Nano-gap electrode pair and method of manufacturing same

• US 10,466,228 B2
• Filed: 11/02/2018
• Issued: 11/05/2019
• Est. Priority Date: 10/16/2013
• Status: Active Grant

• Current Assignee: Quantum Biosystems Inc.
• Original Assignee: Quantum Biosystems Inc.
• Inventors: Ikeda, Shuji, Oldham, Mark, Nordman, Eric S.
• Primary Examiner(s): Kaur, Gurpreet
• Application Number:
  US16/178,924
• Publication Number:
  US 20190310240A1
• Time in Patent Office: 368 Days
• CPC Class Codes: C23C 16/45525 Atomic layer deposition [ALD]
• CPC Class Codes: G01N 27/3278 involving nanosized elements, e.g. nanogaps or nanoparticles nanopores G01N33/48721; magnetic beads G01N27/745
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• 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

A system for detecting a biomolecule comprises a nano-gap electrode device including a first electrode and a second electrode adjacent to the first electrode. The first electrode can be separated from the second electrode by a nano-gap that is dimensioned to permit the biomolecule to flow through the nano-gap. The nano-gap can have at least a first gap region and a second gap region. The second gap region can be oriented at an angle that is greater than zero degrees with respect to a plane having the first gap region. The system can further include an electrical circuit coupled to the nano-gap electrode device. The electrical circuit can receive electrical signals from the first electrode and the second electrode upon the flow of the biomolecule through the nano-gap.

Claims

1. A method for detecting a biomolecule, comprising:

(a) directing a biomolecule to a nano-gap electrode device having a first electrode and a second electrode adjacent to said first electrode, wherein said first electrode is separated from said second electrode by a nano-gap that is dimensioned to permit said biomolecule to access said nano-gap, wherein said nano-gap has at least a first gap region and a second gap region, and wherein said second gap region is oriented at an angle that is greater than zero degrees with respect to a plane having said first gap region, wherein said first electrode comprises a first portion and a second portion that is adjacent to said first portion, wherein said first portion and said second portion are adjacent to a substrate, wherein said first portion has a surface that partially defines said second gap region, and wherein said second portion has a surface that partially defines said first gap region;

(b) using said nano-gap electrode device to measure electrical signals upon said biomolecule accessing said nano-gap; and

(c) detecting said biomolecule using said electrical signals measured in (b).

2. The method of claim 1, wherein said first portion has a greater thickness than said second portion.

3. The method of claim 1, wherein said detecting comprises comparing said electrical signals to reference signals that are indicative of said biomolecule or a portion thereof.

4. The method of claim 1, wherein said detecting comprises identifying said biomolecule or a portion thereof.

5. The method of claim 1, wherein said biomolecule is a nucleic acid molecule, and wherein said detecting in (c) comprises sequencing said nucleic acid molecule.

6. The method of claim 1, wherein said electrical signals include electrical current, wherein said electrical current is tunneling current.

7. The method of claim 1, wherein said second gap region is oriented at an angle that is about 90°

with respect to said plane having said first gap region.

8. The method of claim 1, wherein a portion of said first electrode or said second electrode has a single atom tip.

9. The method of claim 1, wherein said biomolecule is directed to said nano-gap through at least one channel that is in fluid communication with said nano-gap.

10. The method of claim 1, wherein said nano-gap electrode device is part of an array of independently addressable nano-gap electrode devices.

11. The method of claim 1, wherein upon said biomolecule accessing said nano-gap, a portion of said biomolecule accesses said first gap region and a remainder of said biomolecule accesses said second gap region.

12. A method for manufacturing nano-gap electrodes for use in detecting a biomolecule, comprising:

(a) providing a first electrode-forming part adjacent to a substrate;

(b) forming a gap-forming layer adjacent to a surface of said first electrode-forming part;

(c) forming a second electrode-forming part adjacent to said gap-forming layer; and

(d) removing a portion of said gap-forming layer to form a nano-gap between said first electrode part and said second electrode part, wherein said nano-gap is dimensioned to permit said biomolecule to access said nano-gap, wherein said nano-gap has at least a first gap region and a second gap region, wherein said second gap region is oriented at an angle that is greater than zero degrees with respect to a plane having said first gap region, wherein said first electrode-forming part comprises a first portion and a second portion that is adjacent to said first portion, wherein said first portion and said second portion are adjacent to a substrate, wherein said first portion has a surface that partially defines said second gap region, and wherein said second portion has a surface that partially defines said first gap region.

13. The method of claim 12, further comprising, subsequent to (c), exposing a surface of said first electrode-forming part, a surface of said second portion of said gap-forming layer, and a surface of said second electrode-forming part.

14. The method of claim 13, further comprising patterning said second electrode-forming part, said gap-forming layer and said first electrode-forming part to provide a first electrode part and a second electrode part each having a predetermined shape.

15. The method of claim 12, wherein said second gap region is oriented at an angle that is greater than about 25°

with respect to said plane having said first gap region.

16. The method of claim 12, further comprising processing said first electrode part or said second electrode part to have a single atom tip.

17. The method of claim 12, wherein (a) comprises forming an insulating layer adjacent to a portion of said electrode-forming part having a lower thickness than another portion of said electrode-forming part, and forming said gap-forming layer adjacent to said insulating layer.

18. The method of claim 12, wherein a terminal end of said second gap region is coupled to said first gap region.

19. The method of claim 12, wherein said first electrode-forming part has a level difference on said substrate.

20. The method of claim 12, wherein said first gap region is parallel to said substrate.