NANOFLUIDIC CHANNELS WITH INTEGRATED CHARGE SENSORS AND METHODS BASED THEREON

• US 20110227558A1
• Filed: 07/09/2009
• Published: 09/22/2011
• Est. Priority Date: 07/11/2008
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Mannion, John T., Craighead, Harold C.
• Granted Patent: US 10,670,559 B2
• Time in Patent Office: Days
• US Class Current: 324/71.1
• 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 comprising a nanofluidic channel and a charge sensor, wherein:

the charge sensor is selected from the group consisting of nanowire, nanotube, transistor and capacitor, and

a portion of the charge sensor is integrated in the nanofluidic channel, whereby the charge sensor is contacted by fluid in the nanofluidic channel.

4. The electrical detector of claim 1 comprising charge sensor electrodes disposed within, or on the surface of, the channel.

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

9. The electrical detector of claim 1 wherein the nanofluidic channel depth is smaller than, on the order of, or 2-10 times the Debye screening length.

12. The electrical detector of claim 1 wherein the nanofluidic channel depth is 0.1 nm to 1 mm.

15. The electrical detector of claim 1 wherein the width of the nanofluidic channel 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.

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

19. The electrical detector of claim 1 wherein the transistor is a field effect transistor (FET).

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

28. The electrical detector of claim 1, wherein the charge sensor is an addressable semiconducting charge sensor that behaves as an electrolyte gated field effect transistor.

30. The electrical detector of claim 1, wherein the charge sensor is functionalized.

31. The electrical detector of claim 30 wherein the charge sensor is functionalized with a molecule selected from the group consisting of an antibody (or portion thereof) and an oligonucleotide.

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

43. 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 is monitored.

45. The electrical detector of claim 1 comprising a source and drain electrode pair electrically connected to the charge sensor by electrical contacts.

49. The electrical detector of claim 1 wherein the dimensions of the nanofluidic channel constrain or confine a molecule or particle of interest to within a sensing range of the charge sensor.

58. 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 of the electrical detector; and

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

64. 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 of the electrical detector; and

contacting the charge sensor with the solution, thereby producing a detectable local solution potential signal.

68. The method of claim 67 comprising providing the electrical detector of claim 1, wherein the electrical detector comprises the nanoslit and the nanofluidic channel.

2-3. -3. (canceled)

6-8. -8. (canceled)

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17-18. -18. (canceled)

20. (canceled)

22-27. -27. (canceled)

29. (canceled)

32. (canceled)

34-42. -42. (canceled)

44. (canceled)

46-48. -48. (canceled)

50-57. -57. (canceled)

59-63. -63. (canceled)

65-66. -66. (canceled)

67. A method for measuring conformation, length, speed or label intensity of a charged molecule or particle of interest comprising:

providing;

a charged molecule or particle of interest labeled with an optically detectable label (or feature, tag or modification),

a nanoslit,

a nanofluidic channel, and

two spatially separated focal volumes defined by lasers focused sequentially on the nanochannel;

driving electrophoretically the labeled charged molecule or particle from the nanoslit into the nanofluidic channel;

transporting the labeled charged molecule or particle through the two spatially separated focal volumes, thereby generating a first optically detectable signal and a second optically detectable signal shifted in time relative to each other;

detecting photon bursts (or photon count signals) from the first and second optically detectable signals;

measuring the photon bursts (or photon count signals) from the first and second optically detectable signals;

performing a speed or a cross correlation measurement using the measurement from the photon bursts (or photon count signals) from the first and second optically detectable signals; and

calculating the conformation, length, speed or label intensity of the molecule or particle of interest from the speed or cross correlation measurement.

69-73. -73. (canceled)