ANALYTE SENSOR APPARATUSES COMPRISING MULTIPLE IMPLANTABLE SENSOR ELEMENTS AND METHODS FOR MAKING AND USING THEM

• US 20100030045A1
• Filed: 07/31/2008
• Published: 02/04/2010
• Est. Priority Date: 07/31/2008
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Chiu, Chia, Shah, Rajiv, Gottlieb, Rebecca K., Larson, Eric Allan
• Granted Patent: US 8,700,114 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• 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 5/6848 Needles
• CPC Class Codes: A61B 5/6849 in combination with a needle set
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Embodiments of the invention provide analyte sensors having optimized elements and/or configurations of elements as well as methods for making and using such sensors. Typical embodiments of the invention include glucose sensors used in the management of diabetes.

Claims

1. An apparatus for monitoring an analyte in a patient, the apparatus comprising:

a base element adapted to secure the apparatus to the patient;

a first piercing member coupled to and extending from the base element;

a first electrochemical sensor operatively coupled to the first piercing member and comprising a first electrochemical sensor electrode for determining at least one physiological characteristic of the patient at a first electrochemical sensor placement site;

a second piercing member coupled to and extending from the base element;

a second electrochemical sensor operatively coupled to the second piercing member and comprising a second electrochemical sensor electrode for determining at least one physiological characteristic of the patient at a second electrochemical sensor placement site; and

wherein;

at least one physiological characteristic monitored by the first or the second electrochemical sensor comprises a concentration of a naturally occurring analyte in the patient;

the first and second piercing members are disposed on the base in a configuration selected so that the first piercing member disposes the first electrochemical sensor in a first tissue compartment of the patient and the second piercing member disposes the second electrochemical sensor in a second tissue compartment of the patient; and

the first and second piercing members are disposed on the base in a configuration selected to avoid a physiological response that can result from implantation of the first electrochemical sensor from altering a sensor signal generated by the second electrochemical sensor.

2. The apparatus of claim 1, further comprising:

a contact pad;

an electrical conduit which connects an electrochemical sensor electrode to an electrical connection element that is operatively coupled to the contact pad; and

wherein;

the base comprises a flexible sensor substrate; and

the contact pad, the electrical conduit and the electrochemical sensor electrode are operatively coupled to the flexible sensor substrate in a configuration that allows the apparatus to function as it twists and bends in response to movement of implanted electrochemical sensors in the patient.

3. The apparatus of claim 2, wherein the apparatus comprises two contact pads connected to two electrical conduits and two sets of electrochemical sensor electrodes comprising a working, a counter and a reference electrode that are disposed on the flexible sensor substrate in a configuration such that:

the two contact pads are disposed together in a central region of the flexible sensor substrate so as to facilitate electrical connection to a power source and each of the two sets of electrochemical sensor electrodes is disposed on an opposite side of the flexible sensor substrate so as to maximize sensor separation;

the two contact pads are disposed together one side of the flexible sensor substrate so as to facilitate electrical connection to a power source and the two sets of electrochemical sensor electrodes are disposed together in a row on an opposite side of the flexible sensor substrate so as to provide a compact design for patient use;

or

the two contact pads are disposed together one side of the flexible sensor substrate so as to facilitate electrical connection to a power source and the two sets of electrochemical sensor electrodes are disposed together in a staggered arrangement on an opposite side of the flexible sensor substrate so as to provide a compact design for patient use while providing a greater distance between each set of electrochemical sensor electrodes as compared to sensor electrodes not disposed together in a staggered arrangement.

4. The apparatus of claim 1, wherein at least one electrochemical sensor electrode comprises oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase.

5. The apparatus of claim 4, wherein:

the first and second electrochemical sensor comprises a working electrode, a counter electrode and a reference electrode;

a working electrode in the first electrochemical sensor is coated with glucose oxidase; and

no working electrode in the second electrochemical sensor is coated with glucose oxidase.

6. The apparatus of claim 1, wherein the first and second electrochemical sensors are operatively coupled to:

a sensor input capable of receiving signals from the first and second electrochemical sensors; and

a processor coupled to the sensor input, wherein the processor is capable of characterizing one or more signals received from the first and second electrochemical sensors.

7. The apparatus of claim 6, wherein a pulsed voltage is used to obtain a signal from an electrode.

8. The apparatus of claim 6, wherein the processor is capable of comparing a first signal received from a working electrode in response to a first working potential with a second signal received from a working electrode in response to a second working potential.

9. The apparatus of claim 1, wherein the first and second electrochemical sensors comprise a plurality of working, counter and reference electrodes that are grouped together as a unit and positionally distributed in a repeating pattern of units.

10. An apparatus for monitoring glucose concentrations in a patient, the apparatus comprising:

a flexible sensor substrate adapted to secure the apparatus to the patient;

a first piercing member coupled to and extending from the flexible sensor substrate,

wherein the first piercing member is operatively coupled to a first electrochemical sensor comprising

a first electrochemical sensor electrode for measuring glucose concentrations at a first electrochemical sensor placement site;

a second piercing member coupled to and extending from the flexible sensor substrate, wherein the second piercing member is operatively coupled to a second electrochemical sensor comprising a second electrochemical sensor electrode for determining at least one physiological characteristic of the patient at a second electrochemical sensor placement site;

a processor capable of characterizing a plurality of signals received from the first and second electrochemical sensors; and

wherein;

the first piercing member disposes the first electrochemical sensor in a first tissue compartment of the patient and the second piercing member disposes the second electrochemical sensor in a second tissue compartment of the patient; and

the first and second piercing members are disposed on the flexible sensor substrate in a configuration selected to avoid a physiological response to the implantation of the first electrochemical sensor from effecting a sensor signal generated by the second electrochemical sensor.

