Methods for calibrating an array of chemically-sensitive sensors

• US 9,989,489 B2
• Filed: 02/07/2017
• Issued: 06/05/2018
• 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): GORDON, MATTHEW E
• Application Number:
  US15/427,047
• Publication Number:
  US 20170241943A1
• Time in Patent Office: 483 Days
• Field of Search: 257253, 257E2308, 438 10
• 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 for operating 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) having an output, each sensor being 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 a column of sensors in the array, the method comprising:

providing a reference voltage to the plurality of column output circuits during a calibration operation; and

using outputs of the plurality of column output circuits in response to the provided reference voltage to compensate for variances among the plurality of column output circuits,

wherein a column output circuit in the plurality of column output circuits includes a column sample and hold capacitor, and using the column sample and hold capacitor to sample the signal from each sensor in the column of sensors in sequence, wherein each sensor in the plurality of sensors includes a chemical sample well,

wherein the chemFET in each sensor in the plurality of sensors 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.

2. The method of claim 1, including using the chemFET in each sensor in the plurality of sensors to produce an output that is a function of a threshold voltage of the chemFET.

3. The method of claim 1, including coupling a dummy chemically-sensitive field effect transistor (chemFET) to a column output circuit in the plurality of column output circuits, and acquiring data from the dummy chemFET and said chemFET during a read out operation.

4. The method of claim 3, 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 a read out operation.

5. The method of claim 1, 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.

6. The method of claim 5, 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.