a cover 1228 attached to the upper chamber 1202.

[0132] In use, the radiologist performing the needle biopsy unscrews cap 1228 from upper chamber 1202, inserts a hollow needle 1060 containing solid tissue 1062 and D-cells 1064 into upper chamber 1202, and vortexes the hollow needle 1060 to detach the solid tissue 1062 and D-cells 1064. The user then pulls handle 1210 to pull solid surface 1208 away from the upper chamber 1202 and lower chamber 1204, away from sieve surface 1206, releasing D-cells 1064 into a buffer solution in lower chamber 1204, where they mix with reagents (e.g., Zymo DNA / RNA Shield™ reagent) in lower chamber 1204. The user then pushes handle 1210 back to its original position, sealing D-cells 1064 in the solution in the lower chamber 1204, and then inverts biopsy container device 1200 to release solid tissue 1062 from the upper chamber 1202 into a standard formalin-containing vial for transport to a paraffin preparation laboratory. The user then screws cap 1228 back on and sends biopsy container device 1200 containing D-cells 1064 in solution for molecular testing. As shown in Figure 30, biopsy container device 1200 may also include a vertical protrusion 1212 that allows the sieve surface 1206 holding solid tissue 1062 to be removed from biopsy container device 1200 and placed into a standard formalin-containing vial for transport to a paraffin preparation laboratory.

[0133] The embodiments described herein provide improved apparatus and methods for isolating tissue samples for use in a variety of diagnostic modalities. The advantages of the disclosed apparatus and methods are that D-cells can be collected on-site, the process is easily performed, pre-analytical variability is almost completely eliminated, and, importantly, prior to exposure to formalin for fixation. This front-end approach (collection and stabilization occurring before fixation) contrasts with other proposed solutions to biopsy sample material shortages, which seek to improve sample material after it has been fixed and damaged in formalin (back-end approaches). Prototype testing has shown that specimens collected using this method for D-cell collection yield more than sufficient amounts of high-quality nucleic acids for molecular studies.

[0134] Figures 32 through 37 illustrate a first example embodiment of a biopsy container device 2010 for recovering solid tissue and D-cells from a biopsy according to the present disclosure. In the illustrated embodiment, the biopsy container device 2010 includes a buffer container 2012, a basket sieve 2014, and a sample collection container 2016, which are three separable elements that can be attached prior to a biopsy and then separated during the method of use disclosed herein. As shown, the buffer container 2012 and the basket sieve 2014 are configured for removable attachment to the sample collection container 2016. Figures 32 through 34 show the buffer container 2012, the basket sieve 2014, and the sample collection container 2016 attached together, while Figures 35 and 36 show the buffer container 2012, the basket sieve 2014, and the sample collection container 2016 separated from each other.

[0135] Buffer container 2012 includes a buffer chamber 2020 for storing or receiving buffer solution 2021. The bottom edge 2023 of the buffer chamber 2020 is sealed and waterproof, such that the internal space 2022 of the buffer chamber 2020 retains the buffer solution 2021. In an embodiment, the buffer chamber 2020 is pre-filled with buffer solution 2021 within the internal space 2022. In an embodiment, the buffer solution 2021 is a sterile phosphate-buffered saline (PBS) buffer solution. In an embodiment, the buffer chamber 2020 contains 1 to 2 mL of buffer solution. In an embodiment, the buffer chamber 2020 is pre-filled with approximately 1-2 mL of buffer solution. While PBS is the most likely buffer choice, any similar buffer solution, such as the Roswell Park Memorial Institute (“RPMI 1640 medium”) buffer solution, will serve the same purpose.

[0136] In the illustrated embodiment, the buffer container 2012 includes a funnel to assist the user in placing a biopsy sample from a core needle into a buffer solution 2021 within the buffer chamber 2020. More specifically, the buffer container 2012 includes a funnel portion 2024 leading to the buffer chamber 2020. The funnel portion 2024 expands outward from bottom to top, while the buffer chamber 2020 has a generally cylindrical shape for insertion into a basket sieve 2014 and / or a sample collection container 2016, as shown in Figure 34. The funnel portion 2024 is configured to guide solid tissue and D-cells from the biopsy into the buffer chamber 2020 when ejected from the core needle, as discussed in more detail below.

[0137] In the illustrated embodiment, the buffer solution container 2012 includes a top opening 2026 and a cap 2028. The cap 2028 is attached to or near the top of the funnel portion 2024 to cover the top opening 2026 and seal the internal space 2022, so that the buffer solution 2021 will not overflow if the biopsy container device 2010 is inverted. The cap 2028 can be attached by screwing it onto or near the top of the funnel portion 2024 of the buffer solution container 2012 or by another suitable attachment mechanism. In the illustrated embodiment, the cap 2028 is configured to attach to both the buffer solution container 2012 and the sample collection container 2016, such that the user can remove the cap 2028 from the buffer solution container 2012 when starting to use the biopsy collection device 2010 and then later place the cap 2028 on the sample collection container 2016 to seal its contents, as shown in FIG48.

[0138] In the illustrated embodiments shown in Figures 35 and 36, the cap 2028 includes a first attachment mechanism 2029 to enable a second attachment mechanism 2030 for removable attachment to the buffer solution container 2012. As shown in Figure 48, the first attachment mechanism 2029 also enables a third attachment mechanism 2031 for removable attachment to the sample collection container 2016, such that the cap 2028 can be attached to the sample collection container 2016 after removal from the buffer solution container 2012. In the illustrated embodiment, the buffer solution container 2012 also includes a fourth attachment mechanism 2032 to enable removable attachment to the third attachment mechanism 2031 of the sample collection container 2016. In the illustrated embodiment, the inner surface of the cap 2028 includes a first attachment mechanism 2029, the outer surface of the buffer solution container 2012 includes a second attachment mechanism 2030, the outer surface of the sample collection container 2016 includes a third attachment mechanism 2031, and the inner surface of the buffer solution container 2012 includes a fourth attachment mechanism 2032. When attached as shown in Figures 32 to 34, the first attachment mechanism 2029 and the second attachment mechanism 2030 create a waterproof seal between the buffer solution container 2012 and the cap 2028, and the third attachment mechanism 2031 and the fourth attachment mechanism 2032 create a waterproof seal between the buffer solution container 2012 and the sample collection container 2016, such that if the biopsy container device 2010 is inverted, liquid will not spill from the buffer solution container 2012 or the sample collection container 2016. Figure 48When attached as shown, the first attachment mechanism 2029 and the third attachment mechanism 2031 create a waterproof seal between the cap 2028 and the sample collection container 2016, so that if the biopsy container device 2010 is inverted, liquid will not spill from the sample collection container 2016.

[0139] In the illustrated embodiment, attachment mechanisms 2029, 2030, 2031, and 2032 are threaded. The threads of the first attachment mechanism 2029 and the fourth attachment mechanism 2032 have approximately the same dimensions, and the threads of the second attachment mechanism 2030 and the third attachment mechanism 2031 have approximately the same dimensions. Those skilled in the art will recognize from this disclosure that other attachment mechanisms are possible.

[0140] In the illustrated embodiment, the buffer solution container 2012 includes a skirt 2034 having a fourth attachment mechanism 2032 on its inner surface. As shown in Figures 34 and 36, the skirt 2034 surrounds the buffer solution chamber 2020. The buffer solution container 2012 also includes a handle 2036 projecting from the skirt 2034. The handle 2036 enables the user to (i) hold the biopsy container device 2010 with one hand while unscrewing the cap 2028 with the other hand, (ii) stabilize the biopsy container device 2010 with one hand while manipulating the hollow needle 2060 containing the tissue sample into the funnel 2024 and releasing the contents therein, (iii) unscrew the buffer container 2012 from the sample collection container 2016, and (iv) lift and pour the contents of the buffer container 2012 (e.g., solid tissue 2062, D-cells 2064, and buffer solution 2021) into the basket sieve 2014 and the sample collection container 2016.

