Methods and apparatus for detecting molecular interactions using FET arrays

• US 10,415,079 B2
• Filed: 06/24/2016
• Issued: 09/17/2019
• 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): Crow, Robert T.
• Application Number:
  US15/192,225
• Publication Number:
  US 20170029873A1
• Time in Patent Office: 1,180 Days
• Field of Search: None
• 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 method for expression profiling comprising:

providing a sensor array device including an array of sensor elements, wherein each sensor element includes a chemical detection circuit comprising;

a chemically-sensitive field effect transistor having a body terminal, a first terminal and a second terminal, the body terminal coupled to a body biasing voltage source line and the first terminal coupled to a first readout signal line;

a first switch coupling the second terminal of the chemically-sensitive field effect transistor to a current source; and

a second switch coupling the second terminal of the chemically-sensitive field effect transistor to a second readout signal line;

introducing a first nucleic acid analyte to the sensor array device, wherein the first nucleic acid analyte is obtained from a first sample in a first state;

determining a first expression level of the first nucleic acid analyte;

introducing a second nucleic acid analyte to the sensor array device, wherein the second nucleic acid analyte is obtained from a second sample in a second state;

determining a second expression level of the second nucleic acid analyte; and

comparing the first expression level and the second expression level.

2. The method of claim 1, wherein one of either the first sample or the second sample is from an untreated tissue, and the other of the first or the second sample is from a tissue treated with a drug.

3. The method of claim 1, wherein determining the first expression level of the first nucleic acid analyte and the second expression level of the second nucleic acid analyte includes identifying a concentration of the first and the second nucleic acid analyte.

4. The method of claim 2, further comprising determining an effective therapeutic regimen based on a comparison of an expression level from an untreated tissue to an expression level from a tissue treated with a drug.

5. The method of claim 1, further comprising amplifying the first and second nucleic acid analyte before introducing the first and second nucleic acid analyte to the sensor array device.

6. The method of claim 1, wherein the determining the first expression level and the determining the second expression level includes sequencing the first and the second nucleic acid analyte.