Granted Patent
B2
US 12,258,623 · App. 18/177,238 · Granted Mar 25, 2025
Multiomic analysis device and methods of use thereof
Inventors:
Sandor Kovacs (Encinitas, CA); Eli N. Glezer (San Diego, CA); Christopher Frye (San Diego, CA)
Assignee:
Singular Genomics Systems, Inc.
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Abstract
Disclosed herein, inter alia, are devices, compositions, kits, and methods for interrogating biological samples.
Claims (31)
1. A method of detecting a plurality of proteins of a cell; said method comprising:
heating the cell to about 50° C. to about 120° C.;
associating a barcode from a known set of barcodes with each of the plurality of proteins by hybridizing a probe to two adjacent nucleic acid sequences of a target oligonucleotide attached to a protein, wherein the probe is a single-stranded polynucleotide comprising a barcode or the oligonucleotide comprises a barcode; sequencing each barcode to obtain a multiplexed signal; demultiplexing the multiplexed signal by comparison with the known set of barcodes; and detecting the plurality of proteins by identifying the associated barcodes,
wherein said cell is attached to a solid support and the solid support is coupled to a device comprising:
a sample stage and a heating element thermally coupled to the sample stage;
an imaging system configured to detect one or more fluorescent signals; and
a lid configured to form a channel comprising the solid support.
2. The method of claim 1 , wherein the device is configured to perform temperature cycling.
3. The method of claim 2 , wherein the device is configured to thermally cycle between about 35° C. and about 65° C.
4. The method of claim 1 , wherein the solid support comprises 4, 6, 12, 24, 48, 96, 384 or 1536 sample wells.
5. The method of claim 4 , wherein the sample wells each comprise 10,000 to 100,000 cells per sample well.
6. The method of claim 1 , wherein the solid support comprises glass.
7. The method of claim 1 , wherein sequencing comprises detecting a sequence of fluorescent signals.
8. The method of claim 1 , wherein sequencing comprises sequencing-by-synthesis, sequencing by ligation, sequencing-by-hybridization, or pyrosequencing, and sequencing generates a sequencing read.
9. The method of claim 1 , wherein the cell is within a plurality of cells, wherein the plurality of cells is attached to the solid support.
10. The method of claim 1 , said method further comprising imaging the cell.
11. The method of claim 1 , wherein the imaging system comprises a three-dimensional imager, a TDI sensory array, a laser, a camera, an autofocus, and/or a transilluminator.
12. The method of claim 1 , wherein the device further includes a display and a graphical user interface.
13. The method of claim 1 , wherein the sample stage is a motorized translation stage.
14. The method of claim 1 , wherein the sample stage is capable of moving independently relative to imaging system.
15. The method of claim 1 , wherein the imaging system comprises a camera capable of moving along a polar angle formed between a z axis and a normal vector of the solid support.
16. The method of claim 15 , wherein the imaging system comprises a time delay integration (TDI) sensor array.
17. A method of detecting two proteins of a cell in situ; said method comprising:
associating a different barcode from a known set of barcodes with each protein;
sequencing each barcode to obtain a multiplexed signal in situ; and
demultiplexing the multiplexed signal by comparison with the known set of barcodes;
and detecting the proteins by identifying the associated barcodes,
wherein said cell is permeabilized and attached to a solid support within a microfluidic channel.
18. The method of claim 17 , further comprising contacting the cell with eosin and detecting the eosin.
19. The method of claim 17 , wherein sequencing comprises hybridizing a primer to a nucleic acid molecule comprising the barcode, incorporating a labeled nucleotide into the primer, followed by incorporating an unlabeled nucleotide.
20. The method of claim 19 , wherein the cell forms part of a tissue.
Assignments (2)
SECURITY INTEREST
Recorded Mar 7, 2025
From: SINGULAR GENOMICS SYSTEMS, INC.
