US2024044805A1PendingUtilityA1

Systems and methods for in-operating-theatre imaging of fresh tissue resected during surgery for pathology assessment

86
Assignee: SAMANTREE MEDICAL SAPriority: Mar 31, 2015Filed: Oct 18, 2023Published: Feb 8, 2024
Est. expiryMar 31, 2035(~8.7 yrs left)· nominal 20-yr term from priority
G01N 21/77G02B 21/0032G02B 21/004G02B 21/0076G02B 21/0088G02B 21/26G02B 21/34G02B 21/361G01N 21/6458G01N 21/6428G01N 33/4833G02B 21/16G02B 21/0044G02B 21/24G02B 21/0012G01N 2021/6439G01N 2021/6463G01N 2201/0633G01N 2201/068G01N 2021/7786
86
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Claims

Abstract

The disclosed technology brings histopathology into the operating theatre, to enable real-time intra-operative digital pathology. The disclosed technology utilizes confocal imaging devices image, in the operating theatre, “optical slices” of fresh tissue—without the need to physically slice and otherwise process the resected tissue as required by frozen section analysis (FSA). The disclosed technology, in certain embodiments, includes a simple, operating-table-side digital histology scanner, with the capability of rapidly scanning all outer margins of a tissue sample (e.g., resection lump, removed tissue mass). Using point-scanning microscopy technology, the disclosed technology, in certain embodiments, precisely scans a thin “optical section” of the resected tissue, and sends the digital image to a pathologist rather than the real tissue, thereby providing the pathologist with the opportunity to analyze the tissue intra-operatively. Thus, the disclosed technology provides digital images with similar information content as FSA, but faster and without destroying the tissue sample itself.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A system for in-operating-theatre imaging of fresh tissue samples resected during surgery (e.g., cancer surgery) for pathology assessment, the system comprising:
 a light source for providing (e.g., laser or other light source providing light with a wavelength of 488 nm or between 450-490 nm) an illumination beam that illuminates a fluorescent stained, fresh sample (e.g., a fluorescent-stained fresh sample) (e.g., an unsliced sample preserved for definitive assessment in follow-up testing), wherein the fresh sample is held by a sample holder located in an operating theatre;   a beam expander (e.g., collimating lens (e.g., for use with a monomode fibered laser) or a telecentric afocal magnification relay (e.g., for use with a collimated laser)) for expanding the waist of the illumination beam to a size comparable to the field of view to be illuminated, thereby providing a collimated illumination beam;   a beam splitter (e.g., dichroic mirror/filter, prism, or grating(s)) located between the sample and a detector array, for directing the collimated illumination beam toward a micro optical element array;   the micro optical element array (e.g., comprising refractive lenses, Fresnel zone plates, micro reflective objectives, and/or GRIN lenses; e.g., a micro lens array) for focusing the collimated illumination beam from the beam splitter onto the sample, thereby forming an array of tight foci for exciting the fluorescence in the sample to produce the back-emitted light, wherein the micro optical element array is configured such that:
 the micro optical element array collects back-emitted light from the sample, and the collected back-emitted light propagates (e.g., as individual collimated beams) and is directed (e.g., by a set of optics) to a detector array; and 
 a gap (e.g., an airgap) of less than 500 μm (e.g., 50-150 μm, 80-120 μm) is maintained between the micro optical element array and a window (e.g., a transparent window, e.g., made of glass, quartz, sapphire, plastic) onto which (e.g., above which) the sample is placed for imaging; 
   a scanning stage for moving a position of the micro optical element array relative to the transparent window and the detector array such that back-emitted light collected by the micro optical element array is detected by the detector array to form a scanned confocal image (e.g., to construct an optical slice of the sample), wherein:
 the position of the transparent window relative to the detector array is fixed (e.g., during imaging of the sample by the system), and 
 the scanning stage and micro optical element array are confined (e.g., fully confined) within the system such that the scanning stage and micro optical element array are protected from the sample (e.g., and the outside environment) by the transparent window; 
   an aperture stop for spatially filtering the back-emitted light (e.g., fluorescent light between 510-520 nm, or light with a wavelength greater than or equal to 490 nm and, in some implementations, less than 530 nm; between 491 nm and 520 nm), thereby rejecting out-of-focus light (e.g., filtering out collected sample information that does not originate from the foci of the micro optical elements prior to detection by the detector array), wherein the detector array comprises a plurality of detectors, each detector independently detecting a portion of the back-emitted light originating from a micro optical element in the micro optical element array; and   a computing device comprising a processor and a memory storing instructions thereon that, when executed by the processor, cause the processor to construct an image representing an optical slice of the fresh tissue sample based on the back-emitted light detected by the detector array.   
     
