METHODS AND APPARATUS FOR MEASURING ANALYTES

• US 20120013392A1
• Filed: 05/31/2011
• Published: 01/19/2012
• Est. Priority Date: 05/29/2009
• Status: Abandoned Application

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: ROTHBERG, Jonathan M., BUSTILLO, James M., MILGREW, Mark J., SCHULTZ, Jonathan C., MARRAN, David, REARICK, Todd M., JOHNSON, Kim L.
• Application Number:
  US13/149,279
• Publication Number:
  US 20120013392A1
• Time in Patent Office: Days
• US Class Current: 327/509
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 27/27 Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
• CPC Class Codes: G01N 27/414 Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
• 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: Y10T 29/49002 Electrical device making

Abstract

Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Claims

1. A chemical detection device, comprising:

an array of chemical detection pixels formed in columns and rows, each column including a plurality of chemical detection pixels, each chemical detection pixel including;

a chemically-sensitive field effect transistor having a first terminal and a body terminal, the first terminal of the chemically-sensitive transistor coupled to a first readout signal line common to all chemical detection pixels of a respective column and the body terminal coupled to a body biasing voltage source line common to all pixels;

a first row addressing circuit configured to provide a row address of a selected pixel;

a first column addressing circuit configured to provide a column address of the selected pixel; and

a first analog-to-digital converter (ADC) to convert an analog output signal from the selected pixel to a digital output signal.

2. The chemical detection device of claim 1, wherein the first ADC is shared by all pixels of the array.

3. The chemical detection device of claim 1, further comprising:

a second row addressing circuit;

a second column addressing circuit; and

a second ADC;

wherein the array of chemical detection pixels includes a first group of pixels and a second group of pixels;

wherein the first group of pixels is addressed by the first row addressing circuit and the first column addressing circuit, and shares the first ADC; and

wherein the second group of pixels is addressed by the second row addressing circuit and the second column addressing circuit, and shares the second ADC.

4. A chemical detection device, comprising:

an array of chemical detection pixels formed in columns and rows, each column including a plurality of chemical detection pixels, each chemical detection pixel including;

a chemically-sensitive field effect transistor having a first terminal and a body terminal, the first terminal of the chemically-sensitive transistor coupled to a first readout signal line common to all chemical detection pixels of a respective column and the body terminal coupled to a body biasing voltage source line common to all pixels;

a first row addressing circuit configured to provide a row address of a selected pixel;

a first column addressing circuit configured to provide a column addresses of the selected pixel; and

a plurality of analog-to-digital converters (ADCs), each ADC to convert an analog output signal to a digital output signal.

5. The chemical detection device of claim 4, wherein each respective ADC is shared by all pixels of a respective column.

6. The chemical detection device of claim 5, further comprising:

a second row addressing circuit;

a second column addressing circuit; and

wherein the array of chemical detection pixels includes a first group of pixels and a second group of pixels;

wherein the first group of pixels is addressed by the first row addressing circuit and the first column addressing circuit, and each respective column of the first group of pixels shares a respective ADC, and

wherein the second group of pixels is addressed by the second row addressing circuit and the second column addressing circuit, and each respective column of the second group of pixels shares a respective ADC.

7. The chemical detection device of claim 4, wherein each pixel of the array has one respective ADC.

8. The chemical detection device of claim 7, further comprising a plurality of memories, wherein an output for each ADC is stored in a respective memory.

9. The chemical detection device of claim 8, further comprising a plurality of column sense amplifiers, each amplifier coupled to a respective output line for a column of pixels.

10. The chemical detection device of claim 4, wherein each column of pixels are divided into a plurality of subdivisions, and wherein pixels of each subdivision share a corresponding ADC.

11. The chemical detection device of claim 10, further comprising a plurality of memories, wherein an output for each ADC is stored in a respective memory.

12. The chemical detection device of claim 4, further comprising a multiplexer, wherein one digital output signal among the converted digital output signals is selected as an output of the chemical detection device via the multiplexer.

13. A method of fabricating a chemical detection device, comprising:

forming an array of chemical detection pixels in columns and rows, each column including a plurality of chemical detection pixels, each chemical detection pixel including;

a chemically-sensitive field effect transistor having a first terminal and a body terminal, the first terminal of the chemically-sensitive transistor coupled to a first readout signal line common to all chemical detection pixels of a respective column and the body terminal coupled to a body biasing voltage source line common to all pixels;

forming a first row addressing circuit configured to provide a row address of a selected pixel;

forming a first column addressing circuit configured to provide a column addresses of the selected pixel; and

forming a plurality of analog-to-digital converters (ADCs), each ADC to convert an analog output signal to a digital output signal.