To: FIRST-CITIZENS BANK & TRUST COMPANY
Reel/Frame 070440/0465 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 2, 2023
From: KOVACS, SANDOR; GLEZER, ELI N.; FRYE, CHRISTOPHER
To: SINGULAR GENOMICS SYSTEMS, INC
Reel/Frame 063505/0017 →
Continuity (3)
Continuation
PCTUS2022027630
· May 4, 2022
Provisional Application
63184684
· May 5, 2021
References Cited (257)
US 4318846A
· Khanna et al.
· 1982
[cited by applicant]
US 4792520A
· Stambrook et al.
· 1988
[cited by applicant]
US 5034506A
· Summerton et al.
· 1991
[cited by applicant]
US 5066580A
· Lee et al.
· 1991
[cited by applicant]
US 5188934A
· Menchen et al.
· 1993
[cited by applicant]
US 5235033A
· Summerton et al.
· 1993
[cited by applicant]
US 5366860A
· Bergot et al.
· 1994
[cited by applicant]
US 5538724A
· Butcher
· 1996
[cited by examiner]
US 5599675A
· Brenner
· 1997
[cited by applicant]
US 5688648A
· Mathies et al.
· 1997
[cited by applicant]
US 5750341A
· Macevicz
· 1998
[cited by applicant]
US 5763594A
· Hiatt et al.
· 1998
[cited by applicant]
US 5800996A
· Lee et al.
· 1998
[cited by applicant]
US 5808045A
· Hiatt et al.
· 1998
[cited by applicant]
US 5847162A
· Lee et al.
· 1998
[cited by applicant]
US 5872244A
· Hiatt et al.
· 1999
[cited by applicant]
US 6210891B1
· Nyren et al.
· 2001
[cited by applicant]
US 6218122B1
· Friend et al.
· 2001
[cited by applicant]
US 6232465B1
· Hiatt et al.
· 2001
[cited by applicant]
US 6258568B1
· Nyren
· 2001
[cited by applicant]
US 6271022B1
· Bochner
· 2001
[cited by applicant]
US 6274320B1
· Rothberg et al.
· 2001
[cited by applicant]
US 6365367B1
· Friedman
· 2002
[cited by examiner]
US 6664079B2
· Ju et al.
· 2003
[cited by applicant]
US 7057026B2
· Barnes et al.
· 2006
[cited by applicant]
US 7264929B2
· Rothberg et al.
· 2007
[cited by applicant]
US 7271952B2
· Suzuki et al.
· 2007
[cited by applicant]
US 7390463B2
· He et al.
· 2008
[cited by applicant]
US 7541444B2
· Milton et al.
· 2009
[cited by applicant]
US 8003354B2
· Shen et al.
· 2011
[cited by applicant]
US 8039817B2
· Feng et al.
· 2011
[cited by applicant]
US 8178360B2
· Barnes et al.
· 2012
[cited by applicant]
US 8241573B2
· Banerjee et al.
· 2012
[cited by applicant]
US 8551710B2
· Bernitz et al.
· 2013
[cited by applicant]
US 9371598B2
· Chee
· 2016
[cited by applicant]
US 9556473B2
· Bernitz et al.
· 2017
[cited by applicant]
US 9593365B2
· Frisen et al.
· 2017
[cited by applicant]
US 9598723B2
· Ammann et al.
· 2017
[cited by applicant]
US 20010054691A1
· Park et al.
· 2001
[cited by applicant]
US 20020159919A1
· Churchill et al.
· 2002
[cited by applicant]
US 20030032024A1
· Lizardi et al.
· 2003
[cited by applicant]
US 20030082556A1
· Kaufman et al.
· 2003
[cited by applicant]
US 20030143536A1
· Lizardi
· 2003
[cited by applicant]
US 20050089860A1
· Arita
· 2005
[cited by applicant]
US 20050208644A1
· Takiguchi et al.
· 2005
[cited by applicant]
US 20060050376A1
· Houston
· 2006
[cited by examiner]
US 20090298718A1
· Denman et al.
· 2009
[cited by applicant]
US 20100055733A1
· Lutolf et al.
