Methods and apparatus for high speed operation of a chemically-sensitive sensor array

• US 8,592,154 B2
• Filed: 09/07/2012
• Issued: 11/26/2013
• Est. Priority Date: 05/29/2009
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Rearick, Todd
• Primary Examiner(s): CROW, ROBERT THOMAS
• Application Number:
  US13/607,433
• Publication Number:
  US 20130004949A1
• Time in Patent Office: 445 Days
• Field of Search: 435/6, 435/6.1, 435/283.1, 435/287.1, 435/287.2, 257/253
• US Class Current: 435/6.1
• 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: G01N 27/27 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 Class Codes: G01N 27/414 Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 27/4148 Integrated circuits therefor, e.g. fabricated by CMOS processing CMOS processing per se H01L21/82
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10T 29/49002 Electrical device making

Abstract

Methods and apparatus relating to FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Claims

1. A method for operating a plurality of chemically-sensitive sensors, the method comprising:

placing the plurality of sensors in a reference condition;

acquiring first reference data from the plurality of sensors at a first data rate that is equal to or lower than a reciprocal of a settling time of readout circuitry coupled to the sensors;

acquiring second reference data from the plurality of sensors at a second data rate that is faster than the first data rate;

determining a correction factor based on the first reference data and the second reference data;

exposing the plurality of sensors to an analyte;

acquiring sensor data from the plurality of sensors at the second data rate; and

applying the correction factor to the sensor data to produce data representative of a property of the analyte.

2. The method of claim 1, wherein the sensor data indicates an ion-concentration in the analyte.

3. The method of claim 1, wherein the sensor data indicates sequencing reactions detected by the plurality of sensors.

4. A method for operating an array of sensors, each sensor in the array including a chemically-sensitive field effect transistor, the method comprising:

placing sensors in the array in a reference condition;

acquiring reference data from the array of sensors at a first data rate and at a second data rate faster than the first data rate;

exposing the plurality of sensors to an analyte;

acquiring sensor data from the array of sensors at a sensing rate faster than the first data rate; and

applying a correction factor to the sensor data based on said acquired reference data to produce data representative of an analyte property.

5. The method of claim 4, wherein the reference data is acquired while the array is in the reference condition, and the sensor data is acquired while the sensors in the array are exposed to an analyte.

6. The method of claim 4, including determining the correction factor based on the acquired reference data.

7. The method of claim 4, including using the chemically-sensitive field effect transistor in a given sensor to produce an output as a function of a threshold of the chemically-sensitive field effect transistor.

8. The method of claim 4, wherein the chemically-sensitive field effect transistor in a given sensor in the plurality includes a floating gate and a passivation layer, and including using the chemically-sensitive field effect transistor in the given sensor in the plurality to produce an output that indicates an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.