# US 11,111,603 B2 · Methods and materials for multiplexed collections of functional ligands > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,111,603 B2 - Document ID: US11111603B2 - Status: Granted - Kind: B2 - Application number: 16/262,825 - Filed: 2019-01-30 - Published: 2019-08-08 - Granted: 2021-09-07 - Earliest claimed: 2018-01-30 - Assignees: Base Pair Biotechnologies, Inc. - Applicants: Base Pair Biotechnologies, Inc. - Inventors: George W. Jackson; Robert Batchelor; Alexander S. Chiu; Rafal Drabek; Deepak Thirunavukarasu; Caitlin Bruns - Web page: https://patentgrep.com/patent/US11111603B2 ## CPC - C40B 40/06: Libraries containing nucleotides or polynucleotides, or derivatives thereof - C12Q 1/6811: Selection methods for production or design of target specific oligonucleotides or binding molecules - C12Q 1/6837: using probe arrays or probe chips (C12Q1/6874 takes precedence) - C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract This invention relates to methods and materials for multiplexed utilization of collections of functional ligands, particularly to methods and materials for selecting for and/or utilizing particular desirable traits of functional ligands in a multiplexed manner, and more particularly to methods and materials for selecting for and/or utilizing particular structural changes of functional ligands in a multiplexed manner. ## Claims ### Claim 1 A method for generating and utilizing a nucleic acid array comprising: providing a substrate with a plurality of single-stranded nucleic acid labels located and attached at predetermined addresses on said substrate, said single-stranded nucleic acid labels comprising an identical hybridization sequence and having a spacing region between said hybridization sequence and said substrate; performing a hybridization of a single-stranded nucleic acid ligand to each of said plurality of single-stranded nucleic acid labels, each of said single-stranded nucleic acid ligands being potential aptamers with a complementary region to said hybridization sequence and a target binding region which is identical for each of said single-stranded nucleic acid ligands hybridized to one of said single-stranded nucleic acid labels at one of said predetermined addresses, wherein the identity of said single-stranded nucleic acid ligand hybridized at each predetermined address is known and is previously correlated to binding at least one target molecule, each of said hybridizations of said single-stranded nucleic acid ligands and said single-stranded nucleic acid labels comprising a signal interacting pair producing a signal interaction; incubating said substrate with a sample; and performing a detection operation to detect potential changes in said signal interactions after said incubating correlated to said addresses; wherein said potential changes indicate binding of said at least one of said known target molecules to at least one of said plurality of single-stranded nucleic acid ligands when said potential change occurs after adding said sample. ### Claim 2 (depends on 1) The method of claim 1, wherein said single-stranded nucleic acid ligands are selected for potential conformational changes upon binding to at least one of said target molecules. ### Claim 3 (depends on 1) The method of claim 1, wherein each of said single-stranded nucleic acid ligands is preselected for known changes in said signal interactions in response to at least one of said target molecules. ### Claim 4 (depends on 1) The method of claim 1, wherein each of said signal interacting pairs comprise a radiation-emitting label:radiation-modulating proximity interacting pair. ### Claim 5 (depends on 1) The method of claim 1, wherein said potential changes are utilized to identify conformational changing aptamers from a collection of aptamers. ### Claim 6 (depends on 1) The method of claim 1, wherein said potential changes are utilized to discriminate the relative binding affinity of said potential aptamers to said target molecule. ### Claim 7 (depends on 1) The method of claim 1, wherein said potential changes are utilized to determine a relative abundance of said target molecule in a sample. ### Claim 8 (depends on 1) The method of claim 1, wherein said spacing region is between 5 and 20 nucleotides in length. ### Claim 9 (depends on 1) The method of claim 1, wherein said at least one target molecule is selected from the group consisting of proteins, cells, small molecules and portions thereof. ### Claim 10 (depends on 1) The method of claim 1, wherein said substrate is selected from the group consisting of a multiwell plate, a collection of discrete droplets, labeled beads and coated glass. ### Claim 11 (depends on 1) The method of claim 1, wherein said target binding region is between 22 and 42 nucleotides in length. ### Claim 12 (depends on 11) The method of claim 11, wherein said target binding region is a randomized sequence. ### Claim 13 (depends on 1) The method of claim 1, wherein said target binding region comprises a binding sequence which was selected for potential binding to said at least one target molecule. ### Claim 14 (depends on 13) The method of claim 13, wherein said binding sequence was selected by SELEX. ### Claim 15 (depends on 1) The method of claim 1, wherein said complementary region is between 9 and 29 nucleotides in length. ### Claim 16 (depends on 4) The method of claim 4, wherein each of said signal interactions comprises a fluorescent signal which changes in response to the presence of at least one of said target molecules.