· 2010
[cited by applicant]
US 20110059865A1
· Smith et al.
· 2011
[cited by applicant]
US 20110223585A1
· Gullberg et al.
· 2011
[cited by applicant]
US 20120301886A1
· Farrell et al.
· 2012
[cited by applicant]
US 20140056811A1
· Jacob
· 2014
[cited by examiner]
US 20140057799A1
· Johnson et al.
· 2014
[cited by applicant]
US 20170107563A1
· Samusik et al.
· 2017
[cited by applicant]
US 20190017106A1
· Frisen et al.
· 2019
[cited by applicant]
US 20190071668A1
· Schmidt et al.
· 2019
[cited by applicant]
US 20190113423A1
· Goodman et al.
· 2019
[cited by applicant]
US 20190155835A1
· Daugharthy
· 2019
[cited by examiner]
US 20190376123A1
· Bobrow et al.
· 2019
[cited by applicant]
US 20200277663A1
· Ramachandran Iyer et al.
· 2020
[cited by applicant]
US 20200277664A1
· Frenz
· 2020
[cited by applicant]
US 20200362334A1
· Regev et al.
· 2020
[cited by applicant]
US 20210039062A1
· Mirkin et al.
· 2021
[cited by applicant]
US 20210108195A1
· Bernate et al.
· 2021
[cited by applicant]
US 20210382033A1
· Mir
· 2021
[cited by applicant]
US 20210388424A1
· Bava
· 2021
[cited by applicant]
US 20230100215A1
· Glezer et al.
· 2023
[cited by applicant]
JP 2005265627A
· 2005
[cited by applicant]
JP 5970959B2
· 2016
[cited by applicant]
WO WO1989010977A1
· 1989
[cited by applicant]
WO WO1996007669A1
· 1996
[cited by applicant]
WO WO2004018497A2
· 2004
[cited by applicant]
WO WO2004018497A3
· 2004
[cited by applicant]
WO WO2013090360A2
· 2013
[cited by applicant]
WO WO2013090360A3
· 2013
[cited by applicant]
WO WO2014030066A2
· 2014
[cited by applicant]
WO WO2014030066A3
· 2014
[cited by applicant]
WO WO2018091676A1
· 2018
[cited by applicant]
WO WO2018148723A1
· 2018
[cited by applicant]
WO WO2019068880A1
· 2019
[cited by applicant]
WO WO2019199579A1
· 2019
[cited by applicant]
WO WO2020028194A1
· 2020
[cited by applicant]
WO WO2020056044A1
· 2020
[cited by applicant]
WO WO2020076976A1
· 2020
[cited by applicant]
WO WO2020076979A1
· 2020
[cited by applicant]
WO WO2020096687A1
· 2020
[cited by applicant]
WO WO2020099640A1
· 2020
[cited by applicant]
WO WO2020160044A1
· 2020
[cited by applicant]
WO WO2022056385A1
· 2022
[cited by applicant]
Chen et al, Nucl. Acids Res, vol. 46, No. e22; pp. 1-10, published online Nov. 28, 2017.
[cited by examiner]
Fijnvandraat et al, Microscopy Research and Techniques, vol. 58, pp. 387-394, published 2002.
