Needle biopsy holder

Abstract

An imaging system and biopsy sample holder with a housing, a hollow cavity within the housing, a vacuum port positioned at an end of the housing and connected to the hollow cavity, a groove in the upper surface of the housing positioned between the ends of the housing, and a plurality of holes positioned in the groove and extending into the hollow cavity are provided. The groove is configured to receive a tissue sample or a biopsy needle for placement of a tissue sample in the groove. The tissue sample is held in place by negative pressure created by applying a vacuum source to the vacuum port. The holder can couple with the specimen stage of many different types of imagers and is well-suited for use with slide-free imaging techniques such as Fluorescence Imitating Brightfield Imaging (FIBI).

Description

NEEDLE BIOPSY HOLDERCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, U.S. provisional patent application serial number 63 / 637,187 filed on April 22, 2024, incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under CA277527, CA278544, and CA269191 awarded by the National Institutes of Health. The government has certain rights in the invention.NOTICE OF MATERIAL SUBJECT TO COPYRIGHT PROTECTION

[0003] A portion of the material in this patent document may be subject to copyright protection under the copyright laws of the United States and of other countries. The owner of the copyright rights has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the United States Patent and Trademark Office publicly available file or records but otherwise reserves all copyright rights whatsoever. The copyright owner does not hereby waive any of its rights to have this patent document maintained in secrecy, including without limitation its rights pursuant to 37 C. F. R. § 1 .14.BACKGROUND

[0004] 1. Technical Field

[0005] This technology pertains generally to diagnostic imaging devices and methods, and more particularly to a biopsy sample holder and imaging system that uses slide-free techniques for capturing surface images from nonsectioned, freshly excised or fixed specimens to provide histology-grade images within minutes. The vacuum assisted needle biopsy device holds a tissue sample in place for staining and imaging. Additionally, the vacuumassisted methodology, and system has been scaled for handling larger samples, alternative materials, and may be adapted to different clinical settings.

[0006] 2. Background

[0007] Histological diagnoses obtained through minimally invasive biopsies are critical to providing timely and accurate diagnoses of oncologic and infectious diseases. A core needle biopsy is a standard clinical procedure that uses a hollow needle or probe to remove tissue from the body of a patient for analysis. Tissue biopsies are very fragile and the handling of such tissues, including staining and imaging, can damage the sample tissues. Biopsy samples can be degraded during the preparation and imaging processes so that new samples may be required. Although minimally invasive, needle biopsy procedures also pose a risk of damaging tissue or blood vessels during sample acquisition.

[0008] An adequate and representative biopsy sample is essential for an accurate diagnostic assessment and a correct diagnosis. Biopsy samples need to be representative of the lesion and have adequate cellu larity for morphological study and specific diagnostic tests. Inadequate, nonrepresentative biopsy samples may result in the need for repeated biopsies producing delays in diagnosis, impacting patient care, increasing healthcare costs, and heightened patient anxiety. Inadequate tissue sampling occurs in over 20% of cases.

[0009] Rapid on-site evaluation (ROSE) is a diagnostic technique that is used in cytology and pathology to assess the adequacy of acquired biopsy samples for use in available targeted testing. Immediate diagnostic adequacy assessments of samples at the location and time of the biopsy identifies the need for a change in sample target location or a need to obtain additional diagnostic cytological material. An immediate quality assessment also ensures that the biopsy sample has been handled properly and meets all of the requirements for subsequent diagnostic testing of the sample.

[0010] The success of ROSE and similar immediate cytologic assessment techniques depends upon effective diagnostic devices and procedures and proper sample handling. Proper sample handling and processing, both duringand after the assessments, may allow the accurate division of the sample into smaller segments of interest and ensure that sufficient quantities of relevant cells or tissue are present to permit a complete diagnostic workup.BRIEF SUMMARY

[0011] A direct-to-digital imaging system is provided that integrates tissue collection, sample staining, and imaging into a single process. The system eliminates traditional slide preparation steps and can provide immediate, diagnostic-quality images within minutes of sample acquisition. The imaging system is particularly suited for ROSE diagnostic adequacy assessments of individual biopsy samples. There is a strong economic incentive to improve the reliability of the biopsy sampling with high-cost procedures such as endobronchial ultrasound guided (EBUS) sampling and endoscopic ultrasound-guided (EUS) fine needle aspiration biopsy procedures, for example. The system is also suited for use in settings where there is limited access to pathology evaluation infrastructure because it can reduce the number of needle passes and associated costs and potential complications as well as increase access to early diagnosis and reduce treatment delays.

[0012] The diagnostic imaging system is centered on a sample holder subsystem that is sized and configured to be used in conjunction with many different types of slide-free direct to digital imagers. The needle biopsy subsystem includes a holder coupled to a vacuum source that facilitates the extraction of the tissue sample from the needle biopsy device and holds the tissue in place for staining and diagnostic imaging. Fragile samples are sequestered and protected by the holder and staining and imaging can take place without further sample transfer steps.

[0013] The needle biopsy holder provides an effortless way of managing small tissues, fresh or fixed, with minimum steps by providing an integrated solution for extracting, staining, and imaging all on the same device. The apparatus and system enable the employment of slide-free imaging techniques to immediately image the biopsy samples after harvesting to provide diagnostic quality images, significantly improving upon the current needle biopsy procedure protocols.

[0014] The imaging subsystem includes an imager that utilizes slide-free techniques including, for example, Fluorescence Imitating Brightfield Imaging (FIBI), UV surface excitation microscopy (MUSE), multiphoton microscopy, confocal microscopy in brightfield reflection mode, nonlinear microscopy, structured-illumination microscopy with phase-mask detection, full-field optical coherence tomography, light-sheet microscopy, and photoacoustic microscopy. The holder can be adapted for use with a variety of imagers that are capable of slide-free imaging. However, FIBI imaging is particularly suitable for intraoperative tissue assessments. FIBI is a technique that bypasses formalin fixation and paraffin embedding (FFPE) processes by capturing images of the surface of non-sectioned, freshly excised specimens to provide histology-grade images within minutes.

