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: Transfer of genetic and other materials to cells is conducted in a hands-free, automated, high throughput, continuous process. A system using a microfluidic hydrodynamic sheath flow configuration includes arrangements for pushing cells from side streams containing a cell culture medium to a central stream containing an electroporation buffer. Electroporation can be conducted in an assembly in which two or more microfluidic channels are provided in a parallel configuration and in which various layers can be stacked together to form a laminate type structure.

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: Transfer of genetic and other materials to cells is conducted in a hands-free, automated, high throughput, continuous process. A system using a microfluidic hydrodynamic sheath flow configuration includes arrangements for pushing cells from side streams containing a cell culture medium to a central stream containing an electroporation buffer. Electroporation can be conducted in an assembly in which two or more microfluidic channels are provided in a parallel configuration and in which various layers can be stacked together to form a laminate type structure.

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: A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.

Abstract: A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.

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: A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.

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: 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: 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: The present disclosure provides a handpiece for trans-canal delivery of a therapeutic substance to the inner ear. The handpiece can be inserted into the middle ear via a surgical tympanotomy approach. The handpiece can be integrated with a micropump and a fluid reservoir. The handpiece can enable a controlled injection of a therapeutic substance directly through the round window membrane and into the inner ear. The direct delivery of the therapeutic substance to the inner ear can enable the delivery of a precise amount of therapeutic substance into the inner ear. The micropump can include a self-contained fluid reservoir that can provide predetermined volumes of fluid to precise areas of the patient.

Abstract: The present solution provides systems and methods for trans-round window membrane drug delivery. As an overview, a system can include a micropump that is connected to a flexible cannula. The cannula can be threaded through a handpiece that can be used to pierce the round window membrane of a patient. Using the handpiece, the cannula can be inserted through the round window membrane 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-round window membrane 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: A system for cell bioprocessing and cell therapy manufacturing can include a series of microfluidic modules to enable continuous-flow end-to-end cell bioprocessing. Each module can implement a different technology, and the modules can be coupled to one another to perform various unit operations in the cell bioprocessing or cell-therapy manufacturing chain to enable direct processing of a blood or blood product sample. The system can automatically and continuously process the sample into genetically-modified lymphocytes or T cells for cellular therapy. The technologies implemented by each module in the system can include any combination of microfluidic acoustophoresis, microfluidic acoustophoretic media exchange or cell washing, and continuous-flow microfluidic electrotransfection. Modules implementing these microfluidic technologies can be interconnected with plastic tubing or with a custom manifold.

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: 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: 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: Transfer of genetic and other materials to cells is conducted in a hands-free, automated, high throughput, continuous process. A system using a microfluidic hydrodynamic sheath flow configuration includes arrangements for pushing cells from side streams containing a cell culture medium to a central stream containing an electroporation buffer. Electroporation can be conducted in an assembly in which two or more microfluidic channels are provided in a parallel configuration and in which various layers can be stacked together to form a laminate type structure.