[cited by examiner]
Agrawal, S. et al. (Nov. 15, 2016). “Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy,”
[cited by applicant]
Alon, S. et al. (2020). “Expansion Sequencing: Spatially Precise In Situ Transcriptomics in Intact Biological Systems,”
[cited by applicant]
Arce, S. H. et al. (Jul. 24, 2013). “Fast and accurate automated cell boundary determination for fluorescence microscopy,”
[cited by applicant]
Auld, D. S. et al. (Jun. 1, 2020). “Microplate Selection and Recommended Practices in High-throughput Screening and Quantitative Biology,” In S. Markossian (Eds.) et al.,
[cited by applicant]
Bains, W. et al. (Dec. 7, 1988). “A novel method for nucleic acid sequence determination,”
[cited by applicant]
Bains, I. et al. (May 28, 2009). “Quantifying the development of the peripheral naive CD4+ T-cell pool in humans,”
[cited by applicant]
Bullinger, L. et al. (Apr. 15, 2004). “Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia,”
[cited by applicant]
Cai, M. (2019). “Spatial mapping of single cells in human cerebral cortex using Dartfish: a highly multiplexed method for in situ quantification of targeted RNA transcripts,”
[cited by applicant]
Carow, B. et al. (2019). “Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma,”
[cited by applicant]
Carpenter, A. E. et al. (Oct. 31, 2006). “CellProfiler: image analysis software for identifying and quantifying cell phenotypes,”
[cited by applicant]
Chen, F. et al. (Jan. 30, 2015, e-published Jan. 15, 2015). “Optical imaging. Expansion microscopy,”
[cited by applicant]
Christian, A.T. et al. (Dec. 4, 2001, e-published Nov. 27, 2001). “Detection of DNA point mutations and mRNA expression levels by rolling circle amplification in individual cells,”
[cited by applicant]
Dirks, R. M. et al. (Oct. 18, 2004). “Triggered amplification by hybridization chain reaction,”
[cited by applicant]
Drmanac, S. et al. (Jan. 1998). “Accurate sequencing by hybridization for DNA diagnostics and individual genomics,”
[cited by applicant]
El-Sagheer, A. H. et al. (Aug. 21, 2012, e-published Mar. 22, 2012).“Click nucleic acid ligation: applications in biology and nanotechnology,”
[cited by applicant]
Fan, T. et al. (Jul. 7, 2018). “Branched rolling circle amplification method for measuring serum circulating micro RNA levels for early breast cancer detection,”
[cited by applicant]
Feeney, R. E. et al. (Apr. 1, 1982). “Chemical modification of proteins: an overview,”
[cited by applicant]
Fodor, S.P. et al. (Feb. 15, 1991). “Light-directed, spatially addressable parallel chemical synthesis,”
[cited by applicant]
Ganusov, V. V. et al. (Dec. 2007, e-published Oct. 26, 2007). “Do most lymphocytes in humans really reside in the gut?,”
[cited by applicant]
Gelali, E. et al. (Apr. 9, 2019). “iFISH is a publically available resource enabling versatile DNA FISH to study genome architecture,”
[cited by applicant]
Gore, A. et al. (Mar. 2, 2011). “Somatic coding mutations in human induced pluripotent stem cells,”
[cited by applicant]
Gyllborg, D. et al. (Nov. 4, 2020). “Hybridization-based in situ sequencing (HybISS) for spatially resolved transcriptomics in human and mouse brain tissue,”
[cited by applicant]
Hagai, T. et al. (Nov. 2018, e-published Oct. 24, 2018). “Gene expression variability across cells and species shapes innate immunity,”
[cited by applicant]
Hamaday, M. et al. (Mar. 2008). “Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex,”
[cited by applicant]
Hamilton, N. (2009). “Quantification and its applications in fluorescent microscopy imaging,”
[cited by applicant]
Hardenbol, P. et al. (2003). “Multiplexed genotyping with sequence-tagged molecular inversion probes,”
[cited by applicant]
Heintzmann, R. et al. (Dec. 13, 2017, e-published Nov. 10, 2017). “Super-Resolution Structured Illumination Microscopy,”
[cited by applicant]
Hu, Y. et al. (2014). “Sensitive quantification of messenger RNA with a real-time ligase chain reaction by using a ribonucleotide-modified DNA probe,”
[cited by applicant]
International Search report mailed on Sep. 19, 2022, for PCT application PCT/US2022/027630, filed May 4, 2022, 5 pages.
[cited by applicant]
International Search Report mailed on Nov. 23, 2021, for PCT Application No. PCT/US2021/045104, filed Aug. 6, 2021, 4 pages.