[0141] The sample collection container 2016 includes a reagent chamber 2038 for storing or receiving reagent 2039. In Figure 34, the sample collection container 2016 includes an upper portion 2040 and a lower portion 2042, with the reagent chamber 2038 located within and / or formed by the lower portion 2042. The bottom edge 2044 of the sample collection container 2016 is sealed and waterproof, allowing the reagent chamber 2038 to retain the reagent 2039. In an embodiment, the reagent chamber 2038 is pre-filled with reagent 2039 within its internal space 2046. In an embodiment, reagent 2039 is a solution for lysing cells and preserving nucleic acids at a concentration approximately twice the normal concentration of commercially available cell lysis reagents. In an embodiment, reagent 2039 is Zymo DNA / RNA Shield™ reagent, or an equivalent for lysing cells and preserving nucleic acids, at a concentration twice the normal concentration defined and provided by Zymo. In one embodiment, reagent chamber 2038 includes 1 to 2 mL of reagent 2039. In another embodiment, reagent chamber 2038 is pre-filled with 1-2 mL of double-concentration cell lysis / nucleic acid stabilizing reagent 2039. In yet another embodiment, reagent chamber 2038 includes a first amount of reagent 2039, and buffer chamber 2020 includes a second amount of buffer solution 2021, the volume of which is approximately equal to the volume of the first amount of reagent.

[0142] In the illustrated embodiment, the upper portion 2040 of the sample collection container 2016 is cylindrical, and the lower portion 2042 of the sample collection container 2016 tapers inward from top to bottom, with the lower portion 2042 near the bottom edge 2044 having a smaller inner diameter than the upper portion 2040. As shown in Figures 36 and 37, the upper portion 2040 of the sample collection container 2016 includes a flange 2050 configured to support the basket sieve 2014. In an alternative embodiment, the upper portion 2040 and the lower portion 2042 may have approximately the same diameter, and the sample collection container 2016 may include an internal ridge line within or between the upper portion 2040 and the lower portion 2042, which is configured to support the basket sieve 2014.

[0143] The basket sieve 2014 includes a sieve surface 2054 configured to allow D-cells from a biopsy to pass through but not solid tissue from a biopsy. The sieve has an aperture of approximately 40-100 micrometers in diameter per pore (pore opening size) to allow D-cells to fall through. In the illustrated embodiment, the sieve surface 2054 is the lower surface of the basket sieve 2014. As shown in Figures 35 and 36, the basket sieve 2014 also includes a lip 2056 sized to rest on the flange 2050 of the sample collection container 2016 such that when the biopsy container assembly 2010 is assembled as shown in Figure 34, the basket sieve 2014 is suspended within the sample collection container 2016, above the reagent chamber 2038 and below the buffer chamber 2020. In an alternative example embodiment, the basket sieve 2014 may include annular or hook-shaped vertical members to assist the user in lifting the basket sieve 2014 upwards during use to remove the basket sieve 2014 (and the tissue it carries) from the sample collection container 2016. Figure 48 As shown, the basket sieve 2014c is sized and shaped to be sealed in the corresponding specimen cup 2066 and sent to the histopathology laboratory.

[0144] As shown in Figure 34, when the buffer solution container 2012, the basket sieve 2014, and the sample collection container 2016 are attached to each other, the basket sieve 2014 is suspended above the reagent chamber 2038 of the sample collection container 2016, and the buffer solution chamber 2020 is suspended above the sieve surface 2054 via attachment of the third attachment mechanism 2031 to the fourth attachment mechanism 2032. Those skilled in the art will recognize from this disclosure that there are other ways of attaching and / or arranging elements besides this. Figure 32-37 An example embodiment is shown.

[0145] As also shown in Figure 34, when the basket sieve 2014 is attached to the sample collection container 2016, the basket sieve 2014 is at least partially located within the sample collection container 2016. In Figure 34, the basket sieve 2014 is almost entirely located within the sample collection container 2016, except for the lip 2056 protruding from the top of the sample collection container 2016. Similarly, when the buffer container 2012 is attached to the sample collection container 2016, the buffer container 2012 may be at least partially or entirely located within the sample collection container 2016. In Figure 34, the buffer container 2012 is partially located within the sample collection container 2016, with the reagent chamber 2020 partially located within the sample collection container 2016, but the funnel portion 2024 is located outside the sample collection container 2016. More specifically, the buffer chamber 2020 of the buffer container 2012 is at least partially located within the sample collection container 2016, and the funnel portion 2024 of the buffer container 2012 is at least partially located outside the sample collection container 2016. Those skilled in the art will recognize from this disclosure that there are various arrangements of the buffer container 2012, the basket sieve 2014, and the sample collection container 2016 beyond the example embodiments shown in Figures 32-37. In other embodiments, the buffer container 2012 and / or the basket sieve 2014 may be removably attached to the outside of the sample collection container 2016.

[0146] The dimensions of the biopsy container device 2010 according to this disclosure are variable. In Figures 32-34, the overall height of the biopsy container device 2010 is approximately 12.4 cm, the height of the sample collection container 2016 is approximately 7.6 cm, the outer diameter of the upper portion 2040 of the sample collection container 2016 is approximately 3.0 cm, the outer diameter of the basket sieve 2014 is approximately 2.7 cm, the flange 2056 has an outer diameter of approximately 2.9 cm, and the outer diameter of the lid 2028 is approximately 3.3 cm. Referring to Figures 34 and 36, the buffer chamber 2020 has an inner diameter of approximately 10 mm and a height of approximately 30 mm. Those skilled in the art will recognize from this disclosure that these dimensions are merely examples and may vary with different embodiments.

[0147] Figure 38 illustrates an example embodiment of a method 2100 for recovering solid tissue and D-cells from a biopsy using a biopsy container device 2010 according to the present disclosure. Figures 39 through 48 illustrate the various steps of method 2100, and Figure 49 shows an example graphical summary of method 2100. Those skilled in the art will recognize from the present disclosure that certain steps may be added, removed, or modified without departing from the spirit and scope of the present disclosure.

[0148] In step 2102 (Figures 39 and 40), the user (e.g., an interventional radiologist or other clinical user) uses a core needle 2060 to obtain an image-guided biopsy from a patient with a suspicious mass lesion in the body (e.g., liver, lung, kidney, etc.). The core needle 2060 removes both solid tissue 2062 and exfoliated cells 2064 (D-cells) from the patient.

[0149] In step 2104 (Figure 41), the user removes the cap 2028 from the buffer container 2012. The cap 2028 can be set aside and subsequently reused in step 2118 to seal the sample collection container 2016.

[0150] In step 2106 (Figure 42), the user releases the contents of the hollow needle 2060, including solid tissue 2062 and D-cells 2064, into the buffer solution 2021 within the buffer chamber 2020. The user releases the acquired tissue sample by vortexing the CNB needle tip within the closed distal end of the funnel shape 2024, similar to the action a person would make when using a hand whisk, if the whisk is a hollow needle. The funnel portion 2024 allows the user to easily coordinate the CNB needle tip and the target area spatially and provides a convenient way to place the needle tip (and therefore the tissue sample) near or inside the buffer solution 2021. That is, the larger funnel shape 2024 of this disclosure makes the buffer chamber 2020 easier to hit because the user’s hand is about eight (8) inches away from the needle tip (holding the handle; not the tip), and the other hand holds the buffer container 2012 or a conventional tray or stand (not shown) on which the buffer container 2012 is placed or otherwise unavailable and not typically used for the tip of the guide needle.

[0151] In step 2108 (Figure 43), the user removes the buffer solution container 2012 from the sample collection container 2016. The user removes the buffer solution container 2012 from the sample collection container 2016, for example by disengaging (e.g., unscrewing) the third attachment mechanism 2031 and the fourth attachment mechanism 2032.

[0152] In step 2110 (Figure 44), the user pours the contents of buffer container 2012 (solid tissue 2062, D-cells 2064, and buffer solution 2021) into basket sieve 2014 located within sample collection container 2016. Figure 44 As shown, solid tissue 2062 is captured by sieve surface 2054 and retained within basket sieve 2014, while buffer solution 2021 and D-cells 2064 fall through sieve surface 2054 and mix with reagent 2039 in reagent chamber 2038 of sample collection container 2016. Since reagent 2039 is 2-fold concentrated, the additional volume of buffer solution 2021 and exfoliated cells 2064 restores the reagent concentration to normal.

[0153] In step 2112 (Figure 45), the user may discard the buffer solution container 2012.

[0154] In step 2114 (Figure 46), the user removes the basket sieve 2014 containing solid tissue 2062 from the sample collection container 2016 containing buffer solution 2021, reagent 2039 and exfoliated cells 2064.

[0155] In step 2116 (Figure 47), the user places a basket sieve 2014 containing solid tissue 2062 into a specimen cup 2066 containing formalin. The specimen cup 2066 is sealed and sent to a histopathology laboratory. The tissue core can then undergo conventional tissue processing, for example, to create slide images for pathologists to diagnose.