     
         2 . A system for in-operating-theatre imaging of fresh tissue samples resected during surgery (e.g., cancer surgery) for pathology assessment, the system comprising:
 a light source for providing (e.g., laser) an illumination beam that illuminates a fluorescent stained, fresh sample (e.g., a preserved sample—i.e., unsliced thereby preserving the sample for definitive assessment) held by a sample holder in an operating theatre;   a beam expander (e.g., collimating lens) for expanding a waist of the illumination beam, thereby providing a collimated illumination beam;   a beam splitter (e.g., dichroic mirror/filter, prism, or grating(s)), located between the sample and a detector array, for directing the collimated illumination beam toward a micro optical element array (e.g., using refractive lenses, Fresnel zone plates, micro reflective objectives, and/or GRIN lenses; e.g., a micro lens array);   the micro optical element array for focusing the collimated illumination beam from the beam splitter onto the sample, thereby forming an array of tight foci for exciting the fluorescence in the sample to produce back-emitted light, wherein:
 the micro optical element array collects back-emitted light from the sample, and the collected back-emitted light propagates (e.g., as individual collimated beams) and is directed (e.g., by a set of optics) to a detector array; and, 
 a gap (e.g., an airgap) of less than 500 μm (e.g., 50-150 μm, 80-120 μm) is maintained between the micro optical element array and a transparent window (e.g., glass, quartz, sapphire, plastic) onto which (e.g., above which) the sample is placed for imaging; 
   a scanning stage for moving a position of the transparent window relative to the micro optical element array and the detector array such that back-emitted light collected by the micro optical element array is detected by the detector array to form a scanned confocal image (e.g., to construct an optical slice of the sample), wherein the position of the micro optical element array relative to the detector array is fixed (e.g., during imaging of the sample by the system);   an aperture stop for spatially filtering the back-emitted light (e.g., fluorescent light between 510-520 nm, or light with a wavelength greater than or equal to 490 nm and, in some implementations, less than 530 nm, or between 491 nm and 520 nm), thereby rejecting out-of-focus light (e.g., filtering out collected sample information that is not originating from the foci of the micro optical elements prior to detection by the detector array), wherein the detector array comprises a plurality of detectors, each detector independently detecting a portion of the back-emitted light originating from a micro optical element in the micro optical element array; and   a computing device comprising a processor and a memory storing instructions thereon that, when executed by the processor, cause the processor to construct an image representing an optical slice of the fresh tissue sample based on the back-emitted light detected by the detector array.   
     
     
         3 . The system of any one of the preceding claims, wherein the memory stores instructions thereon that, when executed by the processor, cause the processor to send, via a network, the image to a second computing device such that a pathologist in a remote location (e.g., outside of the operating theatre) can perform the pathology assessment. 
     
     
         4 . The system of any one of the preceding claims, wherein the micro optical element array comprises a plurality of micro optical elements having curved surfaces facing the sample. 
     
     
         5 . The system of any one of the preceding claims, wherein the micro optical element array comprises a plurality of micro optical elements having curved surfaces facing the collimated illumination beam. 
     
     
         6 . The system of  claim 4  or  5 , wherein the curved surface of each micro optical element has a conical shaped surface. 
     
     
         7 . The system of  claim 6 , wherein the curved surface of each micro optical element has a hyperbolic shaped surface. 
     