[0015] Generally, the needle biopsy holder apparatus has a rectangular boxlike housing structure enclosing a small internal chamber oriented axially along its length. This internal chamber within the housing is configured to be connected to an external vacuum pump, through a housing output that is fluidly coupled to a hose creating a sealed system.

[0016] The top external surface of the housing has a groove along part of the length. Within the groove is at least one array of small holes transecting the top surface and the internal chamber wall creating openings from the housing surface to the inside of the chamber, enabling airflow through the housing. This array of openings within the groove is contained inside the interior of the groove. The width, depth and length dimensions of the groove may be adjusted to approximate the gauge size of a conventional needle biopsy tissue needle and collected sample to ensure a proper fit of the needle within the groove.

[0017] In addition, the number and location of the holes within the groove may be selected to allow some control over the volume and location of air flow. The geometry, quantity, and placement of the openings may be selected based on the characteristics of the target tissue and are not limited to any particular number, size, or pattern. For example, the openings may comprise any suitable discrete aperture shape or, alternatively, may take the form of one or more elongate slots or channels.

[0018] After harvesting the tissue sample using the needle biopsy gun, the needle with the acquired sample can easily be placed into the groove of the holder. The tissue unloading process begins when the vacuum pump is turned on. The negative pressure created by the vacuum through the holes within the groove assists with the detachment of the tissue sample from the biopsy gun needle and thereafter secures the biopsy sample inside of the groove of the holder for staining and further processing.

[0019] In one embodiment, the top surfaces of the housing of the holder on both sides of the groove can be inclined toward the groove. This inclination of surfaces helps with guiding any applied solutions towards the sample and to the groove during the rinsing and staining process.

[0020] The stains that are used for staining the sample can be applied using manual or active fluid pumps while the vacuum pump of the holder is on. In addition to holding the sample, the suction from the vacuum pump through the holes also helps to remove unused tissue stains or excess wash solution in order to keep the surface of the biopsy sample clean and free of any residual fluids. The removed extra fluids can be collected in a bypass container to prevent the excess fluids from reaching the vacuum pump.

[0021] In another embodiment, the tissue sample from the biopsy needle is extracted onto a porous mesh platform that sits on top of the groove of the holder. Air is drawn by the vacuum through the mesh, holes and chamber to secure the sample to the mesh platform and holder. The same diagnostic sample processing and imaging steps as above are applied. After the imaging of the sample is completed, the mesh platform with the biopsy sample on top is removed from the needle biopsy holder and the sample may be dropped into formalin or otherwise prepared for subsequent targeted diagnostic procedures.

[0022] In a further embodiment, the holder has a slot beneath and parallel to the groove. The bottom of the groove is open along some or all of its length to the slot below and the plurality of holes extends from the bottom of the slot through the wall of the interior chamber. An insert of mesh or filter paper, for example, is disposed in the slot. The sample may be removed from the biopsy needle and placed into the groove and to the insert within the slot andthereafter secured with negative pressure in preparation for imaging.

[0023] After the staining and washing steps, while the needle biopsy sample is still loaded in the groove or insert of the needle biopsy holder, the holder and sample combination can then be transferred to the imaging device. The vacuum may remain turned on throughout the whole staining and imaging process as it will help to secure the tissue in place and to remove excess fluids. However, the vacuum pump can also be turned off during imaging depending on the tissue type of the sample and clinical setting.

[0024] In one embodiment, the biopsy holder is a permanent fixture of an imaging system. The loading, staining, washing and imaging processes take place in one apparatus in this embodiment.

[0025] After imaging is completed, the airflow direction through the holder can be reversed to help to remove the biopsy sample from the holder, usually for placement into a container of fixative solution. The images of the biopsy sample can be analyzed, and the sample can then be submitted into the regular clinical workflow of additional testing and diagnosis.

[0026] The apparatus and sample preparation processes address the concerns of cost, time, and sample adequacy and identification for downstream immunohistochemistry, sequencing, or other molecular analyses. FIBI imaging, for example, has demonstrated significant promise in facilitating accurate diagnoses by providing clinical concordance rates of 97% when compared to standard slide-based diagnoses.

[0027] Further aspects of the technology described herein will be brought out in the following portions of the specification, wherein the detailed description is for the purpose of fully disclosing preferred embodiments of the technology without placing limitations thereon.BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The technology described herein will be more fully understood by reference to the following drawings which are for illustrative purposes only:

[0029] FIG. 1 A is a top perspective view of a needle biopsy sample holder for use with an imaging system shown schematically according to one embodiment of the technology.

[0030] FIG. 1 B is a top perspective view of a needle biopsy holder showing biopsy sample placement in the surface groove.

[0031] FIG. 1 C is a perspective lengthwise cross-sectional view of the needle biopsy holder along the groove showing the internal chamber and vacuum outlet of the housing.

[0032] FIG. 2A is a top perspective view of a needle biopsy holder showing a lengthwise groove and top surfaces angled toward the groove corresponding to the embodiment of FIG. 1 .

[0033] FIG. 2B is a top plan view of a needle biopsy holder showing the groove and array of holes within the groove.

[0034] FIG. 2C is a detailed view of a section of the groove showing the array of holes within the groove.

[0035] FIG. 2D is an end view the needle biopsy holder showing the vacuum port, groove and angled top surfaces.

[0036] FIG. 2E is a side view of the biopsy holder.

[0037] FIG. 2F is a cross-sectional view taken along the lines FIG. 2F — FIG.2F of FIG. 2A and FIG. 2B showing the interior chamber, vacuum port and array of transverse holes in the groove.

[0038] FIG. 2G is a cross-sectional view taken along the lines FIG. 2G — FIG. 2G of FIG. 2B showing the interior chamber, groove and angled top surfaces.

[0039] FIG. 3A is a top perspective view of a needle biopsy holder showing angled top surfaces and arrays of holes located at the proximal and distal ends of the groove and mesh holder according to a first alternative embodiment of technology.

[0040] FIG. 3B is a top plan view of the needle biopsy holder of FIG. 3A showing the placement of arrays of holes in the groove.

[0041] FIG. 3C is a detailed view of a section of the groove showing diamond shaped holes.

[0042] FIG. 3D is an end view of the needle biopsy holder of FIG. 3A showing the vacuum port, groove and angled top surfaces.

