Abstract: An implantable medical device is provided for use with an external detector to detect an analyte in vivo. In one embodiment, the device consisting essentially of a substrate; a plurality of discrete reservoirs located in the substrate, each reservoir having at least one opening; a reacting component contained in each reservoir; and at least one non-degradable barrier layer covering each reservoir opening, the barrier layer being permeable to an analyte to be detected, wherein the reacting component remains inside the reservoirs and can react with the analyte to be detected, and wherein the device is adapted for implantation into the body of a patient.

Abstract: Methods are provided for controlled reservoir opening, including the steps of (a) providing a biocompatible implantable device which comprises at least one substrate, a plurality of reservoirs in the substrate, reservoir caps each of which covers one of the reservoirs, and molecules sealed inside the reservoirs; and (b) selectively heating each reservoir cap in an amount effective to rupture the reservoir cap and open the reservoir. In another embodiment, the method steps include (a) implanting into a patient a biocompatible device which comprises at least one substrate, a plurality of reservoirs in the substrate, reservoir caps each of which covers one of the reservoirs, and molecules sealed inside the reservoirs; and (b) selectively heating each reservoir cap in an amount effective to rupture the reservoir cap and open the reservoir.

Abstract: Electrochemical sensor devices are provided, in various amperometric, potentiometric, and conductometric sensor device configurations. An amperometric sensor device may include a structural body which has at least one reservoir that has at least one opening; a working electrode located within the reservoir; analyte sensor chemistry located within the reservoir and deposited on at least the working electrode; an auxiliary electrode located outside of the reservoir; a reference electrode; at least one reservoir cap closing the opening to isolate the working electrode and analyte sensor chemistry within the reservoir and to prevent an analyte outside of the reservoir from contacting the analyte sensor chemistry; and means for rupturing or displacing the reservoir cap to permit the analyte from outside of the reservoir to contact the analyte sensor chemistry.

Abstract: Devices are provided for use in medical diagnostics which include a substrate, a plurality of discrete reservoirs located in the substrate, each reservoir having at least one opening, at least one diagnostic substance contained in each reservoir, and at least one non-degradable barrier layer covering each reservoir opening, the barrier layer being permeable to an agent to be detected, wherein the diagnostic substance remains inside the reservoirs and can react with the agent to be detected.

Abstract: Methods are provided for making a multi-reservoir device comprising (i) patterning one or more photoresist layers on a substrate; (ii) depositing onto the substrate at least one metal layer by a sputtering process to form a plurality of reservoir caps and conductive traces; (iii) removing the photoresist layers using a liftoff process; (iv) forming a plurality of reservoirs in the substrate; (v) loading each reservoir with reservoir contents (such as a drug or sensor); and (vi) sealing each reservoir. Optionally, the reservoir cap comprises a first conductive metal layer coated with one or more protective noble metal films. To enhance the resistance of the substrate (e.g., a silicon substrate) to etching in vivo, the interior sidewalls of the reservoirs optionally can include a protective coating (e.g., gold, platinum, carbon, silicon carbide, silicon dioxide, and platinum silicide), or sidewalls comprising silicon can be doped with boron or another impurity.

Abstract: Devices are provided for the controlled exposure of a sensor or sensor component. The device may include a substrate; at least one reservoir provided in the substrate; at least one sensor or sensor component located in the at least one reservoir; at least one reservoir cap closing an opening in the at least one reservoir to isolate the sensor or sensor component from a selected environmental component outside of the at least one reservoir; at least one intermediate barrier layer disposed in the at least one reservoir between the reservoir cap and the sensor or sensor component; and means for disintegrating the reservoir cap to expose the sensor or sensor component to the selected environmental component.

