# US 12,002,572 B2 · Methods, apparatuses, systems and devices for mobile digital spatial profiling of pathological specimens > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,002,572 B2 - Document ID: US12002572B2 - Status: Granted - Kind: B2 - Application number: 17/413,674 - Filed: 2019-12-20 - Published: 2022-03-10 - Granted: 2024-06-04 - Earliest claimed: 2018-12-21 - Assignees: NanoString Technologies, Inc. - Applicants: NanoString Technologies, Inc. - Inventors: Joseph M. Beechem; Dwayne Dunaway; Jaemyeong Jung; Peter E. Schultz; Eliot Sosin; Grant Tremel - Web page: https://patentgrep.com/patent/US12002572B2 ## CPC - G01N 33/5302: {Apparatus specially adapted for immunological test procedures} - G16H 30/40: for processing medical images, e.g. editing - G01N 21/01: Arrangements or apparatus for facilitating the optical investigation - G01N 21/255: {Details, e.g. use of specially adapted sources, lighting or optical systems} - G02B 21/0052: {Optical details of the image generation} - G02B 21/08: Condensers - G02B 21/16: adapted for ultraviolet illumination {; Fluorescence microscopes (G02B21/0076 takes precedence)} - G02B 21/367: {providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison} - G06V 10/255: {Detecting or recognising potential candidate objects based on visual cues, e.g. shapes} - G16H 70/60: relating to pathologies - H04W 4/80: Services using short range communication, e.g. near-field communication [NFC], radio-frequency identification [RFID] or low energy communication - G01N 21/6458: {Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16)} - G01N 2021/0118: {Apparatus with remote processing} - G01N 2201/0221: Portable; cableless; compact; hand-held - G01N 2201/067: Electro-optic, magneto-optic, acousto-optic elements - G06F 2218/10: by analysing the shape of a waveform, e.g. extracting parameters relating to peaks - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA - G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS - G06V: IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING - H04W: WIRELESS COMMUNICATION NETWORKS (broadcast communication H04H; communication systems using wireless links for non-selective communication, e.g. wireless extensions H04M1/72) - G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N) ## Abstract Embodiments of the present disclosure are directed to a compact, mobile, digital spatial profiling (DSP) system, and associated apparatuses, devices and methods, which are configured to image one or more regions-of-interest (ROIs), and then using UV light to cleave, for example, oligos off antibodies in one or more ROIs (“photocleaving”), and collect the photocleaved oligos for later hybridization and counting. ## Claims ### Claim 1 A digital spatial profiling (DSP) system comprising: a housing or other structure for containing at least one component of the DSP system, comprising: a power source; an ultraviolet (UV) light source (UVS); a visible light source (VLS) for bright field imaging; a chamber comprising a slot configured to receive at least a portion of a slide having a tissue sample thereon; a personal mobile computing device (PMD) comprising a user interface and a camera sensor, the PMD being arranged relative to the chamber in order to image the tissue sample on the slide within the chamber; photomasking means configured to selectively illuminate the tissue sample with UV light from the UVS and/or visible light from the VLS; optic means configured to at least one of direct and/or focus the UVS and/or VLS toward at least one of the tissue sample, the chamber, the photomasking means, and the camera sensor; and processing circuitry configured to acquire, via the camera sensor, an image of the tissue sample, display, via the user interface of the PMD, the image of the tissue sample, receive, via the user interface of the PMD, user input regarding a region of interest (ROD of the tissue sample, and illuminate, using the photomasking means, the ROI with UV light, wherein the PMD is removably attachable to the housing and/or the chamber. ### Claim 2 (depends on 1) The system of claim 1, wherein: the photomasking means comprises an LCD having a backlight, and wherein the VLS comprises the LCD backlight or external VLS, the optics means comprises a first set for the UVS comprising a condenser lens or scan lens, a dichroic mirror, and a second set of optics comprising an objective lens, the dichroic mirror is configured to redirect light from multiple sources into one optical axis; the photomasking means comprises an LCD configured as a programmable aperture so as to structure at least one of UV light or visible light to reach the tissue sample only in the ROI; and/or the photomasking means comprises at least one of a digital micro-mirror device (DMD), a liquid crystal on silicon (LCoS) display, organic light-emitting diode (OLED), micro light-emitting diode (p LED) array, fiber optic bundle, a liquid crystal display (LCD), a scanning laser, and a physical barrier. ### Claim 3 (depends on 2) The system of claim 2, wherein: the photomasking means comprises an LCD including a pixel grid, and wherein the LCD is arranged at a predetermined distance from the tissue sample; the predetermined distance is configured such that the tissue sample is not obscured by the pixel grid; the predetermined distance is selected to be between approximately 0.01 to 5 mm, 0.50 to 2.5 mm, 0.75 to 2.25 mm, or 1 to 2 mm; and/or the predetermined distance is configured to provide clear visualization of the tissue sample, and/or to minimize diffusion of UV light. ### Claim 4 (depends on 1) The system of claim 1, wherein: the system further comprises: a pump system configured to provide a flow of a solution to the chamber, and/or a software application operating on the processing circuitry and configured to cause the PMD to display, as the user