IP Library Granted Patent US 12,510,744
Granted Patent B1
US 12,510,744 · App. 19/270,264 · Granted Dec 30, 2025

Methods and systems for volumetric imaging

Inventors: Mark Pratt (Boston, MA); Riley Shamloufard (Boston, MA); Ye Fu (Boston, MA)
Assignee: Stellaromics, Inc.
G02B21/367G01N21/6458G02B21/16
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Quick Facts
Patent No.
US 12,510,744
App. No.
19/270,264
Filed
Jul 15, 2025
Granted
Dec 30, 2025
Kind
B1
Art Unit
2485
USPC
348/79
Abstract

The present disclosure provides a methods and systems for analyzing one or more samples. The method may comprise using a plurality of sensors to substantially continuously integrate through a plurality of object planes of the sample. The integration can then generate a volumetric measurement of the sample.

Claims (25)

1 . A method of imaging a sample, the method comprising:

(a) providing:

(i) said sample disposed adjacent to a stage, wherein said sample has a thickness of at least 10 micrometers (μm); and

(ii) an imaging module configured to create an image, said imaging module comprising an objective lens configured to transmit photons from one or more object planes within said sample to one or more sensors in optical communication with said objective lens;

(b) moving said objective lens relative to said sample while simultaneously using said imaging module to acquire a series of images corresponding to a plurality of object planes within said sample, wherein said objective lens is moving with a velocity of at least about 0.5 μm s −1 ; and

(c) extracting signals from said series of images within 120 seconds of acquiring said series of images.

2 . The method of claim 1 , wherein said series of images correspond to a plurality of adjacent object planes within said sample.

3 . The method of claim 1 , wherein said one or more sensors comprises a complementary metal-oxide-semiconductor (CMOS) sensor.

4 . The method of claim 1 , wherein said one or more sensors comprises an array of pixels.

5 . The method of claim 1 , wherein said imaging module is a confocal microscope.

6 . The method of claim 1 , wherein said imaging module is a light sheet microscope.

7 . The method of claim 1 , wherein said samples has a thickness of at least 100 μm.

8 . The method of claim 1 , wherein said objective lens is moving with a velocity of at least about 5 μm s −1 .

9 . The method of claim 1 , wherein (c) is performed within 50 seconds of acquiring said series of images.

10 . The method of claim 1 , wherein said sample is a tissue sample.

11 . The method of claim 10 , wherein said tissue sample is a cleared and hydrogel stabilized tissue sample.

12 . The method of claim 1 , wherein (b) comprises imaging a region within said sample multiple times.

13 . The method of claim 1 , wherein said signals are fluorescence signals.

14 . The method of claim 13 , wherein said fluorescence signals provide information related to expression of ribonucleic acid (RNA) in said sample.

15 . The method of claim 14 , wherein said fluorescence signals provide information related to expression of at least 500 RNA in said sample.

16 . The method of claim 1 , wherein said series of images comprises a video.

17 . The method of claim 1 , wherein said one or more sensors comprises a rolling shutter sensor.

18 . The method of claim 1 , wherein (b) comprises illuminating said sample with a laser.

19 . The method of claim 1 , wherein (b) comprises acquiring said series of images at a rate of at least about 100,000,000 voxels/second on each of two or more wavelength channels.

