Sensor systems having multiple probes and electrode arrays

• US 9,215,995 B2
• Filed: 06/21/2011
• Issued: 12/22/2015
• Est. Priority Date: 06/23/2010
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Gottlieb, Rebecca K., Chiu, Chia-Hung, Ramachandran, Meena, Dangui-Patel, Nandita, Rose, Jefferson, Rao, Ashwin K., Wang, Hsifu, Luo, Ying
• Primary Examiner(s): Kahelin, Michael
• Assistant Examiner(s): Alter, Mitchell E
• Application Number:
  US13/165,061
• Publication Number:
  US 20110319734A1
• Time in Patent Office: 1,645 Days
• Field of Search: 600/345, 600/347
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0017 transmitting optical signals transmission by light H04B10/00
• 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/726 using Wavelet transforms
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: G01N 27/307 Disposable laminated or multilayered electrodes G01N27/3272 takes precedence

Abstract

Embodiments of the invention provide amperometric analyte sensors having multiple related structural elements (e.g. sensor arrays comprising a working, counter and reference electrode) and algorithms designed for use with such sensors. While embodiments of the innovation can be used in a variety of contexts, typical embodiments of the invention include glucose sensors used in the management of diabetes.

Claims

1. An amperometric analyte sensor system comprising:

a probe platform;

a first probe coupled to the probe platform and adapted to be inserted in vivo, wherein the first probe comprises;

a first electrode array comprising a working electrode, a counter electrode and a reference electrode; and

a second electrode array comprising a working electrode, a counter electrode and a reference electrode;

a second probe coupled to the probe platform and adapted to be inserted in vivo, wherein the second probe comprises;

a third electrode array comprising a working electrode, a counter electrode and a reference electrode; and

a fourth electrode array comprising a working electrode, a counter electrode and a reference electrode;

wherein the first, second, third and fourth electrode arrays are configured to be electronically independent of one another; and

the system further comprises;

a processor;

a computer-readable program code having instructions, which when executed cause the processor to;

assess signal data obtained from each of the first, second, third and fourth electrode arrays against one or more reliability parameters;

rank signal data from each of the first, second, third and fourth electrode arrays in accordance with the assessment against the one or more reliability parameters; and

compute an analyte concentration based upon the ranking of signal data obtained from each of the first, second, third and fourth electrode arrays.

2. The amperometric analyte sensor system of claim 1, wherein:

the first and second electrode arrays are disposed at different locations along the first probe so that the first and second electrode arrays are located at different depths when inserted into an in vivo environment;

or

the third and fourth electrode arrays are disposed at different locations along the second probe so that the third and fourth electrode arrays are located at different depths when inserted into an in vivo environment.

3. The amperometric analyte sensor system of claim 1, wherein the system further comprises an adhesive patch adapted to secure the probe platform to the skin of a patient.

4. The amperometric analyte sensor system of claim 1, wherein one or more electrodes in the first electrode array, the second electrode array, the third electrode array and the fourth electrode array are coated with a plurality of layered materials comprising:

an interference rejection layer;

an analyte sensing layer;

a protein layer;

an adhesion promoting layer; and

an analyte modulating layer, wherein the analyte modulating layer comprises a composition that modulates the diffusion of an analyte diffusing through the analyte modulating layer.

5. The amperometric analyte sensor system of claim 4, wherein the interference rejection layer comprises crosslinked primary amine polymers having an average molecular weight between 4 and 500 kilodaltons;

or crosslinked Poly(2-hydroxyethyl methacrylate) polymers having an average molecular weight between 100 and 1000 kilodaltons.

6. The amperometric analyte sensor system of claim 4, wherein the analyte modulating layer comprises a blended mixture of:

a linear polyurethane/polyurea polymer, and

a branched acrylate polymer; and

the linear polyurethane/polyurea polymer and the branched acrylate polymer are blended at a ratio of between 1;

1 and 1;

20 by weight %.

7. The amperometric analyte sensor system of claim 1, wherein:

electrodes in the first electrode array and the third electrode array;

(a) comprise a platinum having a first set of material properties;

or

(b) are coated with a first set of layered materials; and

electrodes in the second electrode array and the fourth electrode array;

(c) comprise platinum having a second set of material properties;

or

(d) are coated with a second set of layered materials.

8. The amperometric analyte sensor system of claim 1, wherein the size of the working electrodes in the first and third electrode arrays are at least 1.5, 2 or 2.5 fold larger that the size of working electrodes in the second and fourth electrode arrays.

9. The amperometric analyte sensor system of claim 1, wherein the first, second, third and fourth electrode arrays generate:

a current signal (Isig), wherein the current signal comprises a signal generated by the first, second, third or fourth electrode arrays in the presence of an analyte; and

a voltage signal (Vcntr), wherein the voltage signal comprises a signal generated by the first, second, third or fourth electrode arrays in response to voltage applied to the first, second, third or fourth electrode array.

