Active chemically-sensitive sensors with correlated double sampling

• US 8,742,469 B2
• Filed: 08/30/2012
• Issued: 06/03/2014
• 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: Milgrew, Mark
• Primary Examiner(s): Le, Thao X
• Assistant Examiner(s): GORDON, MATTHEW E
• Application Number:
  US13/599,913
• Publication Number:
  US 20120329044A1
• Time in Patent Office: 642 Days
• Field of Search: 257/253, 257/E23.08, 438/10
• US Class Current: 257/253
• 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 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. An apparatus, comprising:

an array of sensors, a sensor in the array including;

a chemically-sensitive field effect transistor (chemFET) having a first conduction terminal, a second conduction terminal coupled to a first supply voltage conductor, and a sensor surface;

a first transistor having a first conduction terminal coupled to the first conduction terminal of the chemFET, a second conduction terminal coupled to a second supply voltage conductor, and a gate coupled to a bias voltage conductor; and

a second transistor having a gate coupled to a first control signal conductor, a first conduction terminal coupled to the first conduction terminal of the chemFET, and a second conduction terminal coupled to an amplifier node;

a reset circuit coupled to the amplifier node and having an input coupled to a second control signal conductor, the reset circuit to reset the amplifier node to a reference voltage in response to a signal on the second control signal conductor;

an amplifier having an input connected to the amplifier node and having an output coupled to an output conductor, the amplifier includes;

a third transistor having a gate coupled to the amplifier node, a first conduction terminal coupled to a third supply voltage conductor, and a second conduction terminal; and

a fourth transistor having a gate coupled to a select signal conductor, a first conduction terminal coupled to the second conduction terminal of the third transistor, and a second conduction terminal coupled to the output conductor; and

a controller to cause the amplifier to provide a first output while the amplifier node is reset to the reference voltage, and to cause the amplifier to provide a second output while the chemFET is coupled to the amplifier node.

2. The apparatus of claim 1, wherein the reset circuit includes a third transistor having a gate coupled to the second control signal conductor, a first conduction terminal coupled to the amplifier node, and a second conduction terminal coupled to a supply voltage conductor.

3. The apparatus of claim 1, wherein the output conductor is a column bus, and the second control signal conductor is a row select signal conductor.

4. The apparatus of claim 1, wherein the bias conductor is coupled to a source of a bias voltage having a level setting the first transistor is a sub-threshold mode.

5. The apparatus of claim 1, wherein the bias conductor is coupled to a source of a bias voltage having a level setting the first transistor is a reverse-biased diode mode.

6. The apparatus of claim 1, wherein the first supply voltage conductor is coupled to ground, and the second supply voltage conductor is coupled to a positive supply voltage.

7. The apparatus of claim 1, wherein the chemFET includes a floating gate and a passivation layer, and the sensor surface is a surface of the passivation layer over the floating gate.

8. The apparatus of claim 7, wherein a difference between the first output of the amplifier and the second output of the amplifier indicates an ion-concentration of an analyte solution coupled to the floating gate via the passivation layer.

9. The apparatus of claim 1, including a chemical sample well including the sensor surface of the chemFET, and reference electrode coupled to an analyte solution in fluid flow communication with the chemical sample well.