20 . The method of claim 1 , wherein said sample comprises at least 500,000 cells.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 13, 2025
From: PRATT, MARK; SHAMLOUFARD, RILEY; FU, YE
To: STELLAROMICS, INC.
Reel/Frame 072009/0229 →
Continuity (3)
Continuation PCTUS2025018783 · Mar 6, 2025
Provisional Application 63745212 · Jan 14, 2025
Provisional Application 63562543 · Mar 7, 2024
References Cited (294)
US 4318846A · Khanna et al. · 1982 [cited by applicant]
US 4663161A · Mannino et al. · 1987 [cited by applicant]
US 4757141A · Fung et al. · 1988 [cited by applicant]
US 4797368A · Carter et al. · 1989 [cited by applicant]
US 4849336A · Miyoshi et al. · 1989 [cited by applicant]
US 4871488A · Mannino et al. · 1989 [cited by applicant]
US 4945050A · Sanford et al. · 1990 [cited by applicant]
US 5036006A · Sanford et al. · 1991 [cited by applicant]
US 5066580A · Lee · 1991 [cited by applicant]
US 5067805A · Corle et al. · 1991 [cited by applicant]
US 5091519A · Cruickshank · 1992 [cited by applicant]
US 5100792A · Sanford et al. · 1992 [cited by applicant]
US 5135855A · Moss et al. · 1992 [cited by applicant]
US 5139941A · Muzyczka et al. · 1992 [cited by applicant]
US 5151507A · Hobbs, Jr. et al. · 1992 [cited by applicant]
US 5173414A · Lebkowski et al. · 1992 [cited by applicant]
US 5179022A · Sanford et al. · 1993 [cited by applicant]
US 5188934A · Menchen et al. · 1993 [cited by applicant]
US 5198537A · Huber et al. · 1993 [cited by applicant]
US 5219740A · Miller et al. · 1993 [cited by applicant]
US 5344757A · Hoeltke et al. · 1994 [cited by applicant]
US 5354657A · Holtke et al. · 1994 [cited by applicant]
US 5366860A · Bergot et al. · 1994 [cited by applicant]
US 5371015A · Sanford et al. · 1994 [cited by applicant]
US 5387742A · Cordell · 1995 [cited by applicant]
US 5399346A · Anderson et al. · 1995 [cited by applicant]
US 5478744A · Sanford et al. · 1995 [cited by applicant]
US 5535052A · Jorgens · 1996 [cited by applicant]
US 5538871A · Nuovo et al. · 1996 [cited by applicant]
US 5580859A · Felgner et al. · 1996 [cited by applicant]
US 5589466A · Felgner et al. · 1996 [cited by applicant]
US 5612818A · Kumagai et al. · 1997 [cited by applicant]
US 5619371A · Pontius · 1997 [cited by examiner]
US 5676950A · Small, Jr. et al. · 1997 [cited by applicant]
US 5688648A · Mathies et al. · 1997 [cited by applicant]
US 5702888A · Holtke et al. · 1997 [cited by applicant]
US 5789245A · Dubensky, Jr. et al. · 1998 [cited by applicant]
US 5831005A · Zuckerman et al. · 1998 [cited by applicant]
US 5843723A · Dubensky, Jr. et al. · 1998 [cited by applicant]
US 5847162A · Lee et al. · 1998 [cited by applicant]
US 5990479A · Weiss et al. · 1999 [cited by applicant]
US 6054274A · Sampson et al. · 2000 [cited by applicant]
US 6094300A · Kashima et al. · 2000 [cited by applicant]
US 6207392B1 · Weiss et al. · 2001 [cited by applicant]
US 6235502B1 · Weissman et al. · 2001 [cited by applicant]
US 6251303B1 · Bawendi et al. · 2001 [cited by applicant]
US 6291187B1 · Kingsmore et al. · 2001 [cited by applicant]
US 6316229B1 · Lizardi et al. · 2001 [cited by applicant]
US 6319426B1 · Bawendi et al. · 2001 [cited by applicant]
US 6322901B1 · Bawendi et al. · 2001 [cited by applicant]
US 6323009B1 · Lasken et al. · 2001 [cited by applicant]
US 6344329B1 · Lizardi · 2002 [cited by applicant]
US 6368801B1 · Faruqi · 2002 [cited by applicant]
US 6423551B1 · Weiss et al. · 2002 [cited by applicant]
US 6426513B1 · Bawendi et al. · 2002 [cited by applicant]
US 6444143B2 · Bawendi et al. · 2002 [cited by applicant]
US 6558928B1 · Landegren · 2003 [cited by applicant]
US 6566118B1 · Atkinson et al. · 2003 [cited by applicant]
US 6576291B2 · Bawendi et al. · 2003 [cited by applicant]
