Abstract: 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.

Abstract: Acoustophoretic devices and methods for concentrating targeted biological cells in a reduced volume using multi-dimensional acoustic standing waves are disclosed. The methods include flowing a mixture of a host fluid and the biological cells through an acoustophoretic device. The acoustophoretic devices include an inlet, an outlet, and a flow chamber having an ultrasonic transducer-reflector pair. Biological cells, such as T cells, are separated from a host fluid for utilization in allergenic or autologous cell therapies. The disclosed devices and methods are capable of concentrating biological cells to at least 100 times their original cell concentration. The disclosed methods and devices are further capable of decreasing an original feed volume to a final concentrated volume that is less than one percent of the original feed volume.

Abstract: 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.

Abstract: Devices for separating a host fluid from a second fluid or particulate are disclosed. The devices include an acoustic chamber, a fluid outlet at a top end of the acoustic chamber, a concentrate outlet at a bottom end of the acoustic chamber, and an inlet on a first side end of the acoustic chamber. An ultrasonic transducer and reflector create a multi-dimensional acoustic standing wave in the acoustic chamber that traps and separates particulates (e.g. cells) from a host fluid. The host fluid is collected via the fluid outlet, and the particulates are collected via the concentrate outlet. The device is a large-scale device that is able to process liters/hour, and has a large interior volume.

Abstract: 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.

Abstract: Acoustic perfusion devices for separating biological cells 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.

Abstract: An acoustophoresis device includes an acoustic chamber with a piezoelectric element located within its volume. The piezoelectric element vibrates and generates acoustic standing waves from both sides, so that particles can be separated from fluid passing through the acoustic chamber. This permits the element to be cooled more efficiently, reducing transient heat loads in the fluid traveling through the device.

Abstract: Acoustophoretic devices and methods for separating biological cells (particularly T-cells) from other fluids/materials using multi-dimensional acoustic standing waves are disclosed. The devices include an inlet, at least two outlets, and a flow chamber having an ultrasonic transducer-reflector pair. Specifically, T cells, B cells, or NK cells can be separated from other blood components. A dual-pass acoustophoretic system including two acoustophoretic devices arranged in series and fluidly connected to one another is also illustrated. Means for pre-chilling the mixture prior to separation in the devices or system can be used to improve retention, concentration, and clarification and to prevent outgassing.

Abstract: Separation of particles or droplets from a host fluid may be achieved using a transducer and/or reflector that is a thin, non-planar structure. The thin non-planar structure improves operation of an acoustic standing wave generated by an acoustic transducer. The structure may operate as a pressure release boundary and may be constructed as plastic film.

Abstract: A system for enhancing the separation of particles or fluids from water is disclosed. A settling tank or skim tank is provided with an open submersible acoustophoretic separator. In a skim tank, the separator captures and holds oil droplets or particles, permitting them to coalesce until they are large enough and have sufficient buoyant force to float to the top of the tank. In a settling or sediment tank, separator captures and holds particles until they are large enough that the force of gravity causes them to settle out of the water. The acoustophoretic device thus speeds up separation of the particles or droplets from the water.

Abstract: Acoustophoretic devices and methods for using such devices in various applications are disclosed. The devices include a flow chamber having an inlet; a phononic crystal within an active volume of the flow chamber; and ultrasonic transducer(s) that create an acoustic standing wave in the active volume. This combination results in the creation of high-pressure nodes within the active volume, having a value of at least 50 MPa, which is useful for different applications.

Abstract: 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.

Abstract: A system having improved trapping force for acoustophoresis is described where the trapping force is improved by manipulation of the frequency of the ultrasonic transducer. The transducer includes a ceramic crystal. The crystal may be directly exposed to fluid flow. The crystal may be air backed, resulting in a higher Q factor.

Abstract: 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.

Abstract: A system is provided that includes one or more acoustic microfilters through which is flowed a mixture of a fluid and a particulate to selectively filter particles from the fluid. Also included are one or more phononic crystal units coupled to the acoustic microfilter(s) to further selectively filter particles from the fluid. Related apparatus, systems, techniques and articles are also described.

Abstract: A series of multi-dimensional acoustic standing waves is set up inside a growth volume of a bioreactor. The acoustic standing waves are used to hold a cell culture in place as a nutrient fluid stream flows through the cell culture. The nutrient fluid stream dislodges some cells from the cell culture, which can then be recovered for cell therapy applications. The cell culture continues to expand and reproduce, permitting continuous recovery of cells from the bioreactor.

Abstract: An acoustic standing wave is utilized to separate components from a multi-component fluid, such as oil from an oil-water mixture, in a fluid flow scheme with an acoustophoresis device. For example, the flow scheme and device allows for trapping of the oil as the oil coalesces, agglomerates, and becomes more buoyant than the water.

Abstract: 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.

Abstract: A method for separating a second fluid or a particulate from a host fluid is disclosed. The method includes flowing the mixture through an acoustophoretic device comprising an acoustic chamber, an ultrasonic transducer, and a reflector. The transducer includes a piezoelectric material driven by a voltage signal to create a multi-dimensional acoustic standing wave in the acoustic chamber. A voltage signal is sent to drive the ultrasonic transducer in a displacement profile that is a superposition of a combination of different mode shapes that are the same order of magnitude to create the multi-dimensional acoustic standing wave in the acoustic chamber such that the second fluid or particulate is continuously trapped in the standing wave, and then agglomerates, aggregates, clumps, or coalesces together, and subsequently rises or settles out of the host fluid due to buoyancy or gravity forces, and exits the acoustic chamber.

Abstract: Methods for generating particulate clusters and nodal trapping lines having desired widths are disclosed. The devices include an acoustic chamber having an inlet and an outlet. An ultrasonic transducer and reflector create a multi-dimensional acoustic standing wave that generates particulate clusters separated by a channel of fluid running therebetween and creates nodal trapping lines. The frequency of the multi-dimensional acoustic standing wave can be selectively tuned so as to selectively control at least one of (a) a width of each particulate cluster, or (b) a width of each channel of fluid. The frequency of the multi-dimensional acoustic standing wave can also be selectively tuned so as to selectively control the width of each nodal trapping line. Also disclosed are particulate clusters separated by a channel of fluid, wherein a ratio of the widths of the particulate clusters and the channel of fluid can be varied as desired.