Concentrating a target molecule for sensing by a nanopore

Patent metadata

Field	Value
Publication number	US-2025019742-A1
Application number	US-202418420048-A
Country	US
Kind code	A1
Filing date	Jan 23, 2024
Priority date	Nov 9, 2012
Publication date	Jan 16, 2025
Grant date	—

Abstract

Methods and related products are disclosed that improve the probability of interaction between a target molecule and a nanopore by capturing the target molecule on a surface comprising the nanopore. The captured target molecule, the nanopore, or both, are able to move relative to each other along the surface. When the leader of the target molecule is in proximity with the nanopore, interaction of the target portion of the target molecule with the nanopore occurs, thereby permitting sensing of the target portion. Confining the target molecule and nanopore in this manner leads to significantly enhanced interaction with the nanopore.

First claim

1 . A method for concentrating a target molecule for nanopore sensing, comprising:
capturing the target molecule on a surface,
wherein the surface comprises a nanopore and a hydrophobic domain,
wherein the target molecule comprises a target portion, a hydrophobic capture element and a leader for interaction with the nanopore, and
wherein the hydrophobic capture element is associated with, and capable of movement along, the hydrophobic domain of the surface to bring the leader in proximity with the nanopore; and
sensing at least the target portion upon interaction with the nanopore.

2 . The method of claim 1 , wherein the step of capturing the target molecule on the surface comprises contacting the surface with the target molecule, wherein the target molecule comprises, prior to the contacting step, the target portion, the hydrophobic capture element and the leader.

3 . The method of claim 1 , wherein the step of capturing the target molecule on the surface comprises linking the hydrophobic capture element associated with the surface to the target portion and leader, thereby capturing the target molecule on the surface.

4 . (Original The method of claim 1 , wherein the nanopore is a biological nanopore.

5 . The method of claim 1 , wherein the surface is a lipid bilayer.

6 . The method of claim 1 , wherein the surface is a solid-state or synthetic membrane.

7 . (canceled)

8 . The method of claim 1 , wherein the target portion comprises a linear polymer.

9 . The method of claim 1 , wherein the target portion comprises a molecular bar code.

10 . The method of claim 1 , wherein the target portion comprises an Xpandomer.

11 . The method of claim 1 , wherein the leader is a hydrophilic polymer.

12 . The method of claim 1 , wherein the hydrophobic capture element is an aliphatic hydrocarbon.

13 . The method of claim 1 , wherein the target molecules comprises two or more hydrophobic capture elements.

14 . The method of claim 10 , wherein the Xpandomer is a measurable polymer comprising high signal-to-noise reporters that are separated by approximately 10 nm.

15 . The method of claim 12 , wherein the aliphatic hydrocarbon comprises over 5 repeats of a 12 carbon monomer.

16 . The method of claim 15 , wherein the aliphatic hydrocarbon comprises 6 repeats of a 12 carbon monomer.

17 . The method of claim 11 , wherein the hydrophilic polymer comprises polyethylene glycol monomers.

18 . The method of claim 11 , wherein the hydrophilic polymer comprises 25 repeats of the polyethylene glycol monomers.

Assignees

• Roche Sequencing Solutions Inc

Inventors

• Kokoris Mark Stamatios
• Mcruer Robert N

Classifications

• G01N33/54373

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