Abstract: Devices, systems, and methods are provided for wirelessly powering and/or communicating with microchip devices used for the controlled exposure and release of reservoir contents, such as drugs, reagents, and sensors. In one embodiment, the system includes (1) a microchip device comprising a substrate having a plurality of reservoirs containing reservoir contents for release or exposure; and (2) a rechargeable or on-demand power source comprising a local component which can wirelessly receive power from a remote transmitter wherein the received power can be used, directly or following transduction, to activate said release or exposure of the reservoir contents. In another embodiment, the system comprises (1) a microchip device comprising a substrate a plurality of reservoirs containing reservoir contents for release or exposure; and (2) a telemetry system for the wireless transfer of data between the microchip device and a remote controller.

Abstract: Methods are provided for hermetically sealing an opening in a reservoir of a containment device. The method comprises applying a polymeric material to an opening in a reservoir of a containment device, the reservoir comprising reservoir contents (such as a drug or a sensor) to be hermetically isolated within the reservoir, the applied polymeric material closing off the opening and forming a temporary seal; and adhering a hermetic sealing material onto the polymeric material to hermetically seal the opening. The reservoir can be a micro-reservoir. The containment device can comprises an array of two or more of reservoirs, and the method comprises hermetically sealing each of the two or more reservoirs.

Abstract: Devices are provided for the controlled release of drug or other molecules. The devices include (1) a substrate, which optionally includes two or more substrate portions bonded together, (2) at least two reservoirs in the substrate, (3) a release system disposed in the reservoirs that includes the molecules for release and optionally a matrix material, and (4) active or passive means for controlling release of the molecules from the reservoirs. In one embodiment, a reservoir cap is positioned on, or within a portion of, the reservoir and over the molecules, so that the molecules are controllably released from the device by diffusion through or upon disintegration of the reservoir cap.

Abstract: Devices are provided for medical diagnostics comprising a substrate; an array of reservoirs; one or more electrodes located at least partially inside the reservoirs; a plurality of discrete reservoir caps covering openings in the plurality reservoirs; control circuitry for selectively disintegrating or permeabilizing the reservoir cap over a reservoir opening; and, optionally, a diagnostic reagent in the reservoirs. Devices also are provided for the controlled delivery of molecules comprising a substrate; an array of reservoirs; a release system in the reservoirs comprising molecules for release; one or more electrodes attached to the substrate inside the reservoirs or to a surface outside of the reservoirs, wherein the electrodes are not reservoir caps; and means for applying an electric current or potential across the electrodes effective to activate release of the molecules from the reservoirs. The devices can be adapted for implantation for in vivo diagnostics or drug delivery.

Abstract: Devices for the controlled release of one or more drugs into a patient are provided. The devices include an implantable stent, at least two reservoirs in the stent, and a release system contained in each of the at least two reservoirs, wherein the release system may have one or more drugs for release at a controlled rate. Reservoir caps optionally are provided to control the time at which release of the one or more drugs is initiated.

Abstract: Microchip device arrays that can conform to a curved surface are provided for the controlled release or exposure of reservoir contents. The arrays comprise two or more microchip device elements, each of which includes a plurality of reservoirs that contain molecules for controlled release or components for selective exposure, and a means for flexibly connecting the device elements. The reservoirs can contain one or more drugs and/or one or more secondary devices, such as a sensor or a component thereof. Preferably, the microchip devices contain and controllably release therapeutic, prophylactic, and diagnostic molecules to and into the eye of a patient in need thereof.

Abstract: Microchip devices and methods of manufacture thereof are provided to increase the uniformity and reliability of active exposure and release of microchip reservoir contents. In one embodiment, the microchip device for the controlled release or exposure of molecules or secondary devices comprises: (1) a substrate having a plurality of reservoirs; (2) reservoir contents comprising molecules, a secondary device, or both, located in the reservoirs; (3) reservoir caps positioned on the reservoirs over the reservoir contents; (4) electrical activation means for disintegrating the reservoir cap to initiate exposure or release of the reservoir contents in selected reservoirs; and (5) a current distribution means, a stress induction means, or both, operably engaged with or integrated into the reservoir cap, to enhance reservoir cap disintegration.

