Granted Patent
B2
US 12,306,093 · App. 17/513,877 · Granted May 20, 2025
Methods and systems for integrated on-chip single-molecule detection
Inventors:
Pierre Indermuhle (Berkeley, CA); Elliott Sorelle (San Carlos, CA); David Stern (San Carlos, CA); Parag Mallick (San Mateo, CA); Sujal M. Patel (Seattle, WA)
Assignee:
Nautilus Subsidiary, Inc.
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Abstract
The present disclosure provides methods and systems for performing single-molecule detection using fabricated integrated on-chip devices. Provided herein is a composition, comprising: (a) a substrate; (b) a structured nucleic acid particle coupled to the substrate, wherein a biological entity is coupled to the structured nucleic acid particle; and (c) a fluorescent detection agent, wherein the fluorescent detection agent comprises an affinity reagent attached to another structured nucleic acid particle, wherein the affinity reagent is bound to the biological entity.
Claims (27)
1. A composition, comprising:
a. a substrate;
b. a first structured nucleic acid particle coupled to the substrate, wherein a biological entity is coupled to the first structured nucleic acid particle; and
c. a fluorescent detection agent, wherein the fluorescent detection agent comprises an affinity reagent attached to a second structured nucleic acid particle, wherein the affinity reagent is bound to the biological entity, wherein the first structured nucleic acid particle is coupled to the substrate by binding between a first oligonucleotide and a second oligonucleotide, wherein the first oligonucleotide is attached to the substrate, and wherein the second oligonucleotide comprises a strand of the structured nucleic acid particle.
2. The composition of claim 1 , wherein the biological entity comprises a protein.
3. The composition of claim 1 , wherein the biological entity comprises a small molecule, a DNA, an RNA, a glycoprotein, a metabolite, a carbohydrate, an enzyme, or an antibody.
4. The composition of claim 1 , wherein the biological entity consists essentially of a single protein.
5. The composition of claim 1 , wherein the first structured nucleic acid particle comprises a nucleic acid origami.
6. The composition of claim 5 , wherein the nucleic acid origami comprises a long nucleic acid strand and one or more short nucleic acid strands.
7. The composition of claim 6 , wherein the nucleic acid origami comprises at least 100 short nucleic acid strands.
8. The composition of claim 7 , wherein the nucleic acid origami comprises a landing surface that preferentially contacts the substrate.
9. The composition of claim 1 , wherein the second structured nucleic acid particle comprises a nucleic acid origami.
10. The composition of claim 1 , wherein the first structured nucleic acid particle comprises a short nucleic acid strand hybridized to a long nucleic acid strand.
11. The composition of claim 1 , wherein the fluorescent detection agent comprises two or more affinity reagents coupled to the second structure nucleic acid particle.
12. The composition of claim 1 , wherein the affinity reagent comprises an antibody or an antibody fragment.
13. The composition of claim 1 , wherein the affinity reagent comprises an aptamer.
14. The composition of claim 1 , wherein the affinity reagent comprises a mini-peptide binder or a peptimer.
15. The composition of claim 1 , wherein the affinity reagent comprises a known degree of nonspecificity.
16. The composition of claim 1 , wherein the substrate comprises silicon, silica, fused silica, quartz, or glass.
17. The composition of claim 1 , wherein the substrate comprises a microstructure that is coupled to the first structured nucleic acid particle.
18. The composition of claim 1 , wherein the substrate further comprises a passivating layer.
19. The composition of claim 1 , wherein the substrate further comprises a functionalized region.
20. The composition of claim 1 , wherein the functionalized region comprises a filamentous molecule.
21. The composition of claim 20 , wherein the filamentous molecule comprises an oligonucleotide or a nanoparticle.
22. The composition of claim 20 , wherein the first structured nucleic acid particle comprises a moiety that is bound to the filamentous molecule.
23. The composition of claim 1 , wherein the substrate comprises a light-sensing device.
24. The composition of claim 23 , wherein the light-sensing device comprises a charge-coupled device, a complementary metal-oxide semiconductor sensor, a charge injection device, or a JOT image sensor.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 17, 2023
From: NAUTILUS BIOTECHNOLOGY, INC.
To: NAUTILUS SUBSIDIARY, INC.
Reel/Frame 063350/0113 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 26, 2022
From: INDERMUHLE, PIERRE; SORELLE, ELLIOTT; STERN, DAVID; MALLICK, PARAG; PATEL, SUJAL M.
To: NAUTILUS BIOTECHNOLOGY, INC.
Reel/Frame 058766/0974 →
Continuity (3)
Continuation
PCTUS2020030501
· Apr 29, 2020
Provisional Application
62840209
· Apr 29, 2019
References Cited (322)
US 5324633A
· Fodor et al.
· 1994
[cited by applicant]
US 5445934A
· Fodor et al.
· 1995
[cited by applicant]
US 5695934A
· Brenner
· 1997
[cited by applicant]
US 5849878A
· Cantor et al.
· 1998
[cited by applicant]
US 5863722A
· Brenner
· 1999
[cited by applicant]
US 5888737A
· DuBridge et al.
