# US 7,612,165 B2 · Solid-phase synthesis is a capillary

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- Number: US 7,612,165 B2
- Document ID: US7612165B2
- Status: Granted
- Kind: B2
- Application number: 11/361,128
- Filed: 2006-02-24
- Published: 2006-09-07
- Granted: 2009-11-03
- Earliest claimed: 2005-03-03
- Assignees: PhyNexus, Inc.
- Inventors: Douglas T. Gjerde
- Web page: https://patentgrep.com/patent/US7612165B2

## CPC

- C07K 1/045: {using devices to improve synthesis, e.g. reactors, special vessels}
- C07H 21/02: with ribosyl as saccharide radical
- C08B 37/0021: {Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran}
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)

## Abstract

The invention provides, inter alia, methods for synthesizing a molecule on the channel surface of a capillary, comprising the steps of: (i) covalently attaching a first chemical entity to the channel surface of a capillary; and (ii) covalently attaching a second chemical entity to the first chemical entity, wherein the covalent attachment steps are part of a process for synthesizing a molecule on the channel surface.

## Claims

### Claim 1

A method of synthesizing a biopolymer on the internal surface of a capillary, comprising the steps of:
(i) covalently attaching a first chemical entity to the internal surface of a capillary; and
(ii) covalently attaching a second chemical entity to the first chemical entity,
(iii) optionally repeating the attachment iteratively with the attachment of additional chemical entities, wherein the covalent attachment steps are part of a process for synthesizing the biopolymer on the internal surface of the capillary, and
wherein the capillary has an internal diameter from a lower limit of 20 μm to an upper limit of 1 mm and a length greater than 1 cm and less than 5 m.

### Claim 2 (depends on 1)

The method of claim 1, wherein the capillary is tubular.

### Claim 3 (depends on 1)

The method of claim 1, wherein the capillary comprises an inorganic substance selected from silica, fused silica, porous glass, aluminosilicates, borosilicates, metal oxides, or clay, or an organic substance selected from polyamide, polyether, polystyrene, polycarbonate, fluoropolymers, or mixtures thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the synthesized biopolymer is cleaved off the internal surface by passing a slug of cleavage solution through the capillary, wherein the slug of cleavage solution has a volume less than the total capillary volume.

### Claim 5 (depends on 4)

The method of claim 4, wherein the synthesized biopolymer is collected in the leading edge of the slug of cleavage solution.

### Claim 6 (depends on 1)

The method of claim 1, wherein the biopolymer is a polypeptide.

### Claim 7 (depends on 1)

The method of claim 1, wherein the biopolymer is a polysaccharide.

### Claim 8 (depends on 1)

The method of claim 1, wherein the biopolymer is a polynucleotide.

### Claim 9

A method of synthesizing a biopolymer on the internal surface of a capillary, comprising the steps of:
(i) covalently attaching a first chemical entity to the internal surface of a capillary; and
(ii) covalently attaching a second chemical entity to the first chemical entity,
(iii) optionally repeating the attachment iteratively with the attachment of additional chemical entities, wherein the covalent attachment steps are part of a process for synthesizing the biopolymer on the internal surface of the capillary,
(iv) optionally removing substantially all liquid from the capillary; and
(v) passing a slug of cleavage solution through the capillary to cleave the synthesized biopolymer off the internal surface of the capillary,
wherein the capillary has an internal diameter from a lower limit of 20 μm to an upper limit of 1 mm and a length greater than 1 cm and less than 5 m, and
wherein the slug of cleavage solution has a volume less than the total capillary volume.

### Claim 10 (depends on 9)

The method of claim 9, wherein the capillary comprises an inorganic substance selected from silica, fused silica, porous glass, aluminosilicates, borosilicates, metal oxides, or clay, or an organic substance selected from polyamide, polyether, polystyrene, polycarbonate, fluoropolymers, or mixtures thereof.

### Claim 11 (depends on 9)

The method of claim 9 wherein the capillary is tubular.

### Claim 12 (depends on 9)

The method of claim 9, wherein the synthesized biopolymer is collected in the leading edge of the slug of cleavage solution.

### Claim 13 (depends on 9)

The method of claim 9, wherein the total number of chemical entities is at least 40.

### Claim 14 (depends on 9)

The method of claim 9, wherein step (iv) is performed and the slug of cleavage solution is passed back and forth through the channel.

### Claim 15 (depends on 9)

The method of claim 9, wherein the linkage between the first chemical entity and the internal surface comprises a chemical handle.

### Claim 16 (depends on 9)

The method of claim 9, wherein the first chemical entity is covalently attached to the internal surface by use of an activated functional group.

### Claim 17 (depends on 9)

The method of claim 9, wherein the biopolymer is a polypeptide.

### Claim 18 (depends on 9)

The method of claim 9, wherein the biopolymer is a polysaccharide.

### Claim 19 (depends on 9)

The method of claim 9, wherein the biopolymer is a polynucleotide.

### Claim 20

A method of synthesizing biopolymers on the internal surface of a plurality of capillaries, comprising the steps of:
(i) covalently attaching a first chemical entity to the internal surface of each capillary; and
(ii) covalently attaching a second chemical entity to the first chemical entity,
(iii) optionally repeating the attachment iteratively with the attachment of additional chemical entities, wherein the covalent attachment steps are part of a process for synthesizing the biopolymers on the internal surface of the capillaries,
(iv) optionally removing substantially all liquid from the capillaries; and
(v) passing a slug of cleavage solution through the capillaries to cleave the synthesized biopolymer off the internal surface of the capillaries,
wherein each capillary has an internal diameter from a lower limit of 20 μm to an upper limit of 1 mm and a length greater than 1 cm and less than 5 m, wherein each capillary is addressable and wherein the slug of cleavage solution has a volume less than the total capillary volume.