Method and Apparatus for Identifying Defects in a Chemical Sensor Array

• US 20130143221A1
• Filed: 11/30/2012
• Published: 06/06/2013
• Est. Priority Date: 12/01/2011
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Beauchemin, Mark
• Granted Patent: US 9,970,984 B2
• Time in Patent Office: Days
• US Class Current: 435/6.12
• 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 27/416 Systems G01N27/27 takes precedence
• CPC Class Codes: G01R 31/2621 for testing field effect transistors, i.e. FET's
• CPC Class Codes: G01R 31/2851 Testing of integrated circuits [IC] G01R31/317 takes precedence; testing individual devices G01R31/26; testing printed circuits G01R31/2801

Abstract

In one implementation, a method for operating an apparatus is described. The method includes applying a bias voltage to place a transistor of a reference sensor in a known state. The reference sensor is in an array of sensors that further includes a chemical sensor coupled to a reaction region for receiving at least one reactant. The method further includes acquiring an output signal from the reference sensor in response to the applied bias voltage. The method further includes determining a defect associated with the array if the output signal does not correspond to the known state.

Claims

1. An apparatus, comprising:

an array of sensors including a chemical sensor and a reference sensor, the chemical sensor coupled to a reaction region for receiving at least one reactant, and the reference sensor including a transistor having a control terminal coupled to a reference node; and

a controller to;

apply a bias voltage to the reference node to place the transistor in a known state;

acquire an output signal from the reference sensor in response to the applied bias voltage; and

determine a defect associated with the array if the output signal does not correspond to the known state.

2. The apparatus of claim 1, wherein the chemical sensor is a chemically-sensitive transistor.

3. The apparatus of claim 1, wherein the bias voltage is sufficient to place the transistor in one of an on state or an off state.

4. The apparatus of claim 1, wherein the chemical sensor generates a sensor signal in response to a chemical reaction occurring within the reaction region.

5. The apparatus of claim 1, wherein the chemical reaction is a sequencing reaction.

6. The apparatus of claim 1, wherein the chemical sensor and the reference sensor share an access circuit coupled to the array, and the determination comprises determining that the shared access circuit is defective if the output signal does not correspond to the known state.

7. An apparatus, comprising:

an array of sensors including a plurality of chemical sensors and a plurality of reference sensors, each chemical sensor coupled to a corresponding reaction region for receiving at least one reactant, and each reference sensor comprising a field effect transistor having a gate coupled to a corresponding reference line;

an access circuit for accessing the chemical sensors and the reference sensors; and

a controller to;

apply bias voltages to the reference lines to select corresponding reference sensors;

acquire output signals from the selected reference sensors; and

identify one or more defects in the access circuit based on differences between the acquired output signals and expected output signals.

8. The apparatus of claim 7, wherein:

the applied bias voltages include first bias voltages to place the field effect transistors of the selected reference sensors in a first known state, and include second bias voltages to place the field effect transistors of the selected reference sensors in a second known state;

the acquired output signals include first output signals from the selected reference sensors in response to applying the first bias voltages, and second output signals from the selected reference sensors in response to applying the second bias voltages; and

the one or more defects are identified based on differences between the acquired first output signals and expected first output signals, and based on differences between the acquired second output signals and expected second output signals.

9. The apparatus of claim 7, wherein the array of sensors are arranged in a plurality of rows and a plurality of columns, a given column in the plurality of columns including at least one chemical sensor and at least one reference sensor.

10. The apparatus of claim 7, wherein the plurality of reference sensors includes a first set of reference sensors commonly coupled to a first reference line, and a second set of reference sensors commonly coupled to a second reference line.

11. The apparatus of claim 10, wherein the first set of reference sensors and the second set of reference sensors are arranged in rows and columns of the array in an alternating fashion, so that adjacent reference sensors in the first set are separated by a single reference sensor in the second set, and adjacent reference sensors in the second set are separated by a single reference sensor in the first set.

12. The apparatus of claim 7, wherein a given chemical sensor is a chemically-sensitive transistor.

13. The apparatus of claim 7, wherein a given chemical sensor generates a sensor signal in response to a chemical reaction occurring within the corresponding reaction region.

14. The apparatus of claim 13, wherein the chemical reaction is a sequencing reaction.

15. A method for operating an apparatus, the method comprising:

applying a bias voltage to place a transistor of a reference sensor in a known state, the reference sensor in an array of sensors that further includes a chemical sensor coupled to a reaction region for receiving at least one reactant;

acquiring an output signal from the reference sensor in response to the applied bias voltage; and

determining a defect associated with the array if the output signal does not correspond to the known state.

16. The method of claim 15, wherein the chemical sensor is a chemically-sensitive transistor.

17. The method of claim 15, wherein the bias voltage is sufficient to place the transistor in one of an on state or an off state.

18. The method of claim 15, further comprising:

initiating a chemical reaction proximate to the chemical sensor if the output signal from the reference sensor corresponds to the known state; and

acquiring a sensor signal from the chemical sensor based on the chemical reaction.

19. The method of claim 18, wherein initiating the chemical reaction comprises initiating a sequencing reaction.

20. The method of claim 19, wherein initiating the sequencing reaction comprises:

disposing a plurality of template nucleic acids in the reaction region; and

introducing known nucleotides into the reaction region.