· 1999
[cited by applicant]
US 5919626A
· Shi et al.
· 1999
[cited by applicant]
US 6140489A
· Brenner
· 2000
[cited by applicant]
US 6175002B1
· DuBridge et al.
· 2001
[cited by applicant]
US 6255469B1
· Seeman et al.
· 2001
[cited by applicant]
US 6391625B1
· Park et al.
· 2002
[cited by applicant]
US 6589726B1
· Butler et al.
· 2003
[cited by applicant]
US 6610482B1
· Fodor et al.
· 2003
[cited by applicant]
US 6720595B2
· Clevenger et al.
· 2004
[cited by applicant]
US 6737236B1
· Pieken et al.
· 2004
[cited by applicant]
US 6806361B1
· Kajisa et al.
· 2004
[cited by applicant]
US 6824866B1
· Glazer et al.
· 2004
[cited by applicant]
US 6998241B2
· Boga
· 2006
[cited by applicant]
US 7022515B2
· Herron et al.
· 2006
[cited by applicant]
US 7148058B2
· Charych et al.
· 2006
[cited by applicant]
US 7158224B2
· Montagu
· 2007
[cited by applicant]
US 7239860B2
· Stoks
· 2007
[cited by applicant]
US 7252954B2
· Wang et al.
· 2007
[cited by applicant]
US 7259258B2
· Kozlov et al.
· 2007
[cited by applicant]
US 7375234B2
· Sharpless et al.
· 2008
[cited by applicant]
US 7427678B2
· Pieken et al.
· 2008
[cited by applicant]
US 7545496B2
· Prins et al.
· 2009
[cited by applicant]
US 7598363B2
· Seeman et al.
· 2009
[cited by applicant]
US 7635562B2
· Harris et al.
· 2009
[cited by applicant]
US 7763736B2
· Sharpless et al.
· 2010
[cited by applicant]
US 7794799B1
· Kim et al.
· 2010
[cited by applicant]
US 7842793B2
· Rothemund
· 2010
[cited by applicant]
US 7932060B2
· Nadeau et al.
· 2011
[cited by applicant]
US 8133719B2
· Drmanac et al.
· 2012
[cited by applicant]
US 8445194B2
· Drmanac et al.
· 2013
[cited by applicant]
US 8467061B2
· McCAFFREY et al.
· 2013
[cited by applicant]
US 8501923B2
· Rothemund
· 2013
[cited by applicant]
US 8680483B2
· Haga et al.
· 2014
[cited by applicant]
US 8865077B2
· Chiou et al.
· 2014
[cited by applicant]
US 8951781B2
· Reed et al.
· 2015
[cited by applicant]
US 9193996B2
· Buermann et al.
· 2015
[cited by applicant]
US 9275871B2
· Sandhu
· 2016
[cited by applicant]
US 9330932B1
· Sills et al.
· 2016
[cited by applicant]
US 9340416B2
· Maune et al.
· 2016
[cited by applicant]
US 9466504B1
· Sills et al.
· 2016
[cited by applicant]
US 9528984B2
· Mitra
· 2016
[cited by applicant]
US 9606058B2
· Rothberg et al.
· 2017
[cited by applicant]
US 9678012B2
· Rothberg et al.
· 2017
[cited by applicant]
US 9717685B2
· Shih et al.
· 2017
[cited by applicant]
US 9796749B2
· Yin et al.
· 2017
[cited by applicant]
US 9880175B2
· Mitra
· 2018
[cited by applicant]
US 9921157B2
· Rothberg et al.
· 2018
[cited by applicant]
US 9975916B2
· Yin et al.
· 2018
[cited by applicant]
US 20030049626A1
· Jendoubi
· 2003
[cited by applicant]
US 20030054408A1
· Ravi et al.
· 2003
[cited by applicant]
US 20030143569A1
· Abrams
· 2003
[cited by applicant]
US 20040023413A1
· Opalsky
· 2004
[cited by applicant]
US 20040209383A1
· Yin et al.
· 2004
[cited by applicant]
US 20050054118A1
· Lebrun
· 2005
[cited by applicant]
US 20050095577A1
· Yang et al.
· 2005
[cited by applicant]
US 20050287523A1
· Letant et al.
· 2005
[cited by applicant]
US 20060035220A1
· Tashiro et al.
· 2006
[cited by applicant]
US 20060160234A1
· Lopez-Avila et al.
· 2006
[cited by applicant]
US 20070003959A1
· Ehben et al.
· 2007
[cited by applicant]
US 20070218503A1
· Mitra
· 2007
[cited by applicant]
US 20090018028A1
· Lindsay et al.
· 2009
[cited by applicant]
US 20090161100A1
· Minot et al.
· 2009
[cited by applicant]
US 20090214591A1
· Manucharyan et al.
· 2009
[cited by applicant]
US 20090247414A1
· Obradovic et al.
· 2009
[cited by applicant]
US 20100081134A1
· Mirkin et al.
· 2010
[cited by applicant]
US 20120141502A1
· Dixon et al.
