Abstract: This disclosure provides systems and methods for seeding cell cultures in a microfluidic device. The systems and methods of this disclosure can enable flow of a cell solution from one side of a scaffold, such as a porous substrate or membrane, to the other side of the scaffold. Flow of the liquid can pass through the scaffold while the cells themselves do not, resulting in the cells driven to the surface of the scaffold for consequent attachment. A microfluidic device can include a microfluidic feature structured to create a seal between a cell seeding tool and an inlet to a microchannel of the microfluidic device. This can enable a pressure-driven flow to push fluid down the channel and through pores of the membrane. In contrast, traditional gravity fed seeding of cells may not create enough pressure to drive fluid through the pores of the scaffold.

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: This disclosure provides systems and methods for integrating an array of electronic sensors capable of performing trans-epithelial electrical resistance (TEER) measurements into a microfluidic device that includes a well plate. In some implementations, the sensors can include electrodes that are submerged into fluidically connected wells of the microfluidic device, which can contain an electrically conductive fluid such as the cell culture media or a buffered salt solution. An array of such electrodes can be integrated into a lid of the system that includes the microfluidic device. These electrodes can be routed using a printed circuit board through a number of multiplex switches that can allow addressing of a desired unit of the device through a microprocessor in communication with a computer.

Abstract: This disclosure provides systems and methods for seeding cell cultures in a microfluidic device. The systems and methods of this disclosure can enable flow of a cell solution from one side of a scaffold, such as a porous substrate or membrane, to the other side of the scaffold. Flow of the liquid can pass through the scaffold while the cells themselves do not, resulting in the cells driven to the surface of the scaffold for consequent attachment. A microfluidic device can include a microfluidic feature structured to create a seal between a cell seeding tool and an inlet to a microchannel of the microfluidic device. This can enable a pressure-driven flow to push fluid down the channel and through pores of the membrane. In contrast, traditional gravity fed seeding of cells may not create enough pressure to drive fluid through the pores of the scaffold.

Abstract: Systems and methods disclosed herein related to an apparatus including a fluid flow plate and a microfluidic valve assembly. The fluid flow plate includes a plurality of polymer layers that define a fluid flow passage through the microfluidic valve assembly. The microfluidic valve assembly includes a valve seat, a flexible membrane, a valve cavity, a valve head, and an actuator. The actuator is configured to selectively control pressure applied by the valve head to the flexible membrane, such that in a first actuator state the valve head depresses the flexible membrane into the valve cavity and into contact with the valve seat, thereby preventing fluid flow through the valve assembly, and in a second state, the valve head and the flexible membrane are retracted substantially out of the valve cavity allowing fluid to flow through the valve assembly. In various implementations, the valve seat and/or the flexible membrane include an elastomer layer.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the organ systems are fluidically connected with a constant-volume pump.

Abstract: Systems and methods disclosed herein related to an apparatus including a fluid flow plate and a microfluidic valve assembly. The fluid flow plate includes a plurality of polymer layers that define a fluid flow passage through the microfluidic valve assembly. The microfluidic valve assembly includes a valve seat, a flexible membrane, a valve cavity, a valve head, and an actuator. The actuator is configured to selectively control pressure applied by the valve head to the flexible membrane, such that in a first actuator state the valve head depresses the flexible membrane into the valve cavity and into contact with the valve seat, thereby preventing fluid flow through the valve assembly, and in a second state, the valve head and the flexible membrane are retracted substantially out of the valve cavity allowing fluid to flow through the valve assembly. In various implementations, the valve seat and/or the flexible membrane include an elastomer layer.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the organ systems are fluidically connected with a constant-volume pump.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the organ systems are fluidically connected with a constant-volume pump.

Abstract: An implantable drug delivery device that uses multiple reservoir elements to contain and release doses of active pharmaceutical ingredients. The device includes a first shell element, which has a first enclosed cavity volume and forms a low-permeability barrier. The first shell element is configured to absorb light irradiation from a laser source, the laser irradiation causing a breach in the first shell element. A first active pharmaceutical ingredient is contained in the first enclosed cavity volume and is released when the first shell element is breached. The device also includes a second shell element, which has a second enclosed cavity volume and also forms a low-permeability barrier. A second active pharmaceutical ingredient is contained in the second enclosed cavity volume. The device also includes an envelope element containing the first and second shell elements.

Abstract: The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the organ systems are fluidically connected with a constant-volume pump.