Abstract: The present invention comprises methods and devices for thermal treatment of a barrier to increase the permeability of the barrier. One form of increasing the permeability of the barrier comprises forming micropores which may be used for administration of active agents across the barrier, or may be used for sampling or collecting fluids, or may be used for detecting, measuring or determining analytes, or may be used for monitoring of physiological or other conditions. Devices of the present invention may comprise microheaters that are activated by inductive or ohmic heating power supply components.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: Simple microneedle devices for delivery of drugs across or into biological tissue are provided, which permit drug delivery at clinically relevant rates across or into skin or other tissue barriers, with minimal or no damage, pain, or irritation to the tissue. The devices include a substrate to which a plurality of hollow microneedles are attached or integrated, and at least one reservoir, containing the drug, selectably in communication with the microneedles, wherein the volume or amount of drug to be delivered can be selectively altered. The reservoir can be formed of a deformable, preferably elastic, material. The device typically includes a means, such as a plunger, for compressing the reservoir to drive the drug from the reservoir through the microneedles, In one embodiment, the reservoir is a syringe or pump connected to the substrate.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: Various apparatuses, arrangements, and methods are provided for creating various structures including microstructures. In one embodiment, a method for creating a microstructure is provided comprising packing a plurality of particles into a micromold, and then applying energy to the particles in the micromold. As a result of the application of energy, a microstructure is formed in the micromold out of the particles. Thereafter, the microstructure is removed from the micromold.

Abstract: A method for reversibly, or irreversibly, altering the permeability of cells, tissues or other biological barriers, to molecules to be transported into or through these materials, through the application of acoustic energy, is provided. The acoustic energy is applied indirectly to the cells or tissue whose permeability is to be altered, at a frequency and intensity appropriate to alter the permeability to achieve the desired effect, such as the transport of endogenous or exogenous molecules and/or fluid, for drug delivery, measurement of analyte, removal of fluid, alteration of cell or tissue viability or alteration of structure of materials. In the preferred embodiment, the method includes applying the ultrasound in combination with devices for monitoring and/or implementing feedback controls.

Abstract: Methods and devices are provided for administering a drug to a patient's eye. The methods include (a) inserting a hollow microneedle into the sclera or corneal stroma without penetrating across the sclera or corneal stroma; and (b) infusing a fluid drug formulation through the microneedle and into the sclera or cornea. It further may include partially retracting the microneedle before infusion to enhance delivery. Alternatively, the methods may include (a) inserting a solid microneedle into the sclera or corneal stroma without penetrating across the sclera or corneal stroma, wherein the solid microneedle comprises a first quantity of a drug formulation and inserting causes the solid microneedle to form a pocket in the sclera or corneal stroma; and (b) releasing the drug formulation into the pocket to form a drug depot, whereby a drug is released from the depot. The methods and devices may include an array of multiple microneedles.

Abstract: Microneedle devices are provided for transport of therapeutic and biological molecules across tissue barriers and for use as microflameholders. In a preferred embodiment for transport across tissue, the microneedles are formed of a biodegradable polymer. Methods of making these devices, which can include hollow and/or porous microneedles, are also provided. A preferred method for making a microneedle includes forming a micromold having sidewalls which define the outer surface of the microneedle, electroplating the sidewalls to form the hollow microneedle, and then removing the micromold from the microneedle. In a preferred method of use, the microneedle device is used to deliver fluid material into or across a biological barrier from one or more chambers in fluid connection with at least one of the microneedles. The device preferably further includes a means for controlling the flow of material through the microneedles.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: Various apparatuses, arrangements, and methods are provided for creating various structures including microstructures. In one embodiment, a method for creating a microstructure is provided comprising packing a plurality of particles into a micromold, and then applying energy to the particles in the micromold. As a result of the application of energy, a microstructure is formed in the micromold out of the particles. Thereafter, the microstructure is removed from the micromold.

Abstract: The various embodiments of the present invention relate generally to methods and apparatus for surface ablation. More particularly, various embodiments of the present invention are related to methods and apparatus for ablation of barrier surfaces, such as skin, to increase the permeability of the barrier surface. Embodiments of the present invention comprise rapid thermo-mechanical ablation of the skin by a microfluidic jet generated by an arc discharge to produce micron-scale holes localized to the stratum corneum, which increases skin permeability.