· 2012
[cited by applicant]
US 20140087963A1
· Johnston et al.
· 2014
[cited by applicant]
US 20150004193A1
· Chang et al.
· 2015
[cited by applicant]
US 20150185199A1
· Joo et al.
· 2015
[cited by applicant]
US 20150330974A1
· Staker et al.
· 2015
[cited by applicant]
US 20160046984A1
· Nguyen et al.
· 2016
[cited by applicant]
US 20160060687A1
· Zhu et al.
· 2016
[cited by applicant]
US 20160102344A1
· Niemeyer et al.
· 2016
[cited by applicant]
US 20160160272A1
· Mir
· 2016
[cited by applicant]
US 20160161472A1
· Jungmann
· 2016
[cited by applicant]
US 20170044245A1
· Meng et al.
· 2017
[cited by applicant]
US 20170081713A1
· Kim et al.
· 2017
[cited by applicant]
US 20170327888A1
· Ong et al.
· 2017
[cited by applicant]
US 20180148514A1
· Williams
· 2018
[cited by applicant]
US 20190195869A1
· Fan et al.
· 2019
[cited by applicant]
US 20200082914A1
· Patel et al.
· 2020
[cited by applicant]
US 20200286584A9
· Patel et al.
· 2020
[cited by applicant]
US 20210132053A1
· Chandradoss et al.
· 2021
[cited by applicant]
US 20210239705A1
· Mallick
· 2021
[cited by applicant]
US 20210355483A1
· Chee et al.
· 2021
[cited by applicant]
US 20220017567A1
· Gremyachinskiy et al.
· 2022
[cited by applicant]
US 20220333215A1
· Xu et al.
· 2022
[cited by applicant]
US 20230221243A1
· Indermuhle et al.
· 2023
[cited by applicant]
CN 100500865C
· 2009
[cited by applicant]
EP 1105529B2
· 2013
[cited by applicant]
EP 2872898B1
· 2016
[cited by applicant]
EP 3498865B1
· 2020
[cited by applicant]
WO WO0146675A2
· 2001
[cited by applicant]
WO WO02086081A2
· 2002
[cited by applicant]
WO WO2005065814A1
· 2005
[cited by applicant]
WO WO2006135527A2
· 2006
[cited by applicant]
WO WO2007117444A2
· 2007
[cited by applicant]
WO WO2008016644A1
· 2008
[cited by applicant]
WO WO2007120208A3
· 2008
[cited by applicant]
WO WO2007123744A3
· 2008
[cited by applicant]
WO WO2009012343A2
· 2009
[cited by applicant]
WO WO2010065531A1
· 2010
[cited by applicant]
WO WO2014078855A1
· 2014
[cited by applicant]
WO WO2015097077A2
· 2015
[cited by applicant]
WO WO2016174525A1
· 2016
[cited by applicant]
WO WO2017127762A1
· 2017
[cited by applicant]
WO WO2018102759A1
· 2018
[cited by applicant]
WO WO2019036055A2
· 2019
[cited by applicant]
WO WO2019059961A1
· 2019
[cited by applicant]
WO WO2019133892A1
· 2019
[cited by applicant]
WO WO2019195633
· 2019
[cited by applicant]
WO WO2019211631A1
· 2019
[cited by applicant]
WO WO2019236749A2
· 2019
[cited by applicant]
WO WO2020106889A1
· 2020
[cited by applicant]
WO WO2020108588A1
· 2020
[cited by applicant]
WO WO2020223368A1
· 2020
[cited by applicant]
WO WO2021074087A1
· 2021
[cited by applicant]
WO WO2021087402A1
· 2021
[cited by applicant]
WO WO2020254684A1
· 2021
[cited by applicant]
Office Action in CA3135206, mailed Aug. 29, 2023, 5 pages.
[cited by applicant]
Anonymous. List of protein hydrodynamic diameters. Dynamic Biosensors. May 17, 2017, XP055857934, Available at https://www.dynamic-biosensors.com/project/list-of-protein-hydrodynamic-diameters/. Retrieved on Nov. 4, 202…
[cited by applicant]
Co-pending U.S. Appl. No. 17/534,405, inventor Mallick; Parag, filed on Nov. 23, 2021.
[cited by applicant]
EP19781106.0 Extended European Search Report dated Nov. 19, 2021.
[cited by applicant]
Hung, Albert M., et al. Large-area spatially ordered arrays of gold nanoparticles directed by lithographically confined DNA origami. Nature nanotechnology 5.2 (2010): 121-126.
[cited by applicant]
Rusmini, Federica et al. Protein immobilization strategies for protein biochips. Biomacromolecules vol. 8,6 (2007): 1775-89. doi:10.1021/bm061197b.
[cited by applicant]
U.S. Appl. No. 16/791,456 Final Office Action dated Jan. 21, 2022.
[cited by applicant]
U.S. Appl. No. 17/390,666 Office Action dated Jan. 28, 2022.
[cited by applicant]
Extended European Search Report for Application No. 20798234.9, 10 pages, Jun. 19, 2023.
