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

• US 8,685,230 B2
• Filed: 07/24/2012
• Issued: 04/01/2014
• 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): Ball, J. Christopher
• Application Number:
  US13/556,634
• Publication Number:
  US 20120293158A1
• Time in Patent Office: 616 Days
• Field of Search: 257/253, 205/789, 205/792, 205/793.5, 422 8201- 8203, 436103-105, 436/150, 436/182, 506/1, 506/9
• US Class Current: 205/793.5
• 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, each sensor in the array including;

a chemically-sensitive field effect transistor (chemFET), and

a cell output circuit having an input connected to the chemFET, and responsive to one of a plurality of row select signals to produce a sensor signal indicating a threshold voltage of the chemFET;

a plurality of column output circuits coupled to the sensors in a column of the array, and responsive to respective column read out signals, wherein the plurality of column output circuits comprise sample and hold capacitors; and

timing circuitry that controls the timing of the row select signals and the column select signals.

2. The apparatus of claim 1, including at least one array output circuit coupled to at least some of the column output circuits in the plurality of column output circuits, which produces an array output.

3. The apparatus of claim 1, including an analog to digital converter coupled to the array output.

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

5. The apparatus of claim 1, wherein the timing circuitry enables sensors in the array row by row in corresponding row enable time intervals, and enables column output drivers column by column in response to column read out signals to produce output signals, the column read out signals for a particular row occurring after the row enable time interval for the particular row, and during the row enable time interval for a next row.

6. The apparatus of claim 1, wherein the row enable timing window has a duration sufficient for the column output circuits to produce output signals for a plurality of sensors in a row.

7. A method of operating an apparatus comprising an array of chemically sensitive sensors arranged in rows and columns, the sensors comprising chemically-sensitive field effect transistors (chemFETs), comprising:

enabling a first row of sensors in the array for a first time interval;

for a second time interval, enabling a second row of sensors in the array and reading signals from the sensors in the first row sequentially; and

after the second time interval, during a third time interval, reading signals from the sensors in the second row in sequence.

8. The method of claim 7, wherein:

said reading sensor signals for the sensors in the first row includes sequentially enabling column output circuits coupled to sensors in corresponding columns in response to column select signals during the second time interval; and

said reading sensor signals for the sensors in the second row includes sequentially enabling the column output circuits coupled to sensors in corresponding columns in response to column select signals during the third time interval.

9. The method of claim 7, including applying a chemical sample to chemical sample wells coupled to the plurality of sensors.

10. The method of claim 7, wherein the chemFET includes a floating gate and a passivation layer, and the sensor signal for a particular sensor indicates an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.