DEVICE FOR DETERMINING A MONOMER MOLECULE SEQUENCE OF A POLYMER COMPRISING DIFFERENT ELECTRODES AND USE THEREOF

• US 20130334047A1
• Filed: 06/14/2013
• Published: 12/19/2013
• Est. Priority Date: 06/14/2012
• Status: Active Grant

• Current Assignee: Samsung Electronics Co. Ltd.
• Original Assignee: Samsung Electronics Co. Ltd.
• Inventors: SHIM, Jeo-young, EOM, Kun-sun, LEE, Dong-ho, JEON, Tae-han, JEONG, Heejeong
• Granted Patent: US 9,310,326 B2
• Time in Patent Office: Days
• US Class Current: 204/452
• CPC Class Codes: G01N 27/00 Investigating or analysing materials by the use of electric, electrochemical, or magnetic means G01N3/00 – G01N25/00 take precedence; measurement or testing of electric or magnetic variables or of electric or magnetic properties of materials G01R
• CPC Class Codes: G01N 27/4473 by electric means
• CPC Class Codes: G01N 33/48721 Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68

Abstract

Provided is a device for determining a monomer molecule sequence of a polymer including different electrodes, and a method of efficiently determining a monomer molecule sequence of a polymer.

Claims

1. A device for determining a monomer molecule sequence of a polymer comprising:

a pair of first electrodes that are formed of a first material and separated from each other by a gap;

a pair of second electrodes that are separated from each other by a gap and formed of a material having electrical characteristics different from the electrical characteristics of the material of the pair of first electrodes;

a pair of insulating materials between the pair of first electrodes and the pair of second electrodes, wherein the pair of insulating materials are separated from each other by a gap;

wherein the gap separating the pair of first electrodes, the gap separating the pair of insulating materials, and the gap separating the pair of second electrodes are stacked in alignment to form a path through which a polymer can move;

electrical signal detectors respectively connected to the pair of first electrodes and the pair of second electrodes;

a polymer positioning unit for disposing the polymer in the path; and

a polymer moving unit for rotating or left-right shifting or moving longitudinally along the path the polymer disposed in the path.

2. The device of claim 1, wherein the path has a cross-sectional length of about 10 nm or less.

3. The device of claim 1, wherein the pair of first electrodes include a carbonaceous electrode, a metal electrode, or any combination thereof, and the pair of second electrodes include a carbonaceous electrode, a metal electrode, or any combination thereof.

4. The device of claim 1, wherein the polymer positioning unit for disposing the polymer in the path is an electric field supply unit, a mechanical pressure supply unit, an optical tweezer, a magnetic tweezer, or any combination thereof.

5. The device of claim 1, wherein the polymer moving unit for rotating or left-right shifting the polymer disposed in the path is an optical tweezer, a magnetic tweezer, or any combination thereof.

6. The device of claim 1, wherein the polymer is DNA, RNA, or chimeric molecules thereof.

7. The device of claim 1, further comprising a signal processor that is electrically connected to the electrical signal detectors and comprises a storage medium storing a computer readable program that determines a monomer sequence of a polymer by using a method comprising:

setting a first threshold value of an intensity of a signal received from the pair of first electrodes according to a monomer molecule of the polymer and identifying the type of the monomer from a signal having an intensity higher than the first threshold value; and

setting a second threshold value of an intensity of a signal received from the pair of second electrodes according to the monomer molecule of the polymer and identifying the type of the monomer from a signal having an intensity higher than the second threshold value.

8. The device of claim 7, wherein the signal comprises an average of the signal with respect to a travel angle or distance according to the rotation or left-right shift of the polymer.

9. The device of claim 1, wherein the pair of first electrodes, the pair of second electrodes, or both are formed of a combination of different materials.

10. A method of determining a monomer molecule sequence of a polymer, the method comprising:

disposing monomer molecules of a polymer in the path of the device of claim 1;

detecting electrical signals respectively from the pair of first electrodes and the pair of second electrodes;

setting a first threshold value of an intensity of a signal received from the pair of first electrodes according to a monomer molecule of the polymer and identifying the type of the monomer molecule from a signal having an intensity higher than the first threshold value, and setting a second threshold value of an intensity of a signal received from the pair of second electrodes according to the monomer molecule of the polymer and identifying the type of the monomer molecule from a signal having an intensity higher than the second threshold value; and

determining the monomer molecule sequence of the polymer by combining the type of the monomer molecule identified by using the signal from the pair of first electrodes and the type of the monomer molecule identified by using the signal from the pair of second electrodes.

11. The method of claim 10, wherein the method comprises disposing multiple polymers in the path by disposing one polymer at a time.

12. The method of claim 10, wherein the polymer is DNA, RNA, or any combination thereof.

13. The method of claim 10, wherein the disposing of the polymer comprises holding the polymer in the path or passing the polymer through the path.

14. The method of claim 13, wherein the holding of the polymer is performed by holding the polymer at a predetermined position of the path by using an optical tweezer or magnetic tweezer.

15. The method of claim 10, wherein the polymer comprises a nanoparticle or microparticle immobilized on at least one of a first end or second end of the polymer allowing the polymer to be moved by an optical tweezer or magnetic tweezer.

16. The method of claim 10, wherein the path comprises a first end to which the polymer is input and a second end from which the polymer is discharged, and the method further comprises immobilizing the polymer on a substrate movable with respect to the first end and the second end in the longitudinal direction along the path.

17. The method of claim 10, wherein the path has a cross-sectional length of about 10 nm or less.

18. The method of claim 10, wherein the pair of first electrodes includes a carbonaceous electrode, a metal electrode, or any combination thereof, and the pair of second electrodes includes a carbonaceous electrode, a metal electrode, or any combination thereof.

19. The method of claim 10, wherein the pair of first electrodes includes a graphene electrode, and the pair of second second electrodes includes a gold electrode.

20. The method of claim 19, wherein the polymer is DNA, and the method further comprises setting a first threshold value of an intensity of a signal received from the pair of first electrodes according to a monomer molecule of a polymer as about 1 pA and identifying a base G or T from a signal having an intensity higher than the first threshold value, and setting a second threshold value of an intensity of a signal received from the pair of second electrodes according to a monomer molecule of a polymer as about 1 pA and identifying the type of the monomer molecule from a signal having an intensity higher than the second threshold value as a base A.

21. The method of claim 10, wherein the detecting of the electrical signals comprises detecting a signal according to a travel angle or distance while rotating or left-right shifting the polymer.

22. The method of claim 14, wherein the detecting of the electrical signals comprises detecting a signal according to a travel angle or distance while rotating or left-right shifting the polymer, and calculating an average of the detected signal according to the travel angle or distance.