Implantable enzyme-based monitoring systems adapted for long term use
First Claim
1. An implantable monitoring system comprising an enzyme solution and means, within the monitoring system, for replenishing the enzyme solution,wherein the enzyme solution moves freely within the means for replenishing the enzyme solution, the enzyme solution moving through a channel on a substrate.
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Abstract
Improved implantable monitoring systems suitable for long-term in vivo use to measure the concentration of one or more prescribed substances, such as glucose, are described herein. In particular, an implantable enzyme-based glucose monitoring system is described that includes at least one of the following: means for replenishing the enzyme solution as it is consumed by the enzymatic reaction; means for replenishing the electrolyte solution bathing the electrode assembly; and microprocessing means proximal the electrode assembly. In preferred embodiments, a microprocessor assembly is hermetically associated with the substrate to which the electrode assembly is affixed. Further, the monitoring systems employ one or more reservoir systems in fluid communication with enzyme and electrolyte chambers wherein the enzyme and electrolyte solutions are used. In a further embodiment, the monitoring systems use enzyme and electrolyte reservoir bulbs in fluid communication with the enzyme and electrolyte reservoirs, respectively, and positioned near the skin surface, thereby providing ready access to the enzyme and electrolyte solutions without the need for explantation of the device. Further provided herein is an enzyme solution comprising microspheres in association with the enzyme; whereby the enzyme is immobilized by the microspheres and the microspheres are in a fluid, flowable solution. Also provided herein is a method of extending the useful life of an implantable enzyme-based monitoring system, which method comprises providing means, within the system, to replenish the enzyme and/or electrolyte solution.
911 Citations
32 Claims
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1. An implantable monitoring system comprising an enzyme solution and means, within the monitoring system, for replenishing the enzyme solution,
wherein the enzyme solution moves freely within the means for replenishing the enzyme solution, the enzyme solution moving through a channel on a substrate.
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2. An implantable monitoring system comprising an electrode assembly bathed in an electrolyte solution and means, within the monitoring system, for replenishing the electrolyte solution.
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3. An implantable monitoring system comprising:
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an enzyme chamber;
an enzyme reservoir in fluid communication with the enzyme chamber; and
an enzyme solution within the enzyme chamber and enzyme reservoir, wherein the enzyme solution moves freely between the enzyme chamber and enzyme reservoir, the enzyme solution moving through a channel on a substrate.
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4. An implantable monitoring system comprising:
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an electrolyte chamber;
an electrolyte reservoir in fluid communication with the electrolyte chamber; and
an electrolyte solution within the electrolyte chamber and the electrolyte reservoir.
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5. An implantable monitoring system comprising:
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an electrolyte chamber;
an electrolyte solution within the electrolyte chamber;
an electrolyte reservoir in fluid communication with the electrode chamber;
an enzyme chamber proximate the electrolyte chamber;
an enzyme solution within the enzyme chamber; and
an enzyme reservoir in fluid communication with the enzyme chamber.
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6. An implantable monitoring system for determining the in vivo concentration of at least one prescribed substance, the system comprising:
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a housing, at least a portion of which is permeable to the at least one prescribed substance;
an enzyme chamber within the housing;
an enzyme reservoir in fluid communication with the enzyme chamber;
and an enzyme solution contained within the enzyme chamber and enzyme reservoir, wherein the enzyme solution moves freely between the enzyme chamber and enzyme reservoir, the enzyme solution moving through a channel on a substrate. - View Dependent Claims (7)
an electrolyte chamber within the housing;
an electrode assembly within the electrolyte chamber;
an electrolyte reservoir in fluid communication with the electrolyte chamber; and
an electrolyte solution contained within the electrolyte chamber and electrolyte reservoir.
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8. An implantable monitoring system for determining the in vivo concentration of at least one prescribed substance, the system comprising:
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a housing, at least a portion of which is permeable to the at least one prescribed substance;
a substrate within the housing;
an electrode assembly affixed to the substrate and having an active surface;
an electrolyte chamber surrounding the active surface of the electrode assembly;
an electrolyte reservoir in fluid communication with the electrolyte chamber; and
an electrolyte solution contained within the electrolyte chamber and electrolyte reservoir. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
an opening within the housing, a membrane covering the opening, said membrane being permeable to the at least one prescribed substance;
an enzyme chamber within said housing and adjacent to the opening therein;
an enzyme reservoir in fluid communication with the enzyme chamber; and
an enzyme solution located within said enzyme reservoir.
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10. The implantable monitoring system of claim 9, wherein the enzyme solution comprises microspheres associated with a prescribed enzyme.
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11. The implantable monitoring system of claim 9, further comprising:
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a microprocessor assembly hermetically associated with the substrate and in electrical communication with the electrode assembly; and
a lead system in electrical communication with the microprocessor assembly.
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12. The implantable monitoring system of claim 11, wherein the housing is oxygen permeable and glucose impermeable.
