Nanofluidic channels with integrated charge sensors and methods based thereon

• US 10,670,559 B2
• Filed: 07/09/2009
• Issued: 06/02/2020
• Est. Priority Date: 07/11/2008
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Mannion, John T., Craighead, Harold G.
• Primary Examiner(s): Le, Son T
• Assistant Examiner(s): Clarke, Adam S
• Application Number:
  US13/003,490
• Publication Number:
  US 20110227558A1
• Time in Patent Office: 3,981 Days
• CPC Class Codes: B01L 2300/0896 Nanoscaled
• 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 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 27/414 Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
• CPC Class Codes: G01N 27/4473 by electric means
• 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

An electrical detector is provided that comprises a nanofluidic channel with an integrated nanoscale charge sensor. The charge sensor can be an unfunctionalized nanowire, nanotube, transistor or capacitor and can be of carbon, silicon, carbon/silicon or other semiconducting material. The nanofluidic channel depth is on the order of the Debye screening length. Methods are also provided for detecting charged molecules or biological or chemical species with the electrical detector. Charged molecules or species in solution are driven through the nanofluidic channel of the electrical detector and contact the charge sensor, thereby producing a detectable signal. Methods are also provided for detecting a local solution potential of interest. A solution flowing through the nanofluidic channel of the electrical detector contacts the charge sensor, thereby producing a detectable local solution potential signal.

Claims

1. An electrical detector for detecting a single charged molecule or particle of interest or a plurality of charged molecules or particles of interest comprising:

a nanofluidic channel or plurality of nanofluidic channels, wherein the channel depth of each nanofluidic channel is smaller than, on the order of, or 2-10 times the Debye screening length;

a source and drain electrode pair or a plurality of source and drain electrode pairs,

a charge sensor or a plurality of charge sensors associated with each nanofluidic channel, wherein;

the charge sensor or each charge sensor in the plurality of charge sensors is one continuous individually addressable nanowire or one continuous individually addressable nanotube,

the charge sensor or each charge sensor in the plurality of charge sensors is electrically connected by electrical contacts to, and is addressable by, a single source and drain electrode pair; and

at least one portion of the charge sensor or of each charge sensor in the plurality of charge sensors is in the interior of the nanofluidic channel, whereby the charge sensor or each charge sensor in the plurality of charge sensors is contacted by fluid in the nanofluidic channel.

2. The electrical detector of claim 1, wherein the plurality of nanofluidic channels is 2-10, 10-50, 50-100, 100-500, 500-1000, or 1000-5000 channels.

3. The electrical detector of claim 1 wherein the width of the nanofluidic channel(s) is 0.1 nm 1 nm, 1 nm-5 nm, 5 nm-10 nm, 10 nm-50 nm, 50 nm-100 nm, 100 nm-500 nm, 500 nm-1 μ

m, 1 μ

m-5 μ

m or 5 μ

m-10 μ

m.

4. The electrical detector of claim 1 wherein the nanotube is a p-type or n-type nanotube.

5. The electrical detector of claim 1 comprising a microfluidic or macrofluidic structure fluidically connected to the nanofluidic channel or channels.

6. The electrical detector of claim 1, wherein the charge sensor, or at least one of the charge sensors in the plurality of charge sensors, is an addressable semiconducting charge sensor that behaves as an electrolyte gated field effect transistor.

7. The electrical detector of claim 1, wherein the charge sensor or sensors is or are functionalized.

8. The electrical detector of claim 7 wherein the charge sensor or sensors is or are functionalized with a molecule selected from the group consisting of an antibody, a portion of an antibody, and an oligonucleotide.

9. The electrical detector of claim 1 comprising a substrate.

10. The electrical detector of claim 1 wherein:

a constant source-drain bias voltage is applied with a constant source-drain bias voltage applicator, and

current through the charge sensor or sensors is monitored.

11. The electrical detector of claim 1 wherein the dimensions of the nanofluidic channel or channels constrain or confine—

the single charged molecule or particle of interest or the plurality of charged molecules or particles of interest to within a sensing range of the charge sensor.

12. A method for detecting a biological or chemical species of interest or a tag associated with the species comprising:

providing the electrical detector of claim 1;

flowing the species or an entity comprising the species through the nanofluidic channel or a nanofluidic channel of the plurality of nanofluidic channels of the electrical detector; and

contacting the charge sensor or a charge sensor of the plurality of the charge sensors with the species or the tag, thereby producing a detectable signal indicative of the presence of the biological or chemical species of interest.

13. A method for detecting a local solution potential of interest comprising:

providing the electrical detector of claim 1;

flowing the solution through the nanofluidic channel or a nanofluidic channel of the plurality of nanofluidic channels of the electrical detector; and

contacting the charge sensor or a charge sensor of the plurality of the charge sensors with the solution, thereby producing a detectable local solution potential signal.

14. The electrical detector of claim 1, additionally comprising:

an insulator insulating electrical contacts of;

the source electrode and the drain electrode of the source and drain electrode pair, or

a source electrode and a drain electrode of a source and drain electrode pair of the plurality of source and drain electrode pairs.

15. The electrical detector of claim 1, wherein the charge sensor or each charge sensor in the plurality of charge sensors is located on a bottom surface of the nanofluidic channel or on a bottom surface of each of the nanofluidic channels in the plurality of nanofluidic channels, thereby allowing the single charged molecule or particle of interest or the plurality of charged molecules or particles of interest to pass above the charge sensor or the plurality of charge sensors located on the bottom surface of the nanofluidic channel or on the bottom surface of each of the nanofluidic channels in the plurality of nanofluidic channels.