Tri-electrode apparatus and methods for molecular analysis

• US 10,641,721 B2
• Filed: 03/06/2015
• Issued: 05/05/2020
• Est. Priority Date: 03/07/2014
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Prasad, Shalini, Panneer Selvam, Anjan
• Primary Examiner(s): Ayad, Tamir
• Application Number:
  US14/640,408
• Publication Number:
  US 20150276637A1
• Time in Patent Office: 1,887 Days
• Field of Search: None
• CPC Class Codes: G01N 27/026 Dielectric impedance spectroscopy electrochemical impedance spectroscopy for measuring corrosion G01N17/02
• CPC Class Codes: G01N 27/028 Circuits therefor measuring impedance per se G01R27/02
• CPC Class Codes: G01N 33/48707 by electrical means G01N33/49, G01N33/493 take precedence
• CPC Class Codes: Y10T 29/49128 Assembling formed circuit to base

Abstract

The claimed invention is an apparatus and method for performing impedance spectroscopy with a handheld measuring device. Conformal analyte sensor circuits comprising a porous nanotextured substrate and a conductive material situated on the top surface of the solid substrate in a circuit design may be used alone or in combination with a handheld potentiometer. Also disclosed are methods of detecting and/or quantifying target analytes in a sample using a handheld measuring device.

Claims

1. A method of detecting or quantifying multiple types of target analytes in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of:

(a) placing a sample containing multiple target analytes on a conformal substrate having a sensor circuit comprising a first electrode, a second electrode, and a third electrode, wherein the sensor circuit of the conformal analyte comprises;

a solid substrate having a top surface, wherein the solid substrate comprises a porous nanotextured substrate that is an insulating substrate; and

a conductive material stenciled on the top surface of the solid substrate in a circuit design;

(b) applying a first electric field with a first alternating electric voltage between the first electrode and the second electrode at a first phase angle;

(c) applying a second electric field with a second alternating electric voltage between the third electrode and the second electrode at a second phase angle, wherein the first electric field and the second electric field are locked in phase and wherein the first phase angle and the second phase angle are separated by a constant delta phase angle;

(d) measuring the output current at different frequencies and varying phase angles for different analytes;

(e) amplifying an output current flowing from the first electrode and from the third electrode through the second electrode using a programmable gain amplifier;

(f) varying the first phase angle of the first alternating electric voltage and the second phase angle of the second alternating electric voltage;

(g) identifying the first phase angle and the second phase angle at which a maximum impedance change occurs;

(h) measuring the impedance identified at the first phase angle and the second phase angle, wherein the measured impedance is non-faradaic; and

(i) using the measured impedance and associated phase angle and output current at different frequencies to detect multiple target analytes or calculate concentrations of target analytes by use of a standard calibration curve.

10. The method of claim 1, wherein the first alternating electric voltage and the second alternating electric voltage have a frequency between 50 Hz and 5,000 Hz.

11. The method of claim 1, wherein the first alternating electric voltage and the second alternating electric voltage are between 100 mV and 500 mV.

2. A method of detecting or quantifying a target analyte in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of:

(a) placing a sample containing multiple target analytes on a conformal substrate having a sensor circuit comprising a first electrode, a second electrode, a third electrode, a fourth electrode, a fifth electrode and a sixth electrode, wherein the sensor circuit of the conformal analyte comprises;

a solid substrate having a top surface, wherein the solid substrate comprises a porous nanotextured substrate that is an insulating substrate; and

a conductive material stenciled on the top surface of the solid substrate in a circuit design;

(b) applying a first electric field with a first alternating electric voltage between the first electrode and the second electrode at a first phase angle;

(c) applying a second electric field with a second alternating electric voltage between the third electrode and the second electrode at a second phase angle, wherein the first electric field and the second electric field are locked in phase and wherein the first phase angle and the second phase angle are separated by a first constant delta phase angle;

(d) measuring a first output current at different frequencies over a first range of frequencies and varying phase angles over a first range of phase angles;

(e) amplifying the first output current flowing from the first electrode and from the third electrode through the second electrode using a programmable gain amplifier;

