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.

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: 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 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: 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: 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: 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 invention concerns arrays of solid-forms of substances, such as compounds and rapid-screening methods therefor to identify solid-forms, particularly of pharmaceuticals, with enhanced properties. Such properties include improved bioavailability, solubility, stability, delivery, and processing and manufacturing characteristics. The invention relates to a practical and cost-effective method to rapidly screen hundreds to thousands of samples in parallel. The invention further provides methods for determining the conditions and/or ranges of conditions required to produce crystals with desired compositions, particle sizes, habits, or polymorphic forms. In a further aspect, the invention provides high-throughput methods to identify sets of conditions and/or combinations of components compatible with particular solid-forms, for example, conditions and/or components that are compatible with advantageous polymorphs of a particular pharmaceutical.

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: Dosage forms prepared by solid free form fabrication (SFF) provide release of medicament in multiple phases.

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: Dosage forms prepared by solid free form fabrication (SFF) provide release of medicament in multiple phases.

Abstract: A process for selective electroless plating onto a substrate, including providing a substrate having at least a catalytic surface; providing a plating gel comprising a carrier vehicle, an electroless platable metal compound capable of providing metal ions to the carrier vehicle at a specific pH, a reducing agent, and a polymeric thickening agent; applying said plating gel to the substrate surface in a selected pattern, and inducing plating of said metal on the substrate surface in said selected pattern. A stabilizer, and/or buffering and/or organic chelating agent, and/or surfactant and/or a humectant may be included in the plating gel. Preferably the metal compound is a gold complex, and the substrate is aluminum nitride.

Abstract: Solid free-form fabrication (SFF) methods are used to manufacture devices for allowing tissue regeneration and for seeding and implanting cells to form organ and structural components, which can additionally provide controlled release of bioactive agents, wherein the matrix is characterized by a network of lumens functionally equivalent to the naturally occurring vasculature of the tissue formed by the implanted cells, and which can be lined with endothelial cells and coupled to blood vessels at the time of implantation to form a vascular network throughout the matrix. The SFF methods can be adapted for use with a variety of polymeric, inorganic and composite materials to create structures with defined compositions, strengths, and densities, using computer aided design (CAD). Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP).

Abstract: An oxide superconductor article is provided having an oxide superconductor film having a thickness of greater than 0.5 microns disposed on a substrate, said article having a transport critical current density (Jc) of greater than or equal to about 105 A/cm2 at 77 K, zero field. The oxide superconductor film is characterized by high Jc and high volume percent of c-axis epitaxial oxide grains, even with thicknesses of up to 1 micron.

Abstract: Solid free-form fabrication (SFF) methods are used to manufacture devices for allowing tissue regeneration and for seeding and implanting cells to form organ and structural components, which can additionally provide controlled release of bioactive agents, wherein the matrix is characterized by a network of lumens functionally equivalent to the naturally occurring vasculature of the tissue formed by the implanted cells, and which can be lined with endothelial cells and coupled to blood vessels at the time of implantation to form a vascular network throughout the matrix. The SFF methods can be adapted for use with a variety of polymeric, inorganic and composite materials to create structures with defined compositions, strengths, and densities, using computer aided design (CAD).Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP).

Abstract: Fabrication methods are provided for microchips that control both the rate and time of release of multiple chemical substances and allow for the release of a wide variety of molecules in either a continuous or pulsatile manner. In all of the preferred embodiments, a material that is impermeable to the drugs or other molecules to be delivered and the surrounding fluids is used as the substrate. Reservoirs are etched into the substrate using either chemical (wet) etching or plasma (dry) etching techniques well known in the field of microfabrication. Hundreds to thousands of reservoirs can be fabricated on a single microchip using these techniques. A release system, which includes the molecules to be delivered, is inserted into the reservoirs by injection, inkjet printing, or spin coating methods. Exemplary release systems include polymers and polymeric matrices, non-polymeric matrices, and other excipients or diluents. The physical properties of the release system control the rate of release of the molecules.

Abstract: A technique for smoothing and otherwise changing the surfaces of porous bodies, such as ceramic molds, made using layer manufacturing processes, such as three dimensional printing processes. The surface finish of the mold can be smoothed by casting a slip of fine particles onto the surface to form a generally level, and preferably non-conformal, coating on the surfaces. In general, the fine particles of the slip are caused to be filtered out from the liquid, so that the fine particles come to rest at or near the surface of the body formed. They are typically, preferentially drawn toward concave regions of the surface, as compared to convex regions, thereby forming a non-conformal coating. Furthermore, other surface properties can be changed by tailoring the slip to produce those properties. The coating can be applied to external surfaces, and internal surfaces, such as would become the surface against which a molded part would be formed.

Abstract: A process for making a component includes the steps of: depositing a layer of a porous material; positioning a mask near to the deposited layer; applying a bonding material that will cause any contacted portions of the porous material to become bonded together, over and through the mask, such that the bonding material is applied to one or more selected regions of the recently deposited layer of porous material; and repeating the foregoing three steps a selected number of times to produce a selected number of successive layers, said bonding material causing each of said successive layers to become bonded to an adjacent layer. Any unbonded porous material that is not at the selected regions is easily removed. The mask may be an open stencil mask, or a screen mask. If open stencil masks are used, there may be more than one mask for a single layer of porous material. Successive masks may be positioned by a continuous sheet, a rotating disk, or individually, such as by a robot.

Abstract: Solid free-form techniques for making medical devices for controlled release of bioactive agent and implantation and growth of cells are described using computer aided design. Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP). The macrostructure and porosity of the device can be manipulated by controlling printing parameters. Most importantly, these features can be designed and tailored using computer assisted design (CAD) for individual patients to optimize therapy.