Apparatus for measuring analytes including chemical sensor array

• US 9,958,414 B2
• Filed: 01/21/2014
• Issued: 05/01/2018
• 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 E
• Application Number:
  US14/160,472
• Publication Number:
  US 20140235463A1
• Time in Patent Office: 1,561 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 having an array, comprising:

a plurality of chemical sensors configured to detect a quantity of a substance;

a selection circuit arranged to select a subset of the chemical sensors for a time period during which the subset of chemical sensors will provide an output signal, wherein the time period is shorter than an amount of time required for the output signal from the chemical sensors to settle and reach their final value from detecting the quantity of the substance;

a plurality of output circuits configured to receive the output signals from the subsets of the chemical sensors during the time period;

a sampling circuit configured to take a plurality of samples from each of the output signals during the time period; and

an estimator that receives the plurality of samples and generates an estimated value for each of the sensors during the time period.

2. The system of claim 1 wherein the output changes gradually to reach a final value during the time period as the quantity is detected by the chemical sensor and the estimated value is an estimation of the final value.

3. The system of claim 1, further comprising a framing device that forms a predetermined number of frames from the estimated values within a predetermined time period.

4. The system of claim 3 further comprising a frame condensing device that takes the predetermined number of frames within the predetermined time period and reduces them to a reduced number of frames for the predetermined time period and a storage device for storing the reduced number of frames.

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

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

7. The system of claim 2 wherein the sampling circuit further comprises an analog to digital conversion circuit associated with each of the subsets of the chemical sensors and the plurality of samples further comprises a series of digital values that are taken during the time period for each of the output signals.