METHODS AND APPARATUS FOR MEASURING ANALYTES

• US 20130210182A1
• Filed: 03/12/2013
• Published: 08/15/2013
• Est. Priority Date: 10/22/2008
• Status: Abandoned Application

• 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
• Application Number:
  US13/797,871
• Publication Number:
  US 20130210182A1
• Time in Patent Office: Days
• US Class Current: 438/49
• 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. A method for manufacturing a sensor device, the method comprising:

depositing a structure over an array of sensors, a sensor of the array of sensors including an electrode structure;

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

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

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

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

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

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

7. The method 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 method 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 method of claim 1, wherein the sensor includes an ion sensitive field effect transistor.

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

11. A method for manufacturing a sensor device, the method comprising:

depositing a structure over an array of sensors, a sensor of the array of sensors including an electrode structure having an upper surface;

defining an array of reaction chambers in the structure, a reaction chamber of the array of reaction chambers having a sidewall surface and having a lower surface defined by the upper surface of the electrode structure; and

applying a buffering inhibitor to the upper surface of the electrode structure.

12. The method of claim 11, wherein the buffering inhibitor includes a phospholipid.

13. The method of claim 12, wherein the phospholipid includes phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, or phosphatidylserine.

14. The method of claim 11, wherein the buffering inhibitor includes a sulfonic acid surfactant.

15. The method of claim 14, wherein the sulfonic acid surfactant includes poly(ethylene glycol) 4-nonylphenyl 3-sulfopropyl ether (PNSE), poly(styrenesulfonic acid), or a salt thereof.

16. The method of claim 11, wherein the buffering inhibitor includes poly(diallydimethylammonium), tetramethyl ammonium, or a salt thereof.

17. The method of claim 11, wherein the buffering inhibitor is covalently bound to the upper surface of the electrode structure.

18. The method of claim 11, wherein the buffering inhibitor is non-covalently bound to the upper surface of the electrode structure.

19. The method of claim 11, wherein the sensor includes an ion sensitive field effect transistor.

20. The method of claim 19, wherein the ion sensitive field effect transistor is responsive to pH.