     
         8 . The system of  claim 7 , wherein the curved surface of each micro optical element has a conic constant from −1.8 to −2.2 (e.g., −2). 
     
     
         9 . The system of any one of the preceding claims, wherein each micro optical element has a Strehl ratio greater than or equal to 0.8. 
     
     
         10 . The system of any one of the preceding claims, wherein each micro optical element has a spot size from 0.2 μm to 5 μm, 0.2 μm to 1 μm, 0.3 μm to 0.6 μm, and 0.4 μm to 0.5 μm. 
     
     
         11 . The system of any one of the preceding claims, wherein a free working distance (i.e., a distance from the tip of the micro optical elements to a focal plane of the micro optical element array) is from 80 μm to 450 μm, 150 μm to 350 μm, or 250 μm to 300 μm. 
     
     
         12 . The system of any one of the preceding claims, wherein the micro optical element array has a focal plane from 10 μm to 200 μm, 20 μm to 150 μm, or 50 μm to 100 μm above the transparent window. 
     
     
         13 . The system of any one of the preceding claims, comprising a kinematic support structure having at least three feet (e.g., four) of adjustable height, the support structure supporting the scanning stage such that the height and tilt of the transparent window relative to the micro optical element array and the corresponding optical path are adjustable. 
     
     
         14 . The system of any one of the preceding claims, comprising:
 a first flat mirror for reflecting the collimated illumination beam onto the beam splitter.   
     
     
         15 . The system of  claim 14 , comprising:
 a second flat mirror for reflecting the collimated illumination beam from the beam splitter to the micro optical element array.   
     
     
         16 . The system of  claim 15 , wherein the second flat mirror reflects the back-emitted light passed through the micro optical element array from the sample through the beam splitter. 
     
     
         17 . The system of any one of the preceding claims, comprising:
 a field lens for focusing the back-emitted light prior to spatially filtering the back-emitted light.   
     
     
         18 . The system of any one of the preceding claims, wherein the beam expander is a collimating lens. 
     
     
         19 . The system of any one of the preceding claims, wherein the ratio of micro optical elements to detectors is from 1:1 to 1:100, 1:5 to 1:80, 1:20 to 1:70, 1:30 to 1:60, or 1:40 to 1:50 (e.g., about 1:1, 1:2, 1:3, 1:4, 1:6, 1:8, or 1:12, e.g., to the nearest whole number, or within a range of any two of these values). 
     
     
         20 . The system of any one of the preceding claims, wherein the micro optical element array comprises from 1000 to 100,000 micro optical elements (e.g., 1600 micro optical elements for a 10 mm field of view; 6400 micro optical elements for a 20 mm field of view, etc.). 
     
     
         21 . The system of any one of the preceding claims, wherein the sample is stained with a fluorescent stain (e.g., proflavine, acridine orange, hematoxylin or eosin). 
     
     
         22 . The system of any one of the preceding claims, wherein the system is configured for in-operating-theatre imaging of tissue (e.g., fresh) resected during surgery (e.g., cancer surgery) in less than 10 minutes (e.g., less than 5 minutes). 
     
     
         23 . The system of any one of the preceding claims, comprising:
 a first computing device for sending information regarding the detected back-emitted light (e.g., an image captured by the camera) to a second computing device (e.g., remote from the first computer device—i.e., outside the operating theatre).   
     
     
         24 . The system of any one of the preceding claims, wherein the sample holder is screwed onto the scanning stage. 
     
     
         25 . The system of any one of the preceding claims, wherein the scanning stage is a three axis positioning stage (e.g., a high precision positioning stage, e.g., with precision equal or better than one micrometer; in other embodiments, the stage is a two-axis positioning stage, e.g., high precision positioning stage). 
     
     
         26 . The system of any one of the preceding claims, wherein the sample holder comprises the transparent window. 
     
     
         27 . The system of any one of the preceding claims, wherein the transparent window is a thin transparent window (e.g., 50-100 μm, or 100-500 μm thick; e.g., thin glass with a thickness from 50-100 μm or 100-500 μm). 
     
