Methods and apparatus for measuring analytes

• US 9,618,475 B2
• Filed: 09/15/2010
• Issued: 04/11/2017
• Est. Priority Date: 09/15/2010
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Rothberg, Jonathan, Rearick, Todd
• Primary Examiner(s): Gordon, Matthew
• Application Number:
  US13/823,494
• Publication Number:
  US 20140235452A1
• Time in Patent Office: 2,400 Days
• Field of Search: 257253, 257E2308, 438 10, 506 2
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• 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

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 system for chemical analysis comprising:

an array of pixels having a plurality of rows and a plurality of columns, each of the pixels having a reaction area and a chemically sensitive sensor that provides an analog output indicative of a reaction occurring proximate to the reaction area for the pixel;

a selection circuit arranged to select at least one of the rows;

a plurality of column circuits, each column circuit arranged to receive the analog output from a selected row during a first sampling period;

a multiplexer to receive a plurality of analog outputs from the array of pixels via the plurality of column circuits;

an analog to digital conversion circuit to

receive the plurality of analog outputs from the multiplexer,

sample the analog outputs from the multiplexer at a second rate that is greater than the first rate, and

generate a series of samples for each of the analog outputs at the second rate for a second sampling period that corresponds to the first sampling period; and

an estimation device to receive the series of samples and determine an estimated pixel value from the series of samples during the first sampling period, wherein

the analog output changes gradually to reach a final pixel value during the first sampling period as reactions within the reaction area are sensed by the chemically sensitive sensor and the estimated pixel value is an estimation of the final pixel value.

2. The system of claim 1, further comprising:

a framing device that forms a frame from the estimated pixel values from at least a portion of the array of pixels at a predetermined time period.

3. The system of claim 2 further comprising:

a condensing device that takes the predetermined number of frames within a predetermined time period and reduces them to a reduced number of frames for the predetermined time period.

4. The system of claim 3 wherein the reduced number of frames is created through averaging.

5. The system of claim 3 further comprising:

a storage device for storing the reduced number of frames.

6. The system of claim 1 wherein the chemically sensitive sensors are ion sensitive sensors.

7. The system of claim 1 wherein the first sampling period is a time period that is too short for the output signal from the chemical sensors to reach their final value.