US 6596535B1 · Carter · 2003 [cited by applicant]
US 6649811B2 · Pasinetti · 2003 [cited by applicant]
US 6989264B2 · Atkinson et al. · 2006 [cited by applicant]
US 6995006B2 · Atkinson et al. · 2006 [cited by applicant]
US 7335898B2 · Donders et al. · 2008 [cited by applicant]
US 7632679B2 · Jessell et al. · 2009 [cited by applicant]
US 8497069B2 · Hutchison et al. · 2013 [cited by applicant]
US 8834546B2 · Deisseroth et al. · 2014 [cited by applicant]
US 9175095B2 · Deisseroth et al. · 2015 [cited by applicant]
US 9279973B2 · Takaya · 2016 [cited by examiner]
US 9359449B2 · Deisseroth et al. · 2016 [cited by applicant]
US 9365628B2 · Deisseroth et al. · 2016 [cited by applicant]
US 9376717B2 · Gao et al. · 2016 [cited by applicant]
US 9423601B2 · Toda et al. · 2016 [cited by applicant]
US 9458208B2 · Deisseroth et al. · 2016 [cited by applicant]
US 9791409B2 · Gordon et al. · 2017 [cited by applicant]
US 9969783B2 · Deisseroth et al. · 2018 [cited by applicant]
US 10000796B2 · Samusik et al. · 2018 [cited by applicant]
US 10006082B2 · Samusik et al. · 2018 [cited by applicant]
US 10052383B2 · Deisseroth et al. · 2018 [cited by applicant]
US 10138509B2 · Church et al. · 2018 [cited by applicant]
US 10196431B2 · Deisseroth et al. · 2019 [cited by applicant]
US 10220092B2 · Deisseroth et al. · 2019 [cited by applicant]
US 10227639B2 · Levner et al. · 2019 [cited by applicant]
US 10266888B2 · Daugharthy et al. · 2019 [cited by applicant]
US 10323272B1 · Rabbani et al. · 2019 [cited by applicant]
US 10364457B2 · Wassie et al. · 2019 [cited by applicant]
US 10478499B2 · Deisseroth et al. · 2019 [cited by applicant]
US 10568307B2 · Deisseroth et al. · 2020 [cited by applicant]
US 10568516B2 · Yang et al. · 2020 [cited by applicant]
US 10583309B2 · Deisseroth et al. · 2020 [cited by applicant]
US RE47983E · Gao et al. · 2020 [cited by applicant]
US 10787701B2 · Chee · 2020 [cited by applicant]
US 10829814B2 · Fan et al. · 2020 [cited by applicant]
US 11008608B2 · Samusik et al. · 2021 [cited by applicant]
US 11085072B2 · Church et al. · 2021 [cited by applicant]
US 11098303B2 · Zhuang et al. · 2021 [cited by applicant]
US 11111521B2 · Church et al. · 2021 [cited by applicant]
US 11168350B2 · Nolan et al. · 2021 [cited by applicant]
US 11187581B2 · Kokota · 2021 [cited by examiner]
US 11299770B2 · Samusik et al. · 2022 [cited by applicant]
US 11377689B2 · Beechem et al. · 2022 [cited by applicant]
US 11447807B2 · Church et al. · 2022 [cited by applicant]
US RE49304E · Gao et al. · 2022 [cited by applicant]
US 11656447B2 · Tsia et al. · 2023 [cited by applicant]
US 12060603B2 · Bava · 2024 [cited by applicant]
US 12157124B2 · Cox et al. · 2024 [cited by applicant]
US 12188085B2 · Bava · 2025 [cited by applicant]
US 12359253B2 · Wang et al. · 2025 [cited by applicant]
US 20020045045A1 · Adams et al. · 2002 [cited by applicant]
US 20030017264A1 · Treadway et al. · 2003 [cited by applicant]
US 20050112639A1 · Wang et al. · 2005 [cited by applicant]
US 20050239184A1 · Ohara et al. · 2005 [cited by applicant]
US 20060141501A1 · Friend et al. · 2006 [cited by applicant]
US 20080124735A1 · Schuster et al. · 2008 [cited by applicant]
US 20090093403A1 · Zhang et al. · 2009 [cited by applicant]
US 20100055733A1 · Lutolf et al. · 2010 [cited by applicant]
US 20100120129A1 · Amshey et al. · 2010 [cited by applicant]
US 20120003657A1 · Myllykangas et al. · 2012 [cited by applicant]
US 20130045872A1 · Zhou et al. · 2013 [cited by applicant]
US 20130178372A1 · Geiss et al. · 2013 [cited by applicant]
US 20130266512A1 · Fox et al. · 2013 [cited by applicant]
US 20140162892A1 · Mir · 2014 [cited by applicant]
US 20140170654A1 · Landegren et al. · 2014 [cited by applicant]
