Amplifier and array for measuring small current

• US 9,086,400 B2
• Filed: 11/25/2008
• Issued: 07/21/2015
• Est. Priority Date: 11/29/2007
• Status: Expired due to Fees

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Ayers, Sunitha Bandla, Lindau, Manfred, Minch, Bradley A.
• Primary Examiner(s): Assouad, Patrick
• Assistant Examiner(s): Nguyen, Hoang X
• Application Number:
  US12/744,891
• Publication Number:
  US 20110121819A1
• Time in Patent Office: 2,429 Days
• Field of Search: 324/123.C, 324/123.R, 324/425, 324/439
• US Class Current: 1/1
• CPC Class Codes: G01N 15/10 Investigating individual particles
• CPC Class Codes: G01N 27/403 Cells and electrode assemblies
• CPC Class Codes: G01N 27/49 Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species
• CPC Class Codes: G01N 33/487 of liquid biological material
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10

Abstract

An array of electrochemical detectors includes an array of electrodes that provide current responsive to oxidation events. Each electrode is coupled to a transistor, an amplifier coupled to an input of the transistor and having a feedback loop coupled to the electrode and providing a bias voltage to the electrode, an integrating capacitor coupled to the transistor operable to integrate charge from the electrode, and a reset switch coupled to the integrating capacitor. The amplifier may have a shared stage with other detectors. A shared buffer circuit may also provide a sampled output from multiple detectors.

Claims

1. A device comprising:

a substrate;

an array of biological cell-sized detector electrodes supported by the substrate including plurality of biological cell-sized detector electrodes paired with one reference electrode;

circuitry supported by the substrate and integrated with the array of electrodes configured to measure transient amperometric oxidation currents from the electrodes and including multiple amplifiers formed with a shared half circuit and a non-shared half circuit, wherein the non-shared half circuit of each amplifier is associated with each electrode and the shared half circuit comprises a non-inverting half of the amplifiers and includes a folded cascode amplifier.

2. The device of claim 1 wherein the circuitry comprises an amplifier and an integrating capacitor for each electrode in the array.

3. The device of claim 2 wherein the amplifier has a feedback loop to bias each electrode at a desired reference voltage.

4. The device of claim 2 wherein the integrating capacitor further comprises a switch for draining charge from the capacitor at desired times.

5. The device of claim 1 wherein the folded cascode amplifier of the shared half circuit is configured to provide a large output voltage swing and provide a low input impedance.

6. The device of claim 1, wherein the non-shared half of each amplifier is a folded cascode amplifier having an output voltage range that is substantially rail to rail.

7. The device of claim 1 wherein the circuitry comprises a current to voltage converter.

8. The device of claim 7 wherein the current to voltage converter is integrating or non-integrating.

9. The device of claim 1 wherein the array comprises at least 25 amplifiers and 25 electrodes.

10. The device of claim 1, wherein a side dimension of a biological cell-sized polarizable detector electrode is included in a range of five to twenty micrometers (5-20 μ

m).

11. A device for measuring current, the device comprising:

a cascode transistor for coupling to an input electrode;

an amplifier coupled to an input of the cascode transistor and having an external feedback loop for coupling to the electrode and providing a bias voltage to the input electrode, wherein the amplifier comprises a split amplifier comprising a first shared input stage, multiple second input stages, and an output stage common to the shared first input stage and multiple second input stages, wherein the first shared input stage includes an internal feedback loop electrically coupled to a circuit node common to the shared first input stage and multiple second input stages;

an integrating capacitor coupled to the cascode transistor for integrating charge from the input electrode; and

a reset switch coupled to the integrating capacitor.

12. The device of claim 11 wherein the device is formed on a single chip having an opening for the input electrode.

13. The device of claim 11 wherein the shared input stage is included in a non-inverting half of the split amplifier and wherein the non-inverting half of the split amplifier functions as an error amplifier.

14. An array of electrochemical detectors comprising:

an array of detector electrodes that provides current responsive to oxidation events, wherein a plurality of detector electrodes is paired with one reference electrode, and wherein each detector electrode is biological cell-sized and coupled to;

a transistor;

a split amplifier coupled to an input of the transistor and having a feedback loop coupled to the electrode and providing a bias voltage to the detector electrode, wherein the split amplifier includes a shared half circuit and a non-shared half circuit, wherein the non-shared half circuit is associated with each electrode and the shared half circuit comprises a non-inverting half of the split amplifier and includes a folded cascode amplifier circuit;

an integrating capacitor coupled to the transistor operable to integrate charge from the detector electrode; and

a reset switch coupled to the integrating capacitor.

15. The array of claim 14 wherein multiple electrodes share a first half of the amplifier.

16. The array of claim 15 wherein electrodes in a row of the array share the first half of the amplifier.

17. The array of claim 15 wherein the first half of the amplifier is a non-inverting half of the amplifier.

18. The array of claim 15 wherein each electrode has a dedicated second, inverting half of the amplifier.

19. The array of claim 14 wherein the amplifier distributes thermal noise of the shared first half of the amplifier among dedicated second inverting halves of the amplifier of the electrodes.

20. The array of claim 14 wherein the amplifier comprises a regulated cascode amplifier.

21. A shared amplifier array comprising:

a first shared non-inverting amplifier stage coupled to a reference voltage; and

multiple second inverting amplifier stages sharing the first shared non-inverting amplifier stage, the inverting amplifier stages formed in a folded cascode arrangement such that it provides a substantially rail to rail output voltage,

wherein the first shared non-inverting amplifier stage includes a feedback loop that lowers an impedance at a circuit node that electrically couples the first shared non-inverting amplifier stage and the multiple second inverting amplifier stages, and wherein an output of a second inverting amplifier stage is electrically coupled to a cascode transistor which is for coupling to an input electrode.

22. The shared amplifier array of claim 21 wherein the feedback loop biases the circuit node relative to a voltage at an input of the first shared non-inverting amplifier stage.

23. The shared amplifier array of claim 21 wherein the first non-inverting amplifier stage includes a negative feedback loop and functions as an error amplifier.

24. A current detector array comprising:

a plurality of detectors, each having a detector electrode biological cell-sized for providing current from oxidation events, a split amplifier for biasing the detector electrodes to a reference voltage, a cascode transistor, and an integrating capacitor, wherein the split amplifier includes a shared half circuit and a non-shared half circuit, wherein the non-shared half circuit is associated with each electrode and the shared half circuit comprises a non-inverting half of the split amplifier and includes a folded cascode amplifier;

a shared output buffer circuit; and

a switch coupled to each detector for alternately switching each of the detectors to the shared output buffer circuit, wherein a plurality of detector electrodes of the plurality of detectors is paired with one reference electrode.

25. A method comprising:

distributing multiple small current producing entities across a substrate having an array of detector electrodes biological cell-sized and supported by the substrate and circuitry supported by the substrate and integrated with the array of detector electrodes configured to measure transient amperometric oxidation currents from the electrodes using multiple amplifiers formed with a shared half circuit and a non-shared half circuit, wherein the non-shared half circuit of each amplifier is associated with each electrode and the shared half circuit comprises a non-inverting half of the amplifiers and includes a folded cascode amplifier; and

measuring current produced by the current producing entities at each electrode in the array of electrodes.