[cited by applicant]
Chandrasekaran, “Programmable DNA scaffolds for spatially-ordered protein assembly”, Nanoscale, vol. 8, No. 8, Jan. 1, 2016, pp. 4436-4446, United Kingdom.
[cited by applicant]
Nangreave et al., “DNA origami: a history and current perspective”, Current Opinion in Chemical Biology, 2010, 14:608-615; available online Jul. 17, 2010.
[cited by applicant]
Rinker et al., “Self-assembled DNA nanostructures for distance-dependent multivalent ligand- protein binding”, Nature Nanotechnology, vol. 3, Jul. 2008, pp. 418-422, published online Jun. 22, 2008.
[cited by applicant]
Asseline, U. et al. “Development and Applications of Fluorescent Oligonucleotides” Curr. Org. Chem. (2006) 10:491-518.
[cited by applicant]
Bauer et al., “Anything You Can Do, I Can Do Better: Can Aptamers Replace Antibodies in Clinical Diagnostic Applications?”, Molecules 24:4377 (2019).
[cited by applicant]
Bruno, “Predicting the Uncertain Future of Aptamer-Based Diagnostics and Therapeutics”, Molecules2015, 20, 6866-6887; doi:10.3390/molecules20046866.
[cited by applicant]
Chen et al., “Protein Microarrays”, BioTechniques, vol. 40, Issue 4, Apr. 2006, pp. 423-429.
[cited by applicant]
Choi, Youngeun et al. “A new reporter design based on DNA origami nanostructures for quantification of short oligonucleotides using microbeads”, Scientific Reports, vol. 9, No. 1, Mar. 18, 2019.
[cited by applicant]
Clever, G.H. et al. “DNA-Metal Base Pairs” Angew. Chem. Int. Ed. (2007) 46:6226-6236.
[cited by applicant]
Cox, W.G. et al. “Fluorescent DNA Hybridization Probe Preparation Using Amine Modification and Reactive Dye Coupling” Biotechniques (2004) 36:114-122.
[cited by applicant]
Evanko, D. et al. “Hybridization Chain Reaction” Nat. Methods (2004) 1:186-187.
[cited by applicant]
Galimidi, R.P. et al. “Intra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1” Cell (2015) 160:433-446.
[cited by applicant]
Gardner, A.F. et al. “Therminator DNA Polymerase: Modified Nucleotides and Unnatural Substrates” Front. Mol. Biosci. (2019) 6:28.
[cited by applicant]
Garmendia, C. et al. “The Bacteriophage Phi29 DNA Polymerase, a Proofreading Enzyme” J. Bio. Chem. (1992) 267:2594-2599.
[cited by applicant]
Gyssels, E. et al. “Interstrand Cross-Linking of Nucleic Acids: From History to Recent and Future Applications” Modified Nucleic Acids in Biology and Medicine (2016) pp. 339-369.
[cited by applicant]
He et al., “In situ synthesis of protein arrays”, Current Opinions in Biotechnology 19: 4-9 (2008).
[cited by applicant]
He, et al. Fluorescence aptameric sensor for strand displacement amplification detection of cocaine. Analytical chemistry 82.4 (2010): 1358-1364.
[cited by applicant]
Itzkovitz, S. et al. “Validating Transcripts with Probes and Imaging Technology” Nat. Methods (2011) 8:512-519.
[cited by applicant]
Janssen, et al. Nucleic acids for ultra-sensitive protein detection. Sensors (Basel). Jan. 21, 2013;13(1):1353-84.
[cited by applicant]
Krufczik, M. et al. “Combining Low Temperature Fluorescence DNA-Hybridization, Immunostaining, and Super-Resolution Localization Microscopy for Nano-Structure Analysis of ALU Elements and Their Influence on Chromatin St…
[cited by applicant]
Li Weiping et al., “Multiplex electrochemical origami immunodevice based on cuboid silver-paper electrode and metal ions tagged nanoporous silver chitosan”, (2014) Biosensors & Bioelectronics, vol. 56, pp. 167-173.
[cited by applicant]
Lian et al., “Ultrasensitive detection of biomolecules with fluorescent dye-doped nanoparticles”, Analytical Biochemistry, vol. 334, 2004, pp. 135-144.
[cited by applicant]
Lundberg, E.P. et al. “A New Fixation Strategy for Addressable Nano-Network Building Blocks” Chem. Comm. (2010) 46:3714-3716.
[cited by applicant]
Musumeci, et al. Fluorescence sensing using DNA aptamers in cancer research and clinical diagnostics. Cancers 9.12 (2017): 174.
[cited by applicant]
Nakamura, S. et al. “Creation of DNA Array Structure Equipped with Heat Resistance by Ultrafast Photocrosslinking” J. Chem. Technol. Biotechnol. (2013) 89:1086-1090.
[cited by applicant]
Nam et al., “Nanoparticle-Based Bio-Bar Codes for the Ultraseneitive Detection of Proteins”, Science 301:1884, Sep. 26, 2003.
