CHEMICALLY-SENSITIVE SENSOR ARRAY CALIBRATION CIRCUITRY

• US 20120283146A1
• Filed: 07/23/2012
• Published: 11/08/2012
• Est. Priority Date: 12/14/2006
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Rothberg, Jonathan M., Hinz, Wolfgang, Johnson, Kim L., Bustillo, James
• Granted Patent: US 8,575,664 B2
• Time in Patent Office: Days
• US Class Current: 506/38
• CPC Class Codes: C12Q 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2533/101 Primer extension
• CPC Class Codes: C12Q 2565/301 Pyrophosphate (PPi)
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• 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: G01N 33/5438 Electrodes
• CPC Class Codes: H01L 27/088 the components being field-effect transistors with insulated gate
• CPC Class Codes: H01L 29/42324 Gate electrodes for transistors with a floating gate
• CPC Class Codes: H01L 29/78 with field effect produced by an insulated gate H01L29/7725, H01L29/775, H01L29/778 take precedence
• CPC Class Codes: H01L 2924/01006 Carbon [C]
• CPC Class Codes: H01L 2924/01013 Aluminum [Al]
• CPC Class Codes: H01L 2924/01015 Phosphorus [P]
• CPC Class Codes: H01L 2924/01073 Tantalum [Ta]
• CPC Class Codes: H01L 2924/14 Integrated circuits
• CPC Class Codes: H01L 2924/1433 Application-specific integrated circuit [ASIC]
• CPC Class Codes: Y10T 436/22 Hydrogen, per se

Abstract

Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Claims

1. An apparatus, comprising:

an array of sensors arranged in rows and columns, a row including a plurality of sensors, each sensor in the plurality including a chemically-sensitive field effect transistor (chemFET) and having an output, configured to use the chemFET to produce a signal on the output in response to a row select signal; and

a plurality of column output circuits coupled to the outputs of corresponding columns of sensors in the array, and coupled to a circuit to apply a reference voltage to the column output circuits during a calibration operation.

2. The apparatus of claim 1, wherein a column output circuit in the plurality includes a column sample and hold capacitor, and a column select switch between a node coupled to the outputs of the plurality of sensors in a corresponding column and the column sample and hold capacitor.

3. The apparatus of claim 1, wherein the chemFET in each sensor in the plurality is configured to produce an output that is a function of a threshold voltage of the chemFET.

4. The apparatus of claim 1, wherein each sensor in the plurality includes a chemical sample well.

5. The apparatus of claim 4, further comprising a reference electrode coupled to the chemical sample well of each sensor in the plurality.

6. The apparatus of claim 1, wherein the chemFET in each sensor in the plurality includes a floating gate and a passivation layer, and the signal on the output indicates an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.

7. The apparatus of claim 1, including a controller which provides the reference voltage to column output circuits in the plurality of column output circuits, and calibrates the column output circuits during the calibration operation.

8. The apparatus of claim 7, further comprising a dummy chemically-sensitive field effect transistor (chemFET) switchably coupled to a column output circuit in the plurality of column output circuit, and wherein controller acquires data from the dummy chemFET and said chemFET during a read out operation.

9. The apparatus of claim 8, wherein the dummy chemFET includes a floating gate structure connected to a circuit that provides a second reference voltage to the floating gate structure during the read out operation.

10. The apparatus of claim 7, including a plurality of dummy chemFETs having floating gate structures connected together by a conductor, and connected to a circuit that provides a second reference voltage to the conductor during the read out operation.

11. The apparatus of claim 10, wherein dummy chemFETs in the plurality of dummy chemFETs comprise elements of dummy sensors disposed in corresponding columns or rows in the array of sensors.

12. An apparatus, comprising:

an array of chemically sensitive sensors with corresponding chemical sample wells, each sensor in the plurality including a floating gate structure coupled to a corresponding chemical sample well;

circuitry to provide at least one reference voltage;

an output circuit; and

at least one switch to selectively connect an output of a sensor in the array and the reference voltage to the output circuit.

13. The apparatus of claim 12, wherein the array is arranged in rows and columns, a column including a plurality of sensors, the output circuit being selectively connectable via the switch to the outputs of the plurality of sensors in the column.

14. The apparatus of claim 12, including at least one reference cell including a circuit emulating the sensors in the array, wherein the circuitry to provide the at least one reference voltage includes a control circuit that determines the at least one reference voltage using the at least one reference cell.

15. The apparatus of claim 12, wherein the output circuit includes a sample and hold capacitor, and a column select switch between a node coupled to the outputs of the plurality of sensors and the sample and hold capacitor.

16. The apparatus of claim 12, including a reference electrode coupled to said corresponding chemical sample wells.

17. The apparatus of claim 12, wherein the sensors each include a passivation layer on the floating gate structure, and have a threshold voltage that indicates an ion-concentration in an analyte solution in the chemical sample well coupled to the floating gate via the passivation layer.

18. The apparatus of claim 12, including circuitry coupled to the array, the output circuit and the switch, which produces signals that connect a plurality of sensors in the array and the at least one reference voltage to the output circuit in a sequence.