[0043] FIG. 3E is a side view of the needle biopsy holder and mesh sample holder.

[0044] FIG. 4A is a top perspective view of the needle biopsy holder showingangled top surfaces and arrays of holes centralized in the groove and a slot for receiving a planar mesh or paper insert according to a second alternative embodiment of technology.

[0045] FIG. 4B is a top plan view of the needle biopsy holder of FIG. 4A showing the placement of holes in the groove and a mesh insert.

[0046] FIG. 4C is an end view of the needle biopsy holder of FIG. 4A showing the vacuum port, groove and angled top surfaces.

[0047] FIG. 4D is a cross-sectional view taken along the lines FIG. 4D — FIG. 4D of FIG. 4B showing the slot, interior chamber, groove and angled top surfaces. The slot is provided in the housing to allow for a mesh or filter paper to slide into and be removed from the holder housing.

[0048] FIG. 4E is a side view of the needle biopsy holder of FIG. 4A.

[0049] FIG. 4F is a cross-sectional view taken along the lines FIG. 4F — FIG.4F of FIG. 4B showing the slot, interior chamber, vacuum port, mesh insert and transverse holes in the groove.

[0050] FIG. 5 is an imaging system diagram with the biopsy sample holder shown schematically according to one embodiment of the technology.DETAILED DESCRIPTION

[0051] Referring more specifically to the drawings, for illustrative purposes, apparatus and methods for a needle biopsy diagnostic imaging combining imaging with slide-free techniques with a needle biopsy holder that provides controlled retention and orientation of a biopsy sample for staining and imaging are generally shown.

[0052] Several embodiments of the technology are described generally in FIG. 1 A to FIG. 5 to illustrate the characteristics and functionality of the apparatus, system and methods. It will be appreciated that the methods may vary as to the specific steps and sequence and the systems and apparatus may vary as to structural details without departing from the basic concepts as disclosed herein. The method steps are merely exemplary of the order that these steps may occur. The steps may occur in any order that is desired, such that it still performs the goals of the claimed technology.

[0053] Turning now to FIG. 1A, FIG. 1 B and FIG. 10, the basic structure ofone embodiment of a needle biopsy sample holder 10 is generally illustrated. Holder 10 has a rectangular box shaped body or housing 12 with a top surface 14 and a vacuum output 20 that is configured to connect to an external vacuum pump and to create a seal with a vacuum tube. In one embodiment, the vacuum output 20 has an interior opening 24 with an internal diameter of approximately 4 mm and an external diameter of approximately 5 mm which allows for a snug fit of an approximately 4 mm internal diameter by approximately 6 mm conventional outer diameter tube (not shown), for example.

[0054] Although housing 12 of the biopsy holder 10 is shown generally as a rectangular prism, the housing 12 can be configured with any shape and dimensions that meet the requirements of a particular slide free imager stage. The housing 12 may also be configured to accommodate larger tissue samples than those produced by conventional core needle biopsies.

[0055] In one illustrative embodiment, for example, the length of housing 12 is approximately 45 mm with a width of approximately 15 mm and a height of approximately 11 .25 mm at its maximum. In one embodiment, chamber 22 is a hollow cylinder that is approximately 40 mm in length with a diameter of approximately 4.78 mm. A biopsy holder 10 with these dimensions has been configured for use with a conventional Fluorescence Imitating Brightfield Imaging (FIBI) imager.

[0056] The exterior of housing 12 may also include rails, slots, brackets or other couplings (not shown) that are necessary to properly engage the housing 12 with a selected diagnostic imager. The housing 12 may be configured with multiple coupling types to permit the transfer of a holder 10 with a prepared sample between different imaging systems.

[0057] The holder 10 may be formed from any suitable material, including, for example, 3D printable polymers (e.g., PLA, resin), metals (e.g., aluminum), or any other biocompatible or imaging compatible material.

[0058] The top surface 14 of housing 12 has a centered groove 16 present along its length that is sized to receive a needle biopsy needle and sample. The groove 16 has a number of transverse holes 18 that extend through the bottom of groove 16 to an internal chamber 22 as seen in FIG. 10. In thisembodiment, housing 12 encloses a small axial internal chamber 22 along a portion of its length that is contiguous with the interior 24 of a vacuum outlet 20 incorporated in the housing 12, as shown in the cross-section of FIG. 1 C. In one embodiment, the cross-sectional dimensions of chamber 22 are uniform along the length of chamber 22.

[0059] As seen in FIG. 1 C, chamber 22 of housing 12 has an outer wall that is open to a plurality of holes 18 within groove 16, forming airflow channels into and out of chamber 22. Holes 18, interior chamber 22 and vacuum outlet 20 provide a flow of air 26 from the exterior of housing 12 through the interior of chamber 22 and back out of housing 12 when a vacuum is applied as indicated by the wide arrows. When a vacuum is applied, a flow 26 of exterior air is drawn through holes 18 to form a channeled air flow 28 into interior chamber 22 and to produce an air flow 30 out of chamber 22 through interior 24 of vacuum outlet 20 to a vacuum source.

[0060] Conversely, a reverse air flow can be used to release a sample from groove 16 or to clear any unwanted matter that may have entered holes 18 during use. Air that is forced from a source through the interior chamber 22 and the holes 18 will cause an outward flow of air from the holes within groove 16.

[0061] Groove 16 dimensions may be selected to approximate the gauge size and linear dimensions of conventional needles used to obtain biopsy samples. In one embodiment, for example, groove 16 is configured to accommodate an 18-gauge needle biopsy gun needle. In one embodiment, groove 16, which runs along the length of housing 12, has a semicircular cross-section with a radius of approximately 0.42 mm and is approximately 0.82 mm in width. In one embodiment, the outer diameter of vacuum outlet 20 is positioned in housing 12 approximately 0.2 mm below the lowest point of the bottom of groove 16.

[0062] During use, a biopsy needle having a tissue sample contained therein can be placed into groove 16 and positioned over holes 18. Activation of the vacuum source can create suction forces within groove 16 that promotes extraction of sample 32 from a biopsy needle as a user pulls the needle away from housing 12. With the biopsy gun needle removed from the groove 16,sample 32 may remained fixed within groove 16. Both secured sample 32 and holder 10 can then be placed on or used in a platform for imaging. The prepared sample 32 can be imaged without removal from the holder 10.