[cited by applicant]
O'Flaherty, D.K. et al. “Site-Specific Covalent Capture of Human 06-alkylguanine-DNA-alkyltransferase Using Single-Stranded Intrastrand Cross-Linked DNA” Org. Biomol. Chem. (2016) 15:189-196.
[cited by applicant]
Rajendran, A. et al. “Photo-Cross-Linking-Assisted Thermal Stability of DNA Origami Structures and Its Application for Higher-Temperature Self-Assembly” JACS (2011) 133:14488-14491.
[cited by applicant]
Randolph, J.B. et al. “Stability, Specificity, and Fluorescence Brightness of Mulitply-Labeled Fluorescent DNA Probes” Nuc. Acids Res. (1997) 25:2923-2929.
[cited by applicant]
Sacca et al., “Orthogonal Protein Decoration of DNA Origami”, Agnew. Chem. Intl. Ed. 49:9378, 2010.
[cited by applicant]
Sacca et al., “Orthogonal Protein Decoration of DNA Origami”, Supporting Information, Agnew. Chem. Intl. Ed. 49:9378, 2010.
[cited by applicant]
Sakamoto et al., “Magnetically Promoted Rapid Immunoreactions Using Functionalized Fluorescent Magnetic Beads: A Proof of Principle”, Clinical Chemistry 60(4) : 610-620 et al. (2014).
[cited by applicant]
Schweitzer et al. Immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection. Proceedings of the National Academy of Sciences. USA. 97(18) (Aug. 2000):10113-10119.
[cited by applicant]
Sinkeldam, R.W. et al. “Fluorescent Analogs of Biomolecular Building Blocks: Design, Properties and Applications” Chem. Rev. (2010) 110:2579-2619.
[cited by applicant]
Sun, H. et al. “Coumarin-Induced DNA Ligation, Rearrangement to DNA Interstrand Crosslinks, and Photorelease of Coumarin Moiety” Chem BioChem (2016) 17:1-9.
[cited by applicant]
Tagawa, M. et al. “Stabilization of DNA Nanostructures by Photo-Cross-Linking” Soft Matter (2011) 7:10931-10934.
[cited by applicant]
Tsourkas et al., “Hybridization kinetics and thermodynamics of molecular beacons”, Nucleic Acids Research, 2003, vol. 31, No. 4, pp. 1319-1330.
[cited by applicant]
Wang, L. et al. “DNA Nanostructures in Cell Biology and Medicine” DNA Nanotechnology for Bioanalysis (2017) pp. 99-127.
[cited by applicant]
Wojcezewski et al., “Fluorescent Oligonucleotides- Versatile Tools as Probes and Primers for DNA and RNA Analysis”, Snylett No. 10:1667-1678 (1999).
[cited by applicant]
Zakeri, B. et al., “Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin” PNAS 109 (12): E690-E697 (2012).
[cited by applicant]
Zlauddin et al., “Microarray of cells expressing defined cDNAs”, Science, 411:107 (2001).
[cited by applicant]
Jaekel, A. et al., “Manipulating Enzymes Properties with DNA Nanostructures” Molecules 24(20):3694 (2019).
[cited by applicant]
Jensen, J.O. et al. “Nanoengineered Bioplatforms Based on DNA Origami [Point of View]” Proceedings of the IEEE 102:1046-1049 (2014).
[cited by applicant]
Kolb, H.C. et al., “Click Chemistry: Diverse Chemical Function from a Few Good Reactions” Angewandte Chemie International Edition. 40 (11): 2004ñ2021 (2001).
[cited by applicant]
Spicer, C.D. et al. “Achieving Controlled BiomoleculeñBiomaterial Conjugation” Chem. Rev. (2018) 118(16):7702-7743.
[cited by applicant]
Stawicki, C.M. et al., “Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins” Scientific Reports 11:19921 (2021) [doi.org/10.1038/s41598-021-99084-4].
[cited by applicant]
Vauquelin, G. et al., “Exploring avidity: understanding the potential gains in functional affinity and target residence time of bivalent and heterobivalent ligands” British Journal of Pharmacology 168:1771-1785 (2013).
[cited by applicant]
Zhang, P. et al., “Capturing transient antibody conformations with DNA origami epitopes” Nature Communications 11:3114 (2020).
[cited by applicant]
Zhao, Z. et al., “Organizing DNA origami tiles into larger structures using preformed scaffold frames” NanoLetters 11:2997-3002 (2011).
[cited by applicant]
3-Aminopropyl)triethoxysilane. Wikipedia.org. Apr. 5, 2019 (Apr. 5, 2019), entire document esp p. 1 (https://en.wikipedia.org/w/index.php?title=(3-Aminopropyl)triethoxysilaneoldid=891131780).
[cited by applicant]
Arnold et al. “The majority of immunogenic epitopes generate CD44- T cells that are dependent on MHC class II-bound peptide-flanking residues,” J Immunol, Jul. 15, 2002 (Jul. 15, 2002), vol. 169, No. 2, pp. 739-749.
