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: The present invention provides systems, devices, and related methods, involving electrochemical actuation. In some cases, application of a voltage or current to a system or device of the invention may generate a volumetric or dimensional change, which may produce mechanical work. For example, at least a portion of the system may be constructed and arranged to be displaced from a first orientation to a second orientation. Systems such as these may be useful in various applications, including pumps (e.g., infusion pumps) and drug delivery devices, for example.

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 said 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: The present invention includes controlled release dosage forms and methods of designing and manufacturing dosage forms to obtain specific release profiles, for example, zero-order release profiles, escalating release profiles or decreasing release profiles. The dosage forms of the present invention can include spatial variation of API concentration in the dosage form and can include nested regions. Dosage forms according to the present invention may be manufactured by any appropriate method for obtaining the internal structure as disclosed herein for producing zero-order release profiles and increasing or decreasing release profiles. The invention further includes methods of manufacturing such dosage forms, such as by three-dimensional printing, possibly also including compression of the dosage form after three-dimensional printing. The invention further includes methods of designing such dosage forms.

Abstract: A method is provided for monitoring the status of a medical device implanted in a patient. The method includes the steps of implanting in a patient a medical device which comprises (i) a substrate in which two or more reservoirs are located, with each covered by a reservoir cap, (ii) a drug or sensor located in the reservoir, (iii) a power source and actuation electronics for disintegrating or permeabilizing the reservoir cap, and (iv) a telemetry system; and then using said telemetry system to wirelessly transmit to a remote controller data about the condition of the power source and/or data about which reservoirs have been or have yet to be activated to release the drug therefrom or to expose the sensor therein.

Abstract: The present invention relates to computer-controlled high-throughput systems, computer-program products, and methods of use to prepare a large number of component combinations, at varying concentrations and identities, at the same time, and high-throughput methods to test tissue barrier transfer, such as transdermal transfer, of components in each combination. The methods of the present invention allow determination of the effects of inactive components, such as solvents, excipients, enhancers, adhesives and additives, on tissue barrier transfer of active components, such as pharmaceuticals. The invention thus encompasses the use of computer-controlled high-throughput systems, computer-program products, and methods of high-throughput testing of pharmaceutical compositions or formulations in order to determine the overall optimal composition or formulation for improved tissue transport, such as transdermal transport.

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: Methods and systems are provided for microscale lyophilization or microscale drying of agents of interest, such as pharmaceutical agents or other molecules that are unstable or easily degraded in solution. The drying method includes (a) providing a liquid comprising an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity (between 1 nL and 10 ?L) of the liquid onto a preselected site of a substrate; and then (c) drying the microquantity by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest. The lyophilization method includes freezing the microquantity of liquid after step (b) and before step (c). By processing the agent of interest in microquantities in controlled contact with a substrate surface, improved heat and mass transfer is provided, yielding better process control over drying of the agent of interest compared to conventional bulk drying or lyophilization.

Abstract: Micron scale dielectric items are manipulated by methods and apparatus taking advantage of spatially non-uniform field. Such fields give rise to a force on dielectric items, directing them generally toward regions of more concentrated field. The electrode may be elongated, either unitary, with a generally planar counter electrode, or dual, such as parallel pins, loops or plates. If dual, particles are generally attracted to regions of high field concentration, including tips, edges and spaces between electrode conductors. Items can be granular, threadlike, or sheets, and microelectronic parts and other shapes. Items can also be collected directly into a recess of a pharmaceutical material delivery microchip, with a conductive membrane of the microchip acting as a manipulating electrode. Items are attracted without regard to their surface charge, or the polarity of the field, which can be AC or DC. Charging, or knowing the charge of items to be manipulated is not necessary.

Abstract: The present invention includes controlled release dosage forms and methods of designing and manufacturing dosage forms to obtain specific release profiles, for example, zero-order release profiles, escalating release profiles or decreasing release profiles. The dosage forms of the present invention can include spatial variation of API concentration in the dosage form and can include nested regions. Dosage forms according to the present invention may be manufactured by any appropriate method for obtaining the internal structure as disclosed herein for producing zero-order release profiles and increasing or decreasing release profiles. The invention further includes methods of manufacturing such dosage forms, such as by three-dimensional printing, possibly also including compression of the dosage form after three-dimensional printing. The invention further includes methods of designing such dosage forms.

Abstract: A drug delivery device such as an oral dosage form (ODF) with a toxic or potent core encapsulated by a non-toxic region. The non-toxic region may be a region including multiple layers, coatings, shells, and combinations thereof, which provides protection to and isolation from the toxic or potent core. The drug in the toxic or potent core is incorporated into the dosage form via, for example, three-dimensional printing, as a solution, solubilization or suspension of solid particles in liquid, rather than by the more conventional handling and compressing of dry powder. This minimizes the likelihood of creating airborne particles of the toxic drug during manufacturing, hence controlling and minimizing the exposure of manufacturing personnel to the hazardous substance. Wet dispensing of the toxic or potent drug further provides greater bioavailability of the drug to the patient.

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: The present invention relates to high-throughput systems and methods to prepare a large number of component combinations, at varying concentrations and identities, at the same time, and high-throughput methods to test tissue barrier transfer, such as transdermal transfer, of components in each combination. The methods of the present invention allow determination of the effects of inactive components, such as solvents, excipients, enhancers, adhesives and additives, on tissue barrier transfer of active components, such as pharmaceuticals. The invention thus encompasses the high-throughput testing of pharmaceutical compositions or formulations in order to determine the overall optimal composition or formulation for improved tissue transport, such as transdermal transport.

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 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: Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms.

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: Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms.

Abstract: A device for controlling or altering the temperature of a liquid at the point of dispensing. A temperature-altering device is thermally coupled to a dispensing device to compensate for heat dissipated into the liquid as it passes through the dispensing device during dispensing. The dispensing device may be for example, a miniature solenoid valve (microvalve), a piezoelectric printhead, or the like. According to aspects of the invention, a temperature-altering device provides or reduces heat at the point of dispensing in order to alter, control or maintain a constant temperature of the dispensed liquid. As a result, improvement is obtained in the consistency of the fluid regime of the dispensed droplet stream. The temperature-altering device may be a thermoelectric device capable of moving heat either from or to the dispensing structure, or may be a heater.

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.