Abstract: The transdermal assay apparatus includes first, second, and third members. The first member has one or more sample surfaces, each of which is configured to receive a sample thereon. The second member defines one or more reservoirs, each of which has an opening on a surface of the second member. Each sample surface is substantially the same size as each opening. The transdermal assay apparatus also includes a magnetic clamp configured to clamp a tissue specimen between the sample surface and the opening. The magnetic clamp preferably includes a magnet having a strength that is selected based on the clamping force required between the first member and the second member. The invention also provides a method for using a transdermal assay apparatus.

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: 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: 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: The transdermal assay apparatus includes first, second, and third members. The first member has one or more sample surfaces, each of which is configured to receive a sample thereon. The second member defines one or more reservoirs, each of which has an opening on a surface of the second member. Each sample surface is substantially the same size as each opening. The transdermal assay apparatus also includes a magnetic clamp configured to clamp a tissue specimen between the sample surface and the opening. The magnetic clamp preferably includes a magnet having a strength that is selected based on the clamping force required between the first member and the second member. The invention also provides a method for using a transdermal assay apparatus.

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: A method of producing an oriented oxide superconducting film. A metal oxyfluoride film is provided on a substrate. The metal oxyfluoride film comprises the constituent metallic elements of an oxide superconductor in substantially stoichiometric proportions. The film is then converted into the oxide superconductor in a processing gas having a total pressure less than atmospheric pressure.

Abstract: Implantable medical devices are provided for controlled release of drugs. In one embodiment, the device comprises a support structure; two or more discrete reservoirs provided in spaced positions across at least one surface of the support structure; and a release system loaded in each of the reservoirs, the release system including drug molecules dispersed in a degradable matrix material, wherein release of the drug molecules from the reservoir is controlled by in vivo disintegration of the matrix material. In another embodiment, the device comprises a support structure; two or more discrete reservoirs provided in spaced positions across at least one surface of the support structure; and a release system loaded in each of the reservoirs, the release system including drug molecules dispersed in a non-degradable matrix material, wherein release of the drug molecules from the reservoir is controlled by in vivo diffusion of the drug molecules from the matrix material.

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 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: The invention includes dispensing a suspension containing solid particles for use in manufacturing a dosage form or other biomedical article by 3DP. The suspension contains solid particles suspended in a liquid. The solid particles may be one or more Active Pharmaceutical Ingredients. The solid particles may be particles of material that are insoluble in the liquid, or they may be particles of a substance that have already dissolved in the liquid up to the saturation level and are present in a concentration beyond what can be dissolved. In addition to solid particles, the liquid may also contain other substances dissolved in it, either substances containing Active Pharmaceutical Ingredients (API) or substances without API. One aspect of the invention includes prevention of agglomeration by adding one or more of several categories of additives to the suspending liquid.

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: 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: A method and apparatus for controlling the migration of binder liquid in a bulk powder. The bulk powder may be deposited in a powder bed and contains at least two different substances, each in powder form. One substance gives the printed part its bulk properties, forms most of the powder, and preferably is either insoluble or not significantly soluble in the binder liquid. The other powder substance is a migration control substance. Upon interaction with the binder liquid, this substance may absorb the binder liquid and form a gel or dissolve into the binder liquid increasing viscosity thereby inhibiting binder migration. No chemical reactions occur between the binder liquid and any of the substances in the powder bed. In another embodiment of the instant invention, binder migration may be further controlled by first printing a barrier region in the powder bed containing the migration control substance.

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 &mgr;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: 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: 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 new mold solves problems that arise from differential changes in geometry inherent to casting metal in a ceramic mold, by control of the internal morphology between the surfaces of the mold that face the casting, and that face the external environment. Layered fabrication techniques are used to create a ceramic mold. For example, an internal geometry composed of a cellular arrangement of voids may be created within the mold wall. Structures may be designed and fabricated so that the ceramic mold fails at an appropriate time during the solidification and/or cooling of the casting. Thus, the casting itself is not damaged. The mold fails to avoid rupture, or even distortion, of the casting. A thin shell of ceramic defines the casting cavity. This shell must be thin enough to fail due to the stresses induced (primarily compressive) by the metal next to it and partly adherent to it.

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.