[cited by applicant]
Ayoglu, et al., Autoantibody Profiling in Multiple Sclerosis Using Arrays of Human Protein Fragments, Molecular & Cellular Proteomics, (12)9 Sep. 1, 2013 (Sep. 1, 2013), pp. 2657-2672, XP055294116, US ,ISSN: 1535-9476, …
[cited by applicant]
Blatch, et al. The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays Nov. 1999;21 (11):932-939.
[cited by applicant]
Buenrostro, et al. Quantitative analysis of RNA-protein interactions on a massively parallel array for mapping biophysical and evolutionary landscapes. Nat Biotechnol. Jun. 2014; 32(6): 562-568.
[cited by applicant]
Bunka et al. “Production and characterization of RNA aptamers specific for amyloid fibril epitopes,” J Biol Chem, Sep. 18, 2007 (Sep. 18, 2007), vol. 282, No. 47, pp. 34500-34509.
[cited by applicant]
Buus, et al. High-resolution mapping of linear antibody epitopes using ultrahigh-density peptide microarrays. Molecular & Cellular Proteomics 11.12 (2012): 1790-1800.
[cited by applicant]
Choung, et al. Determination of B-Cell Epitopes in Patients with Celiac Disease: Peptide Microarrays. PloS one vol. 11(1) e0147777. Jan. 29, 2016, doi:10.1371/journal.pone.0147777.
[cited by applicant]
Co-pending U.S. Appl. No. 17/390,666, inventor Mallick; Parag, filed on Jul. 30, 2021.
[cited by applicant]
Co-pending U.S. Appl. No. 17/424,435, inventors Klein; Joshua et al., filed on Jul. 20, 2021.
[cited by applicant]
Co-pending U.S. Appl. No. 17/496,742, inventors Gremyachinskiy; Dmitriy et al., filed on Oct. 7, 2021.
[cited by applicant]
Domenyuk, et al. Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach. Sci Rep. 2017; 7: 42741.
[cited by applicant]
EP17877076.4 The Extended European Search Report dated Aug. 11, 2020.
[cited by applicant]
EP18846671.8 Extended European Search Report dated Apr. 23, 2021.
[cited by applicant]
Fodor, et al. Light-Directed, Spatially Addressable Parallel Chemical Synthesis. Science , vol. 251, 767-773, 1991.
[cited by applicant]
Ford et al. “Degenerate recognition of T cell epitopes: impact of T cell receptor reserve and stability of peptide:MHC complexes,” Mol Immunol, Feb. 1, 2004 (Feb. 1, 2004), vol. 40, No. 14-15, pp. 1019-1025.
[cited by applicant]
Hung, et al. Large-area spatially ordered arrays of gold nanoparticles directed by lithographically confined DNA origami. Nat Nanotechnol. Feb. 2010;5(2):121-6. doi: 10.1038/nnano.2009.450. Epub Dec. 20, 2009.
[cited by applicant]
Hunniger, et al. Just in time-selection: A rapid semiautomated SELEX of DNA aptamers using magnetic separation and BEAMing. Anal Chem. Nov. 4, 2014;86(21):10940-7.
[cited by applicant]
Kang, H. The prevention and handling of the missing data. Korean journal of anesthesiology vol. 64,5 (2013): 402-6. doi:10.4097/kjae.2013.64.5.402.
[cited by applicant]
Laurenson, et al. Development of peptide aptamer microarrays for detection of HPV16oncoproteins in cell extracts, Analytical Biochemistry, Academic Press, Amsterdam, NL, vol. 410, No. 2, Oct. 30, 2010 (Oct. 30, 2010), p…
[cited by applicant]
Lin et al. Development of a novel peptide microarray for large-scale epitope mapping of food allergens, Journal of Allergy and Clinical Immunology, Elsevier, Amsterdam, Nl, vol. 124, No. 2, Aug. 1, 2009 (Aug. 1, 2009), …
[cited by applicant]
Lutz, et al. Efficient construction of therapeutics, bioconjugates, biomaterials and bioactive surfaces using azide-alkyne “click” chemistry. Adv Drug Deliv Rev. Jun. 10, 2008;60(9):958-70. doi: 10.1016/j.addr.2008.02.0…
[cited by applicant]
McKay, et al. Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation. Chem Biol. Sep. 18, 2014; 21(9): 1075-1101.
[cited by applicant]
Meldal, et al. Cu-catalyzed azide-alkyne cycloaddition. Chem Rev. Aug. 2008;108(8):2952-3015. doi: 10.1021/cr0783479.
[cited by applicant]
Nonobe et al. A tabu search approach to the constraint satisfaction problem as a general problem solver. Eur. J. Oper. Res. 106 (1998): 599-623.
[cited by applicant]
Patronov et al. “Peptide binding prediction for the human class Ii Mhc allele HLA-DP2: a molecular docking approach,” BMC Struct Biol, Jul. 14, 2011 (Jul. 14, 2011), vol. 11, No. 32, pp. 1-10.
[cited by applicant]
PCT/US17/64322 International Search Report and Written Opinion dated Apr. 25, 2018.
