Integrated photonic electronic sensor arrays for nucleic acid sequencing

Patent metadata

Field	Value
Publication number	US-10513734-B2
Application number	US-201715457244-A
Country	US
Kind code	B2
Filing date	Mar 13, 2017
Priority date	Dec 20, 2012
Publication date	Dec 24, 2019
Grant date	Dec 24, 2019

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.

First claim

What is claimed is:

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.

Assignees

• Intel Corp

Inventors

• Su Xing
• Oldham Mark

Classifications

• C12Q1/6869 Primary

  Methods for sequencing · CPC title

• C12Q2521/101

  DNA polymerase · CPC title

• C12Q2521/543

  Immobilised enzyme(s) · CPC title

• C12Q1/6874 Primary

  involving nucleic acid arrays, e.g. sequencing by hybridisation · CPC title

• C12Q2563/116

  electrical properties of nucleic acids, e.g. impedance, conductivity or resistance · CPC title