Methods and apparatus for measuring analytes

• US 9,944,981 B2
• Filed: 03/12/2013
• Issued: 04/17/2018
• Est. Priority Date: 10/22/2008
• 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, Davidson, John, van Oijen, Antoine, Leamon, John, Huber, Martin
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US13/797,865
• Publication Number:
  US 20130210128A1
• Time in Patent Office: 1,862 Days
• Field of Search: None
• 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 2565/607 being a sensor, e.g. electrode
• 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 21/82 to produce devices, e.g. integrated circuits, each consisting of a plurality of components

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 of the array of sensors including an electrode structure in communication with an ion-sensitive field effect-transistor (ISFET);

a structure defining an array of reaction chambers, a reaction chamber of the array of reaction chambers having a sidewall surface and having a lower surface overlying the electrode structure of the sensor; and

a buffering inhibitor disposed on at least one of the sidewall surface or the lower surface of the reaction chamber.

2. The apparatus of claim 1, wherein the buffering inhibitor includes a phospholipid.

3. The apparatus of claim 2, wherein the phospholipid includes phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, or phosphatidylserine.

4. The apparatus of claim 1, wherein the buffering inhibitor includes a sulfonic acid surfactant.

5. The apparatus of claim 4, wherein the sulfonic acid surfactant includes poly(ethylene glycol) 4-nonylphenyl 3-sulfopropyl ether (PNSE), poly(styrenesulfonic acid), or a salt thereof.

6. The apparatus of claim 1, wherein the buffering inhibitor includes poly(diallydimethylammonium), tetramethyl ammonium, or a salt thereof.

7. The apparatus of claim 1, wherein the buffering inhibitor is covalently bound to the at least one of the sidewall surface or the lower surface of the reaction chamber.

8. The apparatus of claim 1, wherein the buffering inhibitor is non-covalently bound to the at least one of the sidewall surface or the lower surface of the reaction chamber.

9. The apparatus of claim 1, wherein the ion sensitive field effect transistor is responsive to pH.

10. The apparatus of claim 1, wherein the ISFET communicates with the electrode through a floating gate.

11. The apparatus of claim 1, wherein the ISFET defines a solid-state device.

12. The apparatus of claim 1, further comprising a floating gate to communicate a charge between the electrode structure and the ISFET.