CHEMICALLY SENSITIVE SENSORS WITH FEEDBACK CIRCUITS

• US 20120280285A1
• Filed: 07/23/2012
• Published: 11/08/2012
• Est. Priority Date: 12/14/2006
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: ROTHBERG, Jonathan M., Hinz, Wolfgang, Johnson, Kim L., Bustillo, James
• Granted Patent: US 8,415,716 B2
• Time in Patent Office: Days
• US Class Current: 257/253
• CPC Class Codes: C12Q 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2533/101 Primer extension
• CPC Class Codes: C12Q 2565/301 Pyrophosphate (PPi)
• 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: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: H01L 27/088 the components being field-effect transistors with insulated gate
• CPC Class Codes: H01L 29/42324 Gate electrodes for transistors with a floating gate
• CPC Class Codes: H01L 29/78 with field effect produced by an insulated gate H01L29/7725, H01L29/775, H01L29/778 take precedence
• CPC Class Codes: H01L 2924/01006 Carbon [C]
• CPC Class Codes: H01L 2924/01013 Aluminum [Al]
• CPC Class Codes: H01L 2924/01015 Phosphorus [P]
• CPC Class Codes: H01L 2924/01073 Tantalum [Ta]
• CPC Class Codes: H01L 2924/14 Integrated circuits
• CPC Class Codes: H01L 2924/1433 Application-specific integrated circuit [ASIC]
• CPC Class Codes: Y10T 436/22 Hydrogen, per se

Abstract

Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Claims

1. An apparatus comprising a sensor, the sensor including:

a chemically-sensitive field effect transistor (chemFET);

a feedback circuit having an input coupled to a terminal of the chemFET; and

a controllable current source responsive to an output from the feedback circuit to provide a current to the chemFET, wherein the current provided to the chemFET tends to maintain a constant voltage at the terminal of the chemFET.

2. The apparatus of claim 1, further comprising an output circuit coupled to the sensor to produce a signal indicating the current provided to the chemFET.

3. The apparatus of claim 1, wherein the sensor further includes a sample and hold capacitor.

4. The apparatus of claim 3, wherein the chemFET is coupled to a passivation layer, and a voltage on the sample and hold capacitor indicates an ion-concentration of an analyte solution coupled to the passivation layer.

5. The apparatus of claim 1, wherein the chemFET is coupled to a passivation layer, and the current provided to the chemFET indicates an ion-concentration of an analyte solution coupled to the passivation layer.

6. The apparatus of claim 1, wherein the feedback circuit includes a first transistor having a gate connected to the terminal of the chemFET, a second transistor in series with the first transistor and having a gate connected to a first control signal line, and a third transistor in series with the second transistor and having a gate connected to a second control signal line, and wherein the output from the feedback circuit is provided at a node between the second and third transistors.

7. The apparatus of claim 1, wherein the controllable current source includes a transistor coupled between a first reference voltage and the chemFET, a gate of the transistor being coupled to the output of the feedback circuit.

8. The apparatus of claim 1, wherein the controllable current source includes a first transistor coupled between a first reference voltage node and the chemFET, and the sensor further includes a second transistor coupled between a second reference voltage node and the chemFET, wherein a gate of the first transistor is connected to the output of the feedback circuit, and the second transistor is configured to limit current in the chemFET.

9. The apparatus of claim 1, wherein the sensor further includes:

a sample and hold capacitor;

a switch coupled between the output of the feedback circuit and the sample and hold capacitor; and

a sensor output circuit having an input coupled to the sample and hold capacitor, and having an output.

10. The apparatus of claim 9, wherein the sensor output circuit is responsive to a select signal, to produce an output signal on the output indicating a voltage on the sample and hold capacitor.

11. The apparatus of claim 1, wherein the sensor includes a first transistor responsive to a first signal to enable sensing of current in the chemFET, a second transistor responsive to a second signal to enable generation of a signal sample from the chemFET, and a third transistor responsive to a third signal to enable a sensor output circuit to produce an output signal using the signal sample.

12. The apparatus of claim 1, including a reaction chamber coupled to the chemFET, and a reference electrode coupled to the reaction chamber.

13. The apparatus of claim 1, wherein the chemFET is coupled to a passivation layer to detect a sequencing reaction, and the current provided to the chemFET indicates presence of the sequencing reaction.

14. An apparatus, comprising:

an array of sensors arranged in rows and columns, a row including a plurality of sensors, each sensor in the plurality including;

a chemically-sensitive field effect transistor (chemFET), a feedback circuit having an input coupled to a terminal of the chemFET, and a controllable current source responsive to an output from the feedback circuit to provide a current to the chemFET, wherein the current provided to the chemFET tends to maintain a constant voltage at the terminal of the chemFET;

a sample and hold capacitor;

a switch coupled between the sample and hold capacitor and a node having a voltage indicating the current provided to the chemFET; and

a sensor output circuit having an input connected to the sample and hold capacitor, and responsive to a row select signal to produce a signal indicating a voltage on the sample and hold capacitor; and

a column output circuit coupled to the sensor output circuits of the plurality of sensors.

15. The apparatus of claim 14, wherein the column output circuit includes a column sample and hold capacitor, and a column select switch between a node coupled to outputs of the plurality of sensors in the row and the column sample and hold capacitor.

16. The apparatus of claim 14, wherein the feedback circuit includes a first transistor having a gate connected to the terminal of the chemFET, a second transistor in series with the first transistor and having a gate connected to a first control signal node, and a third transistor in series with the second transistor and having a gate connected to a second control signal node, and wherein the output from the feedback circuit is provided at a node between the second and third transistors.

17. The apparatus of claim 14, wherein the controllable current source includes a transistor coupled between a first reference voltage line and the chemFET, a gate of the transistor being coupled to the output of the feedback circuit.

18. The apparatus of claim 14, wherein the controllable current source includes a first transistor coupled between a first reference voltage line and the chemFET, and each of the sensors in the plurality further includes a second transistor coupled between a second reference voltage node and the respective chemFETs, a gate of the first transistor being coupled to the output of the feedback circuit, and the second transistor being configured to limit current in the chemFET.

19. The apparatus of claim 14, wherein each sensor in the plurality is coupled to a corresponding passivation layer, and the current provided to each chemFET indicates an ion-concentration of an analyte solution coupled to the corresponding passivation layer.

20. The apparatus of claim 14, wherein the sample and hold capacitor holds a voltage indicating a threshold voltage of the chemFET.

21. An apparatus, comprising:

an array of sensors, including a group having a plurality of sensors, each sensor in the plurality including;

a chemically-sensitive field effect transistor (chemFET);

a switch connected between the sample and hold capacitor and a node having a voltage indicating a threshold voltage of the chemFET; and

a sensor output circuit having an input connected to the sample and hold capacitor, and responsive to a select signal to produce a signal indicating a voltage on the sample and hold capacitor; and

a group output circuit coupled to the sensor output circuits of the plurality of sensors.

22. The apparatus of claim 21, wherein the group output circuit includes a group sample and hold capacitor, and a select switch between a node coupled to the outputs of the plurality of sensors in the group and the group sample and hold capacitor.

23. The apparatus of claim 21, wherein each sensor in the plurality includes a switch responsive to a signal to enable sensing of current in the chemFET.

24. The apparatus of claim 21, wherein the chemFET includes a floating gate and a passivation layer, and the voltage on the sample and hold capacitor indicates an ion-concentration in an analyte solution coupled to the floating gate via the passivation layer.