interface, a graphical-user-interface (GUI) configured to receive the user input to select at least one ROI of the image acquired by the camera sensor and displayed via the user interface of the PMD, and the photomasking means is configured to provide at least one of: an illumination resolution of between approximately 50 and 300 nm, a field of view between approximately 5-12 cm2, and a magnification of between approximately 1-5×; at least one of the housing, the chamber, and the slot is configured to receive and/or retrieve at least one solution, the housing comprises or includes a plurality of scaffolds, a PMD frame, at least one objective lens frame, at least one slide frame, a photomasking frame, at least one condenser frame, and at least one thermal management means, the housing is configured to removably receive a single objective lens frame of a plurality of objective lens frames each having a different objective lens and corresponding magnification, and/or the system is further configured for at least one of dark-field microscopy, bright-field microscopy, phase-contrast microscopy, fluorescence microscopy and microscopy with ultraviolet surface excitation. ### Claim 5 (depends on 1) The system of claim 1, wherein at least one of the housing, the chamber, and the slot are configured to enable the slide to move relative thereto, and/or the housing, the chamber, and the slot is configured to receive and/or retrieve at least one solution. ### Claim 6 (depends on 5) The system of claim 5, wherein receiving and/or retrieving the at least one solution is via fluid transport. ### Claim 7 (depends on 6) The system of claim 6, wherein fluid transport comprises at least one of pipetting and capillary action, and wherein pipetting may be either manual or automatic via robotic means. ### Claim 8 (depends on 1) The system of claim 1, wherein the housing comprises or includes a plurality of scaffolds, a PMD frame, at least one objective lens frame, at least one slide frame, a photomasking frame, at least one condenser frame, and at least one thermal management means. ### Claim 9 (depends on 8) The system of claim 8, wherein the thermal management means comprises at least one of a heat sink, a heat pump, a fan, a liquid cooling system, and a peltier device. ### Claim 10 (depends on 1) The system of claim 1, wherein the housing is configured to removably receive a single objective lens frame of a plurality of objective lens frames each having a different objective lens and corresponding magnification. ### Claim 11 (depends on 10) The system of claim 10, wherein each objective lens frame is configured so as to provide a different spacing from the camera sensor. ### Claim 12 (depends on 1) The system of claim 1, wherein the PMD includes a PMD processor, a display, first wireless communication means for communicating information to a remote device either directly or via a network, and a second wireless communications means for communication with a local device. ### Claim 13 (depends on 1) The system of claim 1, further comprising a temperature sensor configured to determine the temperature in at least one of the housing and the chamber. ### Claim 14 (depends on 1) The system of claim 1, wherein the processor is configured to: receive input from a temperature sensor corresponding to a sensed temperature, and to at least one of: turn off the UVS upon the sensed temperature being greater than a predetermined temperature; and provide at least one of a visual and audible warning upon the sensed temperature being greater than a predetermined temperature. ### Claim 15 (depends on 1) The system of claim 1, further comprising: sealing means to maintain a liquid environment over the tissue sample within the chamber, and/or manual fluid collection guiding means arranged proximate the tissue sample and configured to enable pipetting solution from the tissue sample. ### Claim 16 (depends on 15) The system of claim 15, wherein the manual fluid collection guiding means comprises a microarray configured as or with a flow cell and/or is arranged within or proximate to the chamber; and/or wherein the manual fluid collection guiding means comprises a grid barrier arranged within or proximate to the sealing means. ### Claim 17 (depends on 1) A digital spatial profiling (DSP) method comprising: providing the system according to claim 1, wherein the processing circuitry is further configured to: provide illuminating light to the tissue sample on the slide received within the slot of the chamber, wherein the tissue sample has previously been conjugated with an antibody solution and, prior to insertion, covered in a buffer solution, wherein the slide is received within the slot of the chamber for imaging and is aligned with the photomasking means; image the tissue sample with the camera sensor of the PMD under visible light and display the image via the user interface of the PMD; receive a selection of a plurality via the GUI, wherein the selection forms an outline of a rectangle; define a ROI based on the selected plurality of biomarkers; cease illuminating visible light; and expose the ROI of the tissue sample to UV light illumination for a predetermined period of time sufficient to cleave oligos in the ROI in the tissue sample, wherein the method further comprises collecting a solution from the tissue sample containing cleaved oligos. ### Claim 18 (depends on 17) The method of claim 17, wherein the processing circuitry is further configured to: image the photomasking means prior to receipt of the slide so as to calibrate the photomasking means photomask, and/or change the size of the rectangle outlined by the selected markers. ### Claim 19 (depends on 17) A non-transitory computer readable medium having stored thereon instructions for enabling one or more computer processors to conduct one or more steps of the method of claim 17.