Chemically sensitive sensors with sample and hold capacitors

• US 8,492,800 B2
• Filed: 07/20/2012
• Issued: 07/23/2013
• 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, Hinz, Wolfgang, Johnson, Kim, Bustillo, James
• Primary Examiner(s): Le, Thao
• Assistant Examiner(s): GORDON, MATTHEW E
• Application Number:
  US13/554,585
• Publication Number:
  US 20120286332A1
• Time in Patent Office: 368 Days
• Field of Search: 257/253, 257/E23.08, 438/10
• US Class Current: 257/253
• 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, a sensor in the array including:

a chemically-sensitive field effect transistor (chemFET);

a sample and hold capacitor;

a first switch connected between a first terminal of the chemFET and a first reference voltage line; and

a second switch directly connected between a second terminal of the chemFET and the sample and hold capacitor.

2. The apparatus of claim 1, wherein the chemFET produces an output that is a function of a threshold voltage of the chemFET.

3. The apparatus of claim 1, wherein the first switch and the second switch are responsive to respective control signals to accumulate an output of the chemFET a plurality of times on the sample and hold capacitor.

4. The apparatus of claim 3, wherein the output of the chemFET is accumulated on the sample and hold capacitor without resetting the capacitor between each of the plurality of times.

5. The apparatus of claim 1, including:

a third switch connected between the sample and hold capacitor and a reference voltage; and

a cell output circuit having an input connected to the sample and capacitor, and having an output.

6. The apparatus of claim 5, wherein the cell output circuit includes an output switch responsive to a select signal, to produce a signal on the output indicating a voltage on the sample and hold capacitor.

7. The apparatus of claim 1, including a reaction chamber coupled to the chemFET, and a reference electrode coupled to the reaction chamber.

8. The apparatus of claim 1, wherein the chemFET includes a floating gate and passivation layer on the floating gate, and a voltage on the sample and hold capacitor indicates an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.

9. The apparatus of claim 1, wherein the sample and hold capacitor holds a voltage indicating detection of a sequencing reaction by the chemFET.

10. 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),

a sample and hold capacitor,

a first switch connected between a first terminal of the chemFET and a first reference voltage line,

a second switch directly connected between a second terminal of the chemFET and the sample and hold capacitor, and

a cell output circuit having an input connected to the sample and hold capacitor and having an output, the cell output circuit responsive to a row select signal to produce a signal on the output indicating a voltage on the sample and hold capacitor; and

a column output driver coupled to the outputs of the plurality of sensors.

11. The apparatus of claim 10, wherein the column output circuit 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 the row and the column sample and hold capacitor.

12. The apparatus of claim 10, wherein the chemFET in each sensor in the plurality produces an output that is a function of a threshold voltage of the chemFET.

13. The apparatus of claim 10, wherein the first switch and the second switch in each sensor in the plurality are responsive to respective control signals to accumulate an output of the chemFET a plurality of times on the sample and hold capacitor.

14. The apparatus of claim 13, wherein the output of the chemFET is accumulated on the sample and hold capacitor without resetting the capacitor between each of the plurality of times.

15. The apparatus of claim 10, wherein the chemFET in each sensor in the plurality includes a third switch connected between the sample and hold capacitor and a reference voltage line.

16. The apparatus of claim 10, wherein the cell output circuit includes an output switch responsive to a select signal, to produce a signal on the output indicating a voltage on the sample and hold capacitor.

17. The apparatus of claim 10, wherein each sensor in the plurality further includes a reaction chamber coupled to the chemFET, and a reference electrode is coupled to the reaction chamber.

18. The apparatus of claim 10, wherein the chemFET in each sensor in the plurality includes a floating gate and passivation layer on the floating gate, and a voltage on the sample and hold capacitor indicates an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.

19. The apparatus of claim 10, wherein the sample and hold capacitor in each sensor in the plurality holds a voltage indicating detection of a sequencing reaction by the chemFET.