US 20150377886A1 · Ciceri et al. · 2015 [cited by applicant]
US 20160080632A1 · Iwase · 2016 [cited by examiner]
US 20160129437A1 · Kayyem et al. · 2016 [cited by applicant]
US 20160169923A1 · Holmes et al. · 2016 [cited by applicant]
US 20160252715A1 · Nakano · 2016 [cited by examiner]
US 20160377524A1 · Martin et al. · 2016 [cited by applicant]
US 20170211133A1 · Landegren et al. · 2017 [cited by applicant]
US 20180094320A1 · Li · 2018 [cited by applicant]
US 20180119219A1 · Chen et al. · 2018 [cited by applicant]
US 20180208975A1 · Peterson et al. · 2018 [cited by applicant]
US 20180216161A1 · Chen et al. · 2018 [cited by applicant]
US 20180267283A1 · Matsumoto · 2018 [cited by examiner]
US 20180340221A1 · Davis et al. · 2018 [cited by applicant]
US 20190055594A1 · Samusik et al. · 2019 [cited by applicant]
US 20190085383A1 · Church et al. · 2019 [cited by applicant]
US 20190284603A1 · Shema-Yaacoby et al. · 2019 [cited by applicant]
US 20200199667A1 · Erickstad et al. · 2020 [cited by applicant]
US 20200341259A1 · Chan et al. · 2020 [cited by applicant]
US 20210238662A1 · Bava et al. · 2021 [cited by applicant]
US 20210238665A1 · Samusik et al. · 2021 [cited by applicant]
US 20210238674A1 · Bava · 2021 [cited by applicant]
US 20210262018A1 · Bava et al. · 2021 [cited by applicant]
US 20210293693A1 · Bharadwaj et al. · 2021 [cited by applicant]
US 20210340621A1 · Daugharthy et al. · 2021 [cited by applicant]
US 20210388424A1 · Bava · 2021 [cited by applicant]
US 20220016624A1 · Daugharthy et al. · 2022 [cited by applicant]
US 20220083832A1 · Shah · 2022 [cited by applicant]
US 20220084628A1 · Shah · 2022 [cited by applicant]
US 20220251642A1 · Church et al. · 2022 [cited by applicant]
US 20220290228A1 · Hauling et al. · 2022 [cited by applicant]
US 20220316004A1 · Miller et al. · 2022 [cited by applicant]
US 20220364160A1 · Nolan et al. · 2022 [cited by applicant]
US 20220372570A1 · Costa · 2022 [cited by applicant]
US 20220380838A1 · Kühnemund et al. · 2022 [cited by applicant]
US 20220403458A1 · Bava · 2022 [cited by applicant]
US 20230012607A1 · Kühnemund et al. · 2023 [cited by applicant]
US 20230013775A1 · Chen et al. · 2023 [cited by applicant]
US 20230026886A1 · Chen · 2023 [cited by applicant]
US 20230034039A1 · Shahjamali · 2023 [cited by applicant]
US 20230037182A1 · Bava et al. · 2023 [cited by applicant]
US 20230061542A1 · Kühnemund · 2023 [cited by applicant]
US 20230081232A1 · Weisenfeld et al. · 2023 [cited by applicant]
US 20230109070A1 · Richman et al. · 2023 [cited by applicant]
US 20230115903A1 · Hernández Neuta et al. · 2023 [cited by applicant]
US 20230227894A1 · Nilsson et al. · 2023 [cited by applicant]
US 20230238078A1 · Gonzalez Lozano et al. · 2023 [cited by applicant]
US 20230242974A1 · Costa et al. · 2023 [cited by applicant]
US 20230279480A1 · Kühnemund · 2023 [cited by applicant]
US 20230314327A1 · Hoffman · 2023 [cited by applicant]
US 20230314328A1 · Costa · 2023 [cited by applicant]
US 20230323437A1 · Chen et al. · 2023 [cited by applicant]
US 20230324421A1 · Zhang et al. · 2023 [cited by applicant]
US 20230351619A1 · Tentori et al. · 2023 [cited by applicant]
US 20240019353A1 · Wang et al. · 2024 [cited by applicant]
US 20240033743A1 · Tentori et al. · 2024 [cited by applicant]
US 20240132938A1 · Kühnemund · 2024 [cited by applicant]
US 20240144704A1 · Wang et al. · 2024 [cited by applicant]
US 20240150816A1 · Feng et al. · 2024 [cited by applicant]
US 20240151937A1 · Hoffman · 2024 [cited by applicant]
US 20240167081A1 · Bava et al. · 2024 [cited by applicant]
US 20240167956A1 · Hoffman et al. · 2024 [cited by applicant]
US 20240168273A1 · Monkowski et al. · 2024 [cited by applicant]
US 20240171723A1 · Shutov et al. · 2024 [cited by applicant]