[cited by applicant]
PCT/US18/00364 International Search Report and Written Opinion dated Mar. 22, 2019.
[cited by applicant]
PCT/US2019/025909 International Search Report and Written Opinion dated Jun. 14, 2019.
[cited by applicant]
PCT/US2019/035654 International Search Report and Written Opinion dated Nov. 25, 2019.
[cited by applicant]
PCT/US2019/062482 International Search Report and Written Opinion dated Mar. 3, 2020.
[cited by applicant]
PCT/US2020/030501 International Search Report and Written Opinion dated Aug. 11, 2020.
[cited by applicant]
Price, et al., On silica peptide microarrays for high-resolution mapping of antibody epitopes and diverse protein-protein interactions, Nature Medicine, vol. 18, No. 9, Aug. 19, 2012, pp. 1434-1440, XP055793803, New Yor…
[cited by applicant]
Reineke, et al. Epitope mapping protocols. Preface. Methods in molecular biology (Clifton, N.J.) vol. 524 (2009): v-vi.
[cited by applicant]
Reyes et al. “Critical role of HLA-DR11″ binding peptides' peripheral flanking residues in fully-protective malaria vaccine development,” Biochem Biophys Res Commun, May 23, 2017 (May 23, 2017), vol. 489, No. 3, pp. 339…
[cited by applicant]
Riccelli, et al. Hybridization of single-stranded DNA targets to immobilized complementary DNA probes: comparison of hairpin versus linear capture probes. Nucleic acids research vol. 29,4 (2001): 996-1004. doi:10.1093/n…
[cited by applicant]
Richer, et al., Epitope identification from fixed-complexity random-sequence peptide microarrays, Molecular & cellular proteomics, vol. 14, No. 1, Nov. 3, 2014, pp. 136-147.
[cited by applicant]
Rothemund, et al. Folding DNA to create nanoscale shapes and patterns. Nature. Mar. 16, 2006;440(7082):297-302.
[cited by applicant]
Sant'Angelo et al. “Recognition of core and flanking amino acids of MHC class II-bound peptides by the T cell receptor,” Eur J Immunol, Sep. 1, 2002 (Sep. 1, 2002), vol. 32, No. 9, pp. 2510-2520.
[cited by applicant]
She, et al. Comprehensive and quantitative mapping of RNA-protein interactions across a transcribed eukaryotic genome. Proc Natl Acad Sci U S A. Apr. 4, 2017; 114(14): 3619-3624.
[cited by applicant]
Sjoberg et al. Validation of affinity reagents using antigen microarrays, NEWBIOTECHNOLOGY, vol. 29, No. 5, Jun. 1, 2012 pp. 555-563, XP055793929,NLISSN: 1871-6784, DOI: 10.1016/j.nbt.2011.11.009.
[cited by applicant]
Speltz, et al. Design of Protein-Peptide Interaction Modules for Assembling Supramolecular Structures in Vivo and in Vitro. ACS Chem Biol. Sep. 18, 2015;10(9):2108-15. doi: 10.1021/acschembio.5b00415. Epub Jul. 17, 2015.
[cited by applicant]
Stöhr, et al. A 31-residue peptide induces aggregation of tau's microtubule-binding region in cells. Nat Chem. Sep. 2017; 9(9): 874-881. Published online Apr. 3, 2017.doi: 10.1038/nchem.2754.
[cited by applicant]
Tessler, L. Digital Protein Analysis: Technologies for Protein Diagnostics and Proteomics through Single-Molecule Detection (2011). All Theses and Dissertations (ETDs). 346 https://openscholarship.wustl.edu/etd/346.
[cited by applicant]
U.S. Appl. No. 16/659,132 Notice of Allowance dated Jan. 14, 2021.
[cited by applicant]
U.S. Appl. No. 16/659,132 Office Action dated Oct. 8, 2020.
[cited by applicant]
U.S. Appl. No. 16/788,536 Notice of Allowance dated Dec. 9, 2020.
[cited by applicant]
U.S. Appl. No. 16/788,536 Office Action dated Mar. 10, 2020.
[cited by applicant]
U.S. Appl. No. 16/788,536 Office Action dated Sep. 24, 2020.
[cited by applicant]
U.S. Appl. No. 16/791,456 Office Action dated Jul. 6, 2021.
[cited by applicant]
U.S. Appl. No. 17/062,405 Final Office Action dated Aug. 24, 2021.
[cited by applicant]
U.S. Appl. No. 17/062,405 Notice of Allowance dated Sep. 30, 2021.
[cited by applicant]
U.S. Appl. No. 17/062,405 Office Action dated Apr. 14, 2021.
[cited by applicant]
U.S. Appl. No. 17/191,632 Examiner's Interview Summary dated Nov. 9, 2021.
[cited by applicant]
U.S. Appl. No. 17/191,632 Final Office Action dated Sep. 17, 2021.
[cited by applicant]
U.S. Appl. No. 17/191,632 Office Action dated May 12, 2021.
[cited by applicant]
U.S. Appl. No. 16/426,917 Notice of Allowance dated Oct. 1, 2019.