     
         28 . The system of any one of the preceding claims, comprising an optical interface clamp (e.g., ring-shaped) that maintains the transparent window in place. 
     
     
         29 . The system of any one of the preceding claims, wherein the sample holder comprises a seal at the bottom of the transparent window to protect the system from sample liquid. 
     
     
         30 . The system of any one of the preceding claims, wherein the transparent window provides an optical interface (e.g., transparent and flat between the sample and the micro optical element array. 
     
     
         31 . The system of any one of the preceding claims, wherein the scanning stage is configured to bring the transparent window in close proximity to the micro optical element array (e.g., within 100 μm). 
     
     
         32 . The system of any one of the preceding claims, wherein the sample holder comprises a metallic body. 
     
     
         33 . The system of any one of the preceding claims, wherein the sample holder comprises an opening window (e.g., 40×20 mm, 10-50 mm by 10-50 mm; e.g., covered/filled by the transparent window). 
     
     
         34 . The system of any one of the preceding claims, wherein the scanning stage comprises a translation mechanism which is configured for establishing a relative motion between said sample and said micro optical element array. 
     
     
         35 . The system of any one of the preceding claims, wherein:
 the sample is located in the focus area of the micro optical element array; and   each micro optical element is configured to collect and direct sample information from the sample toward the detector.   
     
     
         36 . The system of any one of the preceding claims, wherein the sample holder is configured (e.g. is sized and shaped) to accommodate a sample having a thickness that is within a range of 0.5-20 mm (e.g., that is within a range of 3-5 mm, 5-10 mm, 7-15 mm, 10-25 mm, 15-30 mm, or 25-35 mm, and/or that is no less than 0.5 mm, no less than 1 mm, no less than 3 mm, or no less than 5 mm). 
     
     
         37 . The system of any one of the preceding claims, comprising a mobile cart. 
     
     
         38 . The system of any one of the preceding claims, comprising an attachment system for attaching a removable sample holder to the scanning stage. 
     
     
         39 . The system of  claim 38 , wherein the attachment system comprises a support base mounted on the scanning stage, the support base having a mount with one or more protrusions extending from the mount, wherein the mount is hollow on the inside and the support base has a corresponding opening therein such that an optical chip can scan a sample through the support base. 
     
     
         40 . A method for in-operating-theatre imaging of fresh tissue samples resected during surgery (e.g., cancer surgery) for pathology assessment, the method comprising:
 providing, by a light source (e.g., laser or other light source providing light with a wavelength of 488 nm or between 450-490 nm), an illumination beam for illuminating a fluorescent stained, fresh sample (e.g., a fluorescent-stained fresh sample) (e.g., an unsliced sample preserved for definitive assessment in follow-up testing) held by a sample holder located in an operating theatre;   directing a collimated light beam via illumination optics onto the fresh sample (e.g., the fresh fluorescent stained sample) held by the sample holder in the operating theatre, wherein the illumination optics comprise:
 a beam expander expanding a waist of the illumination beam, thereby providing the collimated illumination beam, 
 a beam splitter (e.g., dichroic mirror/filter, prism, or grating(s)), located between the sample and a detector array, directing the collimated illumination beam toward a micro optical element array (e.g., the micro optical element array comprising refractive lenses, Fresnel zone plates, micro reflective objectives, and/or GRIN lenses; e.g., a micro lens array), and 
 the micro optical element array for focusing the collimated illumination beam from the beam splitter onto the sample, thereby forming an array of tight foci for exciting the fluorescence in the sample to produce the back-emitted light, wherein:
 each micro optical element focuses a portion of the collimated illumination beam onto the sample, and 
 a gap (e.g., airgap) of less than 500 μm (e.g., 50-150 μm, 80-120 μm) is maintained between the micro optical element array and a transparent window (e.g., glass, quartz, sapphire, plastic) onto which (e.g., above which) the sample is placed for imaging; 
 