US 20240171833A1 · Hoffman et al. · 2024 [cited by applicant]
US 20240177348A1 · Shutov et al. · 2024 [cited by applicant]
US 20240209346A1 · Shastry · 2024 [cited by applicant]
US 20240233415A1 · Hoffman · 2024 [cited by applicant]
US 20240248038A1 · Deisseroth et al. · 2024 [cited by applicant]
US 20240254545A1 · Wang et al. · 2024 [cited by applicant]
US 20240254553A1 · Deisseroth et al. · 2024 [cited by applicant]
US 20240254554A1 · Deisseroth et al. · 2024 [cited by applicant]
US 20240257912A1 · Deisseroth et al. · 2024 [cited by applicant]
US 20240263228A1 · Deisseroth et al. · 2024 [cited by applicant]
US 20240294973A1 · Wang et al. · 2024 [cited by applicant]
US 20240305314A1 · Hoffman et al. · 2024 [cited by applicant]
US 20240369471A1 · Hoffman et al. · 2024 [cited by applicant]
US 20240376530A1 · Wang et al. · 2024 [cited by applicant]
US 20240428880A1 · Marks et al. · 2024 [cited by applicant]
US 20250012786A1 · Skrynnyk et al. · 2025 [cited by applicant]
US 20250052979A1 · Miller et al. · 2025 [cited by applicant]
US 20250061732A1 · Li et al. · 2025 [cited by applicant]
Abbott, Jeffrey. et al. A nanoelectrode array for obtaining intracellular recordings from thousands of connected neurons. Nature biomedical engineering 4(2):232-241 (2020). [cited by applicant]
Achim, Kaia et al. High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin. Nature biotechnology 33(5):503-509 (2015). [cited by applicant]
Arganda-Carreras, Ignacio. et al. Trainable Weka Segmentation: a machine learning tool for microscopy pixel classification. Bioinformatics 33(15):2424-2426 (2017). [cited by applicant]
Bagasra, Omar. Protocols for the in situ PCR-amplification and detection of mRNA and DNA sequences. Nature Protocols 2(11):2782-2795 (2007). [cited by applicant]
Baner, Johan. et al. Signal amplification of padlock probes by rolling circle replication. Nucleic acids research 26(22):5073-5078 (1998). [cited by applicant]
Becht, Etienne. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nature biotechnology 37(1):38-44 (2019). [cited by applicant]
Bleton, Heloise. et al. Cognitive Tasks and Cerebral Blood Flow Through Anterior Cerebral Arteries: a Study via Functional Transcranial Doppler Ultrasound Recordings. BMC Medical Imaging 16:1-12 (2016). [cited by applicant]
Boersma, Sanne. et al. Multi-color single-molecule imaging uncovers extensive heterogeneity in mRNA decoding. Cell 178(2):458-472, e1-e19 (2019). [cited by applicant]
Burke, Kelly S. et al. A Fluorescence in situ hybridization method to quantify mRNA translation by visualizing ribosome-mRNA interactions in single cells. ACS central science 3(5):425-433 (2017). [cited by applicant]
Buxbaum, Adina R. et al. In the right place at the right time: visualizing and understanding mRNA localization. Nature reviews Molecular cell biology 16(2):95-109 (2015). [cited by applicant]
Cao, Junyue. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566(7745):496-502 (2019). [cited by applicant]
Chen, Fei. et al. Nanoscale imaging of RNA with expansion microscopy. Nature methods 13(8):679-684 (2016). [cited by applicant]
Chen, Fei. et al. Optical imaging. Expansion microscopy. Science 347(6221):543-548 (2015). [cited by applicant]
Chen, Kok Hao. et al. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348(6233):aaa6090, 1-14 (2015). [cited by applicant]
Chen, Xiaoyin. et al. Efficient in situ barcode sequencing using padlock probe-based BaristaSeq. Nucleic acids research 46(4):e22, 1-10 (2018). [cited by applicant]
Chen, Xiaoyin. et al. High-Throughput Mapping of Long-Range Neuronal Projection Using In Situ Sequencing. Cell 179(3):772-786 (2019). [cited by applicant]
