Integrated photonic electronic sensor arrays for nucleic acid sequencing

• US 10,513,734 B2
• Filed: 03/13/2017
• Issued: 12/24/2019
• Est. Priority Date: 12/20/2012
• Status: Active Grant

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Su, Xing, Oldham, Mark
• Primary Examiner(s): Priest, Aaron A
• Application Number:
  US15/457,244
• Publication Number:
  US 20170183727A1
• Time in Patent Office: 1,016 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2521/101 DNA polymerase
• CPC Class Codes: C12Q 2521/543 Immobilised enzyme(s)
• CPC Class Codes: C12Q 2537/157 A reaction step characterised by the number of molecules incorporated or released
• CPC Class Codes: C12Q 2563/116 electrical properties of nucleic acids, e.g. impedance, conductivity or resistance
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 27/00 Investigating or analysing materials by the use of electric, electrochemical, or magnetic means G01N3/00 – G01N25/00 take precedence; measurement or testing of electric or magnetic variables or of electric or magnetic properties of materials G01R
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors

Abstract

Devices and methods for detecting, identifying, and sequencing, compounds, complexes, and molecules are described. Electronic detection is combined with optical excitation to determine the presence or identity of an analyte of interest. Embodiments of the invention additionally provide devices and methods that allow highly parallel nucleic acid sequence determination.

Claims

1. A system comprising:

a substrate, having a surface, which comprises an intergrated circuit;

an enzyme to couple to the substrate and to a DNA molecule;

a photosensitizer to couple to a nucleotide and to the enzyme;

sensors, individually addressable through the intergrated circuit, which are on the substrate surface and include a first sensor to couple to the enzyme; and

antennas on the substrate surface, adjacent the first sensor, and oriented to localize light towards the first sensor;

wherein the photosensitizer is configured to communicate electrons between the photosensitizer and at least one of an electron receptor or an electron donor in response to;

(a) the photosensitizer and the DNA molecule both coupling to the enzyme, and (b) the photosensitizer being exposed to localized light from the antennas;

wherein the first sensor is configured to sense the electrons communicated with the photosensitizer to indicate the nucleotide is coupled to the DNA molecule.

2. The system of claim 1, wherein a layer covers a first portion of the first sensor, but not a second portion of the first sensor, and the layer includes a dielectric.

3. The system of claim 2, wherein (a) a first antenna of the antennas is bigger than a second antenna of the antennas, and (b) the first antenna is configured to harvest light of a first wavelength and the second antenna is configured to harvest light of a second wavelength unequal to the first wavelength.

4. The system of claim 3, wherein the first antenna harvests light for both the first sensor and a second sensor included in the sensors.

5. The system of claim 4, wherein the first sensor includes a surface comprising the electron acceptor and the electron acceptor includes a derivative of bipyridium.

6. The system of claim 4, wherein the first sensor includes a surface comprising the electron acceptor.

7. The system of claim 1 wherein (a) a first antenna of the antennas is bigger than a second antenna of the antennas, and (b) the first antenna is configured to harvest light of a first wavelength and the second antenna is configured to harvest light of a second wavelength unequal to the first wavelength.

8. The system of claim 1, wherein the first sensor includes a surface comprising the electron acceptor and the electron acceptor includes a derivative of bipyridium.

9. The system of claim 1, wherein the first sensor includes a surface comprising the electron acceptor.

10. The system of claim 1, wherein a first antenna of the antennas harvests light for both the first sensor and a second sensor included in the sensors.

11. The system of claim 10, wherein:

a layer covers a first portion of a surface of the first sensor but not a second portion of the surface of the first sensor;

the layer includes a dielectric;

the first sensor is between the surface of the first sensor and the substrate;

the substrate includes a long axis that defines its width;

the surface is generally parallel to the long axis.

12. The system of claim 10, wherein:

a layer covers a first portion of a top surface of the first sensor but not a second portion of the top surface;

the top surface directly connects to a side surface of the first sensor;

the side surface is between the top surface and a bottom surface of the first sensor; and

the bottom surface is between the top surface and a bottom surface of the substrate.

13. A system comprising:

a substrate, having a surface, which comprises an integrated circuit;

an enzyme to couple to the substrate and to a DNA molecule;

a photosensitizer to couple to a nucleotide and to the enzyme;

sensors, individually addressable through the integrated circuit, which are on the substrate surface and include a first sensor to couple to the enzyme; and

antennas on the substrate surface, adjacent the first sensor, and oriented to localize light towards the first sensor;

wherein (a) a first antenna of the antennas is bigger than a second antenna of the antennas, and (b) the first antenna is configured to harvest light of a first wavelength and the second antenna is configured to harvest light of a second wavelength unequal to the first wavelength.

14. The system of claim 13 wherein the first antenna harvests light for both the first sensor and a second sensor included in the sensors.

15. The system of claim 13 wherein:

a layer covers a first portion of a surface of the first sensor but not a second portion of the surface of the first sensor;

the layer includes a dielectric;

the first sensor is between the surface of the first sensor and the substrate;

the substrate includes a long axis that defines its width;

the surface is generally parallel to the long axis.

16. The system of claim 15 wherein:

the photosensitizer is to communicate electrons between the photosensitizer and at least one of an electron receptor or an electron donor in response to;

(a) the photosensitizer and the DNA molecule both coupling to the enzyme, and (b) the photosensitizer being exposed to localized light from the antennas;

the first sensor is to sense the electrons communicated with the photosensitizer to indicate the nucleotide is coupled to the DNA molecule.

17. A system comprising:

a substrate, having a surface, which comprises an integrated circuit;

sensors, individually addressable through the integrated circuit, which are on the substrate surface and include a first sensor configured to couple to an enzyme; and

antennas on the substrate surface, adjacent the first sensor, and oriented to localize light towards the first sensor;

wherein (a)(i) a first antenna of the antennas is bigger than a second antenna of the antennas, and (a)(ii) the first antenna is configured to harvest light of a first wavelength and the second antenna is configured to harvest light of a second wavelength unequal to the first wavelength;

wherein the first antenna harvests light for both the first sensor and a second sensor included in the sensors;

wherein;

(b)(i) a layer covers a first portion of a surface of the first sensor but not a second portion of the surface of the first sensor;

(b)(ii) the layer includes a dielectric;

(b)(iii) the first sensor is between the surface of the first sensor and the substrate;

(b)(iv) the substrate includes a long axis that defines its width; and

(b)(v) the surface is generally parallel to the long axis.

18. The system of claim 17 comprising at least one of the enzyme or a photosensitizer, wherein:

the photosensitizer is to communicate electrons between the photosensitizer and at least one of an electron receptor or an electron donor in response to;

(a) the photosensitizer and a DNA molecule both coupling to the enzyme, and (b) the photosensitizer being exposed to localized light from the antennas;

the first sensor is to sense the electrons communicated with the photosensitizer to indicate a nucleotide is coupled to the DNA molecule.