10. The amperometric analyte sensor system of claim 1, further comprising a monitor adapted to display signal information.

11. The amperometric analyte sensor system of claim 1, wherein a reliability parameter is calculated by a method comprising:

determining whether a signal amplitude falls within a predetermined range of amplitudes;

determining a trend in sensor signals from a plurality of signals sensed by an electrode array;

determining an amount of nonspecific signal noise sensed by an electrode array;

determining a mean value for a signal obtained from the first, second, third and fourth electrode arrays; and

/or

determining a standard deviation for a signal obtained from the first, second, third or fourth electrode arrays.

12. The amperometric analyte sensor system of claim 1, wherein:

signal data obtained from each of the first, second, third and fourth electrode arrays is weighted according to one or more reliability parameters; and

the weighted signal data is fused to compute an analyte concentration.

13. The amperometric analyte sensor system of claim 1, wherein signal data from each of the first, second, third and fourth electrode arrays is assessed so as to provide an indication of the reliability of a signal obtained from one or more of the first, second, third and fourth electrode arrays.

14. The amperometric analyte sensor system of claim 1, wherein the processor further calculates a reliability index, wherein the reliability index provides an estimation of the reliability of the analyte concentration computed by the system.

15. The amperometric analyte sensor system of claim 1, wherein:

the analyte sensed is glucose;

at least one electrode array is constructed from materials designed to predominantly sense glucose at a concentration range of 40-100 mg/dL; and

at least one electrode array is constructed from materials designed to predominantly sense glucose at a concentration range of 70-400 mg/dL.

16. The amperometric analyte sensor system of claim 1, wherein:

the analyte sensed is glucose;

at least one electrode array is constructed from materials designed to sense signals resulting from the presence of glucose; and

at least one electrode array is constructed from materials designed to sense;

(a) signals resulting from background noise;

or

(b) signals resulting from interfering compounds.

17. The amperometric analyte sensor system of claim 1, wherein:

the processor evaluates signal data so as to provide evidence of signal drift over time in the amperometric analyte sensor system;

or

the processor evaluates signal data so as to provide information on the hydration of the amperometric analyte sensor system.

18. The amperometric analyte sensor system of claim 17, wherein the processor evaluates data resulting from a plurality of amplitude pulses applied to the system.

19. A method for sensing glucose concentrations in a diabetic patient, the method comprising:

observing signal data generated by a first, second, third and fourth electrode arrays in the presence of glucose in an amperometric analyte sensor system comprising;

a probe platform;

a first probe coupled to the probe platform and adapted to be inserted in vivo, wherein the first probe comprises;

a first electrode array comprising a working electrode, a counter electrode and a reference electrode; and

a second electrode array comprising a working electrode, a counter electrode and a reference electrode;

a second probe coupled to the probe platform and adapted to be inserted in vivo, wherein the second probe comprises;

a third electrode array comprising a working electrode, a counter electrode and a reference electrode; and

a fourth electrode array comprising a working electrode, a counter electrode and a reference electrode;

wherein the first, second, third and fourth electrode arrays are configured to be electronically independent of one another; and

the method further comprises

comparing the signal data from each of the first, second, third and fourth electrode arrays; and

computing an analyte concentration using the comparison of the signal data obtained from each of the first, second, third and fourth electrode arrays.

20. The method of claim 19, wherein the system comprises a processor for comparing the signal data from each of the first, second, third and fourth electrode arrays and the comparison includes:

observing whether a signal obtained from each of the first, second, third and fourth electrode arrays falls within a predetermined range of values;

observing a trend in sensor signal data from each of the first, second, third and fourth electrode arrays;

or

observing an amount of nonspecific signal noise in each of the first, second, third and fourth electrode arrays.

21. The method of claim 20, wherein the comparison is used to identify a signal from an array that is:

indicative of increasing glucose blood concentrations or decreasing blood glucose concentrations in the diabetic patient;

indicative of insufficient sensor hydration;

indicative of sensor signal drift;

or

indicative of sensor loss of sensitivity to glucose.

22. The method of claim 20, further comprising:

weighing signal data obtained from each of the first, second, third and fourth electrode arrays; and

using weighted signal data to compute an analyte concentration.

23. The method of claim 22, further comprising using the processor to:

assess signal data from each of the first, second, third and fourth electrode array; and

generate reliability index that indicates the reliability of a signal obtained from one or more of the first, second, third and fourth electrode arrays.

24. The method of claim 20, wherein one or more electrodes in the first electrode array, the second electrode array, the third electrode array and the fourth electrode array are coated with a plurality of layered materials comprising:

an interference rejection layer;

an analyte sensing layer;

a protein layer;

an adhesion promoting layer; and

an analyte modulating layer, wherein the analyte modulating layer comprises a composition that modulates the diffusion of an analyte diffusing through the analyte modulating layer.