Targeted sequencing of biomolecules by pulling through a liquid-liquid interface with an atomic force microscope

Patent metadata

Field	Value
Publication number	US-9689034-B2
Application number	US-201514602860-A
Country	US
Kind code	B2
Filing date	Jan 22, 2015
Priority date	May 22, 2013
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

A mechanism is provided for sequencing a biopolymer. The biopolymer is traversed from a first medium to a second medium. The biopolymer includes bases. As the biopolymer traverses from the first medium to the second medium, different forces are measured corresponding to each of the bases. The bases are distinguished from one another according to the different measured forces which are measured for each of the bases.

First claim

What is claimed is:

1. A method of sequencing a polymer, comprising:
vertically traversing the polymer from a first medium to a second medium in a chamber, wherein a first end of the polymer is connected to an atomic force microscope and a second end of the polymer is connected to a bottom surface of the chamber;
wherein the polymer comprises blocks;
wherein the first medium is water and the second medium is oil;
as the polymer vertically traverses from the first medium to the second medium, measuring different measured forces corresponding to each of the blocks; and
distinguishing the blocks from one another according to the different measured forces measured for each of the blocks, the distinguishing comprises:
determining a plateau I and plateau II from the different measured forces, the plateau I defined to include a force for unwinding and stretching the polymer while in the first medium, the plateau II defined as crossing a boundary from the first medium to the second medium;
determining a solvophobic force of one block of the polymer by a difference in the plateau I and the plateau II.

2. The method of claim 1 , further comprising attaching large molecules to selected ones of the blocks.

3. The method of claim 2 , further comprising distinguishing the selected ones of the blocks by a large measured force.

4. The method of claim 1 , further comprising attaching one or more different large molecules respectively to the blocks.

5. The method of claim 4 , wherein each of the different large molecules are chemically configured to attach to one type of the blocks.

6. The method of claim 5 , further comprising traversing the polymer from the first medium to the second medium with the different large molecules respectively attached to the blocks causes an increase in the different measured forces measured for each of the blocks.

7. The method of claim 1 , wherein the polymer is a DNA molecule or an RNA molecule.

8. The method of claim 1 , wherein the first medium fills a bottom portion of the chamber and the second medium fills an upper portion of the chamber, the first and second mediums being different.

9. The method of claim 1 , wherein the plateau II is defined to include a saw-tooth shaped curve, wherein a composition of the polymer is determined from the saw-tooth shaped curve.

Assignees

• IBM

Inventors

• Balagurusamy Venkat K
• Polonsky Stanislav

Classifications

• G01Q90/00

  Scanning-probe techniques or apparatus not otherwise provided for · CPC title

• C12Q1/6869 Primary

  Methods for sequencing · CPC title

• G01Q60/24

  AFM [Atomic Force Microscopy] or apparatus therefor, e.g. AFM probes · CPC title

• C12Q2565/601

  being a microscope, e.g. atomic force microscopy [AFM] · CPC title

• C12Q1/68

  involving nucleic acids · CPC title