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13. The implantable monitoring system of claim 12, wherein the at least one prescribed substance is glucose and the enzyme solution comprises glucose oxidase.
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14. The implantable monitoring system of claim 11, wherein the electrolyte reservoir and enzyme reservoir are coaxial and the lead system comprises a first lead located within the electrolyte reservoir and a second lead, coaxial with said first lead, and located within the enzyme reservoir.
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15. The implantable monitoring system of claim 11, further comprising securing means, attached to said substrate, wherein the securing means serves to hold said substrate in a preselected position within said housing.
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16. The implantable monitoring system of claim 15, wherein said securing means comprise at least two epoxy plugs.
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17. The implantable monitoring system of claim 11, further comprising an enzyme reservoir bulb attached in fluid communication with the enzyme reservoir and extending beyond the housing such that, upon implantation, the enzyme reservoir bulb may be positioned proximate the patient'"'"'s skin surface, thereby providing a point of ready access to the enzyme solution.
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18. The implantable monitoring system of claim 17, further comprising an electrolyte reservoir bulb attached in fluid communication with said electrolyte reservoir and extending beyond said housing such that, upon implantation, said electrolyte reservoir bulb may be positioned proximate the patient'"'"'s skin surface, thereby providing a point of ready access to the electrolyte solution.
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19. The implantable monitoring system of claim 18, further comprising a second enzyme reservoir bulb and a second electrolyte reservoir bulb.
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20. An implantable enzyme-based monitoring system wherein the enzyme is immobilized by microspheres.
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21. A monitoring system adapted for implantation into a patient to measure the in vivo concentration of one or more prescribed substances and to measure the in vivo background concentration of oxygen, the sensor assembly comprising:
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a substrate;
a first working electrode bonded to the substrate;
a reference electrode bonded to the substrate;
a collector electrode bonded to the substrate;
means for making electrical contact with the first working electrode, reference electrode, and collector electrode;
a layer of insulation deposited on the substrate and means for making electrical contact so as to be interspersed between the electrodes bonded to the substrate, the active surface of each of the electrodes being exposed through the layer of insulation, whereby the first working electrode, reference electrode and collector electrode are all electrically isolated from each other on the substrate;
first membrane means covering the electrodes and affixed to the substrate, thereby defining an electrolyte chamber;
an electrolyte solution held within the electrolyte chamber, the electrolyte solution being in contact with the electrodes bonded to the substrate;
a housing surrounding the first membrane means and the substrate, the housing having an opening therein above the active surface of the first working electrode;
second membrane means covering the opening in the housing, the second membrane means being permeable to the one or more prescribed substances to be measured;
first and second securing means for securing the substrate within the housing, the first and second securing means being positioned at opposite ends of the substrate such that a first pocket is formed by the housing, the first membrane means and the first and second securing means;
hydrophobic membrane means within the pocket and above the active surface of the second working electrode, the hydrophobic membrane means filling the portion of the pocket above the second electrode such that the portion of the pocket, above the active surface of the first working electrode, forms an enzyme chamber;
a prescribed enzyme solution contained within the enzyme chamber;
an enzyme reservoir within the housing;
an enzyme channel in fluid communication with the enzyme reservoir and the enzyme chamber;
an electrolyte reservoir within the housing and isolated from the enzyme reservoir, the electrolyte reservoir containing an electrolyte solution;
an electrolyte channel in fluid communication with the electrolyte reservoir and the electrolyte chamber; and
means for applying a prescribed reference voltage between the collector electrode and the reference electrode, and between the first and second working electrodes and reference electrode, and for measuring the electrical current that flows from the first and second working electrodes, whereby, after implantation, internal oxygen may penetrate the housing, the hydrophobic membrane means and the first membrane means and alter the current flowing through the second working electrode, thereby providing a measurement of the in vivo background concentration of oxygen; and
whereby, after implantation, the one or more prescribed substances to be measured may penetrate into the enzyme chamber through the second membrane means, react, in the presence of the prescribed enzyme, with oxygen that has penetrated into the enzyme chamber, such that products or reactants then penetrate the first membrane means and alter the current flowing through the first working electrode thereby providing a measurement of the concentrations of the one or more prescribed substances. - View Dependent Claims (22, 23, 24, 25)
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26. In an implantable monitoring system employing an enzyme solution, a method of extending the life of the system, comprising providing means, within the system, to replenish the enzyme solution,
wherein the enzyme solution moves freely within the means for replenishing the enzyme solution, the enzyme solution moving through a channel on a substrate.
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27. In an implantable monitoring system having an electrode assembly bathed in an electrolyte solution, a method of extending the life of the system, comprising providing means, within the system, to replenish the electrolyte solution.
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28. An implantable monitoring system comprising a fluid solution that is altered by operation of the monitoring system and means, within the monitoring system, for replacing the altered fluid solution with unaltered fluid solution,
wherein the fluid solution moves freely within the means for replacing the altered fluid solution with unaltered fluid solution, the enzyme solution moving through a channel on a substrate.
Specification