Abstract: Drug delivery devices and methods of controlled drug delivery to a patient are provided. The drug delivery device may include one or two microchip elements, each of which has a body portion with one or more drug release apertures in fluid communication with at least one containment reservoir. The drug release apertures are closed off by one or more reservoir caps which can be electrically activated to open the drug release apertures. The drug delivery device also includes (i) a drug formulation disposed in the at least one containment reservoir, and (ii) at least one drug-permeable membrane. In some cases, an outer housing is spaced a distance from an exterior wall of the body portion of the microchip element, the outer housing includes the at least one drug-permeable membrane, and a depot space is defined between the drug-permeable membrane and the exterior wall of the body portion of the microchip element.

Abstract: Drug delivery devices and methods of controlled drug delivery to a patient are provided. The drug delivery device may include one or two microchip elements, each of which has a body portion with one or more drug release apertures in fluid communication with at least one containment reservoir. The drug release apertures are closed off by one or more reservoir caps which can be electrically activated to open the drug release apertures. The drug delivery device also includes (i) a drug formulation disposed in the at least one containment reservoir, and (ii) at least one drug-permeable membrane. In some cases, an outer housing is spaced a distance from an exterior wall of the body portion of the microchip element, the outer housing includes the at least one drug-permeable membrane, and a depot space is defined between the drug-permeable membrane and the exterior wall of the body portion of the microchip element.

Abstract: A device for administering a liquid drug formulation to a patient is disclosed. The device includes a reservoir configured to hold a quantity of a liquid drug formulation and a microfluidic circuit that includes at least one flow path configured to transport the liquid drug formulation from the reservoir to a drug release outlet. The microfluidic circuit includes at least one flow restrictor in the at least one flow path. The at least one flow restrictor includes a first substrate secured to a second substrate with a flow channel formed into at least one of the first substrate and the second substrate, and disposed between the first substrate and the second substrate.

Abstract: Devices and methods for administering a medication in fluid form, the systems and methods including a basal flow path and a bolus flow path in parallel to the basal flow path. The bolus flow path comprises a first check valve, a second check valve downstream of the first check valve, a piston pump disposed between the first valve and the second valve, and a pilot operated valve in parallel to the piston pump.

Abstract: Devices and methods for administering a medication in fluid form, the systems and methods including a basal flow path and a bolus flow path in parallel to the basal flow path. The bolus flow path includes a combined piston pump and rotatable valve. The piston pump is configured to prevent partial dosing of a bolus dose.

Abstract: The invention provides devices and systems that help deliver agents of interest, such as therapeutic agents (e.g., nucleic acid vectors) to cells of hollow tissues, such as lung. Also provided herein are methods of using such devices, including methods of treating diseases by delivering therapeutic agents to hollow tissues.

Abstract: Provided herein are methods of delivering therapeutic agents, such as synthetic circular DNA vectors, to target airway cells (e.g., airway epithelial cells). Such methods can be useful in treating respiratory diseases or disorders, such as cystic fibrosis.

Abstract: Provided herein are electrotransfer devices for delivering agents (e.g., nucleic acid vectors) to target cells. Also provided are methods of electrotransfer of therapeutic agents.

Abstract: The present invention involves nucleic acid vectors (e.g., circular DNA vectors) and compositions thereof. Also provided herein are methods of administering nucleic acid vectors (e.g., circular DNA vectors) and compositions thereof, e.g., in combination with pulsed electric field therapy.

Abstract: The present invention involves devices and therapies for ocular diseases or disorders in individuals. Provided herein are therapeutic agents, and devices and methods of delivering therapeutic agents (e.g., nucleic acid vectors) to target ocular cells (e.g., retinal cells) involving methods of administering therapeutic agents to the individual and methods of electrotransfer of therapeutic agents.

Abstract: Systems and methods for sealing a plurality of reservoirs of a microchip element with a sealing grid are provided. For example, in one embodiment, a microchip element comprises a primary substrate having a plurality of reservoirs defined therein. The microchip element also includes a single continuous sealing groove defined in the primary substrate that extends around each of the plurality of reservoirs. In addition, the microchip element includes a sealing substrate comprising a single continuous sealing protrusion extending therefrom. The single continuous sealing protrusion corresponds to and is configured to mate with the single continuous sealing groove to form a hermetic bond between the primary substrate and the sealing substrate. In this manner, the single continuous sealing groove and the single continuous sealing protrusion form a sealing grid about the plurality of reservoirs.

Abstract: Devices and methods for administering a medication in fluid form, the systems and methods including a basal flow path and a bolus flow path in parallel to the basal flow path. The bolus flow path includes a combined piston pump and rotatable valve. The piston pump is configured to prevent partial dosing of a bolus dose.

