Sensor initialization methods for faster body sensor response

• US 10,856,784 B2
• Filed: 06/30/2017
• Issued: 12/08/2020
• Est. Priority Date: 06/30/2017
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Patel, Anuj M.
• Primary Examiner(s): Winakur, Eric F
• Assistant Examiner(s): Mustansir, Abid A
• Application Number:
  US15/639,116
• Publication Number:
  US 20190000358A1
• Time in Patent Office: 1,257 Days
• CPC Class Codes: A61B 2562/02 Details of sensors specially adapted for in-vivo measurements
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48

Abstract

A method of initializing a sensor with a voltage sequence including a ramped voltage combined with a biphasic voltage pulse. The initialization scheme results in faster in-vitro sensor run-in and stabilization times. In various examples, the in-vitro sensor stabilization time is reduced from 200 minutes to 40-55 minutes (a reduction by a factor of least 5 as compared to a non-initialized sensor). In addition, staircase voltage initialization is implemented adaptively so that the voltage step size and sweep rates are changed depending on the state of the sensor (characterized by ISIG magnitude). As a result, individual sensors can be initialized in a customized manner rather than by using a general hardwired and harsh initialization scheme.

Claims

1. An analyte sensor apparatus, comprising:

a base substrate;

an analyte sensing layer disposed over an electrode, wherein the analyte sensing layer detectably alters electrical current at the electrode in a presence of an analyte;

an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates diffusion of the analyte therethrough; and

a circuit coupled to the electrode, the circuit generating and transmitting an initialization voltage to the electrode and the initialization voltage comprising a ramped voltage combined with a biphasic pulse comprising an anodic phase and a cathodic phase with respect to a reference level, wherein;

the electrode comprises a metal forming an electroactive surface of the electrode,

the initialization voltage changes a charge distribution of the metal, so that after less than 1 hour from when the initialization voltage is first applied;

the electrical current is in 5% agreement with a 2 hour moving average electrical current value, and

the electrical current is in 10% agreement with a steady state (non-transient) electrical current.

2. The sensor of claim 1, wherein the ramped voltage comprises a staircase voltage.

3. The sensor of claim 1, wherein:

the circuit comprises a potentiostat connected to a voltage generation circuit,

the voltage generation circuit generates and inputs the initialization voltage to the potentiostat,

the potentiostat transmits the initialization voltage to the electrode, and

the ramped voltage comprises a voltage stepped from an initial voltage, causing charge re-distribution in the electrode, to a final voltage at which the potentiostat is biased when the electrical current provides a reliable measure of the analyte concentration during steady state operation.

4. The sensor of claim 3, wherein the initial voltage is in a range of 250-450 mV and the final voltage is in a range of 400 mV-600 mV.

5. The sensor of claim 3, wherein the initial voltage is at least equal to, or within 5% of, the lowest voltage inputted to the potentiostat for which the electrical current is faradaic.

6. The sensor of claim 5, wherein the voltage generation circuit adjusts a voltage step in the ramped voltage so that the ramped voltage is ramped in less than 1 hour from the initial voltage to the final voltage.

7. The sensor of claim 1, wherein the biphasic pulse has a frequency in a range of 0.1 Hz to 8 kHz.

8. The sensor of claim 1, wherein the ramped voltage is applied for a duration and comprises voltage magnitudes below a threshold, so that metal loss from the electrode and/or the base layer is less than 1%.

9. A method of making a sensor, comprising:

connecting a circuit to a working electrode in a sensor comprising;

a base substrate;

the working electrode on the base substrate, wherein the working electrode comprises metal having an electroactive surface;

an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer detectably alters electrical current at the working electrode in a presence of an analyte; and

wherein;

the circuit generates and transmits an initialization voltage to the working electrode, the initialization voltage comprising a ramped voltage combined with a biphasic pulse so as to form the metal having a stable (steady state) charge distribution, the biphasic pulse comprising an anodic phase and a cathodic phase with respect to a reference level, and

the initialization voltage changes a charge distribution of the metal, so that after less than 1 hour from when the initialization voltage is first applied;

the electrical current is in 5% agreement with a 2 hour moving average electrical current value, and

the electrical current is in 10% agreement with a steady state (non-transient) electrical current.

