METHODS AND APPARATUS FOR HIGH SPEED OPERATION OF A CHEMICALLY-SENSITIVE SENSOR ARRAY

• US 20130004949A1
• Filed: 09/07/2012
• Published: 01/03/2013
• 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
• Granted Patent: US 8,592,154 B2
• Time in Patent Office: Days
• 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. An apparatus, comprising:

a plurality of sensors, each sensor in the plurality including a chemically-sensitive field effect transistor (chemFET), the array of sensors coupled to readout circuitry having a settling time; and

a controller coupled to the plurality of sensors to acquire data from the sensors at an overspeed data rate, relative to the settling time.

2. The apparatus of claim 1, wherein the controller includes logic to apply a correction factor to the acquired data to provide data representative of an analyte property.

3. The apparatus of claim 2, wherein the controller includes logic to acquire reference data from the plurality of sensors at a first data rate and at a second data rate faster than the first data rate, and to determine the correction factor based on the acquired reference data.

4. The apparatus of claim 3, wherein the first data rate is slower than a reciprocal of the settling time.

5. The apparatus of claim 4, wherein the second data rate is faster than a reciprocal of the settling time.

6. The apparatus of claim 1, wherein the chemFET in each sensor in the plurality produces an output that is a function of a threshold of the chemFET.

7. The apparatus of claim 1, wherein each sensor in the plurality includes a chemical sample well and a reference electrode coupled to the chemical sample well.

8. The apparatus of claim 1, wherein the chemFET in a given sensor in the plurality includes a floating gate and a passivation layer, and the given sensor provides data indicating an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.

9. 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; and

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

10. The method of claim 9, further comprising:

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.

11. The method of claim 10, wherein the sensor data indicating an ion-concentration in the analyte.

12. The method of claim 10, wherein the sensor data indicates sequencing reactions detected by the plurality of sensors.

13. The method of claim 9, wherein the second data rate is faster than a reciprocal of the settling time.

14. The method of claim 9, wherein:

each chemically-sensitive sensor in the plurality of sensors includes a chemically-sensitive field effect transistor (chemFET); and

acquiring the first reference data and the second reference data includes using the chemFET in each sensor to produce an output that is a function of a threshold voltage of the chemFET.

15. The method of claim 9, wherein each sensor in the plurality includes a chemical sample well, and placing the plurality of sensors in the reference condition includes coupling a reference electrode to the chemical sample well.

16. A method for operating an array of sensors, each sensor in the array including a chemically-sensitive field effect transistor (chemFET), 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;

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.

17. The method of claim 16, wherein the reference data is acquired while the array is in the reference condition, the sensor data is acquired while the sensors in the array are exposed to an analyte, and the data produced is representative of a property of the analyte.

18. The method of claim 16, wherein the array of sensors are coupled to readout circuitry having a settling time, and the sensing rate is an overspeed data rate relative to the settling time.

19. The method of claim 16, including determining the correction factor based on the acquired reference data.

20. The method of claim 16, including using the chemFET in a given sensor to produce an output as a function of a threshold of the chemFET.

21. The method of claim 16, wherein each sensor in the plurality includes a chemical sample well, and acquiring sensor data includes coupling a reference electrode to the chemical sample well.

22. The method of claim 16, wherein the chemFET in a given sensor in the plurality includes a floating gate and a passivation layer, and including using the chemFET 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.