Clausson, Carl-Magnus. et al. Compaction of rolling circle amplification products increases signal integrity and signal-to-noise ratio. Scientific reports 5:12317, 1-10 (2015). [cited by applicant]
Codeluppi, Simone. et al. Spatial organization of the somatosensory cortex revealed by osmFISH. Nature methods 15(11):932-935 (2018). [cited by applicant]
Co-pending U.S. Appl. No. 18/682,160, inventors Xiao; Wang et al., filed Feb. 8, 2024. [cited by applicant]
Crosetto, Nicola. et al. Spatially resolved transcriptomics and beyond. Nature Reviews Genetics 16(1):57-66 (2015). [cited by applicant]
Deng, Ruijie. et al. DNA-Sequence-Encoded Rolling Circle Amplicon for Single-Cell RNA Imaging. Chem 4(6):1373-1386 (2018). [cited by applicant]
Eng, Chee-Huat Linus. et al. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+. Nature 568(7751):235-239 (2019). [cited by applicant]
Faruqi, Fawad A. et al. High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification. BMC genomics 2:4, 1-10 (2001). [cited by applicant]
Fazal, Furqan M. et al. Atlas of subcellular RNA localization revealed by APEX-Seq. Cell 178(2):473-490, e1-e26 (2019). [cited by applicant]
Fredriksson, Simon. et al. Protein detection using proximity-dependent DNA ligation assays. Nature biotechnology 20(5):473-477 (2002). [cited by applicant]
Gao, Shuai. et al. Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nature cell biology 20(6):721-734 (2018). [cited by applicant]
Goltsev, Yury. et al. Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging. Cell 174(4):968-981, e1-e15 (2018). [cited by applicant]
Halstead, James M. et al. An RNA biosensor for imaging the first round of translation from single cells to living animals. Science 347(6228):1367-1371 (2015). [cited by applicant]
Han, Xiaoping. et al. Mapping the Mouse Cell Atlas by Microwell-Seq. Cell 172(5):1091-1107, e1-e17 (2018). [cited by applicant]
Hendriks, Gert-Jan. et al. NASC-seq monitors RNA synthesis in single cells. Nature communications 10(1):3138, 1-9 (2019). [cited by applicant]
Hrvatin, Sinisa. et al. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nature neuroscience 21(1):120-129 (2018). [cited by applicant]
Ingolia, Nicholas T. Ribosome footprint profiling of translation throughout the genome. Cell 165(1):22-33 (2016). [cited by applicant]
Katz, Zachary B. et al. Mapping translation‘hot-spots’ in live cells by tracking single molecules of mRNA and ribosomes. Elife 5:e10415, 1-16 (2016). [cited by applicant]
Ke, Rongqin et al. In Situ Sequencing for RNA Analysis in Preserved Tissue and Cells. Nature Methods 10(9):857-860 (2013). [cited by applicant]
Keller, Philipp J. et al. Visualizing whole-brain activity and development at the single-cell level using light-sheet microscopy. Neuron 85(3):462-483 (2015). [cited by applicant]
Kishi, Jocelyn Y. et al. SABER amplifies FISH: enhanced multiplexed imaging of RNA and DNA in cells and tissues. Nature methods 16(6):533-544 (2019). [cited by applicant]
Koos, Bjorn. et al. Analysis of protein interactions in situ by proximity ligation assays. Current Topics in Microbiology and Immunology 377:111-126 (2014). [cited by applicant]
Larsson, Chatarina. et al. In situ detection and genotyping of individual mRNA molecules. Nat Methods 7(5):395-397 (2010). [cited by applicant]
Lee, Je Hyuk. et al. Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact cells and tissues. Nature protocols 10(3):442-458 (2015). [cited by applicant]
Lee, Je Hyuk. et al. Highly multiplexed subcellular RNA sequencing in situ. Science 343(6177):1360-1363 (2014). [cited by applicant]
Lein, Ed. et al. The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing. Science 358(6359):64-69 (2017). [cited by applicant]