10. The method of claim 9, wherein the ramped voltage comprises a staircase voltage.

11. A method of making a sensor, comprising:

connecting a circuit to a working electrode in a sensor comprising;

a base substrate;

the working electrode on the base substrate, wherein the working electrode comprises metal having an electroactive surface;

an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer detectably alters electrical current at the working electrode in a presence of an analyte; and

wherein;

the circuit generates and transmits an initialization voltage to the working electrode, the initialization voltage comprising a first ramped voltage combined with a biphasic pulse so as to form the metal having a stable (steady state) charge distribution, the biphasic pulse comprising an anodic phase and a cathodic phase with respect to a reference level,

the circuit comprises a potentiostat connected to a voltage generation circuit,

the voltage generation circuit generates and inputs the initialization voltage to the potentiostat,

the potentiostat transmits the initialization voltage to the electrode,

the first ramped voltage comprises a voltage stepped from an initial voltage, causing charge re-distribution in the electrode, to a final voltage at which the sensor is biased when the electrical current provides a reliable measure the analyte during steady state operation, and

the circuit generates and transmits a second ramped voltage to the electroactive surface, the method further comprising;

measuring the electrical current as a function of the second ramped voltage;

determining, in a computer, the threshold voltage in the second ramped voltage at and above which the electrical current is faradaic; and

generating the initialization voltage, wherein the initial voltage is at least equal to, or within 5% of, the threshold voltage.

12. The method of claim 11, wherein the initial voltage is in a range of 250-450 mV and the final voltage is in a range of 400-600 mV.

13. The method of claim 11, wherein the biphasic pulse has a frequency in a range of 0.1 Hz to 8 kHz.

14. The method of claim 11, further comprising adjusting a voltage step in the ramped voltage so that the ramped voltage is ramped in less than 1 hour from the initial voltage to the final voltage.

15. The method of claim 11, wherein:

the measuring comprises, for each of a plurality of the voltages in the second ramped voltage, measuring the electrical current at a first time and a second time later than the first time, and

the determining comprises;

comparing the electrical current at the first time and the second time; and

selecting the threshold voltage as the lowest voltage in the voltage ramp for which the electrical current measured at the first time is higher than the electrical current measured at the second time.

16. A method of making a sensor comprising:

connecting a circuit to a working electrode in a sensor comprising;

a base substrate;

the working electrode disposed on the base substrate, the working electrode comprising a metal having an electroactive surface;

an analyte sensing layer disposed over the working electrode, wherein;

the analyte sensing layer detectably alters an electrical current at the working electrode in the presence of an analyte, and

the circuit generates and transmits a ramped voltage to the electroactive surface,

measuring the electrical current as a function of the ramped voltage, wherein the measuring comprises, for each of a plurality of the voltages in the ramped voltage, measuring the electrical current at a first time and a second time later than the first time;

determining, in a computer, the threshold voltage in the ramped voltage at and above which the electrical current is faradaic, so that when the circuit generates and transmits an initialization voltage sequence to the working electrode, an initial voltage in the initialization voltage sequence is at least equal to, or within 5%, of the threshold voltage, so as to form the metal having a stable (steady state) charge distribution, wherein the determining comprises;

comparing the electrical current at the two different times; and

selecting the threshold voltage as the lowest voltage in the voltage ramp for which the electrical current measured at the first time is higher than the electrical current measured at the second time.

17. The method of claim 16, wherein:

the circuit comprises a potentiostat connected to a voltage generation circuit,

the voltage generation circuit generates and inputs the initialization voltage to the potentiostat,

the potentiostat transmits the initialization voltage to the electrode, and

the ramped voltage and the initialization voltage sequence each comprise a staircase voltage, the method further comprising;

adjusting a voltage step in the initialization voltage sequence so that the voltage is ramped in less than 1 hour from the initial voltage to a final voltage at which the potentiostat is biased when the electrical current provides a reliable measure the analyte'"'"'s concentration during steady state operation.