Methods and apparatus for measuring analytes using large scale FET arrays

• US 8,313,625 B2
• Filed: 02/28/2011
• Issued: 11/20/2012
• 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, Johnson, Kim L., Bustillo, James
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US13/036,673
• Publication Number:
  US 20110241081A1
• Time in Patent Office: 631 Days
• Field of Search: 204/406, 204/407, 204/416, 257/213, 257/252, 257/253
• 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 circuit, comprising:

a chemically-sensitive transistor having a first terminal and a second terminal, said first terminal coupled to a first readout signal line;

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

a second switch coupling the second terminal of the chemically-sensitive transistor to a second readout signal line, said second switch consisting of a second transistor, wherein the first and second switches are controlled by a selection signal common to the two switches.

2. The chemical detection circuit of claim 1, wherein the chemically-sensitive transistor is a chemically-sensitive field effect transistor.

3. The chemical detection circuit of claim 2, wherein the chemically-sensitive field effect transistor has a body terminal coupled to a body bias voltage line.

4. The chemical detection circuit of claim 1, wherein input and output signals of the chemical detection circuit consist of the current source, common selection signal, and first and second readout signal lines.

5. The chemical detection circuit of claim 1, wherein signal outputs from the first and second readout signal lines correspond to a detectable pH range of approximately 7 to 9.

6. The chemical detection circuit of claim 1, wherein the chemically-sensitive transistor is fabricated using a CMOS process that uses tungsten metal.

7. The chemical detection circuit of claim 1, wherein the chemically-sensitive transistor has a threshold voltage over a range of approximately 0 to 2 Volts, and a corresponding chemical detection pixel output voltage is over a range of approximately 0.5 to 2.5 Volts.

8. A chemical detection circuit, comprising:

an array of chemical detection pixels formed in columns and rows, each chemical detection pixel including

a chemically-sensitive transistor having a first terminal and a second terminal, said first terminal coupled to a first readout signal line;

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

a second switch coupling the second terminal of the chemically-sensitive transistor to a second readout signal line, said second switch consisting of a second transistor, wherein the first and second switches are controlled by a selection signal common to the two switches.

9. The chemical detection circuit of claim 8, wherein each chemically-sensitive transistor is a chemically-sensitive field effect transistor.

10. The chemical detection circuit of claim 9, wherein each chemically-sensitive field effect transistor have a body terminal coupled to a common body bias voltage line.

11. The chemical detection circuit of claim 8, wherein signal outputs from each chemical detection pixel of the array correspond to a detectable pH range of approximately 7 to 9.

12. The chemical detection circuit of claim 8, wherein the array is fabricated using a CMOS process that uses tungsten metal.

13. The chemical detection circuit of claim 8, wherein the first readout signal line of each chemical detection pixel is a first signal line of a readout circuit and the second readout signal line of each chemical detection pixel is a second signal line of the readout circuit.

14. The chemical detection circuit of claim 13, wherein the first and second signal lines of the readout circuit are common to all chemical detection pixels of one column.

15. The chemical detection circuit of claim 8, wherein the array is homogeneous and the chemically-sensitive transistor of each chemically-sensitive transistor pixel is chemically sensitive to a same type of analyte.

16. The chemical detection circuit of claim 8, wherein at least one chemical detection pixel of the array has a chemically-sensitive transistor configured to be chemically sensitive to a first type of analyte, at least another chemical detection pixel of the array has a chemically-sensitive transistor configured to be chemically sensitive to a second analyte different from the first analyte.

17. The chemical detection circuit of claim 8, wherein the current source is common to all chemical detection pixels of one column.

18. The chemical detection circuit of claim 8, wherein the selection signals are common to all pixels in a respective row.

19. The chemical detection circuit of claim 8, wherein each chemically-sensitive transistor of the array has a threshold voltage over a range of approximately 0 to 2 Volts, and a corresponding chemical detection pixel output voltage is over a range of approximately 0.5 to 2.5 Volts.

20. A chemical detection device, comprising:

a substrate of a first semiconductor type; and

a chemical detection pixel including

a chemically-sensitive field effect transistor formed in the substrate;

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;

wherein a channel of the chemically-sensitive field effect transistor, a channel of the first field effect transistor and a channel of the second field effect transistor are each a same semiconductor type.