[cited by applicant]
Kappler, K. et al. (Aug. 2020, e-published Aug. 5, 2020). “Emergence and significance of carbohydrate-specific antibodies,”
[cited by applicant]
Kato, M. et al. (Feb. 1, 1995). “Polymerization of methyl methacrylate with the carbon tetrachloride/dichlorotris-(triphenylphosphine) ruthenium (II)/methylaluminum bis (2, 6-di-tert-butylphenoxide) initiating system: p…
[cited by applicant]
Ke, R. et al. (Sep. 2013). “In situ sequencing for RNA analysis in preserved tissue and cells,”
[cited by applicant]
Klein A. M. et al. (Jul. 25, 2017). “InDrops and Drop-seq technologies for single-cell sequencing,”
[cited by applicant]
Kobori, T. et al. (2014). “Expanding possibilities of rolling circle amplification as a biosensing platform,”
[cited by applicant]
Lage, J. M. et al. (2003). “Whole genome analysis of genetic alterations in small DNA samples using hyperbranched strand displacement amplification and array—CGH,”
[cited by applicant]
Lareau, C. A. et al. (Feb. 13, 2020). “Inference and effects of barcode multiplets in droplet-based single-cell assays,”
[cited by applicant]
Larsson, C. et al. (Apr. 11, 2010). “In situ detection and genotyping of individual mRNA molecules,”
[cited by applicant]
Li, J. B. et al. (May 29, 2009). “Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing,”
[cited by applicant]
Li, J. B. et al. (Jun. 12, 2009). “Multiplex padlock targeted sequencing reveals human hypermutable CpG variations,”
[cited by applicant]
Li, N. et al. (May 21, 2009). “Stand-alone rolling circle amplification combined with capillary electrophoresis for specific detection of small RNA,”
[cited by applicant]
Lizardi, P. M. et al. (Jul. 1998). “Mutation detection and single-molecule counting using isothermal rolling-circle amplification,”
[cited by applicant]
Lohmann, J. S. et al. (Nov. 13, 2007). “Detection of short repeated genomic sequences on metaphase chromosomes using padlock probes and target primed rolling circle DNA synthesis,”
[cited by applicant]
Lugagne, J-B. et al. (Jul. 30, 2018). “Identification of individual cells from z-stacks of bright-field microscopy images,”
[cited by applicant]
Mag, M. et al. (1992) “Synthesis and selective cleavage of an oligodeoxynucleotide containing a bridged non-chiral internucleotide 3′-phosphoramidate linkage,”
[cited by applicant]
Manuguerra, I. et al. (May 1, 2018). “Gene assembly via one-pot chemical ligation of DNA promoted by DNA nanostructures,”
[cited by applicant]
Mirza, S. P. et al. (Mar. 1, 2008). “Methods and approaches for the comprehensive characterization and quantification of cellular proteomes using mass spectrometry,”
[cited by applicant]
Mitra, R.D. et al. (2003) “Fluorescent in situ sequencing on polymerase colonies,”
[cited by applicant]
Moad, G. et al. (Jun. 14, 2005). “Living radical polymerization by the RAFT process,”
[cited by applicant]
Mohammadi-Kambs, M. et al. (2017). “Hamming distance as a concept in DNA molecular recognition,”
[cited by applicant]
Nilsson, M. et al. (Sep. 30, 1994). “Padlock probes: circularizing oligonucleotides for localized DNA detection,”
[cited by applicant]
Noggle, S. et al. (Oct. 5, 2011). “Human oocytes reprogram somatic cells to a pluripotent state,”
[cited by applicant]
Odeh, F. et al. (Dec. 18, 2019). “Aptamers Chemistry: Chemical Modifications and Conjugation Strategies,”
[cited by applicant]
Otsu, T. et al. (Feb. 16, 1982). “Role of initiator-transfer agent-terminator (iniferter) in radical polymerizations: Polymer design by organic disulfides as iniferters,”
[cited by applicant]