   directing the back-emitted light from the sample to the detector array via detecting optics, the detecting optics comprising:
 the micro optical element array, which collects the back-emitted light from the sample, which propagates (e.g., as individual collimated beams) and is directed (e.g., by a set of optics) to the detector array, and 
 an aperture stop spatially filtering the back-emitted light, thereby rejecting out-of-focus light; 
   moving, by a scanning stage, a position of the micro optical element array relative to the transparent window and the detector array such that back-emitted light focused by the micro optical element array is detected by the detector array to form a scanned confocal image (e.g., to construct an optical slice of the sample), wherein:
 the position of the transparent window relative to the detector array is fixed (e.g., during imaging of the sample by the system), and 
 the scanning stage and micro optical element array are confined (e.g., fully confined) within the system such that the scanning stage and micro optical element array are protected from the sample (e.g., and the outside environment) by the transparent window; 
   detecting, by the detector array, the back-emitted light filtered by the aperture stop, wherein the detector array comprises a plurality of detectors, each detector independently detecting a portion of the back-emitted light originating from a micro optical element in the micro optical element array; and   constructing, by a processor of a computing device, an image representing an optical slice of the fresh tissue sample based on the back-emitted light detected by the detector array.   
     
     
         41 . A method for in-operating-theatre imaging of fresh tissue resected during surgery (e.g., cancer surgery) for pathology assessment, the method comprising:
 providing, by a light source (e.g., laser or other light source providing light with a wavelength of 488 nm or between 450-490 nm), an illumination beam for illuminating a fluorescent stained, fresh sample (e.g., a preserved sample—i.e., unsliced thereby preserving the sample for definitive assessment) held by a sample holder in an operating theatre;   directing a collimated light beam via illumination optics onto a fresh (e.g., fluorescent-stained) sample held by a sample holder in an operating theatre, wherein the illumination optics comprise:
 a beam expander expanding a waist of the illumination beam, thereby providing the collimated illumination beam, 
 a beam splitter (e.g., dichroic mirror/filter, prism, or grating(s)), located between the sample and a detector array, directing the collimated illumination beam toward a micro optical element array (e.g., the micro optical element array comprising refractive lenses, Fresnel zone plates, micro reflective objectives, and/or GRIN lenses; e.g., a micro lens array), and 
 the micro optical element array focusing the collimated illumination beam from the beam splitter onto the sample, thereby forming an array of tight foci for exciting the fluorescence in the sample to produce the back-emitted light, wherein:
 each micro optical element in the micro optical element array focuses a portion of the collimated illumination beam onto the sample, and 
 a gap (e.g., airgap) of less than 500 μm (e.g., 50-150 μm, 80-120 μm) is maintained between the micro optical element array and a transparent window (e.g., glass, quartz, sapphire, plastic) onto which (e.g., above which) the sample is placed for imaging; 
 
   directing the back-emitted light from the sample to the detector array via detecting optics, the detecting optics comprising:
 the micro optical element array, which collects the back-emitted light that propagates (e.g., as individual collimated beams) and is directed (e.g., by a set of optics) to a detector array, and 
 an aperture stop spatially filtering the back-emitted light, thereby rejecting out-of-focus light; 
   moving, by a scanning stage, a position of the transparent window relative to the micro optical element array and the detector array such that back-emitted light focused by the micro optical element array is detected by the detector array to form a scanned confocal image (e.g., to construct an optical slice of the sample, wherein the position of the micro optical element array relative to the detector array is fixed (e.g., during imaging of the sample by the system);   detecting, by the detector array, the back-emitted light filtered by the aperture stop, wherein the detector array comprises a plurality of detectors, each detector independently detecting a portion of the back-emitted light originating from a micro optical element in the micro optical element array; and   constructing, by a processor of a computing device, an image representing an optical slice of the fresh tissue sample based on the back-emitted light detected by the detector array.   
     
     
         42 . The method of  claim 40  or  41 , comprising:
 sending, by the processor, via a network, the image to a second computing device such that a pathologist in a remote location (e.g., outside of the operating theatre) can perform the pathology assessment. 
 
