Windowed sequencing

• US 10,655,175 B2
• Filed: 10/08/2018
• Issued: 05/19/2020
• 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, Schultz, Jonathan, Papalias, Chris, Johnson, Kim
• Primary Examiner(s): Zhang, Kaijiang
• Application Number:
  US16/153,898
• Publication Number:
  US 20190106745A1
• Time in Patent Office: 589 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 system comprising:

a sensor array including a plurality of sensors; and

an array controller, communicatively coupled to the sensor array, wherein the array controller includes a processor, the processor configured to;

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

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

enable readout of the sensors in the first group,

bypass 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 from the first group of sensors, and

receive output signals at the processor 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 system of claim 1, wherein the operational characteristic of the sensors of the sensor array 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 system of claim 1, wherein the sensors in the sensor array include chemically-sensitive field effect transistors.

4. The system of claim 3, wherein the chemically-sensitive field effect transistors are arranged in rows and columns and the processor is further configured to select the first group of sensors located in contiguous rows of chemically-sensitive field effect transistors in the sensor array.

5. The system 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 system of claim 1, wherein the output signals are analog signals and the array controller further includes an analog-to-digital converter configured to convert the output signals into digital output signals, wherein the processor is further configured to receive the digital output signals.

7. The system of claim 1, wherein the processor is implemented in a field programmable gate array (FPGA).

8. A system for nucleic acid sequencing, comprising:

an array including a plurality of sensors; and

an array controller, communicatively coupled to the array, wherein the array controller includes a processor, the processor configured to;

analyze output signals of the sensors of the array in response to template nucleic acids provided to at least some of a plurality of locations coupled to the sensors of the array, wherein the output signals are analyzed 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,

select 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,

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

measure the output signals of the first group of sensors in response to known nucleotides introduced within at least some of the plurality of locations 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.

9. The system of claim 8, wherein the sequencing reaction byproducts comprise hydrogen ions.

10. The system of claim 8, wherein the sequencing reaction byproducts resulting from incorporation are of a chemically similar similar composition for each of the known nucleotides.

11. The system of claim 8, wherein the processor is further configured to determine 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.

12. The system of claim 8, 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 at least one of the sequencing reaction byproducts diffuse or contact the sensors to thereby be detected.

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

14. The system of claim 8, wherein the locations are within respective reaction chambers.

15. The system of claim 8, wherein the output signals are analog signals and the array controller further includes an analog-to-digital converter configured to convert the output signals into digital output signals.

16. The system of claim 8, wherein the processor is implemented in a field programmable gate array (FPGA).