Electronic Detectors Inside Nanofluidic Channels For Detection, Analysis, and Manipulation of Molecules, Small Particles, and Small Samples of Material

• US 20100267158A1
• Filed: 04/16/2010
• Published: 10/21/2010
• Est. Priority Date: 04/16/2009
• Status: Active Grant

• Current Assignee: Stephen Y. Chou, Xiaogan Liang
• Original Assignee: Stephen Y. Chou, Xiaogan Liang
• Inventors: Liang, Xiaogan, Chou, Stephen Y.
• Granted Patent: US 9,810,680 B2
• Time in Patent Office: Days
• US Class Current: 436/94
• CPC Class Codes: B01L 2200/0663 Stretching or orienting elongated molecules or particles
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• 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 35/00 Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• 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
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention provides methods and apparatus that can manipulate, detect, and/or analyze single molecules, single small particles or single small samples of matter passing through a nanoscale gap within a nanofluidic channel of a detector.

Claims

1. A method for sampling molecules, small particles, or small samples of material, comprising:

drawing a sample in a solution liquid into a nanofluidic channel;

passing said sample through at least one nanogap detector associated with said nanofluidic channel, said nanogap detector including a nanogap constraining said sample and limiting the number of molecules within the measurement site; and

observing changes in environmental characteristics within nanogap responsive to said passage of said sample through said nanogap.

2. The sampling method of claim 1 wherein said sample is passed through a plurality of nanogap detectors associated with said nanofluidic channel, and wherein changes in environmental characteristics within each of said plurality of nanogap detectors are observed responsive to said passage of said sample.

3. The sampling method of claim 2 wherein said observed changes are processed to identify existence, length, and flow speed of said sample.

4. The sampling method of claim 1 wherein said step of observing includes measuring at least one environmental characteristic including electrical conductance, electrical capacitance, optical properties, and magnetic properties across said nanogap.

5. The sampling method of claim 1 wherein said step of observing includes measuring electron or ion transport across said nanogap.

6. The sampling method of claim 1 wherein said step of observing includes measuring a tunneling current across said nanogap.

7. The sampling method of claim 1 wherein said step of observing includes measuring bio-specific interactions across said nanogap.

8. The sampling method of claim 1 further including the step of stretching said sample into a linear form within said nanofluidic channel prior to passage through said nanogap detector.

9. The sampling method of claim 8 wherein said sample is a label-free single DNA strand.

10. A measurement device for analyzing samples consisting of single molecules, small particles, or small quantities of matter, comprising:

at least one nanofluidic channel through which a solution containing a sample to be analyzed can be drawn, said nanofluidic channel configured to constrain said sample in a linear configuration;

at least one nanogap detector associated with said nanofluidic channel, said nanogap detector consisting of a pair of detector elements defining a nanogap across said nanofluidic channel through which said sample is passed, said nanogap detector providing an output representative of an environmental condition within said nanogap, said environmental condition changing in response to the presence of a sample within said nanogap.

11. The measurement device of claim 10 wherein said pair of detector elements defining said nanogap consists of a pair of nanowires.

12. The measurement device of claim 10 wherein said nanogap detector includes one or more transistors, conductors, or diodes.

13. The measurement device of claim 10 wherein said pair of detector elements defining said nanogap consists of a pair of optical sensors.

14. The measurement device of claim 10 wherein said pair of detector elements defining said nanogap consists of a pair of biological probes.

15. The measurement device of claim 10 wherein said signals from said nanogap detector are representative of at least one of an electrical conductance, an electrical capacitance, an optical characteristic, or a magnetic characteristic across said nanogap.

16. The measurement device of claim 10 wherein said signals from said nanogap detector are representative of electron or ion transport across said nanogap.

17. The measurement device of claim 10 wherein said signals from said nanogap detector are representative of a tunneling current across said nanogap.

18. The measurement device of claim 10 wherein said signals from said nanogap detector are representative of bio-specific interactions across said nanogap.

19. The measurement device of claim 10 wherein said nanofluidic channel is defined by an enclosed passage.

20. The measurement device of claim 10 wherein a width of said nanogap is selected based on a molecular size of said sample to limit the number of molecules of said sample within a measurement area.

21. A method for the manufacture of a detector suitable for manipulating, detecting, and/or analyzing single molecules, single small particles, or single small samples of matter, comprising:

providing a substrate;

forming at least a single nanofluidic channel on said substrate;

disposing a resist layer over said substrate;

fabricating at least a single trench in said resist layer, said single trench aligned normal to said nanofluidic channel;

utilizing said trench in the formation of metallic nanowires and a nanogap within said nanofluidic channel by a metal lift-off procedure;

removing any residual resist layer; and

optionally sealing said nanofluidic channel, said nanowires, and said nanogap with a cover.