     
     
         43 . The method of any one of  claims 40  to  42 , wherein the micro optical element array comprises a plurality of micro optical elements having curved surfaces facing the sample. 
     
     
         44 . The method of any one of  claims 40  to  43 , wherein the micro optical element array comprises a plurality of micro optical elements having curved surfaces facing the collimated illumination beam. 
     
     
         45 . The method of  claim 40  or  44 , wherein the curved surface of each micro optical element has a conical shaped surface. 
     
     
         46 . The method of  claim 45 , wherein the curved surface of each micro optical element has a hyperbolic shaped surface. 
     
     
         47 . The method of  claim 46 , wherein the curved surface of each micro optical element has a conic constant from −1.8 to −2.2 (e.g., −2). 
     
     
         48 . The method of any one of  claims 40  to  47 , wherein each micro optical element has a Strehl ratio greater than or equal to 0.8. 
     
     
         49 . The method of any one of  claims 40  to  48 , wherein each micro optical element has a spot size of 0.1 μm to 2 μm, 0.2 μm to 1 μm, 0.3 μm to 0.6 μm, or 0.4 μm to 0.5 μm. 
     
     
         50 . The method of any one of  claims 40  to  49 , wherein a free working distance (i.e., a distance from the tip of the micro optical elements to a focal plane of the micro optical element array) is from 80 μm to 450 μm, 150 μm to 350 μm, or 250 μm to 300 μm. 
     
     
         51 . The method of any one of  claims 40  to  50 , wherein the micro optical element array has a focal plane from 10 μm to 200 μm, 20 μm to 150 μm, or 50 μm to 100 μm above the transparent window. 
     
     
         52 . The method of any one  claims 40  to  51 , wherein a kinematic support structure having at least three feet (e.g., four) of adjustable height supports the scanning stage such that the height and tilt of the transparent window relative to the micro optical element array (e.g., and the corresponding optical path) are adjustable. 
     
     
         53 . The method of any one of  claims 40  to  52 , wherein the illumination optics comprises:
 a first flat mirror reflecting the collimated illumination beam onto the beam splitter. 
 
     
     
         54 . The method of  claim 53 , wherein the illumination optics comprises:
 a second flat mirror reflecting the collimated illumination beam from the beam splitter to the micro optical element array.   
     
     
         55 . The method of  claim 54 , wherein the second flat mirror reflects the back-emitted light passed through the micro optical element array from the sample through the beam splitter. 
     
     
         56 . The method of any one of  claims 40  to  55 , wherein the detection optics comprises:
 a field lens focusing the back-emitted light prior to spatially filtering the back-emitted light. 
 
     
     
         57 . The method of any one of  claims 40  to  56 , wherein the beam expander is a collimating lens. 
     
     
         58 . The method of any one of  claims 40  to  57 , wherein the ratio of detectors to micro optical elements is from 1:1 to 1:100, 1:5 to 1:80, 1:20 to 1:70, 1:30 to 1:60, or 1:40 to 1:50 (e.g., about 1:1, 1:2, 1:3, 1:4, 1:6, 1:8, or 1:12, e.g., to the nearest whole number, or within a range of any two of these values). 
     
     
         59 . The method of any one of  claims 40  to  58 , wherein the micro optical element array comprises from 1000 to 100,000 micro optical elements (e.g., 1600 micro optical elements for a 10 mm field of view; 6400 micro optical elements for a 20 mm field of view, etc.). 
     
     
         60 . The method of any one of  claims 40  to  59 , wherein the sample is stained with a fluorescent stain (e.g., proflavine, acridine orange, hematoxylin or eosin). 
     
     
         61 . The method of any one of  claims 40  to  60 , wherein the method is performed in less than 10 minutes (e.g., less than 5 minutes). 
     
