METHODS AND APPARATUS FOR MEASURING ANALYTES USING LARGE SCALE FET ARRAYS

• US 20110247933A1
• Filed: 02/28/2011
• Published: 10/13/2011
• 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
• Granted Patent: US 8,313,639 B2
• Time in Patent Office: Days
• US Class Current: 204/406
• 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: 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 27/414 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: H01L 21/306 Chemical or electrical treatment, e.g. electrolytic etching to form insulating layers H01L21/31
• CPC Class Codes: H01L 2224/04105 Bonding areas formed on an encapsulation of the semiconductor or solid-state body, e.g. bonding areas on chip-scale packages
• CPC Class Codes: H01L 2224/16 of an individual bump connector
• CPC Class Codes: H01L 2224/76155 Jetting means, e.g. ink jet
• CPC Class Codes: H01L 2224/82102 using jetting, e.g. ink jet
• CPC Class Codes: H01L 24/18 High density interconnect [HDI] connectors; Manufacturing methods related thereto interconnection structure between a plurality of semiconductor chips H01L23/5389
• CPC Class Codes: H01L 24/20 Structure, shape, material or disposition of high density interconnect preforms
• CPC Class Codes: H01L 24/82 by forming build-up interconnects at chip-level, e.g. for high density interconnects [HDI] interconnection structure between a plurality of semiconductor chips H01L23/5389
• CPC Class Codes: H01L 27/088 the components being field-effect transistors with insulated 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 2924/00 Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/01005 Boron [B]
• CPC Class Codes: H01L 2924/01006 : Carbon [C]
• CPC Class Codes: H01L 2924/01011 : Sodium [Na]
• CPC Class Codes: H01L 2924/01012 : Magnesium [Mg]
• CPC Class Codes: H01L 2924/01013 : Aluminum [Al]
• CPC Class Codes: H01L 2924/01015 : Phosphorus [P]
• CPC Class Codes: H01L 2924/01019 : Potassium [K]
• CPC Class Codes: H01L 2924/0102 : Calcium [Ca]
• CPC Class Codes: H01L 2924/01023 : Vanadium [V]
• CPC Class Codes: H01L 2924/01024 : Chromium [Cr]
• CPC Class Codes: H01L 2924/01027 : Cobalt [Co]
• CPC Class Codes: H01L 2924/01029 : Copper [Cu]
• CPC Class Codes: H01L 2924/0103 : Zinc [Zn]
• CPC Class Codes: H01L 2924/01033 : Arsenic [As]
• CPC Class Codes: H01L 2924/01046 : Palladium [Pd]
• CPC Class Codes: H01L 2924/01047 : Silver [Ag]
• CPC Class Codes: H01L 2924/01052 : Tellurium [Te]
• CPC Class Codes: H01L 2924/01056 : Barium [Ba]
• CPC Class Codes: H01L 2924/01059 : Praseodymium [Pr]
• CPC Class Codes: H01L 2924/01073 : Tantalum [Ta]
• CPC Class Codes: H01L 2924/01074 : Tungsten [W]
• CPC Class Codes: H01L 2924/01075 : Rhenium [Re]
• CPC Class Codes: H01L 2924/01082 : Lead [Pb]
• CPC Class Codes: H01L 2924/1306 : Field-effect transistor [FET]
• CPC Class Codes: H01L 2924/13091 : Metal-Oxide-Semiconductor Field-Effect Transistor [MOSFET]
• CPC Class Codes: H01L 2924/14 : Integrated circuits
• CPC Class Codes: H01L 2924/1433 : Application-specific integrated circuit [ASIC]
• CPC Class Codes: H01L 2924/19041 : being a capacitor
• CPC Class Codes: H01L 2924/19042 : being an inductor
• CPC Class Codes: H01L 2924/19043 : being a resistor
• CPC Class Codes: H01L 2924/30105 : Capacitance
• CPC Class Codes: H01L 2924/3011 : Impedance
• CPC Class Codes: H01L 2924/3025 : Electromagnetic shielding

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 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 pixel including;

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

a first switch coupling the second terminal of the chemically-sensitive transistor to a current source; and

a second switch coupling the second terminal of the chemically-sensitive transistor to a second readout signal line common to all chemical detection pixels of the column; and

a plurality of readout circuits, each readout circuit corresponding to a column of chemical detection pixels of the array, each readout circuit including;

a first operational amplifier having a first input and a first output, the first input coupled to the second readout signal line common to all chemical detection pixels of a respective column;

a second operational amplifier having a second input and a second output, the second output coupled to the first readout signal line common to all chemical detection pixels of the respective column; and

a first transistor coupled between the first output and the second input.

