# US 10,481,153 B2 · Integrated compound discovery systems and methods

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- Number: US 10,481,153 B2
- Document ID: US10481153B2
- Status: Granted
- Kind: B2
- Application number: 15/654,309
- Filed: 2017-07-19
- Published: 2017-11-09
- Granted: 2019-11-19
- Earliest claimed: 2011-12-23
- Assignees: Wake Forest University; NanoMedica LLC
- Applicants: Wake Forest University; NanoMedica LLC
- Inventors: Keith Bonin; Jed C. Macosko; Jason Gagliano; Martin Guthold; Roger Cubicciotti
- Web page: https://patentgrep.com/patent/US10481153B2

## CPC

- G01N 33/54353: {with ligand attached to the carrier via a chemical coupling agent (coatings G01N33/54393)}
- C12Q 1/6837: using probe arrays or probe chips (C12Q1/6874 takes precedence)
- C12Q 2565/514: characterised by the use of the arrayed oligonucleotides as identifier tags, e.g. universal addressable array, anti-tag or tag complement array
- C12Q 2600/136: Screening for pharmacological compounds
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- G01N 2500/20: cell-free systems
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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

Methods, systems, devices and apparatus for use in screening and/or selecting a library of nucleic acid molecules and/or nucleic acid tagged or encoded molecules for binding to or interaction with a target molecule or substance (e.g., for use in new compound or drug discovery) are described. In some embodiments the device comprises: (a) a spatially addressable array, said array comprising a plurality of separate and discrete locations thereon; (b) a plurality of different oligomers operably connected to said spatially addressable array at different ones of said separate and discrete locations; (c) a tag sequence which is complementary to, and is hybridized to, each of said oligomers; and (d) a candidate chemical operably connected to each of said tag sequences, wherein each of said discrete locations is a unique identifier for its corresponding oligomer; and wherein said tag sequence is a unique identifier for its connected candidate chemical.

## Claims

### Claim 1

A sequencing device comprising:
(a) a spatially addressable sequencing array, said array comprising a plurality of separate and discrete sequencing locations thereon, said separate and discrete sequencing locations contacted with at least one sequencing reagent;
(b) a plurality of different oligomers operably connected to said spatially addressable sequencing array at different ones of said separate and discrete sequencing locations;
(c) a tag sequence which is complementary to, and is hybridized to, each of said oligomers; and
(d) a candidate chemical operably connected to each of said tag sequences,
wherein each of said separate and discrete sequencing locations is a unique identifier for its corresponding oligomer
and wherein said tag sequence is a unique identifier for its connected candidate chemical.

### Claim 2 (depends on 1)

The sequencing device of claim 1, wherein said spatially addressable sequencing array is a field-effect transistor array, an electrochemical array or an optical array.

### Claim 3 (depends on 1)

The sequencing device of claim 1, wherein said oligomers and said tag sequences are nucleic acids.

### Claim 4 (depends on 1)

The sequencing device of claim 1, wherein said candidate chemicals are selected from the group consisting of small molecules, peptides, carbohydrates, lipids, monomers, polymers and conjugated molecules.

### Claim 5 (depends on 1)

The sequencing device of claim 1, wherein said sequencing array comprises a substrate having a plurality of wells formed therein, said wells defining said plurality of separate and discrete sequencing locations,
said sequencing device further comprising at least one particle deposited in each well of at least a subset of said plurality of wells, with said oligomers coupled to said particles.

### Claim 6 (depends on 1)

A sequencing-based molecular discovery system comprising the sequencing device of claim 1 and at least one input apparatus.

### Claim 7 (depends on 1)

The sequencing device of claim 1, wherein the sequencing reagent is selected from the group consisting of transcriptases, polymerases, deoxynucleoside triphosphates and oligonucleotide primers.

### Claim 8

A sequencing device comprising:
(a) a spatially addressable sequencing array, said sequencing array comprising a plurality of separate and discrete sequencing locations thereon, said separate and discrete sequencing locations contacted with at least one sequencing reagent;
(b) a plurality of different oligomers operably connected to said spatially addressable sequencing array at different ones of said separate and discrete sequencing locations; and
(c) a detectably labeled nonnucleic acid target molecule noncovalently bound to at least one of said different oligomers, wherein each of said separate and discrete sequencing locations is a unique identifier for its corresponding oligomer.

### Claim 9 (depends on 8)

The sequencing device of claim 8 wherein said nonnucleic acid target molecule comprises at least one of a protein, a peptide, a therapeutic target or a diagnostic analyte.

### Claim 10 (depends on 8)

The sequencing device of claim 8, wherein said spatially addressable sequencing array is a field effect transistor array, an electrochemical array or an optical array.

### Claim 11 (depends on 8)

The sequencing device of claim 8, wherein said oligomers are nucleic acids.

### Claim 12 (depends on 8)

The sequencing device of claim 8, wherein said oligomers are selected from the group consisting of nucleotides, oligonucleotides and nonnaturally occurring nucleic acid molecules.

### Claim 13 (depends on 8)

The sequencing device of claim 8, wherein said oligomers further comprise at least one of a tag sequence or a nonnucleic acid moiety.

### Claim 14 (depends on 8)

The sequencing device of claim 8, wherein said sequencing array comprises a substrate having a plurality of wells formed therein, said wells defining said plurality of separate and discrete sequencing locations,
said sequencing device further comprising at least one particle deposited in each well of at least a subset of said plurality of wells, with said oligomers coupled to said particles.

### Claim 15 (depends on 8)

A sequencing-based molecular discovery system comprising the sequencing device of claim 8 and at least one input apparatus.

### Claim 16 (depends on 8)

The sequencing device of claim 8, wherein the sequencing reagent is selected from the group consisting of transcriptases, polymerases, deoxynucleoside triphosphates and oligonucleotide primers.