Abstract: A device, system and process involve conducting electroporation of microvesicles or exosomes or other target structures in a microfluidic arrangement at pressures that exceed atmospheric pressure. Single as well as multiple flow configurations can be employed. In some cases, the system and its operation are computer-controlled for partial or complete automation.

Abstract: Electroporation is conducted in a system comprising a central fluid stream shielded by fluid streams having different electrical conductivities. The streams can be supported by microchannels. In one example, an inner sheath fluid flow is supported by microchannels at each side of a central microchannel. An outer sheath fluid is supported by outer microchannels at the exterior of the inner sheath fluid flow microchannels.

Abstract: A system for sequential exposure of particles to different fluid streams includes an acoustic actuator device for acoustically driving one or more substrates and a microchannel device of the one or more substrates that receive particles in a first flowing fluid, moves the particles to a second flowing fluid, then moves the particles out of the second flowing fluid using acoustic radiation generated by the acoustic actuator device. The system can control residence times in the streams. According to one use, the first flowing fluid is a cell buffer and the second flowing media is an electroporation buffer. An electroporation system is placed in or downstream of the acoustic actuator device. However, in other uses, the second flowing media might be a wash buffer.

Abstract: A viral transduction and/or electroporation device has s a membrane separating two chambers and two electroporation electrodes for the chambers. An electrical voltage source is used for establishing an electrical field across the membrane and between the two electrodes. In operation, fluid is flowed into the chambers including fluid containing electroporation cargo and viral transduction solution and an electrical field is established across the membrane and between the electrodes to electroporate cells pinned to the membrane and transfecting the cells.

Abstract: Transfer of genetic and other materials to cells is conducted in a hands-free, automated and continuous process that includes flowing the cells between electroporation electrodes to facilitate delivery of a payload into the cells, while acoustophoretically focusing the cells. Also described is a control method for the acoustophoretic focusing of cells that includes detecting locations of cells flowing through a channel, such as with an image analytics system, and modulating a drive signal to an acoustic transducer to change the locations of the cells flowing in the channel. Finally, an electroporation driver module is described that uses a digital to analog converter for generating an electroporation waveform and an amplifier for amplifying the electroporation waveform for application to electroporation electrodes.

Abstract: The present solution provides trans-round window membrane (RWM) drug delivery. As an overview, the system can include a micropump that is connected to a flexible cannula. The cannula can include a stiffened and sharpened tip to facilitate insertion through the RWM. The cannula can be inserted through the RWM to improve the distribution of the delivered drug throughout the inner ear. The present solution can function as a small implantable or wearable device that can be used for both chronic and acute trans-RWM drug delivery. With this configuration, the micropump can constantly or intermittently deliver, over a period of days to months, small volumes of drugs from an internal reservoir.

Abstract: Microfluidic devices and associated methods are disclosed. A microfluidic device includes a target entrainment channel and an effluent channel on opposing sides of a semipermeable membrane. A restrictor channel that is narrower than the effluent channel is interposed between the semipermeable membrane and the effluent channel. Fluid that flows from the target entrainment channel, through the semipermeable membrane and the restrictor channel to the effluent channel, pins target cells along the center of the target entrainment channel for electroporation using an electrode in the channel.

Abstract: Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.

Abstract: A method and system of delivering a charged cargo, such as a biomolecule, to a target structure, such as cells, exosomes, other vesicles or micelles, using an electroactive porous membrane. This method comprises contacting an electroactive porous membrane with a fluid flow toward the membrane. The fluid contains charged biomolecules and the membrane and biomolecules are oppositely charged so that the biomolecules in the fluid are trapped on the membrane as the fluid flows through the pores of the membrane. Acceptor cells of interest are pinned to the membrane by the flow of the fluid, thereby aggregating the cells onto the membrane in close proximity to the trapped biomolecules. Finally, the acceptor cells are permeabilized.

Abstract: Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.

Abstract: A system and method of using a microfluidic electroporation device for cell treatment is provided. The cell or exosome treatment system can include a microfluidic electroporation device, a voltage source coupled to a plurality of electrodes and a controller coupled to the voltage source. The microfluidic electroporation device can include a fluid receptacle, a semipermeable membrane, and a base including a channel in fluid communication with the fluid receptacle and the semipermeable membrane. A first electrode can be positioned within the fluid receptacle and a second electrode coupled to the base. The second electrode is positioned relative to the first electrode to create an electric field sufficient to electroporate cells or exosomes disposed in the fluid receptacle. The controller can be configured to cause the first and second electrodes to apply voltage electroporating the cells and exosomes.

Abstract: Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.

Abstract: The present disclosure provides compositions and methods for treating an auditory disease in a subject in need thereof comprising administering an effective amount of a gel-based precursor that includes an inner ear-specific therapeutic compound directly into the cochlea of the subject.

Abstract: Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.