[0156] In step 2118 (Figure 48), the user seals the sample collection container 2016, containing exfoliated cells 2064, buffer solution 2021, and reagent 2039, for diagnostic testing. The user can seal the sample collection container 2016 by attaching the cap 2028 previously removed from the buffer container 2012. The user can then deliver the sealed sample collection container 2016 and its contents to a molecular laboratory for molecular diagnostic testing. At this point, the buffer container 2012 and basket sieve 2014 have been removed, and the sealed sample collection container 2016 contains a mixture of buffer solution 2021, reagent 2039, and D-cells 2064.

[0157] Figures 50 and 51 illustrate an alternative second example embodiment of the biopsy container device 2010' for recovering solid tissue and D-cells from a biopsy according to the present disclosure. The biopsy container device 2010' includes all the elements of the biopsy container device 2010, except that the buffer container 2012 includes a concave outer surface 2070 surrounding the buffer chamber 2020 instead of a handle. The concave outer surface 2070 reduces the size of the biopsy container device 2010' and allows it to be gripped by a user when operating the biopsy container device 2010 according to method 2010.

[0158] The embodiments described herein provide improved apparatus and methods for isolating tissue samples for use in a variety of diagnostic modalities. The advantages of the disclosed apparatus and methods are that D-cells can be collected on-site, the process is easily performed, pre-analytical variability is almost completely eliminated, and, importantly, prior to exposure to formalin for fixation. This front-end approach, where collection and stabilization occur before fixation, contrasts with other proposed solutions to biopsy sample material shortages that seek to improve sample material after it has been fixed and damaged in formalin (back-end approaches). Prototype testing has shown that using this method as a specimen for D-cell collection yields more than sufficient amounts of high-quality nucleic acids for molecular studies.

[0159] Figures 52 to 59 illustrate example embodiments of the packaging container 3010 according to the present disclosure. The packaging container 3010 can be used to transport one or more medical devices 3100 and then to assist in methods of using one or more medical devices 3100, as described in more detail below. Thus, in embodiments, medical packaging includes the packaging container 3010 and one or more medical devices 3100.

[0160] In the illustrated embodiment, the packaging container 3010 includes an outer component 3012 and an inner component 3014. In use, the inner component 3014 is configured to hold one or more medical devices 3100 during transport and to hold one or more medical devices 3100 vertically during use, while the outer component 3012 is configured to form a housing for the inner component 3014, which can be detached to expose the inner component 3014 during use. In the illustrated embodiment, the inner component 3014 is formed by folding a first single sheet of cardboard along multiple fold lines to form at least one support surface configured to hold one or more medical devices 3100 during transport and to hold one or more medical devices 3100 vertically during use, and the outer component 3012 is formed by folding a second single sheet of cardboard along multiple fold lines to form the housing for the inner component 3014.

[0161] Figure 53 shows the outer component 3012 before it is fully constructed and combined with the inner component 3014. In the illustrated embodiment, the outer component 3012 is a single sheet of flat cardboard that is cut along the outer periphery shown in Figure 53 before being folded and / or self-adhesive to present the shapes shown in Figures 52 and 59. Those skilled in the art will recognize from this disclosure that the outer component 3012 can be formed from cardboard of different types or thicknesses, or from other materials such as thin plastic.

[0162] In the illustrated embodiment shown in Figure 53, the outer component 3012 includes an upper portion 3016 and a lower portion 3018. The outer component 3012 also includes a tear line 3020 that separates the upper portion 3016 and the lower portion 3018. The upper portion 3016 of the outer component 3012 includes a first side surface 3022, a second side surface 3024, a third side surface 3026, a fourth side surface 3028, a top surface 3030, and one or more free ends 3032, 3034, 3036, and 3038, all of which are connected as shown by a fold line 3040. The lower portion 3018 of the outer component 3012 includes a first side surface 3042, a second side surface 3044, a third side surface 3046, a fourth side surface 3048, and a bottom surface 3050 formed by one or more free ends 3051, 3052, 3053, 3054, all of which are connected by a fold line 3055 as shown. The upper portion 3016 is configured to separate from the lower portion 3018 using a tear line 3020, thereby exposing the inner component 3014 to allow the user to use one or more medical devices 3100 held vertically by the inner component 3014. When the upper portion 3016 is removed using the tear line 3020, the lower portion 3018 accommodates the inner component 3014.

[0163] When the outer component 3012 is folded along fold lines 3040 and 3055 and attached to itself using one or more free ends 3032, 3034, 3036, 3038, 3052, 3053, and 3054, the outer component 3012 forms a rectangular box shape as shown in Figures 52 and 59. In the illustrated embodiment, viewed from the perspective shown in Figure 53, all portions of the upper part 3016 are folded in the same direction along fold lines 3040 and 3055 (into the paper or along the -z direction shown). In the illustrated embodiment, free end 3032 is bonded to the fourth side surface 3028, free end 3052 is bonded to the fourth side surface 3048, and / or one or more of free ends 3051, 3052, 3053, and 3054 are bonded to each other. These portions may be bonded, for example, using liquid adhesives (e.g., glue), physical adhesives (e.g., tape), or other types of adhesive methods.

[0164] Figure 54 shows the inner component 3014 before it is fully constructed and combined with the outer component 3012. In the illustrated embodiment, the inner component 3014 is a single sheet of flat cardboard, which is cut along the outer periphery shown in Figure 54 before being folded and / or self-adhesive to present the shapes shown in Figures 55 and 56. Those skilled in the art will recognize from this disclosure that the inner component 3014 may be formed from cardboard of different types or thicknesses, or may be formed from other materials such as plastic. In embodiments, both the outer component 3012 and the inner component 3014 may each be part of the same sheet of cardboard.

[0165] In the illustrated embodiment, the internal component 3014 includes an upper portion 3056 and a lower portion 3058. The internal component 3014 also includes an intermediate portion 3060 located between the upper portion 3056 and the lower portion 3058. The upper portion 3056 is connected to the intermediate portion 3060 via a fold line 3062, and the lower portion 3058 is connected to the intermediate portion 3060 via a fold line 3064.

[0166] As shown in Figure 54, the internal component 3014 includes an upper support surface 3066 and a lower support surface 3068. In the illustrated embodiment, the upper portion 3056 includes the upper support surface 3066, and the lower portion 3058 includes the lower support surface 3068. More specifically, the upper portion 3056 includes the upper support surface 3066, which is connected to the intermediate portion 3060 via a fold line 3062, and the lower portion 3058 includes the lower support surface 3068, which is connected to the intermediate portion 3060 via a fold line 3064.

[0167] In the illustrated embodiment, the upper stent surface 3066 includes one or more upper incisions 3070. The upper incisions 3070 are configured to vertically hold one or more medical devices 3100 during use of the medical device 3100. More specifically, the upper incisions 3070 are configured to hold one or more medical devices 3100 during transport and vertically during use of the medical device 3100. Similarly, in the illustrated embodiment, the lower stent surface 3068 includes one or more lower incisions 3072. The lower incisions 3072 are also configured to vertically hold one or more medical devices 3100 during use of the medical device 3100. More specifically, the lower incisions 3072 are configured to hold one or more medical devices 3100 during transport and vertically during use of the medical device 3100. At least one of the upper cutout 3070 or the lower cutout 3072 may be formed as a hole in at least one of the upper support surface 3066 or the lower support surface 3068. In the embodiments shown in Figures 55 to 58, each lower cutout 3072 is aligned with the upper cutout 3070 in the vertical direction.

[0168] In the illustrated embodiment shown in FIG. 54, the upper cutout 3070 is a hole in the upper support surface 3066, and the lower cutout 3072 is a hole in the lower support surface 3068. As shown in FIG. 54, each of the upper cutouts 3070 includes a central portion 3074 and at least one side portion 3076. More specifically, each of the upper cutouts 3070 includes a central portion 3074 and two side portions 3076. The side portions 3076 are joined with the central portion 3074 to form a hole. The side portions 3076 extend outward from the central portion 3074 along a first direction (the y-direction in FIG. 54) and are smaller than the central portion 3074 in a second direction perpendicular to the first direction (the x-direction in FIG. 54). Similarly, each of the lower cutouts 3072 includes a central portion 3078 and at least one side portion 3080. More specifically, each of the lower cuts 3072 includes a central portion 3078 and two side portions 3080. The side portions 3080 engage with the central portion 3078 to form a hole. The side portions 3080 extend outward from the central portion 3078 along a first direction (the y-direction in FIG. 54) and are smaller than the central portion 3078 in a second direction perpendicular to the first direction (the x-direction in FIG. 54). In the illustrated embodiment, the central portions 3074 and 3078 are circular, and the side portions 3076 and 3080 are generally rectangular and extend from opposite sides of the central portions 3074 and 3078 to opposite fold lines 3062 and 3088 or opposite fold lines 3064 and 3094, respectively. In the illustrated embodiment, the upper cut 3070 and the lower cut 3072 have the same size, shape, and specifications. Those skilled in the art will recognize from this disclosure that the upper cutout 3070 and the lower cutout 3072 can be manufactured in different sizes, shapes, or specifications and / or placed in different locations.

