IP Library Granted Patent US 12,693,513
Granted Patent B2
US 12,693,513 · App. 18/922,794 · Granted Jul 28, 2026

Microscope-based system and method for image-guided microscopic illumination

Inventors: Jung-Chi Liao (Taipei City, TW); Yi-De Chen (Taipei, TW); Chih-Wei Chang (Taipei, TW); Weng Man Chong (Taipei City, TW)
Assignee: Academia Sinica
G02B21/365G02B21/06G02B21/26G06V10/141G06V10/25G06V20/693H04N23/56H04N23/74
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Quick Facts
Patent No.
US 12,693,513
App. No.
18/922,794
Filed
Oct 22, 2024
Granted
Jul 28, 2026
Kind
B2
Art Unit
2483
USPC
348/79
Abstract

A system and method for image-guided microscopic illumination are provided. A processing module controls an imaging assembly such that a camera acquires an image or images of a sample in multiple fields of view, and the image or images are automatically transmitted to a processing module and processed by the first processing module automatically in real-time based on a predefined criterion so as to determine coordinate information of an interested region in each field of view. The processing module also controls an illuminating assembly to illuminate the interested region of the sample according to the received coordinate information regarding to the interested region, with the illumination patterns changing among the fields of view.

Claims (29)

1 . A system for image-guided microscopic illumination of a biological sample comprising:

i) a microscope comprising a stage;

ii) an imaging assembly;

iii) an illuminating assembly;

iv) a first processing module operatively coupled to the microscope and configured to control the stage; and

v) a second processing module comprising a memory unit, wherein the second processing module is operatively coupled to the imaging assembly, the illuminating assembly, and the first processing module;

wherein the second processing module is configured to:

(a) control the imaging assembly to acquire at least one image of a first field of view of the biological sample;

(b) process the at least one image automatically based on a predefined criterion to determine coordinate information of one or more regions of interest in the first field of view; and

(c) control the illuminating assembly to illuminate the biological sample with a light pattern corresponding to the one or more regions of interest in the first field of view according to the coordinate information of the one or more regions of interest in the first field of view;

wherein after the one or more regions of interest in the first field of view is illuminated, the first processing module is configured to control the stage of the microscope to move to a subsequent field of view.

2 . The system of claim 1 , wherein the imaging assembly comprises a camera.

3 . The system of claim 1 , wherein the imaging assembly comprises a camera, an imaging light source, and a first shutter to control the imaging light source.

4 . The system of claim 1 , wherein the memory unit comprises a random access memory (RAM), a flash read-only memory (ROM), or a hard drive.

5 . The system of claim 4 , wherein the RAM comprises a dynamic random access memory (DRAM), a static random access memory (SRAM), or a zero-capacitor random access memory (Z-RAM).

6 . The system of claim 1 , wherein the second processing module is operatively coupled to a signal converter, wherein the signal converter is configured to convert the coordinate information to an analog signal.

7 . The system of claim 1 , wherein the illuminating assembly comprises an illuminating light source and a second shutter to control the illuminating light source.

8 . The system of claim 3 , wherein the first shutter is a non-mechanical shutter.

9 . The system of claim 7 , wherein the second shutter is a non-mechanical shutter.

10 . The system of claim 9 , wherein the non-mechanical shutter comprises an acousto-optic modulator (AOM) or an electro-optic modulator (EOM).

11 . A method for image-guided microscopic illumination of a biological sample comprising:

(a) moving a stage of a microscope to a first position using a first processing module to position the biological sample for imaging of a first field of view;

(b) controlling a camera of an imaging assembly with a second processing module to acquire an image of the first field of view of the biological sample;

(c) performing image processing of the image automatically in real-time based on a predefined criterion with the second processing module to determine one or more regions of interest in the image and obtain coordinate information of the one or more regions of interest;

(d) controlling an illuminating assembly to illuminate the first field of view of the biological sample with a light pattern corresponding to the one or more regions of interest according to the coordinate information of the one or more regions of interest with the second processing module; and

(e) after the one or more regions of interest in the first field of view is illuminated, controlling the stage of the microscope with the first processing module to move to a subsequent field of view.

12 . The method of claim 11 , further comprising, after (b) and prior to (c), transmitting the image of the first field of view of the biological sample automatically from the imaging assembly to the second processing module.

13 . The method of claim 11 , further comprising, after (c) and prior to (d), transmitting the coordinate information corresponding to the one or more regions of interest from the second processing module to the illuminating assembly.