Abstract: Microneedle devices and methods of manufacture and use thereof are provided. The devices may be used in controlled delivery of drug across or into a biological barrier, such as skin, or fluid withdrawal from a biological barrier. In one case, the device includes a base substrate which comprises a drug dispersed in a swellable matrix material; and one or more microneedles extending from the base substrate, wherein the one or more microneedles comprise a water-soluble or water-swellable material, wherein the one or more microneedles will dissolve or swell following insertion into the biological barrier, providing a transport pathway for the drug to pass from the base substrate into the biological barrier.

Abstract: Microneedle devices are provided for transport of therapeutic and biological molecules across tissue barriers and for use as microflameholders. In a preferred embodiment for transport across tissue, the microneedles are formed of a biodegradable polymer. Methods of making these devices, which can include hollow and/or porous microneedles, are also provided. A preferred method for making a microneedle includes forming a micromold having sidewalls which define the outer surface of the microneedle, electroplating the sidewalls to form the hollow microneedle, and then removing the micromold from the microneedle. In a preferred method of use, the microneedle device is used to deliver fluid material into or across a biological barrier from one or more chambers in fluid connection with at least one of the microneedles. The device preferably further includes a means for controlling the flow of material through the microneedles.

Abstract: Methods and devices are provided for delivering a drug to or withdrawing a fluid from a biological tissue, such the skin, sclera, cornea, and conjunctiva. One method includes the steps of inserting at least one microneedle into the biological tissue; partially retracting the at least one microneedle from the tissue; and then delivering at least one drug formulation into the biological tissue via the partially retracted at least one microneedle. The microneedle deforms and penetrates the biological tissue during the insertion step, and the retraction step at least partially relaxes the tissue deformation while maintaining at least part of the tissue penetration, facilitating drug delivery or fluid withdrawal.

Abstract: Coated microneedle devices and methods of making such devices are provided. In one aspect, a method for coating includes providing a microstructure having at least one surface in need of coating; and applying a coating liquid, which comprises at least one drug, to the at least one surface of the microstructure, wherein the surface energy of the coating liquid is less than the surface energy of the surface of the microstructure. The coating liquid may include a viscosity enhancer and surfactant. Microneedles having heterogeneous coatings, pockets, or both are also provided.

Abstract: Microneedle devices are provided for controlled sampling of biological fluids in a minimally-invasive, painless, and convenient manner. The microneedle devices permit in vivo sensing or withdrawal of biological fluids from the body, particularly from or through the skin or other tissue barriers, with minimal or no damage, pain, or irritation to the tissue. The microneedle device includes one or more microneedles, preferably in a three-dimensional array, a substrate to which the microneedles are connected, and at least one collection chamber and/or sensor in communication with the microneedles. Preferred embodiments further include a means for inducing biological fluid to be drawn through the microneedles and into the collection chamber for analysis. In a preferred embodiment, this induction is accomplished by use of a pressure gradient, which can be created for example by selectively increasing the interior volume of the collection chamber, which includes an elastic or movable portion engaged to a rigid base.

Abstract: A method for reversibly, or irreversibly, altering the permeability of cells, tissues or other biological barriers, to molecules to be transported into or through these materials, through the application of acoustic energy, is enhanced by applying the ultrasound in combination with devices for monitoring and/or implementing feedback controls. The acoustic energy is applied directly or indirectly to the cells or tissue whose permeability is to be altered, at a frequency and intensity appropriate to alter the permeability to achieve the desired effect, such as the transport of endogenous or exogenous molecules and/or fluid, for drug delivery, measurement of analyte, removal of fluid, alteration of cell or tissue viability or alteration of structure of materials such as kidney or gall bladder stones.

Abstract: Simple microneedle devices for delivery of drugs across or into biological tissue are provided, which permit drug delivery at clinically relevant rates across or into skin or other tissue barriers, with minimal or no damage, pain, or irritation to the tissue. The devices include a substrate to which a plurality of hollow microneedles are attached or integrated, and at least one reservoir, containing the drug, selectably in communication with the microneedles, wherein the volume or amount of drug to be delivered can be selectively altered. The reservoir can be formed of a deformable, preferably elastic, material. The device typically includes a means, such as a plunger, for compressing the reservoir to drive the drug from the reservoir through the microneedles. In one embodiment, the reservoir is a syringe or pump connected to the substrate.