[0169] In the illustrated embodiment, the upper portion 3056 includes an upper side surface 3082, which is attached to the upper support surface 3066 via a fold line 3084. The upper portion 3056 also includes an upper transverse surface 3086, which is attached to the upper support surface 3066 via a fold line 3088. Similarly, the lower portion 3058 includes a lower side surface 3090, which is attached to the lower support surface 3068 via a fold line 3092. The lower portion 3058 also includes a lower transverse surface 3094, which is attached to the lower support surface 3068 via a fold line 3096.

[0170] As shown in Figures 55 and 56, the inner component 3014 is constructed by folding the lower part 3058 below the upper part 3056 using fold lines 3062 and 3064, such that the upper support surface 3066 and the lower support surface 3068 are substantially parallel and substantially perpendicular to the surface of the middle part 3060. From the view in Figure 54, the upper side surface 3082 and the upper transverse surface 3086 are folded along their respective fold lines 3084 and 3088 in the opposite direction to the folding direction of the lower side surface 3090 and the lower transverse surface 3094 along their respective fold lines 3092 and 3096 (e.g., the -z direction and +z direction in Figure 54). The solid and dashed fold lines in Figure 54 indicate lines folded in opposite directions. That is, the dashed lines in Figure 54 mark fold lines 3092 and 3096, which fold in the opposite direction to the other fold lines 3062, 3064, 3084 and 3088 marked with solid lines.

[0171] When the inner component 3014 is constructed, each upper surface 3082 is positioned abutting against and / or parallel to the corresponding lower surface 3090, and the upper transverse surface 3086 is positioned abutting against and / or parallel to the lower transverse surface 3094. With this configuration, the upper support surface and the lower support surface 3068 are substantially horizontal and substantially parallel to each other, and the upper surface 3082, upper transverse surface 3086, lower surface 3090, and lower transverse surface 3094 are substantially vertical. In an embodiment, the portions of the inner component 3014 are held in place by the outer component 3016 without the need for separate adhesive bonding. In an alternative embodiment, one or both upper surfaces 3082 may be bonded to the corresponding lower surface 3090, and / or the upper transverse surface 3086 may be bonded to the lower transverse surface 3094. These portions may be bonded, for example, using liquid adhesives (e.g., glue), physical adhesives (e.g., tape), or another type of adhesive.

[0172] As shown in Figure 54, the upper support surface 3066 and the lower support surface 3068 have approximately the same dimensions in the x and y directions. The intermediate portion 3060 has the same dimensions in the x direction as the upper support surface 3066 and the lower support surface 3068, but extends a different distance D1 in the y direction. Distance D1 defines the vertical spacing between the upper support surface 3066 and the lower support surface 3068 when the inner component 3014 is constructed. The upper surface 3082 extends outward in the x direction from the fold line 3084 connected to the upper support surface 3066 by a distance D2, and the upper transverse surface 3086 extends outward in the y direction from the fold line 3088 connected to the upper support surface 3066 by a distance D3. The lower surface 3090 extends outward in the x-direction from the fold line 3092 connected to the lower support surface 3068 by a distance D4, and the lower transverse surface 3094 extends outward in the y-direction from the fold line 3096 connected to the lower support surface 3068 by a distance D5. In an embodiment, distance D2 is greater than distance D4, and distance D3 is greater than distance D5, such that when the lower support surface 3068 is folded under the upper support surface 3066, the corresponding outer edges 3083, 3091 of the upper surface 3082 and the lower surface 3090 are substantially aligned, and / or the corresponding outer edges 3087, 3093 of the upper transverse surface 3086 and the lower transverse surface 3094 are substantially aligned. In an embodiment, distance D2 is approximately equal to the sum of distances D1 and D4. In another embodiment, distance D3 is approximately equal to the sum of distances D1 and D5.

[0173] Referring again to Figure 52, the packaging container 3010 is shown as having an outer part 3012 and an inner part 3014 constructed therefrom, with the inner part 3014 located inside the outer part 3012. The side surface 3026 includes a punch 3021 (here, a semicircle) located adjacent to the tear line 3020, allowing a user to insert their fingers into the punch 3021 to grip and tear the upper part 3016 along the tear line 3020 from the lower part 3018.

[0174] Figures 57 and 58 show the remaining packaging container 3010 after the upper part 3016 has been torn off from the lower part 3018 along the tear line 3020. As shown, this exposes the inner component 3014, allowing it to be used as a support while employing one or more medical devices 3100 packaged within it. As shown in Figures 57 and 58, when the inner component 3014 is constructed, the height of the upper support surface 3066 is approximately the same as the height D6 of the lower part 3018 after the upper part 3016 has been removed (e.g., the height D6 of the first side surface 3042, the second side surface 3044, the third side surface 3046, and the fourth side surface 3048 shown in Figure 53).

[0175] Figure 59 shows a fully constructed packaging container 3010 in which multiple medical devices 3100 are positioned. Each medical device 3100 is positioned within a corresponding upper incision 3070 and a corresponding lower incision 3072. The packaging container 3010 shown in Figure 59 (top surface 3030 closed) represents the state in which the medical devices 3100 are transported, for example, to a hospital or clinical laboratory. In the illustrated embodiment, the medical devices 3100 are also individually sealed in separate device packages 3102. Figure 59 As shown, each medical device 3100, individually sealed in a separate device package 3102, is positioned within a corresponding incision 3070, 3072. The central portions 3074, 3078 can be considered as device portions, such that the medical devices 3100, each individually sealed in a separate device package 3102, are fitted into the corresponding incisions 3070, 3072, with the medical devices 3100 located within the device portions (e.g., the central portions 3074, 3078 of the incisions 3070, 3072), and the individual device packages 3102 located within the side portions 3076, 3080 of the incisions 3070, 3072.

[0176] Figures 60 to 62 illustrate example embodiments of the medical device 3100 according to the present disclosure. In the illustrated embodiments, the medical device 3100 separates a tissue sample from exfoliated cells (D-cells) obtained during a biopsy. The packaging container 3010 disclosed herein is particularly advantageous for enabling the medical device 3100 transported therein.

[0177] In the illustrated embodiment, medical device 3100 includes a buffer container 3112 and a sample collection container 3116. The buffer container 3112 is removable from the sample collection container 3116, while the sample collection container 3116 is held upright within at least one incision 3070, 3072. More specifically, medical device 3100 includes a buffer container 3112, a basket sieve 3114, and a sample collection container 3116, these three being separable elements that can be attached to a packaging container 3010 and / or a separate device package 3102, and then detached when used in conjunction with the packaging container 3010. Figures 60 and 61 show medical device 3100 with these components attached together, while Figure 62 shows medical device 3100 with these components separated from each other. In the illustrated embodiment, medical device 3100 is used to separate solid tissue and D-cells obtained in a biopsy using a core needle.

[0178] Buffer container 3112 includes a buffer chamber 3120 for storing or receiving a buffer solution. The bottom edge 3122 of the buffer chamber 3120 is sealed and waterproof, such that the internal space 3124 of the buffer chamber 3120 retains the buffer solution. In an embodiment, when transported within a packaging container 3010, the buffer chamber 3120 is pre-filled with buffer solution within the internal space 3124. In an embodiment, the buffer solution is a sterile phosphate-buffered saline (PBS) buffer solution. In an embodiment, the buffer chamber 3120 includes 1 to 2 mL of buffer solution. In an embodiment, the buffer chamber 3120 is pre-filled with approximately 1 to 2 mL of buffer solution. While PBS is the most likely choice, any similar buffer solution, such as the Roswell Park Memorial Institute (“RPMI 1640 medium”) buffer solution, would serve the same purpose.

[0179] In the illustrated embodiment, the buffer container 3112 includes a funnel to assist the user in releasing a biopsy sample from the core needle into a buffer solution within the buffer chamber 3120 when the medical device is held vertically by the packaging container 3010. More specifically, the buffer container 3112 includes a funnel portion 3128 leading to the buffer chamber 3120. The funnel portion 3128 expands outward from bottom to top, while the buffer chamber 3120 has a generally cylindrical shape. As described in more detail below, the funnel portion 3128 is configured to guide solid tissue and exfoliated cells from the biopsy into the buffer chamber 3120 when ejected from the core needle.

