Methods and apparatus for measuring analytes

• US 8,263,336 B2
• Filed: 05/31/2011
• Issued: 09/11/2012
• Est. Priority Date: 05/29/2009
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Bustillo, James M., Milgrew, Mark J., Schultz, Jonathan C., Marran, David, Johnson, Kim L., Rothberg, Jonathan M, Rearick, Todd M
• Primary Examiner(s): CROW, ROBERT THOMAS
• Application Number:
  US13/149,331
• Publication Number:
  US 20110248320A1
• Time in Patent Office: 469 Days
• Field of Search: None
• US Class Current: 435/6.1
• 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: G01N 27/27 Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
• 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: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10T 29/49002 Electrical device making

Abstract

Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Claims

1. A chemical detection device, comprising:

a chemically-sensitive transistor having a floating gate structure;

a dielectric overlying the floating gate structure and having a well extending to a top surface of the floating gate structure, the well having sidewalls;

an adhesion layer on the sidewalls of the well, and on the top surface of the floating gate structure; and

a passivation layer on the adhesion layer to define an opening in the well.

2. The chemical detection device of claim 1, further comprising signal lines for the chemically-sensitive transistor, wherein at least one of the signal lines is formed on a different metal layer than another of the signal lines.

3. The chemical detection device of claim 1, wherein the well extends to a top surface of a conductor of the floating gate structure within an upper metal layer, and further comprising signal lines for the chemically-sensitive transistor within one or more metal layers below the upper metal layer.

4. The chemical detection device of claim 1, wherein the passivation layer is a layer of metal oxide selected from Al₂O₃, Ta₂O₅, WO₃, HfO₃, Iridium Oxide.

5. The chemical detection device of claim 3, wherein at least one of the signal lines for the chemically-sensitive transistor is separated from the upper metal layer by one or more additional metal layers.

6. The chemical detection device of claim 5, wherein at least one of the signal lines for the chemically-sensitive transistor is separated from the upper metal layer by at least two additional metal layers.

7. The chemical detection device of claim 1, wherein the adhesion layer is Al₂O₂, and the passivation layer is Ta₂O₅.

8. The chemical detection device of claim 7, wherein the adhesion layer has better adhesion properties to the sidewalls of the well and the top surface of the floating gate structure than that of the passivation layer, and the passivation layer has higher sensitivity to pH than that of the adhesion layer.

9. The chemical detection device of claim 1, wherein the adhesion layer and passivation layer are conformal layers within the well.