[0063] Referring now to another embodiment of a needle biopsy holder 40 shown in FIG. 2A through FIG. 2G, a housing 48 with top surfaces 42, 44 that are inclined toward a central groove 46 is illustrated. Groove 46 can be centrally positioned lengthwise along body 48 as seen in FIG. 2B. Left top surface 42 has an incline from a high end at the left side of housing 48 with a low end terminating at groove 46. Similarly, right top surface 44 is inclined from a high point at the right side of housing 48 to a low point at groove 46.

[0064] In one embodiment, the angle of inclination of the left surface 42 and the right surface 44 is approximately ten degrees from horizontal. The incline of the top surfaces 42, 44 can be adjusted or removed, as inclined surfaces are not a requirement but meant as an optional feature to assist with the use of holder 40.

[0065] The inclination of the top surfaces 42, 44 can help guide any applied solution towards a sample contained in groove 46 during a sample preparation process including, for example, rinsing and staining processes. Inclined top surfaces 42, 44 also allow excess fluids from the sample or the preparation process to flow to the groove 46 for removal. Typically applied solutions can include, but are not limited to, deionized water, ethanol, hematoxylin, and eosin.

[0066] FIG. 2B is a top plan view of holder 40 and shows a linear array of holes 50 in groove 46. As can be seen, groove 46 is positioned centrally in the top surfaces of the device and extends longitudinally between both ends of housing 48. A total of nineteen holes 50 centered in groove 46 are shown in this embodiment. However, it will be understood that any number of holes 50 or arrays of holes can be used.

[0067] FIG. 2C is a detailed sectional view of groove 46 taken from the dashed line box of FIG. 2B, showing an illustrative embodiment of holes 50. The detailed view shows three equally spaced square holes rotated to have a diamond shape in relation to the orientation of groove 46. Although holes 50 with a diamond shape are illustrated in FIG. 2C, holes 50 of any shape andspacing may be used.

[0068] In one embodiment, the linear array of holes 50 are centered along the length of groove 46. In one embodiment, the holes are approximately 0.4 mm by approximately 0.4 mm specifically designed to facilitate 3D printing of such small openings. Conventional 3D printers allow for printing overhangs without support when at 45-degree angles so the square pattern may be chosen to facilitate 3D printing at this scale. Once printed, the holes may resemble more of a circular pattern. In the embodiment shown in FIG. 2C, the square holes 50 are arranged in a linear array, each slightly rotated to resemble diamonds. In this embodiment, the nineteen holes 50 centered in groove 48 are spaced approximately 1 .03 mm apart from the corner of each square.

[0069] FIG. 2D is an end view of housing 48 as viewed from an end having a vacuum port 52. FIG. 2D also shows the profile of groove 46 and inclined top surfaces 42, 44 of housing 48.

[0070] FIG. 2E is a side view of the biopsy holder device 40 and FIG. 2F is a cross-sectional side view of the device taken through lines FIG. 2F — FIG. 2F of FIG. 2B. Central chamber 54 and vacuum output 52 of housing 48 can be seen in this view. Groove 46 with the array of air channeling holes 50 that are fluidically coupled to chamber 54 can also be seen.

[0071] The cross-sectional end view of housing 48 taken through lines FIG. 2G — FIG. 2G of FIG. 2B is shown in FIG. 2G. In this embodiment, central chamber 54 is positioned near the top surfaces 42, 44 of housing 48 so that the depth of holes 50 from groove 46 to chamber 54 is comparatively short. In other embodiments, chamber 54 may be positioned in housing 48 so that the depth of holes 50 from groove 46 to chamber 54 are comparatively long. Control over the suction experienced by sample within the groove 46 can be determined by the selection of the dimensions of the holes 50, chamber 54 and the strength of the vacuum source.

[0072] An alternative embodiment of the holder 60 is shown in FIG. 3A through FIG. 3E. Holder 60 has a housing 62 with a vacuum port 64 and a top surface 66 with a groove 68. It will be appreciated that any number of holes 70 (shown in FIG. 3B and FIG. 3C) can be used along the length of groove 68. In some embodiments, the number of holes used may be basedon the length of the needle biopsies being used in conjunction with holder 60. If desired, different arrays of holes 70 can be distributed along the length of groove 68. For example, FIG. 3B shows a first array 76 of holes 70 within groove 68 positioned at a first distal end of groove 68 and second array of holes 70 within groove 68 positioned at a second distal end of groove 68 of housing 62. As a further example, a third array of holes 70 or more (not shown) may be placed in between the first array 76 and second array 78.

[0073] In the top plan view of the holder 60 of FIG. 3B, for example, two arrays of four holes 70 each are positioned in the groove 68 near the ends of housing 62. In this embodiment, the two arrays of holes are separated by a distance of about 30.4 mm. The position and number of the groupings of holes 70 determines the location of the applied force from the vacuum source on the needle, mesh 72 and sample within groove 68. In this illustration, the vacuum forces will be applied on both ends of the sample.

[0074] In the detailed view of FIG. 3C, holes 70 within groove 68 are shown with a diamond shape in an array of four holes. Holes 70 are separated from each other with the same distance as the width of each hole 70. In this example embodiment, holes 70 are diamond shaped and are about 0.5 mm on each side, and have a corner-to-corner spacing of about 0.5 mm. All dimensions that are presented are illustrative and provided as non-limiting examples.

[0075] FIG. 3D is an end view of needle biopsy holder 60 as viewed from the end with the vacuum port 64. The end view shows the profile of the inclined top surfaces and groove 68 and the relative position of the vacuum port 64 in housing 62.

[0076] FIG. 3E is a side view of holder 60 showing housing 62 with vacuum port 64. An optional mesh platform 72 that may be placed on the top surface 68 of housing is shown in FIG. 3A and FIG. 3E. The platform 72 may have a fold or bend 75 that has approximately the same angles of inclination as the top surfaces 66 to provide a good fit with the bend 75 of the platform 72 when positioned over the groove 68 when placed on the top of housing 62. The optional mesh platform 72 may be made of metal, plastic or other materials that are compatible with the sample, stains and selected imager. The meshplatform 72 may also be used with any configuration of holes or hole arrays within groove 68.

