Abstract: Method and devices are provided for extended and controlled delivery of parathyroid hormone to a patient. The method includes implanting a medical device into the patient, the medical device comprising a substrate, a plurality of reservoirs in the substrate, a release system contained in each of the reservoirs, wherein the release system comprises parathyroid hormone; and controllably releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs. The parathyroid hormone can be released intermittently, such as once daily over an extended period (e.g., two months, ten months, or more.). The device can further include reservoirs containing a bone resorption inhibitor or other drug for release. The devices are useful in delivering PTH for the treatment and prevention of bone loss, such as associated with osteoporosis.

Abstract: Devices are provided for the controlled exposure or release of contents stored in hermetically sealed reservoirs. The devices comprise a primary substrate having a front side and a back side, and including one or more hermetic sealing materials; a plurality of reservoirs in the primary substrate positioned between the front side and the back side; reservoir contents, which comprise chemical molecules (such as drugs) or a secondary device (such as a glucose sensor), located inside the reservoirs; a hermetic sealing substrate having a surface composed of one or more hermetic sealing materials; and a hermetic seal formed between and joining the primary substrate and the hermetic sealing substrate, wherein the hermetic seal independently seals the reservoirs.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a substrate, a plurality of reservoirs in the substrate, reservoir contents disposed in the reservoirs, discrete reservoir caps covering each reservoir to seal the reservoir contents in the reservoirs, and control circuitry for selectively disintegrating the reservoir caps to release or expose the reservoir contents in vivo. At least one of the reservoir caps comprises a first electrically conductive layer coated with one or more protective layers. In one embodiment, the control circuitry comprises an electrical input lead and an electrical output lead connected to and directly contacting each of said reservoir caps and a source of electric power for applying an electrical current through each reservoir cap in an amount effective to rupture each of the reservoir caps.

Abstract: An implantable medical device is provided for controlled delivery or exposure of reservoir contents. The device may include a substrate; a plurality of discrete reservoirs in the substrate, wherein the reservoirs have interior walls and at least one opening in the substrate; reservoir contents disposed in the reservoirs; a reservoir cap closing the at least one opening of each of the reservoirs to seal the reservoir contents in each of the reservoirs; and control circuitry for selectively disintegrating the reservoir caps to release or expose the reservoir contents in vivo, wherein the interior walls of the reservoirs comprise a material to protect the substrate in vivo. For example, to enhance the resistance of the substrate to etching in vivo, the interior sidewalls of the reservoirs may include a protective coating (such as gold, platinum, carbon, silicon carbide, silicon dioxide, or platinum silicide), or the sidewalls may include a doped silicon.

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.

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 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: A method for forming a device, comprising providing a first substrate carrying a first set of components disposed in a first encapsulating layer over the first set of components, providing a second substrate carrying a second set of components disposed in a second encapsulating layer over the second set of components, bonding the first and second substrates and functionally interconnecting at least one of the predefined components in the first set of components with at least one of the components in the second set of components.

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: 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: Implantable devices for controlled delivery of a drug are provided which include a substrate; at least two reservoirs in the substrate, each reservoir having an opening; at least one therapeutic agent in each of the reservoirs; a reservoir cap sealing each opening; a mechanical rupturing mechanism which moves into contact with and ruptures the reservoir cap to permit release the therapeutic agent from the reservoir through the opening; and a mixing chamber adjacent the reservoirs, wherein upon release of the therapeutic agent from at least one of the reservoirs, the therapeutic agent is combined with a carrier fluid in the mixing chamber and then transported to a delivery site in a human or animal.

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 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.

Abstract: Devices are provided for the controlled exposure or release of contents stored in hermetically sealed reservoirs. The devices comprise a primary substrate having a front side and a back side, and including one or more hermetic sealing materials; a plurality of reservoirs in the primary substrate positioned between the front side and the back side; reservoir contents, which comprise chemical molecules (such as drugs) or a secondary device (such as a glucose sensor), located inside the reservoirs; a hermetic sealing substrate having a surface composed of one or more hermetic sealing materials; and a hermetic seal formed between and joining the primary substrate and the hermetic sealing substrate, wherein the hermetic seal independently seals the reservoirs.

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: Methods and devices are provided for selective release or exposure of reservoir contents, such as a drug formulation or diagnostic reagent, sealed in a reservoir, e.g., a microreservoir. The devices comprise a substrate; one or more reservoirs located in and defined by the substrate; reservoir contents located inside the reservoirs; a reservoir cap or rupturable layer sealing an outlet of the reservoir; and means for disintegrating the reservoir cap or rupturing the rupturable layer; and means for accelerating the release of the reservoir contents from the reservoir through the outlet, or for enhancing diffusional mass transport of a material into or out of the reservoir. The means for accelerating can, for example, include a shape memory material. In a preferred embodiment, the device is adapted for implantation into a human or animal body and comprises an array of several discrete reservoir, each one being individually openable at a desired time.

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 and methods are provided for the storage and controlled release of a solid form of a drug. The device comprises a body portion; one or more reservoirs located in and defined by the body portion; a solid matrix which comprises a drug and which is contained in each of the one or more reservoirs; and one or more excipient materials dispersed throughout pores or interstices within the solid matrix and substantially filling any space not otherwise occupied by the solid matrix within each of the one or more reservoirs, wherein the excipient material enhances stability of the drug while stored in the one or more reservoirs or enhances release of the drug from each reservoir. In an alternative embodiment, the device provides for the storage and controlled exposure of a chemical sensor material.

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: 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.