11. The apparatus of claim 10, wherein the first and the second electrochemical sensor comprise:

an elongated base layer;

a conductive layer disposed on the base layer and comprising a reference electrode, a working electrode and a counter electrode;

an analyte sensing layer disposed on the conductive layer;

an analyte modulating layer disposed on the analyte sensing layer, wherein the analyte modulating layer comprises a composition that modulates the diffusion of an analyte diffusing through the analyte modulating layer; and

a cover layer disposed on the analyte sensor, wherein the cover layer comprises an aperture positioned on the cover layer so as to facilitate;

an analyte present in the patient contacting and diffusing through the analyte modulating layer; and

contacting the analyte sensing layer.

12. The apparatus of claim 10, wherein the first electrochemical sensor comprises a working electrode coated with glucose oxidase and the second electrochemical sensor comprises no working electrode coated with glucose oxidase and the processor is capable of obtaining information on glucose concentrations in the patient by comparing the signals received from said working electrodes so as to identify a background signal that is not based on a glucose concentrations in the patient.

13. The apparatus of claim 10, wherein the working electrode in the first and second electrochemical sensors are coated with glucose oxidase and the processor is capable of obtaining information on glucose concentrations in the patient by comparing the signals received from said working electrodes coated with glucose oxidase.

14. The apparatus of claim 10, wherein a pulsed voltage is used to obtain a signal from an electrode.

15. The apparatus of claim 10, wherein the processor is capable of comparing a first signal received from a working electrode in response to a first working potential with a second signal received from a working electrode in response to a second working potential.

16. The analyte sensor apparatus of claim 15, wherein at least one working potential is 280, 535 or 635 millivolts.

17. The apparatus of claim 10, wherein the first and second electrochemical sensors comprise a plurality of working, counter and reference electrodes that are grouped together as a unit and positionally distributed on the conductive layer in a repeating pattern of units.

18. The analyte apparatus of claim 10, wherein:

the first and second electrochemical sensors comprise three working electrodes, one counter electrode and one reference electrode;

at least one working electrode in the first and second electrochemical sensors is coated with glucose oxidase;

at least one working electrode in the first and second electrochemical sensors is not coated with glucose oxidase.

19. The apparatus of claim 18, wherein at least two working electrodes in the first and second electrochemical sensors are coated with glucose oxidase.

20. A method of monitoring an analyte within the body of a patient, the method comprising implanting an analyte sensor in to the patient, the analyte sensor comprising:

a base element adapted to secure the apparatus to the patient;

a first piercing member coupled to and extending from the base element;

a first electrochemical sensor operatively coupled to the first piercing member and comprising a first electrochemical sensor electrode for determining at least one physiological characteristic of the patient at a first electrochemical sensor placement site;

a second piercing member coupled to and extending from the base element;

a second electrochemical sensor operatively coupled to the second piercing member and comprising a second electrochemical sensor electrode for determining at least one physiological characteristic of the patient at a second electrochemical sensor placement site;

a sensor input capable of receiving signals from the first and second electrochemical sensors; and

a processor coupled to the sensor input, wherein the processor is capable of characterizing one or more signals received from the first and second electrochemical sensors;

wherein;

at least one physiological characteristic monitored by the first or the second electrochemical sensor comprises a concentration of a naturally occurring analyte in the patient;

the first piercing member disposes the first electrochemical sensor in a first tissue compartment of the patient and the second piercing member disposes the second electrochemical sensor in a second tissue compartment of the patient; and

the first and second piercing members are disposed on the base in a configuration selected to avoid a physiological response that results from implantation of the first electrochemical sensor from altering a sensor signal generated by the second electrochemical sensor; and

sensing alterations in current at the first and second electrochemical sensor electrodes and correlating said alterations in current with the presence or absence of the analyte, so that the analyte is monitored.

21. The method of claim 20, wherein the first electrochemical sensor comprises a working electrode coated with glucose oxidase and the second electrochemical sensor comprises no working electrode coated with glucose oxidase, the method further comprising using the processor to obtain information on glucose concentrations in the patient by comparing the signals received from the working electrodes in said first and second electrochemical sensors so that a background signal that is not based on a glucose concentrations in the patient is characterized.

22. The method of claim 20, wherein the first electrochemical sensor comprises a working electrode coated with glucose oxidase and the second electrochemical sensor comprises a working electrode coated with glucose oxidase, the method further comprising using the processor to obtain information on glucose concentrations in the patient by comparing the signals received from the working electrodes in said first and second electrochemical sensors.

23. The method of claim 20, wherein:

the first and second electrochemical sensors comprise three working electrodes, one counter electrode and one reference electrode;

at least one working electrode in the first and second electrochemical sensors is coated with glucose oxidase;

at least one working electrode in the first and second electrochemical sensors is not coated with glucose oxidase,

the method further comprising using the processor to obtain information on glucose concentrations in the patient by comparing the signals received from the working electrodes coated with glucose oxidase in said first and second electrochemical sensors with the working electrodes not coated with glucose oxidase in said first and second electrochemical sensors so that a background signal that is not based on a glucose concentrations in the patient is characterized.

24. The method of claim 20, further comprising implanting at least one of the first and second electrochemical sensors in an interstitial space.

25. The method of claim 20, wherein the first and second electrochemical sensors comprise a plurality of working, counter and reference electrodes that are grouped together as a unit and positionally distributed on the conductive layer in a repeating pattern of units.