Radio-frequency nanopore sensor

Patent metadata

Field	Value
Publication number	US-9488600-B2
Application number	US-201414444079-A
Country	US
Kind code	B2
Filing date	Jul 28, 2014
Priority date	Jul 28, 2014
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

An electrically conductive nanoscale sensor includes a nanoscale pore that may be employed as a first 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 via a second antenna communicating with the first antenna promises high-speed analysis of long molecules (polymers).

First claim

We claim:

1. A nanochannel sensor comprising:
a first antenna structure providing an electrically conductive material defining a nanoscale through-channel;
a membrane having a first side and a second side and supporting the first antenna structure so that the through-channel provides a passage through the membrane between the first side and second side; and
a second antenna structure proximate to the first antenna structure to electrically couple radiofrequency signals between the first antenna structure and the conductive material of the second antenna structure;
wherein the second antenna structure is configured to communicate with a measurement circuit producing a radiofrequency signal and measuring a change in the radiofrequency signal with the passage of a molecule through the nanoscale through-channel of the first antenna structure caused by a change in impedance of the electrically conductive material of the first antenna structure as coupled to the second antenna structure and the molecule;
wherein the nanoscale through-channel further comprises a nanoscale pore formed by a biomolecule coated with metallic nanoparticles; and
wherein the nanoscale pore has an internal diameter of less than three nanometers.

2. The nanochannel sensor of claim 1 wherein the biomolecule is a DNA with metal particles attached to it.

3. The nanochannel sensor of claim 2 wherein the metal particles are gold particles.

4. The nanochannel sensor of claim 1 wherein the nanoscale through-channel of the first antenna structure extends generally along a first axis and further including at least one conductive side antenna arm extending along a second axis perpendicular to the first axis away from an axis of the nanoscale through-channel toward the second antenna structure.

5. The nanochannel sensor of claim 4 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 through-channel is oriented so that the second axis is substantially aligned with the third axis.

6. The nanochannel sensor of claim 4 wherein the first antenna structure includes at least two side conductive arms extending along the second axis from opposite sides of the first antenna structure.

7. The nanochannel sensor of claim 1 wherein the measurement circuit further comprises a radiofrequency signal source and measuring a change in the reflected, transmitted or radiated electrical radiofrequency signal of the second antenna structure with the passage of the molecule through the nanoscale through-channel of the nanoscale pore.

8. The nanochannel sensor of claim 7 wherein the measurement circuitry monitors 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 structures.

9. The nanochannel sensor of claim 1 wherein the membrane is a lipid bilayer.

10. The nanochannel sensor of claim 1 wherein the nanoscale through-channel includes a substantially cylindrical torus having a height of at least five nanometers.

11. The nanochannel sensor of claim 10 wherein the first antenna structure has an outer diameter of at least five nanometers.

12. A method of sensing molecules using a nanochannel sensor having:
a first antenna structure providing an electrically conductive material defining a nanoscale through-channel;
a membrane having a first side and a second side and supporting the first antenna structure so that the through-channel provides a passage through the membrane between the first side and second side; and
a second antenna structure proximate to the first antenna structure to electrically couple radiofrequency signals between the first antenna structure and the conductive material of the second antenna structure;
wherein the second antenna structure is configured to communicate with a measurement circuit producing a radiofrequency signal and measuring a change in the radiofrequency signal with the passage of a molecule through the nanoscale through-channel of the first antenna structure caused by a change in impedance of the electrically conductive material of the first antenna structure as coupled to the second antenna structure and the molecule;
wherein the nanoscale through-channel further comprises a nanoscale pore formed by a biomolecule coated with metallic nanoparticles; and
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 nanopore sensor based on changes in the reflected, transmitted or radiated electrical radiofrequency signal of the second antenna structure with the passage of the molecule through the first antenna structure.

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

• G01N22/00 Primary

  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

• G01R23/02

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