Chemically-sensitive sensor array calibration circuitry

• US 10,502,708 B2
• Filed: 05/30/2018
• Issued: 12/10/2019
• 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:
  US15/993,544
• Publication Number:
  US 20190017959A1
• Time in Patent Office: 559 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. An apparatus comprising:

a fluidic system including a fluid delivery system configured to be in controllable flow communication with a flow cell;

a sensor device mounted in the flow cell, the sensor device comprising an array of chemical field effect transistor (chemFET) sensors arranged in rows and columns and sensor device circuitry including;

column output circuitry including a plurality of column output circuits coupled to each chemFET sensor output of corresponding columns of sensors in the array, wherein a column output circuit in the plurality includes a column sample and hold capacitor directly connected to an input node of the column output circuit; and

at least one switch to selectively connect an output of a sensor in the array to the column output circuit; and

an array controller configured to provide power and bias voltages, as well as control and timing signals to the sensor array device and output data acquired from the sensor array device.

2. The apparatus of claim 1, wherein each chemFET sensor in the array of chemFET sensors includes a chemically-sensitive passivation layer on a floating gate structure.

3. The apparatus of claim 2, wherein each chemFET sensor has a corresponding chemical sample well coupled to the floating gate structure via the chemically-sensitive passivation layer.

4. The apparatus of claim 1, wherein a center-to-center spacing between each chemFET sensor is between about 1 micron to about 10 micron.

5. The apparatus of claim 1, wherein the array controller is configured to output a frame of data;

said frame of data comprising a collection of output signals from all chemFET sensors in the array.

6. The apparatus of claim 5, wherein the array controller is configured to output a frame of data at a rate of between 1 to 100 frames per second.

7. The apparatus of claim 1, wherein the flow cell has an inlet port in fluid communication with the fluid delivery system and an outlet port in fluid communication with a waste container.

8. The apparatus of claim 7, wherein the fluid delivery system is configured to controllably deliver fluids from each of a plurality of reagent sources to the inlet port of the flow cell.

9. The apparatus of claim 1, wherein the array controller is configured to output data acquired from the sensor array device to a computer.

10. An apparatus comprising:

a fluidic system including a fluid delivery system configured to be in controllable flow communication with a flow cell;

a sensor device mounted in the flow cell, the sensor array device comprising;

an array of chemical field effect transistor (chemFET) sensors arranged in rows and columns, wherein each chemFET sensor includes a floating gate structure coupled to a corresponding chemical sample well;

sensor array device circuitry including;

column output circuitry including a plurality of column output circuits coupled to each chemFET sensor output of corresponding columns of sensors in the array, wherein a column output circuit in the plurality includes a column sample and hold capacitor directly connected to an input node of the column output circuit; and

at least one switch to selectively connect an output of a sensor in the array to the column output circuit; and

an array controller configured to provide power and bias voltages, as well as control and timing signals to the sensor array device.

11. The apparatus of claim 10, wherein each chemFET sensor has a chemically-sensitive passivation layer on the floating gate structure.

12. The apparatus of claim 11, wherein the chemically-sensitive passivation layer is sensitive to ionic species.

13. The apparatus of claim 12, wherein the chemically-sensitive passivation layer is sensitive to hydrogen ion.

14. The apparatus of claim 12, wherein the chemically-sensitive passivation layer is sensitive to pyrophosphate.

15. The apparatus of claim 10, wherein a center-to-center spacing between each chemFET sensor is between about 1 micron to about 10 micron.

16. The apparatus of claim 10, wherein the array controller is configured to output data acquired from the sensor array device.

17. The apparatus of claim 16, wherein the array controller is configured to output a frame of data;

said frame of data comprising a collection of output signals from all chemFET sensors in the array.

18. The apparatus of claim 17, wherein the array controller is configured to output a frame of data at a rate of between 1 to 100 frames per second.

19. The apparatus of claim 10, wherein the flow cell has an inlet port in fluid communication with the fluid delivery system and an outlet port in fluid communication with a waste container.

20. The apparatus of claim 19, wherein the fluid delivery system is configured to controllably deliver fluids from each of a plurality of reagent sources to the inlet port of the flow cell.