METHODS FOR OPERATING CHEMICALLY SENSITIVE SENSORS WITH SAMPLE AND HOLD CAPACITORS

• US 20120288853A1
• Filed: 07/20/2012
• Published: 11/15/2012
• 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 8,764,969 B2
• Time in Patent Office: Days
• US Class Current: 435/6.1
• 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. A method of operating an apparatus comprising an array of sensors arranged in rows and columns, the sensors comprising chemically-sensitive field effect transistors (chemFETs), the method comprising:

precharging the chemFETs in a plurality of sensors in the array;

in response to a first timing signal, after said precharging, transferring charge from the chemFETs to sample and hold capacitors in sensors in a plurality of sensors in a row of the array;

enabling a column output circuit coupled to sensors in a column of the array in response to a column select signal; and

outputting signal samples to the column output circuit from the sample and hold capacitors of the sensors in the column in response to respective row select signals.

2. The method of claim 1, including during said precharging, resetting the sample and hold capacitors.

3. The method of claim 1, further comprising applying chemical samples to chemical sample wells coupled to the plurality of sensors, and wherein the signal samples indicate one or more characteristics of the chemical samples.

4. The method of claim 3, further comprising coupling a reference electrode to the chemical sample wells, and applying a bias voltage to the reference electrode.

5. The method of claim 1, including precharging the chemFETs and transferring charge from the chemFETs to the sample and hold capacitors multiple times, prior to outputting the signal samples from the sample and hold capacitors.

6. The method of claim 1, wherein each of the chemFETs includes a floating gate and a passivation layer, 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.

7. The method of claim 1, wherein voltages on the sample and hold capacitors indicating detection of sequencing reactions by the chemFETs.

8. A method of operating an apparatus comprising an array of chemically sensitive sensors, the sensors comprising chemically-sensitive field effect transistors (chemFETs), the chemFET in each of the sensors producing an output that is a function of a threshold voltage of the chemFET, the method comprising:

performing a charge transfer cycle multiple times, the charge transfer cycle including enabling the chemFETs in a plurality of sensors of the array to accumulate charge, and in response to a first timing signal, after said enabling, disabling the chemFETs and transferring accumulated charge from the chemFETs to sample and hold capacitors; and

after performing the charge transfer cycle multiple times, then outputting signal samples from the sample and hold capacitors.

9. The method of claim 8, wherein the array is arranged in rows and columns, and said outputting includes enabling a column output circuit coupled to sensors in the plurality of sensors in a column, and connecting the sample and hold capacitors in the column to the column output circuit.

10. The method of claim 8, further comprising applying chemical samples to chemical sample wells coupled to the array of sensors, and wherein the signal samples indicate one or more characteristics of the chemical samples.

11. The method of claim 10, further comprising coupling a reference electrode to the chemical sample wells, and applying a bias voltage to the reference electrode.

12. The method of claim 8, wherein:

enabling the chemFETs comprises using first switches responsive to the first timing signal to connect first terminals of the chemFETs to a reference voltage line;

disabling the chemFETs comprises using the first switches responsive to the first timing signal to disconnect the first terminals of the chemFETs from the reference voltage line; and

transferring the accumulated charge from the chemFETs comprises using second switches responsive to a second timing signal to connect second terminals of the chemFETs to the sample and hold capacitors.

13. The method of claim 8, wherein each of the chemFETs includes a floating gate and a passivation layer, and the signal samples indicate ion-concentrations in analyte solutions coupled to the floating gates via the passivation layers in the array of sensors.

14. The method of claim 8, wherein each of the chemFETs includes a floating gate and a passivation layer, and the threshold voltages of the chemFETs indicate ion-concentrations in analyte solutions coupled to the floating gates via the passivation layers in the array of sensors.

15. The method of claim 8, wherein the accumulated charge indicates detection of sequencing reactions by the chemFETs.