Abstract: Microchip devices and methods of use are provided for the controlled exposure of a secondary device. In one embodiment, the microchip device include a substrate, a plurality of reservoirs in the substrate, a secondary device in one or more of the reservoirs, at least one barrier layer covering each of the reservoirs to isolate the secondary device from an environmental component outside the reservoirs, wherein the barrier layer is impermeable to the environmental component, and a microprocessor-controlled actuation means for rendering the barrier layer porous or permeable to the environmental component to expose the secondary device to said environmental component. The secondary device can comprise a sensor or sensing component (e.g., a biosensor). In other embodiments, microchip devices are provided for the controlled exposure of a reacting component, such as an enzyme. In still other embodiments, sensors are provided on the device outside of the reservoirs.

Abstract: Methods are provided for hermetically sealing the reservoirs of microchip devices and for hermetically sealing the substrate assemblies in a hermetic packaging structure.

Abstract: Methods of manufacturing microchip devices are provided for controlled release of molecules, such as drugs. Methods include compression molding and casting, alone or in combination with microfabrication techniques. In preferred embodiments, devices are made by (1) filling a die with a polymer powder; (2) compressing the powder to form a polymer preform; (3) thermal compression molding the preform to form a substrate in a mold having a plurality of protrusions that form reservoirs in the substrate; and (4) filling the reservoirs with a release system comprising the molecules to be released. Alternatively, ceramic devices are formed by casting the substrate from a ceramic powder or a slurry using a mold having protrusions that form reservoirs in the substrate. Control over the release rate and time of the molecules from the reservoirs of the microchip device is provided by incorporating release systems and/or reservoir caps.

Abstract: Methods and devices are provided for enhancing corrosion of an electrode in a biocompatible fluid. The method comprises (1) placing a primary electrode and a counter electrode in an electroconductive biocompatible fluid to form an electrochemical cell; and (2) applying a time-varying potential, through the electrochemical cell, to the primary electrode. In a preferred embodiment, the primary electrode is metal and comprises a reservoir cap of a microchip device for the release of molecules or exposure of device reservoir contents. The potential preferably is characterized by a waveform having a maximum potential effectively anodic to meet or exceed the corrosion potential of the primary electrode. Also, the minimum potential preferably is effectively cathodic to be below the value where re-deposition of metal ions on the metal electrode can substantially occur, thereby corroding the metal electrode.

Abstract: Methods and devices are provided for mechanically sealing the reservoirs of microchip devices to prevent leakage from or between any of the reservoirs. In one embodiment, the method includes sandwiching a microchip device and a gasket material covering the reservoir openings between a front sealing frame and a backplate, such that the gasket material is compressed against the back side of the microchip device by the back plate. The front sealing frame is secured to the back sealing plate using fasteners or welding. The gasket material is preferably a flexible polymeric sheet, which is biocompatible and compatible with the reservoir contents. In another embodiment, a composite backplate is used in place of the back sealing plate and separate gasket material. The composite backplate can include a substrate having sealing plugs defined thereon. The composite backplate also can be designed to hold the drug, thereby combining the assembly steps of reservoir filling and sealing.

Abstract: Microchip delivery devices are provided that control both the rate and time of release of molecules. In one embodiment, an implantable microchip device is provided for the controlled delivery of drug molecules into a patient comprising at least one substrate; a plurality of reservoirs in the substrate; a release system which includes drug molecules for release, the release system being provided in each of the reservoirs; a reservoir cap positioned on or in each of the reservoirs over the release system, the reservoir cap comprising a material that undergoes a phase change in response to a change in temperature; and a heating means capable of selectively causing the phase change independently in each reservoir cap, to release the molecules from the reservoirs. The reservoirs can contain multiple drugs or other molecules in variable dosages. Each of the reservoirs of a single microchip can contain different molecules and/or different amounts and concentrations, which can be released independently.

Abstract: Devices for the controlled release of one or more drugs are provided. The devices include an implantable stent, at least two reservoirs in the stent, and a release system contained in each of the at least two reservoirs, wherein the release system comprises one or more drugs for release.