Super resolution imaging

Patent metadata

Field	Value
Publication number	US-9193998-B2
Application number	US-201313835492-A
Country	US
Kind code	B2
Filing date	Mar 15, 2013
Priority date	Mar 15, 2013
Publication date	Nov 24, 2015
Grant date	Nov 24, 2015

Abstract

A detection apparatus that includes (a) an array of responsive pads on a substrate surface; (b) an array of pixels, wherein each pixel in the array has a detection zone on the surface that includes a subset of at least two of the pads; and (c) an activation circuit to apply a force at a first and second pad in the subset, wherein the activation circuit is configured to apply a different force at the first pad compared to the second pad, and wherein the activation circuit has a switch to selectively alter the force at the first pad and the second pad.

First claim

What is claimed is:

1. A detection apparatus comprising
(a) an array of electrically responsive pads on a substrate surface;
(b) an array of detection pixels, wherein each individual detection pixel in the array has a detection zone on the surface, each detection pixel configured to simultaneously observe a subset of at least two of the electrically responsive pads; and
(c) an activation circuit to apply electric field at a first pad in the subset and a second pad in the subset, wherein the activation circuit is configured to apply different electric field at the first pad compared to the second pad, and wherein the activation circuit comprises a switch to selectively alter the electric field at the first pad compared to the second pad, wherein each detection zone is square and each pad occurs in a corner of four of the detection zones.

2. The apparatus of 1 , wherein each pad is square and each detection zone includes a corner of four of the pads.

3. A detection apparatus comprising
(a) an array of electrically responsive pads on a substrate surface;
(b) an array of detection pixels, wherein each individual detection pixel in the array has a detection zone on the surface, each detection pixel configured to simultaneously observe a subset of at least two of the electrically responsive pads; and
(c) an activation circuit to apply electric field at a first pad in the subset and a second pad in the subset, wherein the activation circuit is configured to apply different electric field at the first pad compared to the second pad, and wherein the activation circuit comprises a switch to selectively alter the electric field at the first pad compared to the second pad, further comprising a readout circuit to acquire signals from the array of detection pixels, further comprising a control module that directs the readout circuit to acquire signals from each of the detection pixels during a sensing period, directs the activation circuit to apply different electric field at the first pad compared to the second pad, during the sensing period, and directs the activation circuit to switch to selectively alter the electric field at the first pad compared to the second pad, during the sensing period.

4. The apparatus of claim 3 , wherein each detection pixel in the array has a detection zone on the surface that includes a subset of four of the pads and the control module directs the activation circuit to sequentially apply differential electric fields at the four pads during the sensing period.

5. A detection apparatus comprising
(a) an array of electrically responsive pads on a substrate surface;
(b) an array of detection pixels, wherein each individual detection pixel in the array has a detection zone on the surface, each detection pixel configured to simultaneously observe a subset of at least two of the electrically responsive pads; and
(c) an activation circuit to apply electric field at a first pad in the subset and a second pad in the subset, wherein the activation circuit is configured to apply different electric field at the first pad compared to the second pad, and wherein the activation circuit comprises a switch to selectively alter the electric field at the first pad compared to the second pad, further comprising an excitation assembly to irradiate the pads.

6. A detection apparatus comprising
(a) an array of electrically responsive pads on a substrate surface;
(b) an array of detection pixels, wherein each individual detection pixel in the array has a detection zone on the surface, each detection pixel configured to simultaneously observe a subset of at least two of the electrically responsive pads; and
(c) an activation circuit to apply electric field at a first pad in the subset and a second pad in the subset, wherein the activation circuit is configured to apply different electric field at the first pad compared to the second pad, and wherein the activation circuit comprises a switch to selectively alter the electric field at the first pad compared to the second pad, wherein the pads comprise target analytes to be detected.

7. The apparatus of claim 6 , wherein the target analytes comprise at least two nucleic acid clusters that are included in the detection zone for a single detection pixel, each of the clusters comprises a different nucleotide sequence from the other cluster.

8. The apparatus of claim 7 , wherein each pad comprises a plurality of nucleic acid clusters and each cluster is included in the detection zone for a single detection pixel.

9. The apparatus of claim 7 , wherein each pad comprises a single nucleic acid cluster and the cluster is included in the detection zones for at least two of the detection pixels.

10. The apparatus of claim 7 , wherein the target analytes comprise fluorescent moieties and the detection pixels are configured to detect emission from the fluorescent moieties.

11. The apparatus of claim 10 , wherein the activation circuit applies a different electric field at the first pad compared to the second pad, wherein the first pad comprises a fluorescence quencher at a higher concentration than at the second pad.

12. The apparatus of claim 10 , wherein the activation circuit applies a different electric field at the first pad compared to the second pad, wherein the first pad comprises a fluorescent probe at a higher concentration than at the second pad.

13. The apparatus of claim 10 , wherein the pads further comprise electrochemical luminescence labels.

14. The apparatus of claim 13 , wherein the activation circuit applies a different electric field at the first pad compared to the second pad, thereby producing more photons at the first pad than at the second pad.

15. The apparatus of claim 6 , wherein the activation circuit is configured to apply an electric field at the first pad while no field is applied at the second pad, and the switch is configured to turn off the electric field at the first pad while applying an electric field at the second pad.

16. The apparatus of claim 6 , wherein the activation circuit is configured to apply a positive electric field at the first pad while applying negative electric field at the second pad, and the switch is configured to apply negative electric field at the first pad while applying positive electric field at the second pad.

17. A method of detecting analytes, comprising
(a) providing the detection apparatus of claim 6 , wherein the two pads comprise different target analytes, respectively;
(b) acquiring signals from each of the detection pixels while selectively applying an electric field at a first of the two pads to preferentially produce signal from a first of the different target analytes compared to a second of the target analytes, thereby preferentially acquiring signals from the first of the target analytes compared to the second of the target analytes; and
(c) acquiring signals from each of the detection pixels while selectively applying an electric field at the second of the two pads to preferentially produce signal from the second of the different target analytes compared to the first of the target analytes, thereby preferentially acquiring signals from the second of the target analytes compared to the first of the target analytes.

18. A detection apparatus comprising
(a) an array of electrically responsive pads on a substrate surface;
(b) an array of detection pixels, wherein each individual detection pixel in the array has a detection zone on the surface, each detection pixel configured to simultaneously observe a subset of at least two of the electrically res

Assignees

• Illumina Inc

Inventors

• Khurana Tarun
• Gunderson Kevin L
• Wu Yir-Shyuan

Classifications

• G01N27/27

  Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter · CPC title

• C12Q1/6874 Primary

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

• G01N27/3275

  Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction · CPC title

• G01N21/6454

  using an integrated detector array · CPC title

• C12Q2565/101

  Interaction between at least two labels · CPC title