Methods and apparatus for measuring analytes using large scale FET arrays

• US 9,134,269 B2
• Filed: 03/11/2013
• Issued: 09/15/2015
• 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): Ball, J. Christopher
• Application Number:
  US13/794,637
• Publication Number:
  US 20130210641A1
• Time in Patent Office: 918 Days
• Field of Search: 257/235, 205/789, 205/792, 205/793.5, 422 8201- 8203, 435/6, 435/285.1, 435/287.1, 435/287.2, 436103-105, 436/150, 436/182, 506/1, 506/9
• US Class Current: 1/1
• 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. An apparatus comprising:

a device structure including an array of sensors, a sensor of the array of sensors including an electrode pad disposed at a surface of the device structure and forming a portion of an ion sensitive field effect transistor; and

a wall structure disposed over the surface of the device structure defining an array of wells substantially corresponding with the array of sensors, wherein the electrode pad of the sensor of the array of sensors underlies a surface of a well proximal to the device structure, the wall structure including at least one layer including a polymeric material.

2. The apparatus of claim 1, wherein the polymeric material includes photoresist.

3. The apparatus of claim 2, wherein the photoresist is a positive photoresist.

4. The apparatus of claim 1, wherein the polymeric material includes polyimide.

5. The apparatus of claim 4, wherein the polyimide is a positive-acting photodefineable polyimide.

6. The apparatus of claim 1, wherein the wall structure has a thickness in a range of 4 μ

m to 12 μ

m.

7. The apparatus of claim 1, wherein the well of the array of wells has an aspect ratio height:

width in a range of 1;

1 to 1.5;

1.

8. The apparatus of claim 1, wherein a pitch between two adjacent wells of the array of wells is 1 micrometer to 10 micrometers.

9. The apparatus of claim 1, wherein the array of wells substantially corresponds with the array of sensors in a one-sensor-per-well configuration.

10. A method of forming an apparatus, the method comprising:

applying a polymeric material layer to define a wall structure over a surface of a device structure including an array of sensors, a sensor of the array of sensors including an electrode pad disposed at the surface of the device structure and forming a portion of an ion sensitive field effect transistor; and

forming an array of wells in the wall structure and through the polymeric material layer, the array of wells substantially corresponding to the array of sensors, the electrode pad of the sensor underlying a surface of a well of the array of wells.

11. The method of claim 10, wherein the polymeric material includes photoresist.

12. The method of claim 11, wherein the photoresist is a positive photoresist.

13. The method of claim 10, wherein the polymeric material includes polyimide.

14. The method of claim 13, wherein the polyimide is a positive-acting photodefineable polyimide.

15. The method of claim 10, wherein the wall structure has a thickness in a range of 4 μ

m to 12 μ

m.

16. The method of claim 10, wherein the well of the array of wells has an aspect ratio height:

width in a range of 1;

1 to 1.5;

1.

17. The method of claim 10, wherein forming the array of wells includes exposing the polymeric material layer to ultraviolet radiation.

18. The method of claim 10, wherein forming the array of wells includes performing contact lithography.

19. The method of claim 10, wherein forming the array of wells includes exposing the polymeric material layer to an oxygen plasma reactive ion etch process.

20. A method of detecting nucleotide incorporation, the method comprising:

flowing a nucleotide solution over an apparatus, the nucleotide solution including at least one type of nucleotide, the apparatus comprising;

a device structure including an array of sensors, a sensor of the array of sensors including an electrode pad disposed at a surface of the device structure and forming a portion of an ion sensitive field effect transistor;

a wall structure disposed over the surface of the device structure and defining an array of wells substantially corresponding with the array of sensors, wherein a well of the array of wells exposes the electrode pad of the sensor of the array of sensors, the wall structure including at least one layer including a polymeric material; and

a template polynucleotide disposed within the well;

measuring a response of the sensor to the flowing of the nucleotide solution.

21. The method of claim 20, wherein the polymeric material includes polyimide.