14. The method of claim 13, wherein each respective ADC is shared by all pixels of a respective column.

15. The method of claim 14, further comprising:

forming a second row addressing circuit; and

forming a second column addressing circuit;

wherein the array of chemical detection pixels includes a first group of pixels and a second group of pixels;

wherein the first group of pixels is addressed by the first row addressing circuit and the first column addressing circuit, and each respective column of the first group of pixels shares a respective ADC, and

wherein the second group of pixels is addressed by the second row addressing circuit and the second column addressing circuit, and each respective column of the second group of pixels shares a respective ADC.

16. The method of claim 13, wherein each pixel of the array has one respective ADC.

17. The method of claim 16, further comprising forming a plurality of memories, wherein an output for each ADC is stored in a respective memory.

18. The method of claim 17, further comprising forming a plurality of column sense amplifiers, each amplifier coupled to a respective output line for a column of pixels.

19. The method of claim 13, wherein each column of pixels are divided into a plurality of subdivisions, and wherein pixels of each subdivision share a corresponding ADC.

20. The method of claim 19, further comprising forming a plurality of memories, wherein an output for each ADC is stored in a respective memory.

21. The method of claim 13, further comprising forming a multiplexer, wherein one digital output signal among the converted digital output signals is selected as an output of the chemical detection device via the multiplexer.

22. A method of fabricating a chemical detection device, comprising:

forming an array of chemical detection pixels formed in columns and rows, each column including a plurality of chemical detection pixels, each chemical detection pixel including;

forming a chemically-sensitive field effect transistor having a first terminal and a body terminal, the first terminal of the chemically-sensitive transistor coupled to a first readout signal line common to all chemical detection pixels of a respective column and the body terminal coupled to a body biasing voltage source line common to all pixels;

forming a first row addressing circuit configured to provide a row address of a selected pixel;

forming a first column addressing circuit configured to provide a column address of the selected pixel; and

forming a first analog-to-digital converter (ADC) to convert an analog output signal from the selected pixel to a digital output signal.

23. The method of claim 22, wherein the first ADC is shared by all pixels of the array.

24. The method of claim 22, further comprising:

forming a second row addressing circuit;

forming a second column addressing circuit; and

forming a second ADC;

wherein the array of chemical detection pixels includes a first group of pixels and a second group of pixels;

wherein the first group of pixels is addressed by the first row addressing circuit and the first column addressing circuit, and shares the first ADC; and

wherein the second group of pixels is addressed by the second row addressing circuit and the second column addressing circuit, and shares the second ADC.

25. A method of generating an output signal for a chemical detection device, the chemical detection device having an array of chemical detection pixels formed in columns and rows, comprising:

applying a row selection signal to a first row addressing circuit of the chemical detection device to select a row,

wherein the row selection signal is to select a row of chemical detection pixels each at a same position from a respective column, each chemical detection pixel of the selected row is to generate an analog signal at the first readout signal line for the respective column, and

wherein each chemical detection pixel includes;

a chemically-sensitive field effect transistor having a first terminal and a body terminal, the first terminal of the chemically-sensitive transistor coupled to a first readout signal line common to all chemical detection pixels of a respective column and the body terminal coupled to a body biasing voltage source line common to all pixels;

applying a column selection signal to a first column addressing circuit of the chemical detection device to select a column; and

converting the analog signal for the selected pixel at the first readout signal line of the selected column to a digital output signal using a first analog-to-digital converter (ADC).

26. The method of claim 25, wherein the array of chemical detection pixels includes a first group of pixels and a second group of pixels,

wherein the selection of an output signal from the first group is controlled by the first row addressing circuit and the first column addressing circuit, and the selection of an output signal from the second group is controlled by a second row addressing circuit and a second column addressing circuit,

wherein the selected output signals from the first group and the second group are converted to digital signals by an ADC respectively and selected to be the output signal for the chemical detection device by a multiplexer.

27. The method of claim 25, wherein each pixel of the array has one respective ADC.

28. The method of claim 25, wherein each respective ADC is shared by all pixels of a respective column.

29. The method of claim 25, further comprising storing the converted digital signal in a memory.

30. The method of claim 25, wherein each column of pixels is divided into a plurality of subdivisions, the pixels of each subdivision sharing a corresponding ADC.