Abstract: Reservoir-based medical devices are provided. In one embodiment, the medical device comprises a substrate; at least two discrete, microfabricated reservoirs provided in spaced positions across at least one surface of the substrate; discrete reservoir caps covering the at least two reservoirs; and control circuitry for selectively disintegrating the reservoir caps to open the reservoirs. The reservoirs of the device can include a diagnostic reagent or other molecules useful in medical diagnostics. In one embodiment, the reservoir cap comprises an anode and the control circuitry comprises a cathode and a power source for creating an electric potential between the cathode and the anode. Application of the electric potential causes the reservoir cap to disintegrate, thereby opening the reservoir.

Abstract: A method is provided for selectively opening a containment reservoir. The method includes providing a device which comprises a substrate in which at least one reservoir is located and covered by a reservoir cap; and directing laser light to the reservoir cap to cause the reservoir cap to disintegrate or become permeable. The device may be an implantable medical device. The reservoirs may contain a drug for controlled release or a biosensor.

Abstract: Methods are provided for medical treatment or diagnosis of a patient. The method includes implanting into the patient a device which comprises (i) a substrate in which at least one reservoir is located and covered by a first reservoir cap, (ii) a drug or sensor located in the reservoir, and (iii) control circuitry and a power source for disintegrating or permeabilizing the reservoir cap, and (iv) an external interface to receive incident light energy; and directing focused light to the external interface of the implanted device to actuate disintegration or permeabilization of the reservoir cap to release the drug or expose the sensor. The device may implanted onto or into the sclera or other tissue surface of the eye of the patient. The focused light may be laser light, which may be used to transmit power or data to the device.

Abstract: A medical device is provided which may include a reservoir which has an opening and contains a sensor; a reservoir cap closing off the opening to isolate the sensor from an environmental component outside the reservoirs, the reservoir cap being impermeable to the environmental component and adapted to selectively undergo a phase change to disintegrate the reservoir cap and thereby expose the sensor to the environmental component. A method of use may include (i) selectively disintegrating a reservoir cap to expose a sensor which is disposed inside a reservoir of a device implanted in a patient, the disintegrating comprising inducing a phase change in the reservoir cap; and (ii) using the sensor to generate an output signal, wherein the output signal is recorded and stored in a writeable computer memory chips, directed to a microprocessor for immediate analysis and processing, or sent to a remote location away from the device.

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: Devices, such as medical devices, are provided which include a body portion having at least one reservoir which has two or more openings, the two or more openings being defined in part by a reservoir cap support; reservoir contents, such as a drug formulation or sensor, disposed inside the reservoir; and a reservoir cap which closes off the two or more reservoir openings. The reservoir cap, which can be ruptured, controls release or exposure of the reservoir contents. In one embodiment, the device is an implantable medical device and provides for the controlled release of drug or exposure of a sensor.

Abstract: Medical devices and methods are provided for electrical stimulation of neural tissue and controlled drug delivery to a patient. The device includes an implantable drug delivery module which comprises a plurality of reservoirs, a release system comprising at least one drug contained in each of the reservoirs, and control means for selectively releasing a pharmaceutically effective amount of drug from each reservoir; a neural electrical stimulator which comprises a signal generator connected to at least one stimulation electrode for operable engagement with a neural tissue of the patient; and at least one microcontroller for controlling operational interaction of the drug delivery module and the neural electrical stimulator. The microcontroller may control the signal generator and the control means of the drug delivery module. The device may further include a sensor operable to deliver a signal to the microcontroller, for example to indicate when to deliver electrical stimulation, drug, or both.

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: Reservoir-based devices are provided in which an individual reservoir has at least two openings with a support structure therebetween and closed by reservoir caps covering the openings to control release or exposure of reservoir contents. In one embodiment, the device is an implantable medical device and provides for the controlled release of drug or exposure of a sensor. The device includes a substrate; at least one reservoir disposed in the substrate, the reservoir having two or more openings; reservoir contents located in the reservoir; two or more discrete reservoir caps, each reservoir cap sealingly covering at least one of the reservoir openings; and control means for selectively disintegrating or permeabilizing the reservoir caps.

Abstract: Medical devices and methods are provided for electrical stimulation of neural tissue and controlled drug delivery to a patient. The device includes an implantable drug delivery module which comprises a plurality of reservoirs, a release system comprising at least one drug contained in each of the reservoirs, and control means for selectively releasing a pharmaceutically effective amount of drug from each reservoir; a neural electrical stimulator which comprises a signal generator connected to at least one stimulation electrode for operable engagement with a neural tissue of the patient; and at least one microcontroller for controlling operational interaction of the drug delivery module and the neural electrical stimulator. The microcontroller may control the signal generator and the control means of the drug delivery module. The device may further include a sensor operable to deliver a signal to the microcontroller, for example to indicate when to deliver electrical stimulation, drug, or both.

Abstract: Devices and methods are provided for transdermal diagnostic sensing, alone or in combination with transdermal drug delivery. The device includes a substrate having a plurality of discrete reservoirs, each reservoir having at least one opening; contents disposed in the reservoirs, the contents of each reservoir including a diagnostic agent or a sensor for measuring an analyte; at least one discrete reservoir cap which cover said at least one opening; control means for disintegrating or permeabilizing the reservoir cap; means for transporting an analyte from the skin to said sensors and/or for transporting said diagnostic agent to the skin following release of said diagnostic agents from said reservoir; and means for securing the device to the skin of a patient.

Abstract: A drug delivery device for implantation into a patient is provided that includes at least one device element that includes a substrate having a plurality of discrete reservoirs disposed therein, the reservoirs containing drug molecules and a degradable matrix material which controls in vivo release of the drug molecules from the reservoirs, wherein the drug delivery device is adapted to conform to a curved bone tissue surface. In one embodiment, the substrate is flexible and conforms to a bone tissue surface. In another embodiment, the device has two or more device elements attached to or integral with a flexible supporting layer.

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 and methods are provided for transdermal administration of a pharmaceutical agent to a patient in need thereof. The device includes a substrate, a plurality of discrete reservoirs in the substrate, one or more pharmaceutical agents stored in the reservoirs, discrete reservoir caps that prevent the pharmaceutical agent from passing out from the reservoirs until desired, control means for actuating release of the one or more pharmaceutical agents from one or more of the reservoirs by disintegrating or permeabilizing the reservoir caps, means for securing the device to the skin of the patient, and means for transporting the pharmaceutical agent to the skin following release from the one or more of the reservoirs. In another embodiment, the device is adapted for diagnostic sensing instead of or in addition to drug delivery.

Abstract: Devices and methods are provided for controlled release of chemical molecules, such as drugs. One device comprises a plurality of reservoirs; a rupturable covering, such as a thin metal film, enclosing a first end of each reservoir; a release formulation in each reservoir comprising chemical molecules for release; an expanding material layer in each reservoir; and a semi-permeable membrane enclosing a second end of each reservoir distal the release formulation, the semi-permeable membrane being operable to permit selected molecules (e.g., water) from outside the reservoir to diffuse to the expanding material layer to expand the expanding material layer and displace the release formulation in an amount effective rupture the rupturable membrane and discharge the release formulation.

Abstract: Microchip devices are provided that include a substrate; a plurality of reservoirs in the substrate, each reservoir defining an internal volume; and a reservoir cap positioned on or in each of the reservoirs bounding the internal volume from an external environment, the reservoir cap being formed of a material that undergoes a phase change upon heating, wherein the internal volume can communicate with the external environment upon heating said reservoir cap to cause said reservoir cap to undergo a phase change and rupture.

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: 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.