Graphene FET devices, systems, and methods of using the same for sequencing nucleic acids

• US 10,020,300 B2
• Filed: 08/01/2016
• Issued: 07/10/2018
• Est. Priority Date: 12/18/2014
• Status: Active Grant

• Current Assignee: Cardea Bio, Inc.
• Original Assignee: Agilome, Inc.
• Inventors: Hoffman, Paul
• Primary Examiner(s): BACHNER, ROBERT G
• Application Number:
  US15/225,764
• Publication Number:
  US 20170053908A1
• Time in Patent Office: 708 Days
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 27/4146 involving nanosized elements, e.g. nanotubes, nanowires
• CPC Class Codes: H01L 27/085 including field-effect components only
• CPC Class Codes: H01L 29/1606 Graphene
• CPC Class Codes: H01L 29/66045 Field-effect transistors

Abstract

Provided herein are integrated circuits for use in performing analyte measurements and methods of fabricating the same. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in chemical and/or biological processes, including DNA hybridization and/or sequencing reactions. The methods for fabricating the integrated circuits include steps of depositing an insulating layer on a semiconducting substrate, and forming trenches in the insulating dielectric layer. Conductive material may be deposited in the trenches to form electrodes, and the insulating layer may be conditioned so that the electrodes protrude above the insulating layer. A 2D material, such as graphene, may be deposited on the electrodes to form a channel between the electrodes.

Claims

1. An integrated circuit for performing a nucleic acid sequencing reaction, the integrated circuit comprising:

a semi-conducting substrate having a plurality of extended planar surfaces offset from one another by a first thickness, being surrounded by one or more side members, and having one or more transistor elements positioned between the plurality of surfaces;

an array of field effect transistors arranged on the substrate, each of the field effect transistors comprising;

a primary layer forming a base layer;

a secondary layer over the primary layer, the secondary layer being formed of a first non-conductive material, the secondary layer comprising a plurality of trenches, each trench offset by a distance, each distance forming a channel region, each trench including an electrically conductive material to form an electrode having a side and top surface that extends above a surface of the of the secondary layer, each electrode on either side of each channel region being either a source electrode or a drain electrode; and

a tertiary layer over the secondary layer, the tertiary layer comprising a 2D material formed over side and top of the source and drain electrodes, the 2D material also formed over the channel region to electrically connect the source and the drain electrodes.

2. The integrated circuit according to claim 1, the tertiary layer further comprising a surface structure that overlaps the source and the drain in the secondary layer, the surface structure further defining a well having side walls and a bottom that extends over at least a portion of the 2D material so as to form a reaction chamber for the performance of a sequencing reaction.

3. The integrated circuit according to claim 2, wherein the surface structure of the tertiary layer is formed of a second nonconductive material selected from the group of second nonconductive materials that consist of:

polymide, BCB, silicon dioxide, silicon oxynitride, and silicon carbide.

4. The integrated circuit according to claim 3, further comprising an ion sensitive layer disposed over the portion of the 2D material, the ion sensitive layer being formed of an ion sensitive material.

5. The integrated circuit according to claim 2, wherein the 2D material comprises a material selected from the group consisting of:

Graphene;

Molybdenum disulfide (MoS₂);

Phosphorene (black phosphorous);

Silicene, Borophene, Tungsten disulfide (WS₂);

Boron Nitride;

WS_e2;

Stanene (2D tin);

Graphane;

Germanane;

Nickel HITP; and

Mxenes (Ti2C, [Ti0.5,Nb0.5], V2C, Nb2C, Ti3C2, Ti3CN, Nb4C3,Ta4C3).

6. The integrated circuit according to claim 2, wherein the primary layer is formed of silicon.

7. The integrated circuit according to claim 6, wherein the source and drain electrodes are in contact with the one or more transistor elements of the semi-conductive substrate.

8. An integrated circuit for performing a nucleic acid sequencing reaction, the integrated circuit comprising:

a substrate having a plurality of extended planar surfaces offset from one another by a first thickness, being surrounded by one or more side members;

an array of field effect transistors arranged on the substrate, each of the field effect transistors comprising;

a primary layer forming a base layer;

a secondary layer over the primary layer, the secondary layer being formed of a first non-conductive material, the secondary layer comprising a plurality of trenches, each trench offset by a distance, each distance forming a channel region, each trench including a first layer of electrically conductive material to form an electrode having a surface that extends above a surface of the secondary layer, each electrode on either side of each channel region being a source electrode and a drain electrode; and

a tertiary layer over the secondary layer, the tertiary layer comprising a 2D material formed over the electrodes and having one or more openings proximate the electrodes, the 2D material also formed over the channel region to electrically connect the source and the drain, and

a second layer of electrically conductive material formed over the openings of the 2D material and in electrical communication with the electrodes and the 2D material.

9. The integrated circuit according to claim 8, the tertiary layer further comprising a surface structure that overlaps the source and the drain in the secondary layer, the surface structure further defining a well having side walls and a bottom that extends over at least a portion of the 2D material so as to form a reaction chamber for the performance of a sequencing reaction.

10. The integrated circuit according to claim 9, wherein the surface structure of the tertiary layer is formed of a second nonconductive material selected from the group of second nonconductive materials that consist of:

polymide, BCB, silicon dioxide, silicon oxynitride, and silicon carbide.

11. The integrated circuit according to claim 8, further comprising an ion sensitive layer disposed over the portion of the 2D material, the ion sensitive layer being formed of an ion sensitive material.

12. The integrated circuit according to claim 8, wherein the 2D material comprises a material selected from the group consisting of:

Graphene;

Molybdenum disulfide (MoS₂);

Phosphorene (black phosphorous);

Silicene, Borophene, Tungsten disulfide (WS₂);

Boron Nitride;

WS_e2;

Stanene (2D tin);

Graphane;

Germanane;

Nickel HITP; and

Mxenes (Ti2C, [Ti0.5,Nb0.5], V2C, Nb2C, Ti3C2, Ti3CN, Nb4C3,Ta4C3).

13. The integrated circuit according to claim 8, wherein the first layer of electrically conductive material comprises a metal selected from the group consisting of:

Al, Cu, Pt, Ni, W and Au.