[0180] In the illustrated embodiment, the buffer solution container 3112 includes a top opening 3130 and a cap 3132. The cap 3132 is attached to or near the top of the funnel portion 3124 to cover the top opening 3130 and seal the internal space 3124, such that the buffer solution will not spill if the medical device 3100 is inverted during transport within the packaging container 3010. In the illustrated embodiment, the cap 3132 is configured to attach to both the buffer solution container 3112 and the sample collection container 3116, such that the user can remove the cap 3132 from the buffer solution container 3112 when starting to use the medical device 3100, and then subsequently place the cap 3132 on the sample collection container 3116 to seal its contents. In an embodiment, the cap 3132 is configured to be attached to the buffer container 3112 via a thread 3134 on the outside of the buffer container 3112, and to the sample collection container 3116 via a thread 3136 of the same or similar size on the outside of the sample collection container 3116.

[0181] Sample collection container 3116 includes a reagent chamber 3138 for storing or receiving reagents. The bottom edge 3140 of sample collection container 3116 is sealed and waterproof, allowing the reagent chamber 3138 to retain reagents. In an embodiment, the reagent chamber 3138 is pre-filled with reagents within its internal space 3142. In an embodiment, the reagent is a solution for lysing cells and preserving nucleic acids, at approximately twice the normal concentration of commercially available cell lysis reagents. In an embodiment, the reagent is Zymo DNA / RNA Shield™ reagent, or an equivalent reagent for lysing cells and preserving nucleic acids at twice the normal concentration defined and provided by Zymo. In an embodiment, the reagent chamber 3138 includes 1 to 2 mL of reagent. In an embodiment, the reagent chamber 3138 is pre-filled with 1 to 2 mL of double-concentration cell lysis / nucleic acid stabilizing reagent. In one embodiment, reagent chamber 3138 includes a first amount of reagent, and buffer chamber 3120 includes a second amount of buffer solution, the volume of which is approximately equal to the volume of the first amount of reagent. In the illustrated embodiment, the diameter D7 of the outer surface 3144 of sample collection container 3116 is approximately equal to or slightly smaller than the diameter of the central portions 3074, 3078 of the cuts 3070, 3072 in packaging container 3010, such that sample collection container 3116 can be placed into and held in place within cuts 3070, 3072 during transport and / or use of medical device 3100.

[0182] The basket sieve 3114 includes a sieve surface 3150 configured to allow exfoliated cells from a biopsy to pass through but not solid tissue from a biopsy. In an embodiment, the pore size of the sieve surface 3150 is approximately 40 to 100 micrometers in diameter per pore (pore opening size) to allow exfoliated cells to pass through. In the illustrated embodiment, the sieve surface 3150 is the lower surface of the basket sieve 3114. In an embodiment, the basket sieve 3114 also includes a lip 3152 sized to rest on the flange 3154 of the sample collection container 3116 such that when the medical device 3100 is assembled as shown in Figures 60 and 61, the basket sieve 3114 is suspended within the sample collection container 3116, above the reagent chamber 3138 and below the buffer chamber 3120.

[0183] Figure 63 illustrates an exemplary method 3200 for using a medical device 3100 in conjunction with a packaging container 3010 according to the present disclosure. In an embodiment, method 3200 is a method for recovering solid tissue and exfoliated cells from a biopsy using the medical device 3100 in conjunction with the packaging container 3010. Those skilled in the art will recognize from the present disclosure that certain steps of method 3200 may be added, removed, or modified without departing from the spirit and scope of the present disclosure. Those skilled in the art will also recognize from the present disclosure that certain steps of method 3200 may be used with other medical devices besides the medical device 3100 disclosed herein.

[0184] Initially, in the illustrated embodiment, prior to or during method 3200, a user (e.g., an interventional radiologist or other clinical user) uses a core needle CN to obtain image-guided biopsies from a patient with suspected space-occupying lesions (e.g., liver, lung, kidney, etc.). The core needle CN obtains solid tissue and exfoliated cells (D-cells) from the patient.

[0185] In step 3202, the user (e.g., an interventional radiologist or other clinical user) removes the upper portion 3016 of the packaging container 3010 from the lower portion 3018. In the illustrated embodiment, the user removes the upper portion 3016 from the lower portion 3018 by inserting a finger into the ejector portion 3021 and separating the upper portion 3016 from the lower portion 3018 along the tear line 3020. The user then leaves the lower portion 3018, which contains the internal component 3014, for example... Figure 57 As shown in Figures 58 and 64 to 67.

[0186] In step 3204, the user removes one of the medical devices 3100 from their individual device packaging 3102 and places the medical device 3100 within one or more incisions 3070, 3072 such that the medical device 3100 is held by the internal component 3014 with its longitudinal axis (the vertical axis in Figures 60 to 62) in a generally vertical position. More specifically, the user places the medical device 3100 within one or more of the devices or central portions 3074, 3078 of the incisions 3070, 3072 in the packaging container 3010. Figure 64 illustrates an example embodiment of step 3204.

[0187] In step 3206, the user removes the cap 3132 from the medical device 3100, leaving the rest of the medical device 3100 upright within the cuts 3070, 3072. More specifically, the user removes the cap 3132 from the buffer solution container 3112 to open the top opening 3130 of the buffer solution container 3112. The cap 3132 can be set aside and subsequently reused in step 3216 to seal the sample collection container 3116. Figure 65 illustrates an example embodiment of step 3206.

[0188] In step 3208, the user places the contents of the core needle CN (including solid tissue and exfoliated cells) into a buffer solution within the buffer chamber 3120. The user can release the acquired tissue sample by vortexing the CNB needle tip in a generally circular motion. The funnel portion 3128 facilitates spatial alignment of the core needle tip with the target area and provides a convenient way for the user to place the needle tip (and thus the tissue sample) near or inside the buffer solution. That is, the combination of the packaging 3010, which holds the medical device 3100 vertically, with the larger funnel portion 3128 makes the buffer chamber 3120 easier to align because the user's hand is approximately eight (8) inches (holding the handle; not the tip) from the needle tip, and the other hand is holding the buffer container 3112 and / or packaging container 3010 or otherwise unavailable and not typically used to guide the needle tip. Figure 66 illustrates an example embodiment of step 3208.

[0189] In step 3210, the user removes the buffer solution container 3112 from the sample collection container 3116. The user may remove the buffer solution container 3112 from the sample collection container 3116, for example, by detaching (e.g., unscrewing) the buffer solution container 3112 from the sample collection container 3116 or another part of the medical device 3100. Once the buffer solution container 3112 is detached, the sample collection container 3116 may remain within or be returned to the incisions 3070, 3072. The basket sieve 3114 remains within the sample collection container 3116.

[0190] In step 3212, the user pours the contents of buffer container 3112 (now including solid tissue and exfoliated cells released from the core needle CN and buffer solution from buffer chamber 3120) into basket sieve 3114 located within sample collection container 3116, which is held within the cuts 3070, 3072 of packaging container 3010. Solid tissue is captured by sieve surface 3150 and retained within basket sieve 3114, while buffer solution and exfoliated cells fall through sieve surface 3150 and mix with reagents in reagent chamber 3138 of sample collection container 3116. Since the reagents are 2-fold concentrated, the additional volume of buffer solution and exfoliated cells restores the reagent concentration to normal. The user can then discard buffer container 3112. Sample collection container 3116 may remain within cuts 3070, 3072. Figure 67 illustrates an example embodiment of step 3212.

[0191] In step 3214, the user removes the basket sieve 3114 containing solid tissue from the sample collection container 3116, which now contains buffer solution, reagents, and exfoliated cells. In an embodiment, the user places the basket sieve 3114 containing solid tissue into a specimen cup. The specimen cup may contain formalin. The specimen cup is sealed and sent to a histopathology laboratory. The tissue core can then undergo routine tissue processing, such as creating slide images for pathologist diagnosis. Once the basket sieve 3114 has been removed, the sample collection container 3116 may remain within or be returned to the incisions 3070, 3072.

[0192] In step 3216, the user can remove and seal the sample collection container 3116 from the cuts 3070 and 3072 for diagnostic testing. The sample collection container 3116 contains exfoliated cells, buffer solution, and reagents. In an embodiment, the user can seal the sample collection container 3116 by attaching the cap 3132, previously removed from the buffer solution container 3112, to the sample collection container 3116. The user can then send the sealed sample collection container 3116 and its contents to a molecular laboratory for molecular diagnostic testing. At this point, the buffer solution container 3112 and the basket sieve 3114 have been removed, and the sealed sample collection container 3116 contains a mixture of buffer solution, reagents, and exfoliated cells.

