Windowed sequencing

• US 10,100,357 B2
• Filed: 02/12/2016
• Issued: 10/16/2018
• Est. Priority Date: 05/09/2013
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Rearick, Todd, Milgrew, Mark James, Schultz, Jonathan, Papalias, Chris, Johnson, Kim L.
• Primary Examiner(s): Zhang, Kiajiang
• Application Number:
  US15/043,296
• Publication Number:
  US 20160168634A1
• Time in Patent Office: 977 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids

Abstract

In one implementation, a method is described. The method includes determining an operational characteristic of sensors of a sensor array. The method further includes selecting a group of sensors in the array based on the operational characteristic of sensors in the group. The method further includes enabling readout of the sensors in the selected group. The method further includes receiving output signals from the enabled sensors, the output signals indicating chemical reactions occurring proximate to the sensors of the sensor array.

Claims

1. A method comprising:

determining an operational characteristic of each sensor of a plurality of sensors located at a portion of a sensor array, the determining occurring before a chemical reaction occurs proximal to each sensor of the plurality of sensors located at the portion of the sensor array;

selecting a first group of sensors from the plurality of sensors located at the portion of the sensor array, wherein the selecting is based on determining that each sensor in the first group of sensors has a similar operational characteristic;

enabling readout of the sensors in the first group of sensors;

bypassing readout of other sensors of the sensor array that are not included in the first group of sensors, wherein the other sensors have a different operational characteristic than the first group of sensors; and

receiving output signals from the first group of sensors, the output signals indicating chemical reactions occurring proximate to the first group of sensors of the sensor array.

2. The method of claim 1, wherein the operational characteristic is selected from the group consisting of a bead loading quality of the sensors of the sensor array, a noise spectrum of the sensors of the sensor array, and a threshold voltage value of the sensors of the sensor array.

3. The method of claim 1, wherein the sensors in the sensor array include chemically-sensitive field effect transistors.

4. The method of claim 3, wherein the chemically-sensitive field effect transistors are arranged in rows and columns and the selecting includes selecting sensors disposed in contiguous rows of chemically-sensitive field effect transistors in the sensor array.

5. The method of claim 3, wherein the output signals further indicate an ion concentration due to sequencing reactions occurring proximate to the chemically-sensitive field effect transistors.

6. The method of claim 3, wherein the output signals are analog signals and the method further includes converting the output signals into digital signals and the receiving output signals further includes receiving the converted digital signals.

7. A method for nucleic acid sequencing, comprising:

providing template nucleic acids to at least some of a plurality of locations coupled to sensors of an array;

analyzing output signals of the sensors of the array to identify which locations in the plurality of locations contain the template nucleic acids and which locations in the plurality of locations do not contain the template nucleic acids;

selecting a first group of sensors from the sensors in the array, wherein sensors in the first group of sensors are selected based on the locations containing the template nucleic acids;

introducing known nucleotides within at least some of the plurality of locations to cause a reaction between the template nucleic acids and the known nucleotides;

enabling readout of the sensors in the first group of sensors in the sensor array including the locations containing the template nucleic acids, and bypassing readout of other sensors of the sensor array, wherein the other sensors are in the locations not containing the template nucleic acids; and

measuring the output signals of the first group of sensors to detect sequencing reaction byproducts resulting from incorporation of the introduced known nucleotides into one or more primers hybridized to at least one of the template nucleic acids,

wherein the first group of sensors is selected prior to the reaction between the template nucleic acids and the known nucleotides.

8. The method of claim 7, wherein the sequencing reaction byproducts comprise hydrogen ions.

9. The method of claim 7, wherein the sequencing reaction byproducts resulting from incorporation are of chemically similar composition for each of the known nucleotides.

10. The method of claim 7, further comprising determining at least a portion of sequences of at least a portion of the template nucleic acids based on the introduced known nucleotides and further based on the measured output signals.

11. The method of claim 7, wherein the sensors comprise field-effect transistors having a chemically sensitive portion responsive to the sequencing reaction byproducts and disposed in proximity to the locations such that the at least one of the sequencing reaction byproducts diffuse or contact the sensors to thereby be detected.

12. The method of claim 11, wherein the chemically sensitive portion of the field-effect transistors of the array is responsive to a plurality of different sequencing reaction byproducts.

13. The method of claim 7, wherein the locations are within respective reaction chambers.

14. The method of claim 7, wherein the measured output signals are analog signals and the method further includes converting the measured output signals into digital signals.

15. A method comprising:

determining an operational characteristic of a plurality of sensors located at a portion of a sensor array, the determining occurring before a chemical reaction occurs proximal to each sensor located at the portion of the sensor array;

selecting a first group of sensors from the plurality of sensors located at the portion of the sensor array, wherein the selecting of the first group of sensors is based on determining that each sensor in the first group of sensors has a first operational characteristic;

selecting a second group of sensors from the plurality of sensors located at the portion of the sensor array, wherein the selecting of the second group of sensors is based on determining that each sensor in the second group of sensors has a second operational characteristic, wherein the first operational characteristic and the second operational characteristic are different;

enabling readout of the sensors in the first group of sensors and the sensors in the second group of sensors;

comparing the readout of the sensors in the first group of sensors and the readout of the sensors in the second group of sensors; and

receiving, based at least partially on the comparison, output signals from the first group of sensors or the second group of sensors, the output signals indicating chemical reactions occurring proximate to the sensors located at the portion of the sensor array.

16. The method of claim 15, wherein comparing the readout of the sensors in the first group of sensors and the readout of the sensors in the second group of sensors comprises:

comparing a quality of an output signal from the sensors in the first group of sensors and a quality of an output signal from the sensors in the second group of sensors.

17. The method of claim 15, wherein the operational characteristic is selected from the group consisting of a bead loading quality of the sensors of the sensor array, a noise spectrum of the sensors of the sensor array, and a threshold voltage value of the sensors of the sensor array.

18. The method of claim 15, wherein the sensors in the sensor array include chemically-sensitive field effect transistors.

19. The method of claim 18, wherein the chemically-sensitive field effect transistors are arranged in rows and columns and the selecting a first group and the selecting a second group includes selecting sensors disposed in contiguous rows of chemically-sensitive field effect transistors in the sensor array.

20. The method of claim 15, wherein the output signals are analog signals and the method further includes converting the output signals into digital signals and the receiving output signals further includes receiving the converted digital signals.