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 and methods are provided for wirelessly powering and/or communicating with implanted medical devices used for the controlled exposure and release of reservoir contents, such as drugs or sensors. The device may include a substrate having a plurality of reservoirs containing reservoir contents for release or exposure; and 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 the release or exposure of the reservoir contents.

Abstract: Devices and methods for the controlled release or exposure of reservoir contents, and methods of manufacture thereof, are provided. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. The controlled release system may be incorporated into an implantable drug delivery or biosensing device.

Abstract: Methods for operating a sensor device are provided, which may include (a) providing at a site (e.g., implanting in a patient) a device which comprises at least first and second reservoirs, a first sensor and corresponding first reference sensor located within the first reservoir, a second sensor and corresponding second reference sensor located within the second reservoir, a first reservoir cap closing an opening in the first reservoir and a second reservoir cap closing an opening in the second reservoir, and a power source, control circuitry, and electrodes for selectively disintegrating each reservoir cap; (b) disintegrating the first reservoir cap and operating the first sensor and reference sensor; and (c) using the first reference sensor to determine whether the first sensor is operating properly. If not operating properly, then the control circuitry initiates disintegration of the second reservoir cap and operation of the second sensor and reference sensor.

Abstract: Methods are provided for making a reservoir-based sensor device. The method may include fabricating a first substrate portion which comprises an upper surface, an opposed lower surface, a plurality of through holes defining reservoirs between said upper surface and said lower surface, and a plurality of reservoir caps closing off one end of said through holes at said upper surface; fabricating a plurality of sensors on an upper surface of a second substrate portion; aligning the first and second substrate portions such that each of said plurality of sensors is in alignment with each of said plurality of reservoirs; and bonding together the lower surface of said first substrate portion and the upper surface of said second substrate portion to seal each of said sensors inside the reservoir with which it is aligned.

Abstract: This invention relates to methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. The invention provides a microsystem platform and a micromanipulation device for manipulating the platform that utilizes the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels. The microsystem platforms of the invention are provided having arrays of thermal control regions, wherein fluid applied to the platform can be placed at a temperature and maintained at that temperature for a time that is dependent on the path length of the channel in the region, the cross-section dimension of the channel, and the rotational speed of the platform. Methods specific for the apparatus of the invention for performing any of a wide variety of microanalytical or microsynthetic processes are provided.

Abstract: Implantable medical devices for cardiac care are provided that include a housing having a power source and control electronics; at least one lead extending from the housing and having one or more discrete reservoirs therein, each reservoir having an opening to an outer surface of the lead; one or more sensors, which monitor or detects an analyte, biomarker, or physical parameter that is associated with cardiac health, located in the reservoirs and in operable communication with said control electronics; and at least one selectively disintegratable reservoir cap sealing each of the reservoir openings, wherein the reservoir cap is operably connected to the power source and control electronics to disintegrate the reservoir cap and expose the sensors in vivo. The sensor may detect an analyte or biomarker selected from potassium ion, sodium ion, lithium ion, magnesium ion, ammonium ion, ionized calcium, lactate, oxygen, carbon dioxide, and creatinine, urea, BUN, and bilirubin.

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: 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: Methods are provided for conformally coating microchip devices and for sealing reservoirs containing molecules or devices in a microchip device. One method comprises (i) providing a substrate having a plurality of reservoirs having reservoir openings in need of sealing; (ii) loading reservoir contents comprising molecules, a secondary device, or both, into the reservoirs; and (iii) applying a conformal coating barrier layer, such as a vapor depositable polymeric material, e.g., parylene, onto the reservoir contents over at least the reservoir openings to seal the reservoir openings. Another method comprises vapor depositing a conformal coating material onto a microchip device having at least two reservoirs and reservoir caps positioned over molecules or devices stored in the reservoirs, and providing that the conformal coating does not coat or is removed from the reservoir caps.

Abstract: This invention provides methods and apparatus for detecting and quantifying particulate matter suspended in a fluid. Specifically, the invention provides an integrated, affinity-binding based, analytical system comprising a platform for performing an affinity-binding based assay for specifically binding particulates including microbial cells, and a detection means for detecting the particulates specifically bound to a defined surface or chamber comprising the platform. Methods for using the analytical systems of the invention are also provided.

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: This invention relates to methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. The invention provides a microsystem platform and a micromanipulation device for manipulating the platform that utilizes the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels. The invention specifically provides devices and methods for performing miniaturized in vitro amplification assays such as the polymerase chain reaction. Methods specific for the apparatus of the invention for performing PCR are provided.

Abstract: This invention provides methods and apparatus for performing microanalytic analyses and procedures, particularly miniaturized cell based assays. These methods are useful for performing a variety of cell-based assays, including drug candidate screening, life sciences research, and clinical and molecular diagnostics.

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: This invention provides methods an apparatus for detecting and quantifying particulate matter suspended in a fluid. Specifically, the invention provides an integrated, affinity-binding based, analytical system comprising a platform for performing an affinity-binding based assay for specifically binding particulates including microbial cells, and a detection means for detecting the particulates specifically bound to a defined surface or chamber comprising the platform. Methods for using the analytical systems of the invention are also provided.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. In one embodiment, the controlled release system is incorporated into an implantable drug delivery device.