[0077] When used, the acquired tissue sample is extracted from the biopsy needle onto the mesh platform 72 that has been placed on the top surface 66 of the housing 66. The extracted sample in bend 75 of platform 72 located over groove 68 will be secured to the platform 72 and housing 62 by negative pressure produced by the vacuum. The secured sample may then be stained or otherwise prepared for imaging by an imager. The imaged sample may then be removed from housing 62 and mesh platform 72 for further diagnostic processing.

[0078] In another alternative embodiment 80, shown in FIG. 4B through FIG. 4F, a housing 82 with a vacuum port 84 and a groove 86 on top surface 88 of the housing 82 are shown in FIG. 4A through FIG. 4F. Housing 82 has an additional feature of a slot 92 that is above and parallel to an internal chamber 94 and is also below and open to the bottom of groove 86 as seen in FIG. 4D. The bottom portion of slot 92 has a plurality of holes 90 that pass through a top wall that forms chamber 94 and the bottom of slot 92. Slot 92 is located between groove 86 and holes 90 within internal chamber 94. Slot 92 is configured to receive an insert 96 made of mesh or other types of compatible filter material such as a paper filter or biopsy bag material. During use, the mesh or filter insert 96 can be inserted prior to securing a sample in groove 86. After the sample is evaluated, the mesh or filter insert 96 and sample can be removed from slot 92 of housing 82.

[0079] FIG. 4A and FIG. 4B show a linear array of holes 90 perforating a wall defining chamber 94. This central array of holes 90 can be similar to the embodiments of FIG. 1A and FIG. 2A. Alternatively, holes 90 can be grouped near the ends of groove 86 and slot 92 as illustrated in the embodiment of FIG. 3A. In addition, holes 90 may have a circular, square, diamond or other geometric shape or may have an elongate slot shape, for example.

[0080] FIG. 4C is an end view of the holder 80 as viewed from the end with vacuum port 84. The profile of the top surfaces 88 and groove 86 of housing 82 with optional inclined edges can be seen.

[0081] FIG. 4D is a cross-sectional end view of the device taken through linesFIG. 4D — FIG. 4D of FIG. 4B. Slot 92, which spans groove 86 and allows for insertion and removal of a mesh or a filter (e.g., filtration paper) insert 96, for example, can be seen in the cross-section of FIG. 4D. Slot 92 is also seen in the cross-section side view of FIG. 4F taken through lines FIG. 4F — FIG. 4F of FIG. 4B. Slot 92 is configured to receive a filter or mesh insert 96 to provide additional security in handling fresh biopsy samples.

[0082] In this embodiment the tissue handling and staining process is the same as described before. However, instead of reversing the airflow direction to remove the biopsy sample from the holder, the pump may be simply turned off and the mesh or filter insert 96 with the sample on top is removed from slot 92 of housing 82 and placed into a container of fixative solution, for example. In one embodiment, the mesh or filter insert 96 can be placed on top of holes 90 inside of slot 92 and damped with rinsing solution while the pump is on, thus creating the required suction to hold the sample in place on top of the mesh or filter.

[0083] An imaging system 100 incorporating the needle biopsy holder and vacuum pump with the imager and imaging process is illustrated schematically in FIG. 5. System 100 has an imager 102 that preferably utilizes slide-free imaging techniques including, for example, Fluorescence Imitating Brightfield Imaging (FIBI), UV surface excitation microscopy (MUSE), multiphoton microscopy, confocal microscopy in brightfield reflection mode, nonlinear microscopy, structured-illumination microscopy with phase-mask detection, full-field optical coherence tomography, light-sheet microscopy, and photoacoustic microscopy.

[0084] Imager 102 has a stage that can be configured to a hold biopsy sample holder 104, which can be patterned after any of the different holder embodiments discussed herein. However, the imager 102 may also have a sample holder 104 incorporated permanently as part of the stage of imager 102.

[0085] In various embodiments, biopsy sample holder 104 can be configured to hold needle biopsy samples from needles of different diameters and lengths. The sample holder 104 may also be configured for holding larger tissue samples produced using other extraction methods. Holder 104 mayhave more than one groove or have grooves with different widths, each groove with holes connected to a central chamber of the holder, for example.

[0086] Holder 104 of imaging device 102 is operably coupled to a vacuum pump 110 through a vacuum hose 106 that may have an optional vacuum line filter or trap 108 for collecting fluids or particulates to keep pump 110 clear of contaminants.

[0087] In the embodiment shown in FIG. 5, imager 102 can be connected to a computing device 112 that has a processor, programming, storage and a display. Computing device 112 can control the functions of imager 102, holder 104 as well as process the images of the sample produced by the imager. In another embodiment, the image computing is performed by imager 102.

[0088] In use, the vacuum port of needle biopsy holder 104 is connected to a vacuum pump 110 and a bypass container 108 through a tube 106. After harvesting the tissue sample using a biopsy gun needle, the biopsy needle portion of the gun is positioned into the groove of the holder 104 for processing and imaging. A tissue unloading process normally begins while the vacuum pump 110 is operating. By way of example, a miniature air pump 110 can be used with a maximum vacuum of less than approximately 420 mmHg. The vacuum assists with tissue detachment from the biopsy gun and in securing the biopsy sample inside of the groove of holder 104.

[0089] Stains can be applied to the secured biopsy sample in the holder using manual or active fluid pumps while vacuum pump 110 is operational. In addition to holding the sample, the suction from vacuum pump 110 through holder 104 can also remove excess stains or wash solutions, which keeps the surface of the biopsy sample clean and free from any residual stains or washing solutions. Any excess stains and washes from holder 104 can be collected in a conventional bypass container 108, which has been placed inline with vacuum pump 110, to prevent the stains from reaching vacuum pump 110.

[0090] After staining and washing steps, while the needle biopsy sample is still loaded on the groove of holder 104, combination of holder 104 and the sample may then be transferred to a conventional imaging device 102.Vacuum pump 110 may remain operating throughout the entire process to help secure the tissue in place on the holder 104 during transfer to the imager 102.