     
         62 . The method of any one of  claims 40  to  61 , comprising:
 sending, by a processor of a first computing device, to a second computing device (e.g., remote from the first computer device—i.e., outside the operating theatre) information regarding the detected back-emitted light (e.g., an image captured by the camera). 
 
     
     
         63 . The method of any one of  claims 40  to  62 , comprising, prior to providing an illumination beam for illuminating the sample:
 staining the sample with a fluorescent stain; and 
 placing the sample in/on the sampler holder. 
 
     
     
         64 . The method of any one of  claims 40  to  63 , wherein the sample holder is screwed onto the scanning stage. 
     
     
         65 . The method of any one of  claims 40  to  64 , wherein the scanning stage is a three axis positioning stage (e.g., high precision positioning stage; e.g., in other embodiments, the scanning stage is a two-axis positioning stage, e.g., high precision positioning stage). 
     
     
         66 . The method of any one of  claims 40  to  65 , wherein the sample holder comprises the transparent window. 
     
     
         67 . The method of any one of  claims 40  to  66 , wherein the transparent window is a thin transparent window (e.g., 50-100 μm, or 100-500 μm thick; e.g., thin glass with a thickness from 50-100 μm or 100-500 μm). 
     
     
         68 . The method of any one of  claims 40  to  67 , wherein the sample holder comprises a seal at the bottom of the transparent window to protect the system from sample liquid. 
     
     
         69 . The method of any one of  claims 40  to  68 , the transparent window provides an optical interface (e.g., transparent and flat) between the sample and the micro optical element array. 
     
     
         70 . The method of any one of  claims 40  to  69 , wherein the scanning stage brings the transparent window in close proximity to the micro optical element array (e.g., within 100 μm). 
     
     
         71 . The method of any one of  claims 40  to  70 , wherein the sample holder comprises a metallic body. 
     
     
         72 . The method of any one of  claims 40  to  71 , wherein the sample holder comprises an opening (e.g., 40×20 mm, 10-50 mm by 10-50 mm) covered/filled by the transparent window. 
     
     
         73 . The method of any one of  claims 40  to  72 , wherein the scanning stage comprises a translation system for establishing a relative motion between the sample and the micro optical element array. 
     
     
         74 . The method of any one of  claims 40  to  73 , wherein:
 the sample is located in the focus area of the micro optical element array; and 
 each micro optical element is configured to collect and direct sample information from the sample towards the detector. 
 
     
     
         75 . The method of any one of  claims 40  to  74 , wherein the sample has a thickness that is within a range of 0.5-20 mm (e.g., that is within a range of 3-5 mm, 5-10 mm, 7-15 mm, 10-25 mm, 15-30 mm, or 25-35 mm, and/or that is no less than 0.5 mm, no less than 1 mm, no less than 3 mm, or no less than 5 mm). 
     
     
         76 . A method for in-operating-theatre imaging of tissue (e.g., fresh tissue) resected during surgery (e.g., cancer surgery) for pathology assessment, the method comprising:
 intraoperatively resecting tissue to obtain a fresh tissue sample;   procuring an image of the fresh tissue sample (e.g., using the system of any one of  claims 1  to  39 ); and   sending, by a processor of a first computing device, to a second computing device (e.g., remote from the first computer device—i.e., outside the operating theatre) the image of the fresh tissue sample.   
     
     
         77 . A sample holding device, comprising:
 a support base that can be mounted on a pathology system, the support base comprising a mount having one or more protrusions extending from the mount, wherein the mount is hollow on the inside and the support base has a corresponding opening therein such that an optical chip can scan a sample through the support base; and   a removable sample holder that is removably attachable to the support base, the removable sample holder comprising:
 a housing having an opening therethrough with one or more (e.g., two) interior protrusions extending into the opening, wherein the size and shape (e.g., round, cylindrical, circular) of the opening in the housing is such that the removable sample holder can be attached over the support base and twisted such that the one or more interior protrusions of the removable sample holder engage the one or more protrusions of the support base, thereby securing the removable sample holder to the support base; and 
 a transparent window on which the sample can be placed and through which the optical chip can image the sample.

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