14 . The method of claim 13 , wherein transmitting the coordinate information corresponding to the one or more regions of interest from the second processing module to the illuminating assembly comprises converting the coordinate information to an analog signal.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 15, 2025
From: LIAO, JUNG-CHI; CHEN, YI-DE; CHANG, CHIH-WEI; CHONG, WENG MAN
To: ACADEMIA SINICA
Reel/Frame 071718/0512 →
Continuity (5)
Continuation 18464125 · Sep 8, 2023
Continuation 17592211 · Feb 3, 2022
Continuation 16013663 · Jun 20, 2018
Provisional Application 62522265 · Jun 20, 2017
Related Publication 20250052993A1 · Feb 13, 2025
References Cited (123)
US 5646413A · Nishi · 1997 [cited by applicant]
US 6522774B1 · Bacus et al. · 2003 [cited by applicant]
US 6614031B2 · Engelhardt et al. · 2003 [cited by applicant]
US 6697526B1 · Abe · 2004 [cited by applicant]
US 6947583B2 · Ellis et al. · 2005 [cited by applicant]
US 6956647B2 · Foster et al. · 2005 [cited by applicant]
US 7133543B2 · Verwoerd et al. · 2006 [cited by applicant]
US 7460732B2 · Recht · 2008 [cited by applicant]
US 7639357B2 · Okugawa · 2009 [cited by applicant]
US 7817273B2 · Bahatt et al. · 2010 [cited by applicant]
US 8187866B2 · Duer · 2012 [cited by applicant]
US 8288157B2 · Duer · 2012 [cited by applicant]
US 8923568B2 · Olson et al. · 2014 [cited by applicant]
US 9019598B2 · Tsurumune · 2015 [cited by applicant]
US 9030547B2 · Vizi et al. · 2015 [cited by applicant]
US 9125562B2 · Spencer et al. · 2015 [cited by applicant]
US 9217694B2 · Sieckmann et al. · 2015 [cited by applicant]
US 9528939B2 · Duer · 2016 [cited by applicant]
US 9557156B2 · Kankaria · 2017 [cited by applicant]
US 9581801B2 · Takamizawa · 2017 [cited by applicant]
US 9696535B2 · Prakash et al. · 2017 [cited by applicant]
US 9788790B2 · Black et al. · 2017 [cited by applicant]
US 9810892B2 · Prakash et al. · 2017 [cited by applicant]
US 9939381B1 · Kimmel et al. · 2018 [cited by applicant]
US 10517482B2 · Sato et al. · 2019 [cited by applicant]
US 10729326B2 · Spencer et al. · 2020 [cited by applicant]
US 10746980B2 · Kenny et al. · 2020 [cited by applicant]
US 10932670B2 · Smith et al. · 2021 [cited by applicant]
US 11265449B2 · Liao et al. · 2022 [cited by applicant]
US 11408821B2 · Boamfa et al. · 2022 [cited by applicant]
US 11513328B2 · Pannhoff et al. · 2022 [cited by applicant]
US 11789251B2 · Liao et al. · 2023 [cited by applicant]
US 20020008904A1 · Engelhardt · 2002 [cited by applicant]
US 20030189676A1 · Kato et al. · 2003 [cited by applicant]
US 20030231791A1 · Torre-Bueno et al. · 2003 [cited by applicant]
US 20040105000A1 · Yuri · 2004 [cited by applicant]
US 20050072920A1 · Inada · 2005 [cited by applicant]
US 20050082494A1 · Motomura · 2005 [cited by applicant]
US 20050089208A1 · Dong et al. · 2005 [cited by applicant]
US 20050179899A1 · Palti Wasserman et al. · 2005 [cited by applicant]
US 20060028717A1 · Dunn · 2006 [cited by applicant]
US 20060226375A1 · Maruo · 2006 [cited by applicant]
US 20070152130A1 · Fomitchov · 2007 [cited by applicant]
US 20080206752A1 · Balakirev et al. · 2008 [cited by applicant]
US 20090195646A1 · Ganser et al. · 2009 [cited by applicant]
US 20090316259A1 · Kenny et al. · 2009 [cited by applicant]
US 20100079857A1 · Sasaki et al. · 2010 [cited by applicant]
US 20100278399A1 · Bednarkiewicz et al. · 2010 [cited by applicant]
US 20110050745A1 · Jung et al. · 2011 [cited by applicant]
US 20120242817A1 · Pan · 2012 [cited by applicant]
US 20130294645A1 · Sibarita · 2013 [cited by applicant]
US 20140022373A1 · Kanarowski et al. · 2014 [cited by applicant]
US 20140152794A1 · Takahashi · 2014 [cited by applicant]
US 20140293407A1 · Amano et al. · 2014 [cited by applicant]
US 20150168702A1 · Harris · 2015 [cited by applicant]
US 20150185456A1 · Kishima · 2015 [cited by applicant]
US 20150258352A1 · Lin et al. · 2015 [cited by applicant]
US 20160124208A1 · Best et al. · 2016 [cited by applicant]
US 20160302740A1 · Iyer et al. · 2016 [cited by applicant]
US 20170059407A1 · Shiraiwa · 2017 [cited by applicant]