Lizardi, Paul M. et al. Mutation Detection and Single-molecule Counting Using Isothermal Rolling-circle Amplification. Nature Genetics 19(3):225-232 (1998). [cited by applicant]
Lubeck, Eric, and Long Cai. et al. Single-cell systems biology by super-resolution imaging and combinatorial labeling. Nature Methods 9(7):743-748 (2012). [cited by applicant]
Moffitt, Jeffrey R. et al. Molecular spatial and functional single-cell profiling of the hypothalamic preoptic region. Science 362(6416): eaau5324, 1-14 (2018). [cited by applicant]
Mondal, Manas. et al. Highly multiplexed single-cell in situ RNA and DNA analysis with bioorthogonal cleavable fluorescent oligonucleotides. Chemical science 9(11):2909-2917 (2018). [cited by applicant]
Moon, Kevin R. et al. Visualizing structure and transitions in high-dimensional biological data. Nature biotechnology 37(12):1482-1492 (2019). [cited by applicant]
Morisaki, Tatsuya. et al. Real-time quantification of single RNA translation dynamics in living cells. Science 352(6292):1425-1429 (2016). With Supplemental Materials. [cited by applicant]
Nawy, Tal. In situ sequencing. Nature Methods 11(1):29 (2014). [cited by applicant]
PCT/US2019/025835 International Search Report dated Jul. 1, 2019. [cited by applicant]
PCT/US2020/055800 International Search Report and Written Opinion dated Feb. 22, 2021. [cited by applicant]
PCT/US2022/030232 International Search Report and Written Opinion dated Oct. 26, 2022. [cited by applicant]
PCT/US2022/030321 International Search Report and Written Opinion dated Oct. 6, 2022. [cited by applicant]
PCT/US2022/030363 International Search Report and Written Opinion dated Sep. 1, 2022. [cited by applicant]
PCT/US2022/030370 International Search Report and Written Opinion dated Sep. 1, 2022. [cited by applicant]
PCT/US2022/030374 International Search Report and Written Opinion dated Sep. 1, 2022. [cited by applicant]
PCT/US2024/046583 International Search Report and Written Opinion dated Jan. 2, 2025. [cited by applicant]
PCT/US2024/060469 International Search Report and Written Opinion dated May 7, 2025. [cited by applicant]
PCT/US2025/018783 International Search Report and Written Opinion dated Jun. 27, 2025. [cited by applicant]
Perkel, Jeffrey M. Starfish enterprise: finding RNA patterns in single cells. Nature 572(7770):549-549 (2019). [cited by applicant]
Player, Audrey N. et al. Single-copy gene detection using branched DNA (bDNA) in situ hybridization. The journal of histochemistry and cytochemistry 49(5):603-612 (2001). [cited by applicant]
Qian, Xiaoyan. et al. Probabilistic cell typing enables fine mapping of closely related cell types in situ. Nature methods 17(1):101-106 (2020). [cited by applicant]
Ren, Jingyi. et al. Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape. Nature Methods 20(5):695-705 (2023). [cited by applicant]
Rosales, Adrianne M., and Kristi S. Anseth. The design of reversible hydrogels to capture extracellular matrix dynamics. Nature Reviews Materials 1(2):15012, 1-15 (2016). [cited by applicant]
Sakaue-Sawano, Asako. et al. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132(3):487-498 (2008). [cited by applicant]
Schweitzer, Barry. et al. Immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection. Proceedings of the National Academy of Sciences 97(18):10113-10119 (2000). [cited by applicant]
Schweitzer, Barry. et al. Multiplexed protein profiling on microarrays by rolling-circle amplification. Nature biotechnology 20(4):359-365 (2002). [cited by applicant]
Shah, Sheel. et al. seqFISH accurately detects transcripts in single cells and reveals robust spatial organization in the hippocampus. Neuron 94(4):752-758, e1 (2017). [cited by applicant]
