Methods and apparatus for measuring analytes using large scale FET arrays

• US 8,530,941 B2
• Filed: 02/08/2011
• Issued: 09/10/2013
• 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): Le, Thao
• Assistant Examiner(s): GORDON, MATTHEW E
• Application Number:
  US13/022,678
• Publication Number:
  US 20120037961A1
• Time in Patent Office: 945 Days
• Field of Search: 257/253, 257/E23.08, 438/10
• US Class Current: 257/253
• 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 fabricating a chemFET sensor, the method comprising:

forming a source and a drain of a first semiconductor type in a substrate of a second semiconductor type;

depositing a gate oxide layer on the substrate between the source and the drain;

forming a floating gate on the gate oxide, the floating gate comprising conductors formed in a plurality of conductor layers and electrically coupled to one another wherein forming the floating gate includes;

depositing a first conductor overlying the gate oxide layer;

depositing a dielectric on the first conductor; and

etching the first conductor and the dielectric together;

forming access lines comprising conductors within at least two of the conductor layers and coupled to the source and the drain

forming a passivation layer coupled to the etched first conductor.

2. The method of claim 1, where forming the floating gate further comprises removing at least a portion of the etched dielectric on the etched first conductor before forming the passivation layer.

3. The method of claim 1, further comprising depositing a patterned photoresist layer on the dielectric before etching the conductor and dielectric together.

4. The method of claim 1, where the first semiconductor type is a p-type semiconductor and the second semiconductor type is an n-type semiconductor.

5. The method of claim 1, further comprising forming an array of sensors having at least 10⁵ chemFET sensors, the array including said sensor.

6. The method of claim 5, where a threshold voltage for a plurality of the chemFET sensors of the array is substantially similar.

7. The method of claim 1, further comprising forming a control circuitry on the substrate to measure an output of the sensor .

8. The method of claim 1, where the control circuitry includes at least one analog to digital converter (“

ADC”

) for measuring an output associated with at least one of the chemFET sensors of the array.

9. The method of claim 1, further comprising depositing a second conductor on the gate oxide layer prior to depositing the first conductor, and wherein depositing the first conductor comprises depositing the first conductor overlying and electrically coupled to the second conductor.

10. The method of claim 1, further comprising:

removing the etched dielectric; and

forming the passivation layer on the etched first conductor.

11. The method of claim 1, wherein forming the passivation layer comprises forming the passivation layer on the etched dielectric layer.

12. The method of claim 1, wherein etching the first conductor and the dielectric layer comprises performing a plasma etching process.

13. A method for fabricating a chemFET sensor, the method comprising:

forming a source and a drain in a semiconductor substrate;

depositing a gate oxide layer on the substrate between the source and the drain;

forming a floating gate on the gate oxide layer, the floating gate comprising conductors formed in a plurality of conductor layers and electrically coupled to one another wherein forming the floating gate includes;

depositing a first conductor overlying the gate oxide layer;

depositing a dielectric overlying the first conductor;

etching the first conductor and the dielectric together;

removing the etched dielectric; and

forming access lines comprising conductors within at least two of the conductor layers and coupled to the source and the drain; and

forming a passivation layer on the etched first conductor.

14. The method of claim 13, wherein the first conductor is an uppermost conductor in the conductors of the floating gate.

15. The method of claim 13, further comprising forming circuitry to measure a threshold voltage of the sensor based on an ion-concentration of an analyte solution coupled to the floating gate via the passivation layer.

16. A method for fabricating a chemFET sensor, the method comprising:

forming a source and a drain of a first semiconductor type in a substrate of a second semiconductor type;

depositing a gate oxide layer on the substrate between the source and the drain;

forming a floating gate on the gate oxide, the floating gate comprising conductors formed in a plurality of conductor layers and electrically coupled to one another wherein forming the floating gate includes;

forming a lower conductor on the gate oxide; and

forming an upper conductor electrically coupled to the lower conductor, wherein

forming the upper conductor comprises forming a dielectric on the upper

conductor and etching the upper conductor and the dielectric together;

forming access lines comprising conductors within at least two of the conductor layers and coupled to the source and the drain; and

forming a passivation layer coupled to the etched upper conductor.

17. The method of claim 16, wherein the access lines are formed within one or more conductor layers interposed between conductor layers containing the lower conductor and the upper conductor.

18. The method of claim 16, further comprising forming circuitry coupled to the access lines to measure a voltage on a first access line of the access lines of the sensor to detect charge coupled to the floating gate.

19. The method of claim 18, wherein the sensed charge indicates an ion-concentration of an analyte solution coupled to the floating gate of the sensor via the passivation layer.

20. The method of claim 18, wherein the voltage on the first access line is responsive to hydrogen ions liberated through incorporation of a nucleotide into one or more primers that are hybridized to at least one template nucleic acid.

21. The method of claim 18, wherein forming the circuitry comprises:

forming bias circuitry to apply a read voltage to a second access line of the access lines and establish a voltage difference between the first access line and the second access line;

forming a current source to provide a bias current through the sensor, thereby establishing a voltage level on the first access line based on the charge coupled to the floating gate; and

forming readout circuitry to read the sensor based on the voltage level on the first access line.