US 20170090176A1 · Pospiech et al. · 2017 [cited by applicant]
US 20170154236A1 · Masuura et al. · 2017 [cited by applicant]
US 20170212342A1 · Rozsa et al. · 2017 [cited by applicant]
US 20170248837A1 · Sato et al. · 2017 [cited by applicant]
US 20170299784A1 · Mikkelsen et al. · 2017 [cited by applicant]
US 20180136451A1 · Soenksen · 2018 [cited by applicant]
US 20180177401A1 · Yang et al. · 2018 [cited by applicant]
US 20180180642A1 · Shetty et al. · 2018 [cited by applicant]
US 20180180885A1 · Holland et al. · 2018 [cited by applicant]
US 20180203221A1 · Dai et al. · 2018 [cited by applicant]
US 20180210183A1 · Nishikawa · 2018 [cited by applicant]
US 20180284419A1 · Peschka et al. · 2018 [cited by applicant]
US 20180348500A1 · Naaman et al. · 2018 [cited by applicant]
US 20190324240A1 · Shroff et al. · 2019 [cited by applicant]
US 20190339456A1 · Ruggles · 2019 [cited by applicant]
US 20190391078A1 · Cohen et al. · 2019 [cited by applicant]
US 20210224954A1 · Guo et al. · 2021 [cited by applicant]
US 20230418041A1 · Liao et al. · 2023 [cited by applicant]
US 20240219703A1 · Liao et al. · 2024 [cited by applicant]
US 20240219704A1 · Liao et al. · 2024 [cited by applicant]
US 20240219705A1 · Liao et al. · 2024 [cited by applicant]
US 20240411122A1 · Liao et al. · 2024 [cited by applicant]
US 20250035910A1 · Liao et al. · 2025 [cited by applicant]
TW 201013817A · 2010 [cited by applicant]
WO WO2016133787A1 · 2016 [cited by applicant]
Alqattan et al.; Direct laser writing of nanophotonic structures on contact lenses; ACS nano; 12(6); pp. 5130-5140; Apr. 2018. [cited by applicant]
Aznar et al.; Gated materials for on-command release of guest molecules; Chemical reviews; 116(2); pp. 561-718; Jan. 27, 2016. [cited by applicant]
Bar et al.; Biotinylation by antibody recognition—a method for proximity labeling; Nature Methods; 15(2); pp. 127-133; (author Manuscript); 19 pages; Feb. 2018. [cited by applicant]
Brieke et al.; Light?controlled tools; Angewandte Chemie International Edition; 51(34); pp. 8446-8476; Aug. 20, 2012. [cited by applicant]
Chen et al.; Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution; Science; 346(6208); 1257998; doi:10.1126/scince.1257998; (Author Manuscript); 28 pages; Oct. 2014. [cited by applicant]
Ezzoukhry et al.; Combining laser capture microdissection and proteomics reveals an active translation machinery controlling formation; Nature Communications; 9(1); doi:10.1038/s41467-018-04461-9; 11 pages; May 2018. [cited by applicant]
Hadley et al.; Determining composition of micron-scale protein deposits in neurodegenerative disease by spatially targeted optical microproteomics; eLife; 21 pages. doi: 10.7554/eLife.09579; Sep. 2015. [cited by applicant]
Hirsch et al.; Easily reversible desthiobiotin binding to streptavidin, avidin, and other bitin-binding proteins: uses for protein labeling, detection, and isolation; Analytical Biochemistry; 308(2); pp. 343-357; Sep. 2… [cited by applicant]
Hung et al.; Protein localization in disease and therapy; Journal of Cell Science; 124(20); pp. 3381-3392; Oct. 2011. [cited by applicant]
Hung et al.; Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2; Nature Protocols; 11(3); pp. 456-475; (Author Manuscript); 39 pages; Mar. 2016. [cited by applicant]
Itzhak et al.; A mass spectrometry-based approach for mapping protein neurons; Cell Reports; 20(11); pp. 2706-2718; Sep. 2017. [cited by applicant]
Jain et al.; ATPase-modulated stress granules contain a diverse proteome and substructure; Cell; 164(3); pp. 487-498; Jan. 2016. [cited by applicant]
Kamburov et al.; The consensusPathDB interaction database: 2013 update; Nucleic Acids Research; 41(D1); pp. D793-D800; Jan. 2013. [cited by applicant]
Kepiro et al.; Molecular tattoo: subcellular confinement of drug effects; Chemistry and Biology; 22(4); pp. 548-558; Apr. 2015. [cited by applicant]
Lam et al.; Directed evolution of APEX2 for electron microscopy and proximity labeling; Nature Methods; 12(1); pp. 51-54; (author Manuscript); 15 pages; Jan. 2015. [cited by applicant]