[0091] After imaging of the sample is complete, the sample can be removed from the holder 104. In one embodiment, the airflow direction can be reversed to help remove the biopsy sample from the holder. In another embodiment, the vacuum can be turned off and a mesh insert can be removed from the holder 104 and the imaged biopsy sample can then be submitted into a clinical workflow for further analysis.

[0092] Embodiments of the technology of this disclosure may be described herein with reference to flowchart illustrations of methods and systems according to embodiments of the technology. Embodiments of the technology of this disclosure may also be described with reference to procedures, algorithms, steps, operations, formulae, or other computational depictions, which may be included within the flowchart illustrations or otherwise described herein. It will be appreciated that any of the foregoing may also be implemented as computer program instructions. In this regard, each block or step of a flowchart, and combinations of blocks (and / or steps) in a flowchart, as well as any procedure, algorithm, step, operation, formula, or computational depiction can be implemented by various means, such as hardware, firmware, and / or software including one or more computer program instructions embodied in computer-readable program code. As will be appreciated, any such computer program instructions may be executed by one or more computer processors, including without limitation a general purpose computer or special purpose computer, or other programmable processing apparatus to produce a machine, such that the computer program instructions which execute on the computer processor(s) or other programmable processing apparatus create means for implementing the function(s) specified.

[0093] Accordingly, blocks of the flowcharts, and procedures, algorithms, steps, operations, formulae, or computational depictions described herein support combinations of means for performing the specified function(s), combinations of steps for performing the specified function(s), and computerprogram instructions, such as embodied in computer-readable program code logic means, for performing the specified function(s). It will also be understood that each block of the flowchart illustrations, as well as any procedures, algorithms, steps, operations, formulae, or computational depictions and combinations thereof described herein, can be implemented by special purpose hardware-based computer systems which perform the specified function(s) or step(s), or combinations of special purpose hardware and computer-readable program code.

[0094] Furthermore, these computer program instructions, such as embodied in computer-readable program code, may also be stored in one or more computer-readable memory or memory devices that can direct a computer processor or other programmable processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory or memory devices produce an article of manufacture including instruction means which implement the function specified in the block(s) of the flowchart(s). The computer program instructions may also be executed by a computer processor or other programmable processing apparatus to cause a series of operational steps to be performed on the computer processor or other programmable processing apparatus to produce a computer- implemented process such that the instructions which execute on the computer processor or other programmable processing apparatus provide steps for implementing the functions specified in the block(s) of the flowchart(s), procedure (s) algorithm(s), step(s), operation(s), formula(e), or computational depiction(s).

[0095] It will further be appreciated that the terms "programming" or "program executable" as used herein refer to one or more instructions that can be executed by one or more computer processors to perform one or more functions as described herein. The instructions can be embodied in software, in firmware, or in a combination of software and firmware. The instructions can be stored locally to the device in non-transitory media or can be stored remotely such as on a server, or all or a portion of the instructions can be stored locally and remotely. Instructions stored remotely can be downloaded (pushed) to the device by user initiation or automatically based on one ormore factors.

[0096] It will further be appreciated that as used herein, the terms controller, microcontroller, processor, microprocessor, hardware processor, computer processor, central processing unit (CPU), and computer are used synonymously to denote a device capable of executing the instructions and communicating with input / output interfaces and / or peripheral devices, and that the terms controller, microcontroller, processor, microprocessor, hardware processor, computer processor, CPU, and computer are intended to encompass single or multiple devices, single core and multicore devices, and variations thereof.

[0097] From the description herein, it will be appreciated that the present disclosure encompasses multiple implementations of the technology which include, but are not limited to, the following:

[0098] A biopsy holder apparatus, comprising: a housing including an upper surface, a groove, a first end, a second end, and a chamber within the housing, wherein the groove is positioned between the first end and the second end along the upper surface and comprises a plurality of openings extending into the chamber to fluidically couple the chamber and the groove; and a vacuum port positioned at the first end, the vacuum port comprising a channel fluidically coupled to the chamber.

[0099] The apparatus of any preceding or following implementation, wherein an application of a vacuum to the vacuum port creates a suction force within the groove.

[0100] The apparatus of any preceding or following implementation, wherein the upper surface of the housing has a first inclined surface with a slope from a first vertical side wall of the housing to the groove and a second inclined surface with a slope from a second vertical side wall of the housing to the groove.

[0101] The apparatus of any preceding or following implementation, wherein an angle of inclination of the first and second inclined surfaces is ten degrees from horizontal.

[0102] The apparatus of any preceding or following implementation, wherein the plurality of openings is evenly distributed across a length of the groove orare grouped together in one or more subsets of openings positioned at different locations along a length of the groove.

[0103] The apparatus of any preceding or following implementation, wherein each of the plurality of openings has a square shaped cross-section.

[0104] The apparatus of any preceding or following implementation, wherein a distance between each opening of a plurality of openings is equal to a crosssection of each opening.

[0105] The apparatus of any preceding or following implementation, further comprising a slot positioned within the housing and extending along a lengthwise portion of the groove, the slot configured to removably receive a mesh or filter.

[0106] The apparatus of any preceding or following implementation, wherein the slot extends from the second end to a location distal to the first end along the length-wise portion of the groove.

[0107] The apparatus of any preceding or following implementation, wherein the slot is fluidically coupled to the groove.

[0108] The apparatus of any preceding or following implementation, further comprising a mesh mounted to the upper surface.

[0109] The apparatus of any preceding or following implementation, wherein the mesh is pre-formed or amenable to conform to surface characteristics of the upper surface.

[0110] A method for using a biopsy holder apparatus comprising a housing including an upper surface, a groove, a first end, a second end, and a chamber within the housing, wherein the groove is positioned between the first end and the second end along the upper surface and comprises a plurality of openings extending into the chamber to fluidically couple the chamber and the groove, and a vacuum port positioned at the first end, the vacuum port comprising a channel extending to the chamber to fluidically couple the vacuum port to the chamber and the groove, the method comprising: receiving, in the groove, a biopsy needle comprising a sample contained therein; applying a vacuum to the vacuum port to create a suction force within the groove; and maintaining the sample in place within or adjacent to the groove, via the suction force, when the sample is removedfrom the biopsy needle.