Patel, A. P. et al. (Jun. 20, 2014, e-published Jun. 12, 2014). “Single-cell RNA- seq highlights intratumoral heterogeneity in primary glioblastoma,”
[cited by applicant]
Pattarone, G. et al. (May 13, 2021, corrected Sep. 24, 2021). “Learning deep features for dead and living breast cancer cell classification without staining,”
[cited by applicant]
Pearson, A. et al. (Aug. 2016, e-published May 13, 2016). “High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial,”
[cited by applicant]
Peerzade, S. A. et al. (May 8, 2020). “Ultrabright Fluorescent Silica Nanoparticles for Multiplexed Detection,”
[cited by applicant]
Peters, J. M. et al. (Jan. 2011). “Multiparameter flow cytometry in the diagnosis and management of acute leukemia,”
[cited by applicant]
Porreca, G. J. et al. (Nov. 2007, e-published Oct. 14, 2007). “Multiplex amplification of large sets of human exons,”
[cited by applicant]
Ronaghi, M. et al. (Nov. 1, 1996). “Real-time DNA sequencing using detection of pyrophosphate release,”
[cited by applicant]
Ronaghi, M. et al. (Jul. 17, 1998). “A sequencing method based on real-time pyrophosphate,”
[cited by applicant]
Ronaghi, M. (Jan. 2001). “Pyrosequencing sheds light on DNA sequencing,”
[cited by applicant]
Rouhanifard, S. H. et al. (2018). “Exponential fluorescent amplification of individual RNAs using clampFISH probes,”
[cited by applicant]
Sansone, A. (Jun. 2019). “Spatial transcriptomics levels up,”
[cited by applicant]
Sapoznik, E. et al. (Nov. 12, 2020). “A versatile oblique plane microscope for large-scale and high-resolution imaging of subcellular dynamics,”
[cited by applicant]
Schlachter, S. et al. (2009). “A method to unmix multiple fluorophores in microscopy images with minimal a priori information,”
[cited by applicant]
Shendure, J. et al. (Sep. 9, 2005, e-published Aug. 4, 2005). “Accurate multiplex polony sequencing of an evolved bacterial genome,”
[cited by applicant]
Shirakawa, H. et al. (Mar. 2004). “Blind spectral decomposition of single-cell fluorescence by parallel factor analysis,”
[cited by applicant]
Suzuki, A. et al. (Dec. 20, 2019). “Characterization of cancer omics and drug perturbations in panels of lung cancer cells,”
[cited by applicant]
Takahashi, H. et al. (2018). “RNase H-assisted RNA-primed rolling circle amplification for targeted RNA sequence detection,”
[cited by applicant]
Veregin, R. P. N. et al. (Sep. 1, 1993). “Free radical polymerizations for narrow polydispersity resins: electron spin resonance studies of the kinetics and mechanism,”
[cited by applicant]
Vickovic, S. et al. (Oct. 2019, e-published Sep. 9, 2019). “High-definition spatial transcriptomics for in situ tissue profiling,”
[cited by applicant]
Walker, J.W., et al. (1998). “Photolabile 1-(2-nitrophenyl) ethyl phosphate esters of adenine nucleotide analogs. Synthesis and mechanism of photolysis,”
[cited by applicant]
Wang, G. et al. (Mar. 19, 2018). “Multiplexed imaging of high-density libraries of RNAs with MERFISH and expansion microscopy,”
[cited by applicant]
Wang, J-S. et al. (May 1, 1995). “Controlled/‘living’ radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes,”
[cited by applicant]
Wang X. et al. (Jul. 27, 2018, e-published Jun. 21, 2018). “Three-dimensional intact-tissue sequencing of single-cell transcriptional states,”
[cited by applicant]
Weibrecht, I. et al. (Jan. 2013). “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.”
[cited by applicant]
Wilson, C.S. et al. (Jul. 15, 2006, e-published Apr. 4, 2006). “Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction,”
[cited by applicant]
Written Opinion mailed on Sep. 19, 2022, for PCT Application No. PCT/US2022/027630, filed Mav 4, 2022, 8 pages.
