Methods and apparatus for detecting molecular interactions using FET arrays

• US 8,492,799 B2
• Filed: 05/31/2011
• Issued: 07/23/2013
• 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
• Primary Examiner(s): Le, Thao
• Assistant Examiner(s): GORDON, MATTHEW E
• Application Number:
  US13/149,250
• Publication Number:
  US 20120061733A1
• Time in Patent Office: 784 Days
• Field of Search: 257/253, 257/E23.08, 438/10
• US Class Current: 257/253
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• 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 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• 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 33/6818 Sequencing of polypeptides
• 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 29/788 with floating gate H01L29/78391 takes precedence
• CPC Class Codes: H01L 2924/01006 Carbon [C]

Abstract

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. 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.

Claims

1. A chemical detection device, comprising:

an array of at least 10⁵ sensors formed in a substrate, the sensors further comprising;

a chemically-sensitive transistor having a floating gate structure;

a dielectric layer formed on top of the floating gate structure;

a molecular recognition site on a surface of the dielectric layer, the molecular recognition site including a recognition molecule having a specificity for a target analyte.

2. The chemical detection device of claim 1, further comprising a well having a tapered shape above the dielectric layer.

3. The chemical detection device of claim 2, wherein the well contains a bump formed at the bottom of the well.

7. The chemical detection device of claim 1, wherein the target analyte includes a charged particle.

8. The chemical detection device of claim 7, wherein the charged particle includes a metal ion.

9. The chemical detection device of claim 8, wherein the metal ion includes a heavy metal ion.

10. The chemical detection device of claim 8, wherein the metal ion includes a potassium ion, a calcium ion, or a sodium ion.

11. The chemical detection device of claim 1, wherein the recognition molecule includes a catcher molecule.

12. The chemical detection device of claim 1, wherein the recognition molecule includes an elongated tether.

13. The chemical detection device of claim 12, wherein the elongated tether;

includes polyethylene glycol (PEG) or poly ethyl acrylate (PEA).

14. The chemical detection device of claim 12, wherein the elongated tether includes a conductive molecule.

15. The chemical detection device of claim 14, wherein conductive molecule includes a carbon nanotube.

4. A chemical detection device, comprising:

an array of at least 10⁵ chemical detection pixels formed in columns and rows, each chemical detection pixel including;

a chemically-sensitive transistor having a floating gate structure;

a dielectric layer formed on top of the floating gate structure; and

a molecular recognition site on a surface of the dielectric layer, the molecular recognition site including a recognition molecule having a specificity for a target analyte.

5. The chemical detection device of claim 4, wherein each chemical detection pixel further comprises a well having a tapered shape above the dielectric layer.

6. The chemical detection device of claim 4, wherein each well includes a bump formed at the bottom of the well.

16. The chemical detection device of claim 4, wherein the target analyte includes a charged particle.

17. The chemical detection device of claim 16, wherein the charged particle includes a metal ion.

18. The chemical detection device of claim 17, wherein the metal ion includes a heavy metal ion.

19. The chemical detection device of claim 17, wherein the metal ion includes a potassium ion, a calcium ion, or a sodium ion.

20. The chemical detection device of claim 4, wherein the recognition molecule includes a catcher molecule.

21. The chemical detection device of claim 4, wherein the recognition molecule includes an elongated tether.

22. The chemical detection device of claim 21, wherein the elongated tether includes polyethylene glycol (PEG) or poly ethyl acrylate (PEA).

23. The chemical detection device of claim 21, wherein the elongated tether includes a conductive molecule.

24. The chemical detection device of claim 23, wherein conductive molecule includes a carbon nanotube.