Chemically encoded spatially addressed library screening platforms

Patent metadata

Field	Value
Publication number	US-10760181-B2
Application number	US-201615553140-A
Country	US
Kind code	B2
Filing date	Feb 24, 2016
Priority date	Feb 24, 2015
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

Provided herein are encoded split pool libraries useful, inter alia, for forming highly diverse and dense arrays for screening and detection of a variety of molecules.

First claim

What is claimed is:

1. A microparticle immobilized on a solid support, wherein said microparticle is covalently attached to:
(i) a ligand domain through a first linker; and
(ii) a nucleic acid domain through a second linker,
wherein said nucleic acid domain identifies said ligand domain;
wherein said second linker comprises an acyl group, a sulfonamide group, or a photocleavable group; and
wherein said second linker is cleavable under a condition that does not cleave said first linker.

2. The microparticle of claim 1 , wherein said ligand domain comprises a removable protecting moiety covalently attached to a reactive moiety.

3. The microparticle of claim 2 , wherein said removable protecting moiety comprises an amino acid side chain, an amino terminus, or a carboxy terminus.

4. The microparticle of claim 1 , wherein said ligand domain is selected from the group consisting of a peptide, a small molecule, and a protein.

5. The microparticle of claim 1 , wherein said ligand domain is bound to a ligand binder.

6. The microparticle of claim 1 , wherein said ligand domain comprises a plurality of ligand domains attached through a plurality of first linkers.

7. The microparticle of claim 1 , wherein said nucleic acid domain comprises a plurality of nucleic acid domains attached through a plurality of second linkers.

8. The microparticle of claim 1 , wherein said nucleic acid domain is bound to a detectably labeled complementary nucleic acid sequence.

9. A solid support comprising a plurality of wells, wherein each of said plurality of wells further comprises an immobilized microparticle, thereby forming an ordered array, wherein each of said immobilized microparticles is covalently attached to:
(i) a ligand domain through a first linker; and
(ii) a nucleic acid domain through a second linker;
wherein said nucleic acid domain identifies said ligand domain;
wherein said second linker comprises an acyl group, a sulfonamide group, or a photocleavable group; and
wherein said second linker is cleavable under a condition that does not cleave said first linker.

10. The solid support of claim 9 , wherein said ligand domain comprises a removable protecting moiety attached to a reactive moiety.

11. The solid support of claim 9 , wherein said ligand domain is bound to a ligand binder.

12. The solid support of claim 9 , wherein said ligand domain is selected from the group consisting of a peptide, a small molecule, and a protein.

13. The solid support of claim 11 , wherein said solid support is within a detection device, wherein said detection device detects said ligand binder bound to said ligand domain and identifies a location of said bound ligand binder on said solid support.

14. The microparticle of claim 1 , wherein said microparticle is selected from the group consisting of a functionalized microbead, a magnetic microbead, a metallic microbead, a polymeric microbead, a silica microbead, a dendrimer, and a branched polymer.

15. The microparticle of claim 2 , wherein said removable protecting moiety is selected from the group consisting of fluorenylmethyloxycarbonyl, tert-butyl, and carboxybenzyl.

16. The microparticle of claim 2 , wherein said reactive moiety is selected from the group consisting of a carboxylic acid, an amine, a thiol, or an alcohol.

17. The solid support of claim 9 , wherein said second linker is a photocleavable linker, an acid labile linker, or an alkali labile linker.

18. The solid support of claim 9 , wherein said nucleic acid domain is bound to a detectably labeled complementary nucleic acid sequence.

19. The solid support of claim 9 , wherein said ordered array includes at least 10,000 microparticles per square millimeter.

20. The solid support of claim 9 , wherein said condition is selected from the group consisting of UV irradiation, light irradiation, trifluoroacetic acid, ammonium hydroxide, ammonia, methylamine, and a mixture of ammonium hydroxide and methylamine.

Assignees

• Hope City

Inventors

• Berlin Jacob
• COPELAND Gregory
• Elison Kathleen
• Muradyan Hurik

Classifications

• C40B70/00 Primary

  Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes · CPC title

• G01N33/54313

  the carrier being characterised by its particulate form · CPC title

• C40B40/10

  Libraries containing peptides or polypeptides, or derivatives thereof · CPC title

• C12N15/1065

  Preparation or screening of tagged libraries, e.g. tagged microorganisms by STM-mutagenesis, tagged polynucleotides, gene tags · CPC title

• G01N33/54346

  Nanoparticles · CPC title