[cited by applicant]
Written Opinion mailed on Nov. 23, 2021, for PCT Application No. PCT/US2021/045104, filed Aug. 6, 2021, 11 pages.
[cited by applicant]
Xu, Q. et al. (2009). “Design of 240,000 orthogonal 25mer DNA barcode probes,”
[cited by applicant]
Yaari, G. et al. (Nov. 20, 2015). “Practical guidelines for B-cell receptor repertoire sequencing analysis,”
[cited by applicant]
Yeole, N. (May 2010). “Thiocarbonylthio compounds,”
[cited by applicant]
York, A.G. et al. (Nov. 2013, e-published Oct. 6, 2013). “Instant super- resolution imaging in live cells and embryos via analog image processing,”
[cited by applicant]
Zhang, K. et al. (Aug. 2009, e-published Jul. 20, 2009). “Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human,”
[cited by applicant]
Zheng, G. X. et al. (Jan. 16, 2017). “Massively parallel digital transcriptional profiling of single cells,”
[cited by applicant]
Ahern, H. (1995) “Biochemical, reagent kits offer scientists good return on investment,”
[cited by applicant]
Edelman, M. J. et al. (May 1997, e-published Feb. 28, 2002). “The utility of follow-up testing after curative cancer therapy: a critical review and economic analysis,”
[cited by applicant]
Guo, J. et al. (Jul. 8, 2008). “Four-color DNA sequencing with 3′-O-modified nucleotide reversible terminators and chemically cleavable fluorescent dideoxynucleotides,”
[cited by applicant]
Jeong, S. et al. (Apr. 2020, e-published Jan. 30, 2020). “Current immunoassay methods and their applications to clinically used biomarkers of breast cancer,”
[cited by applicant]
Nitta, H. et al. (Aug. 2013, e-published Nov. 15, 2015). “New methods for ALK status diagnosis in non-small-Cell lung Cancer: an improved ALK immunohistochemical assay and a new, Brightfield, dual ALK IHC—In situ hybrid…
[cited by applicant]
The Stratagene Catalog (1988), p. 39.
[cited by applicant]
Chen, X. et al. (Feb. 28, 2018, e-published Nov. 28, 2017). “Efficient in situ barcode sequencing using padlock probe-based BaristaSeq,”
[cited by applicant]
Chen, K. H. et al. (Apr. 24, 2015, e-published Apr. 9, 2015). “RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells,”
[cited by applicant]
Daigeler, A. et al. (Jul. 6, 2006). “Clinicopathological findings in a case series of extrathoracic solitary fibrous tumors of soft tissues,”
[cited by applicant]
Denkert, C. et al. (Nov. 1, 2015, e-published Aug. 14, 2015). “Strategies for developing Ki67 as a useful biomarker in breast cancer,”
[cited by applicant]
Fredriksson, S. et al. (Apr. 2007, e-published Mar. 18, 2007). “Multiplexed protein detection by proximity ligation for cancer biomarker validation,”
[cited by applicant]
Fredriksson, S. et al. (May 1, 2002). “Protein detection using proximity-dependent DNA ligation assays,”
[cited by applicant]
Gao, H. et al. (Dec. 2019, e-published Oct. 17, 2019). “Rolling circle amplification for single cell analysis and in situ sequencing,”
[cited by applicant]
Ouladan, S. et al. (Jun. 2015, e-published Apr. 20, 2015). “Differential diagnosis of solitary fibrous tumors: a study of 454 soft tissue tumors indicating the diagnostic value of nuclear STAT6 relocation and ALDH1 expr…
[cited by applicant]
Park, M. S. et al. (May 11, 2013). “The role of chemotherapy in advanced solitary fibrous tumors: a retrospective analysis,”
[cited by applicant]
Schallmeiner, E. et al. (Feb. 1, 2007, e-published Dec. 17, 2006). “Sensitive protein detection via triple-binder proximity ligation assays,”
[cited by applicant]
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