[0193] Figures 68 to 71 illustrate another example embodiment of the packaging container 3310 according to the present disclosure, using similar reference numerals to indicate similar elements as in Figures 52 to 59. For simplicity, all elements identified for the packaging container 3010 in Figures 52 to 59 will not be repeated for the packaging container 3310. Like the packaging container 3010, the packaging container 3310 can be used to transport the medical device 3100 and can then assist in methods of using the medical device 3100, as described above. In embodiments, example embodiments of medical packaging include the packaging container 3310 and the medical device 3100.

[0194] As shown in Figures 68 to 71, the packaging container includes an outer component 3312 and an inner component 3314. The outer component 3312 includes an upper portion 3316 and a lower portion 3318. The outer component 3312 also includes a tear line 3320 that separates the upper portion 3316 and the lower portion 3318. The outer component 3312 also includes a punch 3321 located adjacent to the tear line 3320, allowing a user to insert their fingers into the punch 3321 to grasp the upper portion 3316 and tear it from the lower portion 3318 along the tear line 3320. When the upper portion 3316 is removed using the tear line 3320, the lower portion 3318 accommodates the inner component 3314.

[0195] The inner component 3314 is configured to hold the medical device 3100 during transport and to hold the medical device 3100 vertically during use, while the outer component 3312 is configured to form a housing for the inner component 3314, which can be detached to expose the inner component 3314 during use. Similarly, the inner component 3314 may be formed by folding a first single sheet of cardboard along multiple fold lines to form at least one support surface 3366, 3368, which is configured to hold the medical device 3100 during transport and to hold the medical device 3100 vertically during use, and the outer component 3312 may be formed by folding a second single sheet of cardboard along multiple fold lines to form the housing for the inner component 3314.

[0196] Figures 70 and 71 show the state of the inner component 3314 before it is joined to the outer component 3312. Similar to the embodiments of Figures 52 to 59, the inner component 3314 includes an upper portion 3356 and a lower portion 3358. The inner component 3314 also includes a middle portion 3360 located between the upper portion 3356 and the lower portion 3358. The upper portion 3356 is connected to the middle portion 3360 via a fold line, and the lower portion 3358 is also connected to the middle portion 3360 via a fold line. The inner component 3314 includes an upper support surface 3366 and a lower support surface 3368. More specifically, the upper portion 3356 includes the upper support surface 3366, and the lower portion 3358 includes the lower support surface 3368. The upper support surface 3366 includes an upper cutout 3370. The upper incision 3370 is configured to hold the medical device 3100 vertically during transport and during use. Similarly, the lower support surface 3368 includes a lower incision 3372. The lower incision 3372 is also configured to hold the medical device 3100 vertically during transport and during use. The lower incision 3372 is aligned vertically with the upper incision 3370.

[0197] Similar to the embodiments of Figures 52 to 59, the upper cutout 3370 includes a central portion 3374 and two side portions 3376. The side portions 3376 engage with the central portion 3374 to form a hole. Similarly, the lower cutout 3372 includes a central portion 3378 and two side portions 3380. The side portions 3380 engage with the central portion 3378 to form a hole. The central portions 3374 and 3378 are circular, and the side portions 3376 and 3380 are rectangular and extend from opposite sides of the central portions 3374 and 3378 to opposite fold lines. Those skilled in the art will recognize from this disclosure that the upper cutout 3370 and the lower cutout 3372 can be manufactured in different sizes, shapes, or specifications and / or placed in different locations.

[0198] Figure 72 illustrates the outer component 3012 and inner component 3014 of packaging container 3010, and the outer component 3312 and inner component 3314 of packaging container 3310. Packaging container 3010 is formed by constructing inner component 3014 and inserting inner component 3014 into outer component 3012, as described herein, for example. Packaging container 3310 is formed by constructing inner component 3314 and inserting inner component 3314 into outer component 3312, as described herein, for example. In embodiments, medical device 3100 may be packaged in both container 3010 and packaging container 3310, and may be selectively delivered to hospitals or clinical laboratories based on the desired quantity of medical device 3100.

[0199] Any element of any embodiment described herein may also be included in any other embodiment described herein.

[0200] It should be understood that various changes and modifications to the apparatus and methods described herein will be apparent to those skilled in the art and can be made without diminishing the intended advantages.

[0201] General Explanation of Terms In understanding the scope of this invention, the term "comprising" and its derivatives as used herein are intended to be open-ended terms, indicating the presence of stated features, elements, components, groups, and / or steps, but not excluding the presence of other unstated features, elements, components, groups, integers, and / or steps. The foregoing also applies to words with similar meanings, such as the terms "comprising," "having," and their derivatives. Additionally, the terms "part," "segment," or "element," when used in the singular, may have a dual meaning of a single part or multiple parts.

[0202] As used herein, the term "constructed" to describe a component, section, or part of a device includes hardware constructed to perform the desired function.

[0203] Although only selected embodiments have been chosen to illustrate the invention, it will be apparent to those skilled in the art from this disclosure that various changes and modifications can be made to this document without departing from the scope of the invention as defined by the appended claims. For example, the size, shape, position, or orientation of the various components may be changed as needed and / or desired. Components shown as directly connected or in contact with each other may have an intermediate structure disposed therebetween. The function of one element may be performed by two elements, and vice versa. The structure and function of an embodiment may be employed in another embodiment. Not all advantages must be present simultaneously in a particular embodiment. Each feature that differs from the prior art, alone or in combination with other features, should also be considered as a separate description by the applicant of another invention, including the structural and / or functional concepts embodied by these features. Therefore, the foregoing description of embodiments of the invention is provided for illustrative purposes only and not for limiting the invention as defined by the appended claims and their equivalents.

Claims

1. A biopsy container device for recovering solid tissue and exfoliated cells ("D-cells") from a biopsy, said biopsy container device comprising: A sample collection container, the sample collection container including a reagent chamber; A basket sieve configured to be at least partially removably attached within the sample collection container, the basket sieve including a sieve surface configured to allow the passage of D-cells from the biopsy but not the passage of solid tissue from the biopsy; and A buffer container configured for removable attachment to the sample collection container, the buffer container including a buffer chamber.

2. The biopsy container device according to claim 1, wherein... The buffer container includes a funnel portion configured to guide the solid tissue and D-cells from the biopsy into the buffer chamber.

3. The biopsy container device according to claim 2, wherein... The buffer container is configured to be attached to the sample collection container, and the buffer chamber is at least partially located inside the sample collection container, while the funnel is at least partially located outside the sample collection container.

4. The biopsy container device according to claim 1, wherein... The sample collection container includes a boss or ridge that is configured to suspend the basket sieve within the sample collection container above the reagent chamber.

5. The biopsy container device according to claim 1, wherein... The buffer container includes a first attachment mechanism. The sample collection container includes a second attachment mechanism, and The buffer solution container is removably attached to the sample collection container via the cooperation between the first attachment mechanism and the second attachment mechanism.

6. The biopsy container device according to claim 5, wherein... The first attachment mechanism and the second attachment mechanism include corresponding threads, which enable the buffer container to be screwed onto the sample collection container.

7. The biopsy container device according to claim 5, wherein... The first attachment mechanism and the second attachment mechanism include rubber sleeves that allow the buffer container to be removably attached to the sample collection container.

8. The biopsy container device according to claim 1, comprising: A lid that fits into both the sample collection container and the buffer container.

9. The biopsy container device according to claim 1, wherein... The sample collection container is pre-filled with reagents in the reagent chamber, and The buffer container is pre-filled with buffer solution in the buffer chamber.

10. The biopsy container device according to claim 9, wherein... The sample collection container contains reagents ranging from 1 mL to 2 mL, and The buffer container contains a buffer solution between 1 mL and 2 mL.

11. The biopsy container device according to claim 9, wherein... The sample collection container includes a first amount of reagent, and The buffer container includes a second volume of buffer solution, the volume of which is approximately equal to the volume of the first volume of reagent.

12. The biopsy container device according to claim 1, wherein... The buffer container includes a skirt configured to removably attach to the sample collection container.

13. The biopsy container device according to claim 9, wherein... The buffer solution is a sterile phosphate buffer solution.