2. The chemical detection device of claim 1, wherein the first and second switches of each chemical detection pixel are controlled by a row selection signal common to the two switches,

3. The chemical detection device of claim 1, wherein the first and second switches of each chemical detection pixel consist of a field effect transistor respectively.

4. The chemical detection device of claim 1, wherein a number of chemical detection pixels are configured as reference pixels with their gates coupled to a reference voltage line.

5. The chemical detection device of claim 4, wherein the reference pixels are selected from a perimeter of the array.

6. The chemical detection device of claim 5, wherein the reference pixels are selected from the first and last two columns and two first and two last pixels of the remaining columns.

7. The chemical detection device of claim 1, wherein signal outputs from each chemical detection pixel of the array correspond to a detectable pH range of approximately 7 to 9.

8. The chemical detection device of claim 1, further comprising a row select shift register and at least one column select shift register;

wherein, in combination, the row select shift register and the at least one column select shift register determine a selected pixel of the array for an output of the chemical detection device.

9. The chemical detection device of claim 8, wherein the row select shift register and the at least one column select shift register each include a series of D-type flip-flops.

10. The chemical detection device of claim 1, wherein the array is homogeneous and the chemically-sensitive field effect transistor of each chemical detection pixel is chemically sensitive to a same type of analyte.

11. The chemical detection device of claim 1, wherein at least one pixel of the array has a chemically-sensitive field effect transistor configured to be chemically sensitive to a first type of analyte, at least another pixel of the array has a chemically-sensitive field effect transistor configured to be chemically sensitive to a second analyte different from the first analyte.

12. The chemical detection device of claim 1, wherein each of the first and second operational amplifiers of each readout circuit is configured as a unity gain buffer with a plurality of current mirrors.

13. The chemical detection device of claim 12, wherein each of the first and second operational amplifiers of each readout circuit includes an input for a bias current and is adapted to have transimpedance and bandwidth of the respective amplifier controlled by the bias current.

14. The chemical detection device of claim 13, wherein a higher bias current corresponds to a higher bandwidth for a respective operational amplifier.

15. A chemical detection device, comprising:

a substrate of a first semiconductor type;

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

a chemically-sensitive field effect transistor formed in the substrate, the chemically-sensitive field effect transistor having a body terminal coupled to a body biasing voltage source line common to all pixels;

a first switch consisting of a first field effect transistor formed in the substrate; and

a second switch consisting of a second field effect transistor formed in the substrate; and

a plurality of readout circuits formed in the substrate, each readout circuit corresponding to a column of chemical detection pixels of the array.

16. The chemical detection device of claim 15, wherein each chemical detection pixel further includes a well of a second semiconductor type that is formed in the substrate respectively, and the chemically-sensitive field effect transistor, the first field effect transistor and the second field effect transistor of a respective chemical detection pixel are each formed in a respective well of the respective chemical detection pixel.

17. The chemical detection device of claim 16, wherein the substrate is a p-type substrate, the wells of each chemical detection pixel are each n-wells, and the chemically-sensitive transistor, the first transistor and the second transistor of each chemical detection pixel are each p-channel field effect transistors formed in the respective n-well of the chemical detection pixel.

18. The chemical detection device of claim 16, wherein the substrate is a n-type substrate, the wells of each chemical detection pixel are each p-wells, and the chemically-sensitive transistor, the first transistor and the second transistor of each chemical detection pixel are each n-channel field effect transistors formed in the respective p-well of the chemical detection pixel.

19. A method for calibrating a chemical detection device, comprising:

placing a solution having a known pH level in proximity to a sensor array of the chemical detection device, the sensor array including a plurality of chemical detection pixels each having a chemically-sensitive field effect transistor;

applying a body biasing voltage higher than ground to body terminals of the chemically-sensitive field effect transistors of each chemical detection pixel of the sensor array; and

adjusting a reference electrode voltage applied to the chemical detection device until the array output signals provide pixel voltages at a desired reference level.

20. The method of claim 19, wherein the array is fabricated in a CMOS process that uses tungsten metal.

21. The method of claim 19, wherein the body biasing voltage is a positive power supply voltage to the chemical detection device.

22. The method of claim 19, further comprising

grounding the body terminals of the chemically-sensitive field effect transistors of each chemical detection pixel of the sensor array during a post-fabrication UV irradiation treatment to reduce trapped charge.

23. The method of claim 22, wherein during the post-fabrication UV irradiation, each chemically-sensitive field effect transistor of the sensor array is coupled between a current source and ground to let a current flow through.

24. The method of claim 19, wherein the body biasing voltage is higher than ground during a diagnostic analysis and normal operation.

25. The method of claim 19, wherein a body effect due to non-zero source-to-body voltage is adjusted for by the calibration.