Radio-frequency nanopore sensor

Patent metadata

Field	Value
Publication number	US-10151741-B2
Application number	US-201615287229-A
Country	US
Kind code	B2
Filing date	Oct 6, 2016
Priority date	Jul 28, 2014
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

An electrically conductive nanoscale pore may be employed as an antenna to provide precise localized measurements of the impedance-altering characteristics of a molecule such as DNA or RNA or the like passing through the pore. The use of radiofrequency measurements promises high-speed analysis of long molecules (polymers).

First claim

We claim:

1. A method of sensing molecules using a nanochannel sensor having:
a first antenna structure providing an electrically conductive material defining a nanoscale pore;
a membrane having a first side and a second side and supporting the first antenna structure so that the nanoscale pore provides a passage through the membrane between the first side and second side; and
a second antenna structure electrically proximate to the first antenna structure to electrically couple radiofrequency signals between the second antenna structure and the conductive material of the first antenna structure and from the conductive material of the first antenna structure to a molecule passing through the second antenna structure;
a measurement circuit communicating with the second antenna structure to producing a radiofrequency signal and measuring a change in the radiofrequency signal with the passage of a molecule through the nanoscale pore of the first antenna structure caused by a change in electrical impedance of the electrically conductive material of the first antenna structure as coupled to the second antenna structure and the molecule;
wherein the nanoscale pore has an internal diameter of less than three nanometers, the method comprising the steps of:
(a) applying the radiofrequency signal to the second antenna structure;
(b) sampling an impedance of the second antenna structure at multiple points in time; and
(c) identifying molecules passing through the nanoscale pore based on changes in the electrical impedance of the second antenna structure with the passage of the molecule through the first antenna structure.

2. The method of claim 1 wherein step (c) identifies molecules by at least one of a change in natural resonant frequency, a change in signal amplitude, and a change of phase of the radiofrequency signal by the first and second antenna system.

3. The method of claim 1 wherein the nanoscale pore extends beyond the first and second sides of the membrane along the first axis generally perpendicular to a plane of the membrane.

4. The method of claim 1 wherein the nanoscale pore has a passageway longer than its diameter.

5. The method of claim 1 wherein the membrane is an electrical insulator.

6. The method of claim 5 wherein the membrane is a lipid bilayer.

7. The method of claim 1 wherein the electrically conductive nanoscale pore is a biomolecule formed into a pore and coated with metallic nanoparticles.

8. The method of claim 1 wherein the electrically conductive nanoscale pore is a nanotube or semiconductor nanochannel.

9. The method of claim 1 wherein the passage of the nanoscale pore extends generally along a first axis and further including at least one conductive side antenna structure extending along a second axis perpendicular to the first axis.

10. The method of claim 9 wherein the second antenna structure provides a gap along a third axis across which an electromagnetic field is generated by the measurement circuit and wherein the nanoscale pore is oriented so that the second axis is substantially aligned with the third axis.

11. The method of claim 9 wherein the nanoscale pore includes at least two side conductive antennas extending along the second axis from opposite sides of the nanoscale pore.

12. The method of claim 1 wherein the nanoscale pore includes a substantially cylindrical torus having a height of at least five nanometers.

Assignees

• Wisconsin Alumni Res Found
• Univ Of Hamburg

Inventors

• Blick Robert H
• Bhat Abhishek
• Gwozdz Paul

Classifications

• G01R27/26

  Measuring inductance or capacitance; Measuring quality factor, e.g. by using the resonance method; Measuring loss factor; Measuring dielectric constants {; Measuring impedance or related variables} · CPC title

• G01R23/02

  Arrangements for measuring frequency, e.g. pulse repetition rate; Arrangements for measuring period of current or voltage · CPC title

• G01N22/00

  Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more (G01N3/00 - G01N17/00, G01N24/00 take precedence) · CPC title

• C12Q1/6869

  Methods for sequencing · CPC title

• G01N33/48721 Primary

  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 title