Acoustic perfusion devices and processes for separating biomolecules from other material in a fluid mixture are disclosed. The devices include an inlet port, an outlet port, and a collection port that are connected to an acoustic chamber. An ultrasonic transducer creates an acoustic standing wave in the acoustic chamber that permits a continuous flow of fluid to be recovered through the collection port while keeping the biological cells within the acoustic chamber to be returned to the bioreactor from which the fluid mixture is being drawn.

Aspects of the disclosure are directed to an apparatus for separating a second fluid or a particulate from a host fluid. That apparatus comprises a flow chamber with at least one inlet and at least one outlet. A drive circuit configured to provide a drive signal to a filter circuit configured to receive the drive signal and provide a translated drive signal. An ultrasonic transducer is cooperatively arranged with the flow chamber, and transducer includes at least one piezoelectric element configured to be driven by the current drive signal to create an acoustic standing wave in the flow chamber. At least one reflector opposing the ultrasonic transducer to reflect acoustic energy.

An automated cell culturing device, which expands, detaches and prepares cells, ready to be implanted in vivo is disclosed. The device is composed by a multi-layered cell culture chamber, a cell preparation chamber, and critical parameters control units which automatically drive the cell culture medium circulation, change and refill. The device according to the invention is characterized in that all the components contacting cells and culture medium constitute a totally disposable cartridge in order to avoid cross-contamination and improve safety. The device is particularly useful for expanding and preparing mesenchymal stem cells for osteoarthritis (OA) therapy, and for other cell based therapies in mammals.

Aspects of the disclosure are directed to an apparatus for separating a second fluid or a particulate from a host fluid. That apparatus comprises a flow chamber with at least one inlet and at least one outlet. A drive circuit configured to provide a drive signal to a filter circuit configured to receive the drive signal and provide a translated drive signal. An ultrasonic transducer is cooperatively arranged with the flow chamber, and transducer includes at least one piezoelectric element configured to be driven by the current drive signal to create an acoustic standing wave in the flow chamber. At least one reflector opposing the ultrasonic transducer to reflect acoustic energy.

A cell detachment device includes: a base; a vessel holder, to which a culture vessel is to be fitted; a guide mechanism configured to guide reciprocating movement of the vessel holder; a collided member configured to collide with the vessel holder when the vessel holder is moving; an urging member configured to urge the culture vessel toward the collided member; and a power imparting mechanism configured to impart, to the vessel holder, power for causing the vessel holder to move.

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.

Methods are disclosed for separating beads and cells from a host fluid. The method includes flowing a mixture containing the host fluid, the beads, and the cells through an acoustophoretic device having an ultrasonic transducer including a piezoelectric material driven by a drive signal to create a multi-dimensional acoustic standing wave. A drive signal is sent to drive the at least one ultrasonic transducer to create the multi-dimensional acoustic standing wave. A recirculating fluid stream having a tangential flow path is located substantially tangential to the standing wave and separated therefrom by an interface region. A portion of the cells pass through the standing wave, and the beads are held back from the standing wave in the recirculating fluid stream at the interface region. Also disclosed is an acoustophoretic device having a coolant inlet adapted to permit the ingress of a cooling fluid into the device for cooling the transducer.

A stirring apparatus including a stirring mechanism configured to execute a stirring process on cells in a culture vessel, and a control unit programmed to at least one of control the stirring mechanism, determine the stirring process of the stirring mechanism, and determine whether the stirring process is performed or not.

An acoustophoresis device made up of modular components is disclosed. Several modules are disclosed herein, including ultrasonic transducer modules, input/output modules, collection well modules, and various connector modules. These permit different systems to be constructed that have appropriate fluid dynamics for separation of particles, such as biological cells, from a fluid.

A perfusion bioreactor includes at least one ultrasonic transducer that can acoustically generate a multi-dimensional standing wave. The standing wave can be used to retain cells in the bioreactor, and can also be utilized to dewater or further harvest product from the waste materials produced in a bioreactor.