[0111] The method of any preceding or following implementation, further comprising placing the needle biopsy holder having the sample maintained in place, via the suction force, in an imaging platform.

[0112] The method of any preceding or following implementation, wherein the apparatus further comprises a slot positioned within the housing and extending along a length-wise portion of the groove, the method further comprising receiving a mesh or filter within the slot.

[0113] The method of any preceding or following implementation, wherein the maintaining the sample in place comprises holding the sample in place on the mesh or filter, via the suction force.

[0114] A biopsy imaging system, comprising: an imager with a specimen stage; and a specimen holder adapted to couple to the specimen stage of the imager, the specimen holder comprising: a housing with an internal chamber, an exterior surface with a groove and a plurality of openings within the groove extending to the internal chamber; and a vacuum port fluidly coupled with the internal chamber and plurality of openings.

[0115] The system of any preceding or following implementation, further comprising a vacuum source coupled to the vacuum port, wherein an application of a vacuum to the vacuum port creates a suction force within the groove.

[0116] The system of any preceding or following implementation, further comprising a porous sample platform positioned on the exterior surface of the housing over the groove.

[0117] The system of any preceding or following implementation, wherein the exterior surface of the housing comprises: a first inclined surface with a slope from a first side wall of the housing to the groove; and a second inclined surface with a slope from a second side wall of the housing to the groove.

[0118] The system of any preceding or following implementation, wherein an angle of inclination of the first and second inclined surfaces is ten degrees from horizontal.

[0119] The system of any preceding or following implementation, further comprising: a mesh sample platform with a first angle of inclination configuredto conform with the first inclined surface of the exterior surface of the housing and a second angle of inclination configured to conform with the second inclined surface of the exterior surface of the housing.

[0120] The system of any preceding or following implementation, wherein the apparatus can be scaled up or down for holding larger tissue samples produced using other extraction methods other than conventional core needle biopsies.

[0121] The system of any preceding or following implementation, wherein the imager is adapted to perform imaging selected from the group of Fluorescence Imitating Brightfield Imaging (FIBI), UV surface excitation microscopy (MUSE), multiphoton microscopy, confocal microscopy in brightfield reflection mode, nonlinear microscopy, structured-illumination microscopy with phase-mask detection, full-field optical coherence tomography, light-sheet microscopy, and photoacoustic microscopy.

[0122] As used herein, the term "implementation" is intended to include, without limitation, embodiments, examples, or other forms of practicing the technology described herein.

[0123] As used herein, the singular terms "a," "an," and "the" may include plural referents unless the context clearly dictates otherwise. Reference to an object in the singular is not intended to mean "one and only one" unless explicitly so stated, but rather "one or more."

[0124] Phrasing constructs, such as “A, B and / or C”, within the present disclosure describe where either A, B, or C can be present, or any combination of items A, B and C. Phrasing constructs indicating, such as “at least one of” followed by listing a group of elements, indicates that at least one of these groups of elements is present, which includes any possible combination of the listed elements as applicable.

[0125] References in this disclosure referring to “an embodiment”, “at least one embodiment” or similar embodiment wording indicates that a particular feature, structure, or characteristic described in connection with a described embodiment is included in at least one embodiment of the present disclosure. Thus, these various embodiment phrases are not necessarily all referring to the same embodiment, or to a specific embodiment which differs from all theother embodiments being described. The embodiment phrasing should be construed to mean that the particular features, structures, or characteristics of a given embodiment may be combined in any suitable manner in one or more embodiments of the disclosed apparatus, system, or method.

[0126] As used herein, the term "set" refers to a collection of one or more objects. Thus, for example, a set of objects can include a single object or multiple objects.

[0127] Relational terms such as first and second, top and bottom, upper and lower, left and right, topside and underside, front and back, proximal and distal, leading and trailing, and the like, may be used solely to distinguish one entity, action, or orientation from another entity, action, or orientation without necessarily requiring or implying any actual such relationship or order between such entities, actions, or orientations. Such terms are not intended to be terms of limitation read into the claims.

[0128] The terms "comprises," "comprising," "has", "having," "includes", "including," "contains", "containing" or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, apparatus, or system, that comprises, has, includes, or contains a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, apparatus, or system. An element proceeded by "comprises . . . a", "has . . . a", "includes . . . a", "contains . . . a" does not, without more constraints, preclude the existence of additional identical elements in the process, method, article, apparatus, or system, that comprises, has, includes, contains the element.

[0129] As used herein, the terms "approximately", "approximate", "substantially", "substantial", "essentially", and "about", or any other version thereof, are used to describe and account for small variations. When used in conjunction with an event or circumstance, the terms can refer to instances in which the event or circumstance occurs precisely as well as instances in which the event or circumstance occurs to a close approximation. When used in conjunction with a numerical value, the terms can refer to a range of variation of less than or equal to ± 10% of that numerical value, such as lessthan or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1 %, less than or equal to ±0.5%, less than or equal to ±0.1 %, or less than or equal to ±0.05%. For example, "substantially" aligned can refer to a range of angular variation of less than or equal to ±10°, such as less than or equal to ±5°, less than or equal to ±4°, less than or equal to ±3°, less than or equal to ±2°, less than or equal to ±1 °, less than or equal to ±0.5°, less than or equal to ±0.1 °, or less than or equal to ±0.05°.

[0130] Additionally, amounts, ratios, and other numerical values may sometimes be presented herein in a range format. It is to be understood that such range format is used for convenience and brevity and should be understood flexibly to include numerical values explicitly specified as limits of a range, but also to include all individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly specified. For example, a ratio in the range of about 1 to about 200 should be understood to include the explicitly recited limits of about 1 and about 200, but also to include individual ratios such as about 2, about 3, and about 4, and sub-ranges such as about 10 to about 50, about 20 to about 100, and so forth.

[0131] The term "coupled" as used herein is defined as connected, although not necessarily directly and not necessarily mechanically. A device or structure that is "configured" in a certain way is configured in at least that way but may also be configured in ways that are not listed.