(f) varying the first phase angle of the first alternating electric voltage and the second phase angle of the second alternating electric voltage over the first range of phase angles;

(g) identifying the first phase angle and the second phase angle at which a first maximum impedance change occurs;

(h) measuring the impedance identified at the first phase angle and the second phase angle, wherein the measured impedance is non-faradaic;

(i) using the measured impedance at different frequencies to detect a first target analyte or calculate a concentration of the first target analyte by use of a standard calibration curve;

(j) applying a third alternating electric voltage between the fourth electrode and the fifth electrode at a third phase angle;

(k) applying a fourth alternating electric voltage between the sixth electrode and the fifth electrode at a fourth phase angle, wherein the third phase angle and the fourth phase angle are separated by a second constant delta phase angle;

(l) measuring a second output current at different frequencies over a second range of frequencies and varying phase angles over a second range of phase angles;

(m) amplifying the second output current flowing from the fourth electrode and from the sixth electrode through the fifth electrode using the programmable gain amplifier;

(n) varying the third phase angle of the third alternating electric voltage and the fourth phase angle of the fourth alternating electric voltage over the second range of phase angles;

(o) identifying the third phase angle and the fourth phase angle at which a second maximum impedance change occurs;

(p) measuring the impedance identified at the third phase angle and the fourth phase angle; and

(q) using the measured impedance and phase change at different frequencies to detect a second target analyte or calculate a concentration of the second target analyte by use of a standard calibration curve.

3. The method of claim 2 wherein the first range of frequencies and the second range of frequencies are different.

4. The method of claim 2 wherein the first range of phase angles and the second range of phase angles are different.

5. The method of claim 2 wherein the first range of frequencies and the second range of frequencies are equal.

6. The method of claim 2 wherein the first range of phase angles and the second range of phase angles are equal.

7. The method of claim 2 wherein steps (a)-(i) are performed concurrently with steps (j)-(q).

8. A method of detecting or quantifying a target analyte in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of:

(a) applying a first input electric voltage between a first electrode and a second electrode of a conformal analyte sensor circuit, wherein the conformal analyte sensor circuit comprises;

a solid substrate having a top surface, wherein the solid substrate comprises a porous nanotextured substrate that is an insulating substrate; and

a conductive material situated on the top surface of the solid substrate in a circuit design, thereby creating a circuit comprising the first electrode, the second electrode, and a third electrode, wherein the conductive material is a conductive ink or semi-conductive ink;

(b) applying a second input electric voltage between the third electrode and the second electrode of the conformal analyte sensor circuit;

(c) amplifying an output current flowing from the first electrode and from the third electrode through the second electrode using a programmable gain amplifier;

(d) calculating an impedance by comparing the first input electric voltage and the second input electric voltage to the output current using a programmable microcontroller, wherein the calculated impedance is non-faradaic; and

(e) detecting a target analyte or calculating a target analyte concentration from the calculated impedance using a programmable microcontroller.

9. A method of detecting or quantifying multiple target analytes in a sample using a handheld measuring device and a conformal analyte sensor circuit comprising the steps of:

(a) applying a first input electric voltage between a first electrode and a second electrode of a conformal analyte sensor circuit, wherein the conformal analyte sensor circuit comprises;

a solid substrate having a top surface, wherein the solid substrate comprises a porous nanotextured substrate that is an insulating substrate; and

a conductive material situated on the top surface of the solid substrate in a circuit design, thereby creating a circuit comprising the first electrode, the second electrode, and a third electrode, wherein the conductive material is a conductive ink or semi-conductive ink;

(b) applying a second input electric voltage between the third electrode and the second electrode of the conformal analyte sensor circuit;

(c) shifting an angular orientation of an electric field of the second input electric voltage;

(d) amplifying an output current flowing through the first electrode using a programmable gain amplifier;

(e) calculating an impedance by comparing the first input electric voltage and the second input electric voltage to the output current using a programmable microcontroller, wherein the calculated impedance is non-faradaic; and

(f) detecting a presence of one or more target analytes by comparing the angular orientation of the electric field to the output current.