14. A biopsy container device for recovering solid tissue and exfoliated cells ("D-cells") from a biopsy, said biopsy container device comprising: Upper chamber; Inferior chamber; A sieve surface, located between the upper chamber and the lower chamber, is configured to allow the passage of the D-cells from the biopsy but not the passage of the solid tissue from the biopsy; as well as A solid surface, movably attached relative to the sieve surface, is configured to translate between (i) a first configuration and (ii) a second configuration, in the first configuration, the solid surface overlaps the sieve surface to prevent the D-cell from passing through the sieve surface, and in the second configuration, the solid surface is removed from the sieve surface to allow the D-cell to pass from the upper chamber through the sieve surface to the lower chamber.

15. A method for recovering solid tissue and exfoliated cells ("D-cells") from a biopsy using a buffer container device comprising a buffer container, a basket sieve, and a sample collection container, the method comprising: The solid tissue and D-cells from the biopsy are released into a buffer solution within the buffer container; Remove the buffer solution container from the basket sieve and the sample collection container; While the basket sieve is located inside the sample collection container, the solid tissue, the D-cells, and the buffer solution are poured into the basket sieve; Remove the basket sieve containing the solid tissue from the sample collection container; The basket sieve containing the solid tissue is placed in a sealed container for tissue processing; as well as The seal comprises the D-cells, the buffer solution, and the reagent mixture for use in diagnostic testing.

16. The method of claim 15, comprising: The solid tissue and the D-cells from the hollow needle are released into the buffer chamber.

17. The method of claim 15, wherein Sealing a mixture comprising the D-cells, the buffer solution, and the reagents involves sealing the mixture within the sample collection container.

18. The method of claim 15, comprising: The buffer container device is received, wherein the buffer container, the basket sieve, and the sample collection container are attached together.

19. The method of claim 18, comprising: The buffer container device is received, wherein the sample collection container is pre-filled with reagents, the basket sieve is at least partially located within the sample collection container, and the buffer container is pre-filled with buffer solution and is at least partially located within the sample collection container.

20. The method of claim 15, comprising: Remove the cap from the buffer container before releasing the solid tissue and D-cells from the biopsy into the buffer container, and The sealing process, which involves sealing the mixture of the D-cells, the buffer solution, and the reagents for diagnostic testing, includes using the cap to seal the D-cells, the buffer solution, and the reagents within the sample collection container.

21. A biopsy container device for recovering solid tissue and exfoliated cells ("D-cells") from a biopsy, said biopsy container device comprising: A sample collection container, the sample collection container including a reagent chamber; A basket sieve configured to be at least partially removably attached within the sample collection container, the basket sieve including a sieve surface configured to allow the passage of D-cells from the biopsy but not the passage of solid tissue from the biopsy; and A buffer container configured for removable attachment to the sample collection container, the buffer container including a buffer chamber.

22. The biopsy container device according to claim 21, wherein... The buffer container includes a funnel portion configured to guide the solid tissue and D-cells from the biopsy into the buffer chamber.

23. The biopsy container device according to claim 22, wherein... The buffer container is configured to attach to the sample collection container, wherein the buffer chamber is at least partially located inside the sample collection container, and the funnel is at least partially located outside the sample collection container.

24. The biopsy container device according to claim 21, wherein... The sample collection container includes a flange configured to suspend the basket sieve within the sample collection container above the reagent chamber.

25. The biopsy container device according to claim 21, wherein... The buffer solution container includes an inner surface having a first attachment mechanism. The sample collection container includes an outer surface with a second attachment mechanism, and The buffer solution container is removably attached to the sample collection container via the cooperation between the first attachment mechanism and the second attachment mechanism.

26. The biopsy container device according to claim 25, wherein... The first attachment mechanism and the second attachment mechanism include corresponding threads, enabling the buffer container to be screwed onto the sample collection container.

27. The biopsy container device according to claim 21, comprising: A lid that fits into both the sample collection container and the buffer container.

28. The biopsy container device according to claim 21, wherein... The sample collection container is pre-filled with reagents in the reagent chamber, and The buffer container is pre-filled with buffer solution in the buffer chamber.

29. The biopsy container device according to claim 28, wherein... The sample collection container contains reagents ranging from 1 mL to 2 mL, and The buffer container contains 1 mL of buffer solution between [amount missing].

30. The biopsy container device according to claim 28, wherein... The sample collection container includes a first amount of reagent, and The buffer container includes a second volume of buffer solution, the volume of which is approximately equal to the volume of the first volume of reagent.

31. The biopsy container device according to claim 28, wherein... The buffer solution is a sterile phosphate buffer solution.

32. The biopsy container device according to claim 21, wherein... The buffer solution container includes a skirt configured to removably attach the buffer solution container to the sample collection container.

33. A biopsy container device for recovering solid tissue and exfoliated cells ("D-cells") from a biopsy, said biopsy container device comprising: A sample collection container, the sample collection container comprising reagents; A basket sieve configured to be at least partially removably attached within the sample collection container, the basket sieve including a sieve surface configured to allow the passage of the D-cells from the biopsy but not the passage of the solid tissue from the biopsy; as well as A buffer container configured for removable attachment to the sample collection container, the buffer container comprising a buffer solution.

34. The biopsy container device of claim 33, wherein when the buffer chamber is attached to the sample collection container, the basket sieve is located between the buffer container and the sample collection container.

35. A method for recovering solid tissue and exfoliated cells ("D-cells") from a biopsy using a buffer container device comprising a buffer container, a basket sieve, and a sample collection container, the method comprising: The solid tissue and D-cells from the biopsy are released into a buffer solution within the buffer container; Remove the buffer solution container from the basket sieve and the sample collection container; While the basket sieve is located inside the sample collection container, the solid tissue, the D-cells, and the buffer solution are poured into the basket sieve; Remove the basket sieve containing the solid tissue from the sample collection container; The basket sieve containing the solid tissue is placed in a sealed container for tissue processing; as well as The seal comprises the D-cells, the buffer solution, and the reagent mixture for use in diagnostic testing.

36. The method of claim 35, comprising: The solid tissue and the D-cells are released from the core needle into the buffer chamber.

37. The method of claim 35, wherein... Sealing a mixture comprising the D-cells, the buffer solution, and the reagents involves sealing the mixture within the sample collection container.

38. The method of claim 35, comprising: The buffer container device is received, wherein the buffer container, the basket sieve, and the sample collection container are attached together.

39. The method of claim 38, comprising: The buffer container device is received, wherein the sample collection container is pre-filled with reagents, the basket sieve is at least partially located within the sample collection container, and the buffer container is pre-filled with buffer solution and is at least partially located within the sample collection container.

40. The method of claim 35, comprising: Remove the cap from the buffer container before releasing the solid tissue and D-cells from the biopsy into the buffer container, and The sealing of the mixture for diagnostic testing, comprising the D-cells, the buffer solution, and the reagents, involves sealing the D-cells, the buffer solution, and the reagents within the sample collection container using the cap.

41. A packaging container for one or more medical devices, the packaging container comprising: The internal component includes a support surface having at least one cutout configured to hold the one or more medical devices during transport and to hold the one or more medical devices upright during use. as well as An outer component surrounds the inner component and includes a tear line that allows a user to remove a portion of the outer component and expose the support surface of the inner component, enabling the user to use the one or more medical devices while they are held upright by the inner component.

42. The packaging container according to claim 41, wherein... The internal components and the external components are each formed from a single sheet of cardboard.

43. The packaging container according to claim 41, wherein... The at least one cut is formed as a hole in the surface of the support.

44. The packaging container according to claim 41, wherein The at least one cut includes a central portion and at least one side portion, the at least one side portion being combined with the central portion to form a hole, the at least one side portion extending outward from the central portion along a first direction and being smaller than the central portion in a second direction perpendicular to the first direction.

45. The packaging container according to claim 41, wherein... The external component includes an upper part and a lower part. The upper part is configured to separate from the lower part using the tear line, and When the upper part is removed using the tear line, the lower part accommodates the internal component.

46. ​​The packaging container according to claim 41, wherein... The internal components include an upper support surface and a lower support surface. The upper support surface includes at least one upper incision, the at least one upper incision being configured to hold the one or more medical devices upright during use, and The lower support surface includes at least one lower incision aligned vertically with the upper incision, the at least one lower incision being configured to hold the one or more medical devices upright during use.

47. The packaging container according to claim 41, wherein... The surface of the stent includes multiple incisions configured to hold the medical device upright during transport and during use.