[0132] Benefits, advantages, solutions to problems, and any element(s) that may cause any benefit, advantage, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential feature or element of the technology described herein or any or all the claims.

[0133] In addition, in the foregoing disclosure various features may be grouped together in various embodiments for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments require more features than are expressly recited in each claim. Inventive subject matter can lie in less than all features of a single disclosed embodiment.

[0134] The abstract of the disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.

[0135] It will be appreciated that the practice of some jurisdictions may require deletion of one or more portions of the disclosure after the application is filed. Accordingly, the reader should consult the application as filed for the original content of the disclosure. Any deletion of content of the disclosure should not be construed as a disclaimer, forfeiture, or dedication to the public of any subject matter of the application as originally filed.

[0136] All text in a drawing figure is hereby incorporated into the disclosure and is to be treated as part of the written description of the drawing figure.

[0137] The following claims are hereby incorporated into the disclosure, with each claim standing on its own as a separately claimed subject matter.

[0138] Although the description herein contains many details, these should not be construed as limiting the scope of the disclosure, but as merely providing illustrations of some of the presently preferred embodiments. Therefore, it will be appreciated that the scope of the disclosure fully encompasses other embodiments which may become obvious to those skilled in the art.

[0139] All structural and functional equivalents to the elements of the disclosed embodiments that are known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the present claims. Furthermore, no element, component, or method step in the present disclosure is intended to be dedicated to the public regardless of whether the element, component, or method step is explicitly recited in the claims. No claim element herein is to be construed as a "means plus function" element unless the element is expressly recited using the phrase "means for". No claim element herein is to be construed as a "step plus function" element unless the element is expressly recited using the phrase "step for."

Claims

CLAIMSWhat is claimed is:1 . A biopsy holder apparatus, comprising: a housing including an upper surface, a groove, a first end, a second end, and a chamber within the housing, wherein the groove is positioned between the first end and the second end along the upper surface and comprises a plurality of openings extending into the chamber to fluidically couple the chamber and the groove; and a vacuum port positioned at the first end, the vacuum port comprising a channel fluidically coupled to the chamber.

2. The apparatus of claim 1 , wherein an application of a vacuum to the vacuum port creates a suction force within the groove.

3. The apparatus of claim 1 , wherein the upper surface of the housing has a first inclined surface with a slope from a first vertical side wall of the housing to the groove and a second inclined surface with a slope from a second vertical side wall of the housing to the groove.

4. The apparatus of claim 3, wherein an angle of inclination of the first and second inclined surfaces is ten degrees from horizontal.

5. The apparatus of claim 1 , wherein the plurality of openings are evenly distributed across a length of the groove or are grouped together in one or more subsets of openings positioned at different locations along a length of the groove .

6. The apparatus of claim 1 , wherein each of the plurality of openings has a square shaped cross-section.

7. The apparatus of claim 1 , wherein a distance between each opening of a plurality of openings is equal to a cross-section of each opening.

8. The apparatus of claim 1 , further comprising a slot positioned within the housing and extending along a length-wise portion of the groove, the slot configured to removably receive a mesh or filter.

9. The apparatus of claim 1 , wherein the slot extends from the second end to a location distal to the first end along the length-wise portion of the groove.

10. The apparatus of claim 1 , wherein the slot is fluidically coupled to the groove.11 . The apparatus of claim 1 , further comprising a mesh mounted to the upper surface.

12. The apparatus of claim 11 , wherein the mesh is pre-formed or amenable to conform to surface characteristics of the upper surface.

13. A method for using a biopsy holder apparatus comprising a housing including an upper surface, a groove, a first end, a second end, and a chamber within the housing, wherein the groove is positioned between the first end and the second end along the upper surface and comprises a plurality of openings extending into the chamber to fluidically couple the chamber and the groove, and a vacuum port positioned at the first end, the vacuum port comprising a channel extending to the chamber to fluidically couple the vacuum port to the chamber and the groove, the method comprising: receiving, in the groove, a biopsy needle comprising a sample contained therein; applying a vacuum to the vacuum port to create a suction force within the groove; and maintaining the sample in place within or adjacent to the groove, via the suction force, when the sample is removed from the biopsy needle.

14. The method of claim 13, further comprising placing the needle biopsy holder having the sample maintained in place, via the suction force, in an imaging platform.

15. The method of claim 13, wherein the apparatus further comprises a slot positioned within the housing and extending along a length-wise portion of the groove, the method further comprising receiving a mesh or filter within the slot.

16. The method of claim 15, wherein said maintaining the sample in place comprises holding the sample in place on the mesh or filter, via the suction force.

17. A biopsy imaging system, comprising: an imager with a specimen stage; and a specimen holder adapted to couple to the specimen stage of the imager, said specimen holder comprising: a housing with an internal chamber, an exterior surface with a groove and a plurality of openings within the groove extending to the internal chamber; and a vacuum port fluidly coupled with the internal chamber and plurality of openings.

18. The system of claim 17, further comprising: a vacuum source coupled to the vacuum port, wherein an application of a vacuum to the vacuum port creates a suction force within the groove.

19. The system of claim 17, further comprising: a porous sample platform positioned on the exterior surface of the housing over the groove.

20. The system of claim 17, wherein the exterior surface of the housing comprises: a first inclined surface with a slope from a first side wall of the housing to the groove; anda second inclined surface with a slope from a second side wall of the housing to the groove.21 . The system of claim 20, wherein an angle of inclination of the first and second inclined surfaces is ten degrees from horizontal.

22. The system of claim 20, further comprising: a mesh sample platform with a first angle of inclination configured to conform with said first inclined surface of said exterior surface of the housing and a second angle of inclination configured to conform with said second inclined surface of said exterior surface of the housing.

23. The system of claim 17, wherein said imager is adapted to perform imaging selected from the group of Fluorescence Imitating Brightfield Imaging (FIB I), UV surface excitation microscopy (MUSE), multiphoton microscopy, confocal microscopy in brightfield reflection mode, nonlinear microscopy, structured- illumination microscopy with phase-mask detection, full-field optical coherence tomography, light-sheet microscopy, and photoacoustic microscopy.

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