Devices, systems and methods for linearization of polymers

• US 10,413,903 B2
• Filed: 11/01/2016
• Issued: 09/17/2019
• Est. Priority Date: 05/08/2014
• Status: Active Grant

• Current Assignee: Osaka University
• Original Assignee: Osaka University
• Inventors: Taniguchi, Masateru
• Primary Examiner(s): Hyun, Paul S
• Application Number:
  US15/340,584
• Publication Number:
  US 20170144158A1
• Time in Patent Office: 1,050 Days
• CPC Class Codes: B01L 2200/0663 Stretching or orienting elongated molecules or particles
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0896 Nanoscaled
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore

Abstract

The present disclosure provides methods and structures for systems which can linearize and capture a nucleic acid molecule (e.g., DNA) for re-measurement of the nucleic acid molecule or other polymer prior to detection of the polymer. The structures may allow for quick exchange between different samples or other reagents.

Claims

1. A system for sequencing a biopolymer, comprising:

a nanochannel having a detection region for detecting said biopolymer or a portion thereof upon flow of said biopolymer through said detection region; and

a first entropic trapping component and a second entropic trapping component disposed in or adjacent to said nanochannel, wherein (i) said first entropic trapping component is operable to linearize said biopolymer upon flow of said biopolymer through said first entropic trapping component and towards a first side of said detection region, and (ii) said second entropic trapping component is operable to linearize said biopolymer upon flow of said biopolymer through said second entropic trapping component and towards a second side of said detection region, which first side is different from said second side,

wherein said first entropic trapping component is in said nanochannel, and wherein said first entropic trapping component includes an increase in cross-section of said nanochannel followed by a decrease in cross-section of said nanochannel towards said detection region.

2. The system of claim 1, wherein said first and/or second entropic trapping component permits movement of said biopolymer back and forth in said nanochannel.

3. The system of claim 1, further comprising a fluid channel adjacent to an end of said nanochannel, which fluid channel is larger in cross-section than said nanochannel.

4. The system of claim 3, wherein said fluid channel is at least five times larger in cross-section than said nanochannel.

5. The system of claim 4, wherein said fluid channel is at least ten times larger in cross-section than said nanochannel.

6. The system of claim 3, wherein said fluid channel and said nanochannel are integrated in a substrate.

7. The system of claim 3, further comprising an additional fluid channel adjacent to an additional end of said nanochannel, wherein said additional fluid channel is larger in cross-section than said nanochannel.

8. The system of claim 3, wherein said fluid channel is arranged to permit a fluid containing said biopolymer to flow around said detection region.

9. The system of claim 1, wherein said first and/or second entropic trapping component is configured to entropically trap and concentrate said biopolymer.

10. The system of claim 1, wherein said detection region comprises a pair of electrodes that are spaced apart by a gap, and wherein said pair of electrodes is operable to detect an electrical current across said gap upon flow of said biopolymer through said gap.

11. The system of claim 10, wherein said pair of electrodes comprises tunneling electrodes.

12. The system of claim 11, wherein said electrical current comprises a tunneling current.

13. The system of claim 11, wherein said gap has a spacing that is adjustable.

14. The system of claim 1, wherein said first and/or second entropic trapping component permits flow of said biopolymer towards said detection region at a greater flow rate than away from said detection region.

15. The system of claim 1, wherein said second entropic trapping component includes an increase in cross-section of said nanochannel followed by a decrease in cross-section of said nanochannel away from said detection region.

16. The system of claim 15, wherein in said second entropic trapping component, said decrease in cross-section is abrupt relative to said increase in cross-section.

17. The system of claim 1, wherein in said first entropic trapping component, said increase in cross-section is abrupt relative to said decrease in cross-section.

18. The system of claim 1, wherein said first entropic trapping component is upstream of said detection region and said second entropic trapping component is downstream of said detection region, or vice versa.