48. A packaging container for one or more medical devices, the packaging container comprising: The internal component is formed from a first sheet of cardboard folded along multiple fold lines to form at least a support surface, the support surface being configured to hold the one or more medical devices during transport and to hold the one or more medical devices upright during use. as well as An outer component, formed from a second sheet of cardboard folded along multiple fold lines to form a housing for the inner component, the outer component comprising an upper portion and a lower portion, the upper portion being configured to be separated from the lower portion to expose the inner component.

49. The packaging container according to claim 48, wherein The first sheet of cardboard and the second sheet of cardboard are each part of the same sheet of cardboard.

50. The packaging container according to claim 48, wherein The internal component includes at least one incision configured to hold the one or more medical devices upright during use.

51. The packaging container according to claim 49, wherein... The at least one cut includes a central portion and at least one side portion, the at least one side portion being combined with the central portion to form a hole, the at least one side portion extending outward from the central portion along a first direction and being smaller than the central portion in a second direction perpendicular to the first direction.

52. The packaging container according to claim 48, wherein... The outer component includes a tear line, and The upper part is configured to be removed from the lower part using the tear line.

53. The packaging container according to claim 48, wherein... The internal components include an upper support surface and a lower support surface. The upper support surface includes at least one upper incision, the at least one upper incision being configured to hold the one or more medical devices upright during use, and The lower support surface includes at least one lower incision aligned vertically with the upper incision, the at least one lower incision being configured to hold the one or more medical devices upright during use.

54. The packaging container according to claim 48, wherein The surface of the support includes multiple cutouts configured to hold the medical device during transport and to hold the medical device upright during use.

55. A medical packaging package, comprising: One or more medical devices; as well as A packaging container that houses the one or more medical devices, the packaging container having at least one slit configured to hold the one or more medical devices upright during transport and during use of the one or more medical devices.

56. The medical packaging according to claim 55, wherein... The packaging container includes internal components and external components. The internal component includes a support surface having at least one cutout configured to hold the one or more medical devices during transport and to hold the one or more medical devices upright during use. The outer component surrounds the inner component and includes a tear line that allows the user to remove a portion of the outer component and expose the support surface of the inner component, so that the user can use the one or more medical devices while they are held upright by the inner component.

57. The medical packaging according to claim 55, wherein... The packaging container includes internal components and external components. The internal components are formed from a first sheet of cardboard folded along multiple fold lines to form at least a support surface, the support surface being configured to hold the one or more medical devices upright during transport and during use of the one or more medical devices. The outer component is formed from a second sheet of cardboard folded along multiple fold lines to form a shell for the inner component. The outer component includes an upper portion and a lower portion, the upper portion being configured to be separated from the lower portion to expose the inner component.

58. The medical packaging according to claim 55, wherein... The one or more medical devices will separate tissue samples from exfoliated cells obtained during biopsy.

59. The medical packaging according to claim 55, wherein... The one or more medical devices include a buffer container and a sample collection container, the buffer container being removable from the sample collection container while the sample collection container is held upright within the at least one incision.

60. The medical packaging according to claim 55, wherein... The one or more medical devices include multiple medical devices, each individually sealed in a separate device package. The at least one cut includes a device portion and at least one side portion, and Each of the plurality of individually sealed medical devices is positioned within a corresponding incision, wherein the medical device is located in the device portion and the packaging is located in the side portion.

61. A method for recovering an evaluable analyte from a tissue sample obtained via core needle biopsy, comprising: A hollow needle is provided, wherein the hollow needle contains the tissue sample obtained via biopsy using the hollow needle, wherein the tissue sample includes a tissue core and exfoliated cells; A buffer solution is provided, wherein the buffer solution is sterilized and does not contain formalin; Immerse the portion of the hollow needle containing the tissue sample into the buffer solution; The hollow needle is swirled in the buffer solution until the tissue core and the exfoliated cells detach from the hollow needle to form a first intermediate mixture comprising the buffer solution, the tissue core, and the exfoliated cells; The first intermediate mixture is filtered into the sample tube using a filter at least partially disposed in the sample tube to separate the tissue core from the first intermediate mixture, thereby obtaining the tissue core and a second intermediate mixture, the second intermediate mixture comprising the buffer solution and the exfoliated cells; Add an equal volume of cell lysis and stabilizing agent to the second intermediate mixture to obtain a third mixture comprising lysed exfoliated cells, from which the evaluable analyte can be recovered; Separate the evaluable analytes from the third mixture; as well as Evaluate the evaluable analytes; The analytes described were not exposed to formalin.

62. The method of claim 61, further comprising extracting the tissue core and placing the tissue core within a container, the container being configured for routine tissue processing of the tissue core.

63. The method of claim 61, wherein the evaluable analyte is DNA, RNA, exosomes, or protein.

64. The method of claim 61, wherein the cell lysis and stabilizing agent is a concentrated dual-action cell lysis and nucleic acid stabilizing agent.

65. The method of claim 61, further comprising: The sample tube was rotated using a centrifuge to separate the second intermediate mixture, yielding a supernatant and residue including the exfoliated cells; as well as The supernatant is removed from the sample tube to obtain the sample tube containing the residue including the exfoliated cells, wherein the exfoliated cells include the evaluable analyte and the residue does not include formalin.

66. A system for recovering an evaluable analyte from a tissue sample obtained via core needle biopsy, comprising: A core needle configured to collect tissue samples obtained via a core needle biopsy, wherein the tissue samples include a tissue core and exfoliated cells; Buffer container, the buffer container being configured as follows: To contain buffer solutions; as well as The hollow needle is received, and the tissue sample is disposed in the hollow needle, such that the portion of the hollow needle containing the tissue sample can be immersed in the buffer solution and rotated until the tissue core and the exfoliated cells are detached from the hollow needle, so as to form a first intermediate mixture in the buffer container, the first intermediate mixture comprising the buffer solution, the tissue core and the exfoliated cells; Sample tubes; A filter screen configured to be at least partially disposed within the sample tube, such that the first intermediate mixture can be filtered into the sample tube using the filter screen to separate the tissue core from the first intermediate mixture, yielding the tissue core and a second intermediate mixture, the second intermediate mixture comprising the buffer solution and the exfoliated cells; and The sample tube is configured to add a cell lysis and stabilizing agent in an equal volume to the second intermediate mixture to obtain a third mixture comprising lysed exfoliated cells, from which the evaluable analyte can be recovered. The analytes described were not exposed to formalin.

67. The system of claim 66, further comprising a container configured to store the tissue core.

68. The system of claim 66, wherein the filter is a filter with a density of 40 pm to 100 pm.

69. The system of claim 66, wherein the evaluable analyte is DNA, RNA, exosomes, or protein.

70. A method for recovering an evaluable analyte from a tissue sample obtained via core needle biopsy, comprising: A hollow needle is provided, wherein the hollow needle contains the tissue sample obtained via biopsy using the hollow needle, wherein the tissue sample includes a tissue core and exfoliated cells; Immerse the portion of the hollow needle containing the tissue sample into a buffer solution; The hollow needle is swirled in the buffer solution until the tissue core and the exfoliated cells detach from the hollow needle to form a first intermediate mixture comprising the buffer solution, the tissue core, and the exfoliated cells; The first intermediate mixture is filtered into a sample tube using a filter screen to separate the tissue core from the first intermediate mixture, resulting in the tissue core and a second intermediate mixture, the second intermediate mixture comprising the buffer solution and the exfoliated cells; as well as Adding cell lysis and stabilizing agents to the second intermediate mixture yields a third mixture comprising lysed exfoliated cells, from which the evaluable analyte can be recovered; The analytes described were not exposed to formalin.

71. The method of claim 70, wherein the filter is at least partially disposed in the sample tube.

72. The method of claim 70, wherein the volume of the cell lysis and stabilizing agent is equal to the volume of the second intermediate mixture.

73. The method of claim 70, wherein the cell lysis and stabilizing agent comprises a double concentration up to 5 mL of the cell lysis and stabilizing agent.

74. The method of claim 70, further comprising storing the sample tube in which the third mixture is disposed in a freezing device.

75. The method of claim 74, wherein the refrigeration equipment is operated to maintain an internal temperature of 4°C.

76. The method of claim 70, further comprising separating the evaluable analyte from the third mixture.

77. The method of claim 70, wherein the buffer solution comprises a phosphate buffer solution.

78. The method of claim 70, further comprising sterilizing the buffer solution prior to immersing the hollow needle therein.

79. The method of claim 70, wherein the evaluable analyte is DNA, RNA, exosomes, or protein.

80. The method of claim 70, wherein the cell lysis and stabilizing agent is a concentrated dual-action cell lysis and nucleic acid stabilizing agent.

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