21. The chemical detection device of claim 20, wherein the chemical detection pixel further includes a well of a second semiconductor type that is formed in the substrate, and the chemically-sensitive transistor, the first field effect transistor and the second field effect transistor are each formed in the well.

22. The chemical detection device of claim 21, wherein the substrate is a p-type substrate, the well is a n-well, and the chemically-sensitive transistor, the first field effect transistor and the second field effect transistor are each p-channel field effect transistors formed in the n-well.

23. The chemical detection device of claim 21, wherein the substrate is a n-type substrate, the well is a p-well, and the chemically-sensitive transistor, the first field effect transistor and the second field effect transistor are each n-channel field effect transistors formed in the p-well.

24. The chemical detection device of claim 21, wherein the first field effect transistor and the second field effect transistor have a shared drain.

25. The chemical detection device of claim 21, wherein the chemical detection pixel further includes a highly doped region of the second semiconductor type to provide a body connection to the well, and wherein the body connection is coupled to a metal conductor around a perimeter of the chemical detection pixel.

26. The chemical detection device of claim 20, wherein the chemically-sensitive field effect transistor has a body terminal coupled to a body bias voltage line.

27. The chemical detection device of claim 20, further comprising an analyte-sensitive passivation layer.

28. The chemical detection device of claim 27, wherein the analyte-sensitive passivation layer includes low-temperature plasma-assisted chemical vapor deposition (PEVCD) of silicon nitride or silicon oxynitride.

29. The chemical detection device of claim 20, further comprising a sacrificial field effect transistor formed in the substrate;

wherein the chemically-sensitive field effect transistor has a floating gate coupled to a gate of the sacrificial field effect transistor.

30. The chemical detection device of claim 20, further comprising a metal jumper connected to a floating gate of the chemically-sensitive field effect transistor;

wherein the floating gate is electrically isolated during fabrication of the chemically-sensitive field effect transistor prior to connection with the metal jumper.

31. A chemical detection device, comprising:

a substrate of a first semiconductor type; and

an array of chemical detection pixels, each chemical detection pixel including

a chemically-sensitive field effect transistor formed in the substrate;

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;

wherein a channel of the chemically-sensitive field effect transistor, a channel of the first field effect transistor and a channel of the second field effect transistor are each a same semiconductor type.

32. The chemical detection device of claim 31, 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 transistor, the first transistor and the second transistor of each chemical detection pixel are each formed in the respective well of the chemical detection pixel.

33. The chemical detection device of claim 32, wherein the substrate is a p-type substrate, the wells of each chemical detection pixel are each n-wells, and the chemically-sensitive field effect transistor, the first field effect transistor and the second field effect transistor of each chemical detection pixel are each p-channel field effect transistors formed in the respective n-well of the chemical detection pixel.

34. The chemical detection device of claim 32, wherein the substrate is an-type substrate, the wells of each chemical detection pixel are each p-wells, and the chemically-sensitive field effect transistor, the first field effect transistor and the second field effect transistor of each chemical detection pixel are each n-channel field effect transistors formed in the respective p-well of the chemical detection pixel.

35. The chemical detection device of claim 32, wherein the first field effect transistor and the second field effect transistor of each chemical detection pixel have a shared drain.

36. The chemical detection device of claim 31, wherein each chemical detection pixel further includes a highly doped region of the second semiconductor type to provide a body connection to the respective well of the chemical detection pixel, and wherein the body connection is coupled to a metal conductor around a perimeter of the chemical detection pixel.

37. The chemical detection device of claim 35, wherein the metal conductors of each chemical detection pixel are coupled to a common body bias voltage line.

38. The chemical detection device of claim 31, further comprising an analyte-sensitive passivation layer.

39. The chemical detection device of claim 38, wherein the analyte-sensitive passivation layer includes low-temperature plasma-assisted chemical vapor deposition (PEVCD) of silicon nitride or silicon oxynitride.

40. The chemical detection device of claim 31, wherein each chemical detection pixel further includes a sacrificial field effect transistor formed in the substrate;

and

wherein the chemically-sensitive field effect transistor has a floating gate coupled to a gate of the sacrificial field effect transistor.

41. The chemical detection device of claim 31, wherein each chemical detection pixel further includes a metal jumper connected to a floating gate of the chemically-sensitive field effect transistor;

and

wherein the floating gate is electrically isolated during fabrication of the chemically-sensitive field effect transistor prior to connection with the metal jumper.