Liao et al.; A pioneering high content cell image-registered protein labeling system; 2017 Bio Taiwan Exhibition and Conference; 2 pages; Jun. 29-Jul. 2, 2017. [cited by applicant]
Liao et al.; High content cell image-registered protein labeling system; 2017 Bio Taiwan Exhibition and Conference; 14 pages; Jun. 29-Jul. 2, 2017. [cited by applicant]
Liu et al; Supplementary materials: super-resolution labeling with action-paint; Nature Chemistry; Supplementary Information; doi.org/10.1038/s41557-019-0325-7; 43 pages retrieved from the internet (https://yin.hms.harv… [cited by applicant]
Prier et. al.; Visible light photoredox cataysis with transition metal complexes: applications in organic synthesis; Chemical reviews; 113(7); pp. 5322-5363; (author Manuscript) 141 pages; Jul. 2013. [cited by applicant]
Rhee et al.; Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging; Science; 339(6125); pp. 1328-1331; (Author Manuscript); 8 pages; Mar. 2013. [cited by applicant]
Rost et al.; Multiplexed ion beam imaging analysis for quanitation of protein expression in cancer tissue sections; Laboratory Investigation; 97(8); pp. 992-1003; Aug. 2017. [cited by applicant]
Roux et al.; A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells; Journal of Cell Biology; 196(6); pp. 801-810; Mar. 2012. [cited by applicant]
Roux et al.; BioID: A screen for protein-protein interactions: Current Protocols in protein Science; 91(1); pp. 19-23; (Author Manuscript); 20 pages; Jan. 2018. [cited by applicant]
Thermofisher Scientific: Sulfo-SBED biotin label transfer reagent; (Product Discription); retrieved from the internet (https://www.thermofisher.com/order/catalog/product/33033#/33033); 5 pages; on May 5, 2021. [cited by applicant]
Thul et al.; A subcellular map of the human proteome; Science; 356(6340) eaal3321; 14 pages; May 2017. [cited by applicant]
Zipfel et al.; Nonlinear magic: multiphoton microscopy in the biosciences; Nature Biotechnolgy; 21(11); pp. 1369-1377; Nov. 2003. [cited by applicant]
Huang et al.; U.S. Appl. No. 18/748,710 entitled “Adjustable Support and Optical Module,” filed Jun. 20, 2024. [cited by applicant]
Liao et al.; U.S. Appl. No. 18/909,298 entitled “Microscope-based system and method for image-guided microscopic illumination,” filed Oct. 8, 2024. [cited by applicant]
Liao et al.; U.S. Appl. No. 18/909,323 entitled “Microscope-based system and method for image-guided microscope illumination,” filed Oct. 8, 2024. [cited by applicant]
Liao et al.; U.S. Appl. No. 18/997,408 entitled “Training AI model for a microscope-based pattern photoillumination system,” filed Jan. 21, 2025. [cited by applicant]
Liao et al.; U.S. Appl. No. 18/997,412 entitled “Method of standardizing image pixel values in a microscope-based system,” filed Jan. 21, 2025. [cited by applicant]
Liao et al.; U.S. Appl. No. 19/110,325 entitled “Microscope-based system and method of determining beam processing path,” filed Mar. 10, 2025. [cited by applicant]
Ronneberger et al.; U-net: Convolutional networks for biomedical image segmentation. InMedical image computing and computer-assisted interventionRMICCAI 2015; 18th international conference; Springer international publis… [cited by applicant]
Stegmaier et al.; Real-time three-dimensional cell segmentation in large-scale microscopy data of developing embryos. Developmental Cell; 36(2); pp. 225-240; Jan. 25, 2016. [cited by applicant]
Wikipedia; Biotinylation; 4 pages; retrieved from the internet (https://en.wikipedia.org/w/index.php?title=Biotinylation&oldid=841539236) on May 16, 2018. [cited by applicant]
Liao et al.; U.S. Appl. No. 18/864,988 entitled “Method of calibrating a microscope system,” filed Nov. 12, 2024. [cited by applicant]
Liao et al.; U.S. Appl. No. 18/864,997 entitled “Method of calibrating a microscope system,” filed Nov. 12, 2024. [cited by applicant]
Chen et al.; U.S. Appl. No. 18/877,609 entitled “Microscope-based system and method using a UV-transmission mirror,” filed Dec. 20, 2024. [cited by applicant]