[cited by applicant]
Wilson, et al. Single-Step Selection of Bivalent Aptamers Validated by Comparison with SELEX Using High-Throughput Sequencing. PLoS One. 2014; 9(6): e100572.
[cited by applicant]
Zandian, Arash et al. Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy. Journal of proteome research 16(3) 2017: 1300-1314. doi:10.1021/acs.jproteome.6b0…
[cited by applicant]
Beck, et al., “Trends in Glycosylation, Glycoanalysis and Glycoengineering of Therapeutic Antibodies and Fc-Fusion Proteins,” Current Pharmaceutical Biotechnology, 2008, vol. 9, pp. 482-501.
[cited by applicant]
Gopinath, et al., “Optimized Assembly and Covalent Coupling of Single-Molecule DNA Origami Nanoarrays,” ACS Nano, 2014, vol. 8, No. 12, pp. 12030-12040.
[cited by applicant]
Guan, et al., “Generation of acetyllysine antibodies and affinity enrichment of acetylated peptides,” Nature Protocols, 2010, vol. 5, No. 9, pp. 1583-1595.
[cited by applicant]
Guo, et al., “Immunoaffinity Enrichment and Mass Spectrometry Analysis of Protein Methylation,” Molecular & Cellular Proteomics, 2014, vol. 13, No. 1, pp. 372-387.
[cited by applicant]
Hattori, et al., “Next-generation antibodies for post-translational modifications,” Current Opinion in Structural Biology, Aug. 2018, vol. 51, pp. 141-148.
[cited by applicant]
Kaufmann, et al.,“Use of antibodies for detection of phosphorylated proteins separated by two-dimensional gel electrophoresis,” Proteomics, 2001, vol. 1, pp. 194-199.
[cited by applicant]
Kershner, et al., “Placement and orientation of individual DNA shapes on lithographically patterned surfaces,” Nature Nanotechnology, Sep. 2009, vol. 4, pp. 557-561.
[cited by applicant]
Mimnaugh, et al.,“The measurement of ubiquitin and ubiquitinated proteins,” Electrophoresis, 1999, vol. 20, pp. 418-428.
[cited by applicant]
Office Action in CA3135206, mailed on Oct. 17, 2024, 4 pages.
[cited by applicant]
Goldman et al., “Avidin: A Natural Bridge for Quantum Dot—Antibody Conjugates,” Journal of the American Chemical Society, 2002, vol. 124, pp. 6378-6382.
[cited by applicant]
Goldman et al., “Multiplexed Toxin Analysis Using Four Colors of Quantum Dot Fluororeagents,” Analytical Chemistry, 2004, vol. 76, pp. 684-688.
[cited by applicant]
Hoff et al., “Nanoscale Protein Patterning by Imprint Lithography,” Nano Letters, 2004, vol. 4, No. 5, pp. 853-857.
[cited by applicant]
Kuzuya et al., “Precisely Programmed and Robust 2D Streptavidin Nanoarrays by Using Periodical Nanometer—Scale Wells Embedded in DNA Origami Assembly,” ChemBioChem, 2009, vol. 10, pp. 1811-1815.
[cited by applicant]
Liang et al., “An oligonucleotide microarray for microRNA expression analysis based on labeling RNA with quantum dot and nanogold probe,” Nucleic Acids Research, 2005, vol. 33, No. 2, 8 pages.
[cited by applicant]
Niemeyer et al., “Supramolecular Nanocircles Consisting of Streptavidin and DNA,” Angewandte Chemie International Edition, 2000, vol. 39, No. 17, pp. 3056-3059.
[cited by applicant]
Olsnes, S., “The history of ricin, abrin and related toxins,” Toxicon, 2004, pp. 361-370.
[cited by applicant]
Pires et al., “A rapid magnetic particle-based enzyme immunoassay for human cytomegalovirus glycoprotein B quantification,” Journal of Pharmaceutical and Biomedical Analysis, 2018, vol. 156, pp. 372-378.
[cited by applicant]
Purschke et al., “A DNA Spiegelmer to staphylococcal enterotoxin B,” Nucleic Acids Research, 2003, vol. 31, No. 12, pp. 3027-3032.
[cited by applicant]
Slaughter et al., “Detection of enzyme polymorphism by using monoclonal antibodies,” Proceedings of the National Academy of Sciences, Feb. 1981, vol. 78, No. 2, pp. 1124-1128.
[cited by applicant]
Tesh et al., “The pathogenic mechanisms of Shiga toxin and the Shiga-like toxins,” Molecular Microbiology, 1991, vol. 5, No. 8, pp. 1817-1822.
[cited by applicant]
Wang et al., “Antibody Structure, Instability, and Formulation,” Journal of Pharmaceutical Sciences, Jan. 2007, vol. 96, No. 1, pp. 1-26.
[cited by applicant]
Zhang et al., “The Three-dimensional Crystal Structure of Cholera Toxin,” Journal of Molecular Biology, 1995, vol. 251, pp. 563-573.
[cited by applicant]
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