Shah, Sheel. et al. Single-molecule RNA detection at depth by hybridization chain reaction and tissue hydrogel embedding and clearing. Development 143(15):2862-2867 (2016). [cited by applicant]
Soderberg, Ola. et al. Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nature methods 3(12):995-1000 (2006). [cited by applicant]
Stahl, Patrik L. et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353(6294):78-82 (2016). [cited by applicant]
Strell, Carina. et al. Placing RNA in context and space—methods for spatially resolved transcriptomics. The FEBS journal 286(8):1468-1481 (2019). [cited by applicant]
Tam, Roger Y. et al. Engineering cellular microenvironments with photo- and enzymatically responsive hydrogels: toward biomimetic 3D cell culture models. Accounts of chemical research 50(4):703-713 (2017). [cited by applicant]
Toga, Arthur W. et al. Towards multimodal atlases of the human brain. Nature Reviews Neuroscience 7(12):952-966 (2006). [cited by applicant]
Tom Dieck, Susanne. et al. Direct visualization of newly synthesized target proteins in situ. Nature methods 12(5):411-414 (2015). [cited by applicant]
Tomer, Raju. et al. Advanced Clarity for rapid and high-resolution imaging of intact tissues. Nature protocols 9(7):1682-1697 (2014). [cited by applicant]
Wang, Guiping. et al. Spatial organization of the transcriptome in individual neurons. BioRxiv :1-45 (2020). [cited by applicant]
Wang, Xiao. et al. Supplementary Material: Three-dimensional Intact-tissue Sequencing of Single-cell Transcriptional States. Science 361(6400):eaat5691, 1-39 (2018). [cited by applicant]
Wang, Xiao. et al. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science 361(6400):eaat5691, 1-11 (2018). [cited by applicant]
Weber, Michael. et al. Cell-accurate optical mapping across the entire developing heart. Elife 6:e28307, 1-14 (2017). [cited by applicant]
Weibrecht, Irene. et al. In situ detection of individual mRNA molecules and protein complexes or post-translational modifications using padlock probes combined with the in situ proximity ligation assay. Nature protocols… [cited by applicant]
Weibrecht, Irene. et al. Visualising individual sequence-specific protein-DNA interactions in situ. New biotechnology 29(5):589-598 (2012). [cited by applicant]
Wetmur, James G. DNA probes: applications of the principles of nucleic acid hybridization. Critical Reviews in Biochemistry and Molecular Biology 26(3-4):227-259 (1991). [cited by applicant]
Wu et al., (2016) “Translation dynamaics of single mRNAs in live cells and neurons”, Science, 352(6292):14300-14305. [cited by applicant]
Xia, Chenglong. et al. Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression. Proceedings of the National Academy of Sciences 116(39):19490-1949… [cited by applicant]
Yang, Bin. et al. Single-cell phenotyping within transparent intact tissue through whole-body clearing. Cell 158(4):945-958 (2014). [cited by applicant]
Zeisel, Amit. et al. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347(6226):1138-1142 (2015). [cited by applicant]
Zeng, Hu. et al. Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer's disease. Nature neuroscience 26(3):430-446 (2023). [cited by applicant]
Zhang, Beibei. et al. Detection of nucleic acids with a novel stem-loop primer rolling circle amplification technique. Biotechniques 64(2):69-80 (2018). [cited by applicant]
Zhang, Wei. et al. Proximity-dependent Assay for Specific RNA-protein Interactions in Intact Cells. RNA 22(11):1785-1792 (2016). [cited by applicant]
Zhong, Xiao-bo. et al. Visualization of oligonucleotide probes and point mutations in interphase nuclei and DNA fibers using rolling circle DNA amplification. Proceedings of the National Academy of Sciences 98(7):3940-3… [cited by applicant]
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