Abstract: Devices and methods for administering a medication in fluid form, the systems and methods including a basal flow path and a bolus flow path in parallel to the basal flow path. The bolus flow path includes an inlet check valve, a first outlet check valve downstream of the inlet check valve, and a piston pump disposed between the inlet check valve and the first outlet check valve. The piston pump is configured to prevent partial dosing of a bolus dose.

Abstract: Drug delivery devices and methods of controlled drug delivery to a patient are provided. The drug delivery device may include one or two microchip elements, each of which has a body portion with one or more drug release apertures in fluid communication with at least one containment reservoir. The drug release apertures are closed off by one or more reservoir caps which can be electrically activated to open the drug release apertures. The drug delivery device also includes (i) a drug formulation disposed in the at least one containment reservoir, and (ii) at least one drug-permeable membrane. In some cases, an outer housing is spaced a distance from an exterior wall of the body portion of the microchip element, the outer housing includes the at least one drug-permeable membrane, and a depot space is defined between the drug-permeable membrane and the exterior wall of the body portion of the microchip element.

Abstract: A device for administering a liquid drug formulation to a patient is disclosed. The device includes a reservoir configured to hold a quantity of a liquid drug formulation and a microfluidic circuit that includes at least one flow path configured to transport the liquid drug formulation from the reservoir to a drug release outlet. The microfluidic circuit includes at least one flow restrictor in the at least one flow path. The at least one flow restrictor includes a first substrate secured to a second substrate with a flow channel formed into at least one of the first substrate and the second substrate, and disposed between the first substrate and the second substrate.

Abstract: In one aspect, containment devices are provided that include a microchip element having one or more containment reservoirs that are configured to be electrically activated to open; an electronic printed circuit board (PCB) or a silicon substrate positioned adjacent to the microchip element; one or more electronic components associated with the microchip element or the PCB/silicon substrate; and a first inductive coupling device associated with the microchip element or the PCB/silicon substrate, wherein the first inductive coupling device is in operable communication with the one or more electronic components. In another aspect, implantable drug delivery devices are provided that include a body housing at least one drug payload for actively controlled release, wherein the ratio of the volume of the at least one drug payload to the total volume of the implantable drug delivery device is from about 75 ?L/cc to about 150 ?L/cc.

Abstract: Systems and methods for sealing a plurality of reservoirs of a microchip element with a sealing grid are provided. For example, in one embodiment, a microchip element comprises a primary substrate having a plurality of reservoirs defined therein. The microchip element also includes a single continuous sealing groove defined in the primary substrate that extends around each of the plurality of reservoirs. In addition, the microchip element includes a sealing substrate comprising a single continuous sealing protrusion extending therefrom. The single continuous sealing protrusion corresponds to and is configured to mate with the single continuous sealing groove to form a hermetic bond between the primary substrate and the sealing substrate. In this manner, the single continuous sealing groove and the single continuous sealing protrusion form a sealing grid about the plurality of reservoirs.

Abstract: Devices and methods for administering a medication in fluid form, the systems and methods including a basal flow path and a bolus flow path in parallel to the basal flow path. The bolus flow path includes an inlet check valve, a first outlet check valve downstream of the inlet check valve, and a piston pump disposed between the inlet check valve and the first outlet check valve. The piston pump is configured to prevent partial dosing of a bolus dose.

Abstract: Containment devices and methods of manufacture and assembly are provided. In an embodiment, the device includes at least one microchip element, which includes a containment reservoir that can be electrically activated to open, and a first electronic printed circuit board (PCB) which comprises a biocompatible substrate. The first PCB may have a first side on which one or more electronic components are fixed and an opposed second side on which the microchip element is fixed in electrical connection to the one or more electronic components. The device may further include a second PCB and a housing ring securing the first PCB together with the second PCB. The microchip element may include a plurality of containment reservoirs, which may be microreservoirs, and/or which may contain a drug formulation or a sensor element.

Abstract: Systems and methods for sealing a plurality of reservoirs of a microchip element with a sealing grid are provided. For example, in one embodiment, a microchip element comprises a primary substrate having a plurality of reservoirs defined therein. The microchip element also includes a single continuous sealing groove defined in the primary substrate that extends around each of the plurality of reservoirs. In addition, the microchip element includes a sealing substrate comprising a single continuous sealing protrusion extending therefrom. The single continuous sealing protrusion corresponds to and is configured to mate with the single continuous sealing groove to form a hermetic bond between the primary substrate and the sealing substrate. In this manner, the single continuous sealing groove and the single continuous sealing protrusion form a sealing grid about the plurality of reservoirs.