Macro-scale acousto-fluidics involves the interaction between acoustic radiation force exerted on a particle by bulk acoustic standing waves spanning many wavelengths, fluid drag force, and the gravitational force of the particle. Parameters are particle size, and ratio of particle to fluid density and particle to fluid compressibility. Different acousto-fluidics configurations can be used to manipulate particles in multiple ways. In cell clarification, the configuration is that of a depth flow filter with the added benefit of separating the cells out of the acoustic field, thereby eliminating any issues with filter clogging or fouling. In perfusion of stirred bioreactors, the configuration resembles that of a tangential flow filter. In a third configuration, the bulk acoustic standing wave is angled relative to the fluid velocity resulting in a label-free fractionation tool. Several underlying theoretical and numerical results of acoustic radiation force and particle trajectory calculations will be presented. A theoretical framework to calculate the acoustic radiation force on spherical, spheroidal, and cylindrical particles has been developed for any particle size relative to wavelength. An analytical solution for particle deflection angle in a planar angled standing wave and uniform flow has been developed. Experimental results will be shown to support the theory.

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Chimeric antigen receptor (CAR) T-cell therapy is a promising and evolving immunotherapy approach for cancer treatment. In allogeneic CAR-T therapies, TCR + cells must be removed from the final cell product because of immunogenicity problems. It is accomplished through a negative affinity cell selection process where TCR + cells are affinity bound to a bead. The harvested TCR-cells are the product cells. A multidimensional acoustic standing wave field separates cell-bead complexes from free cells in an acoustic fluidized bed. The feed solution motion is normal to the primary acoustic field. Irrespective of the particle acoustic contrast, an interface between a dense suspension on the bottom and clear fluid on top develops in the field. We examine the physics behind the development of the interface and its subsequent motion. This motion influences the purity, scalability, and recovery of the TCR- cells. We present the effects of different acoustofluidic parameters, e.g., bead concentration, bead acoustic contrast factor, frequency, and flow rate on interface formation and its movement. Theoretical calculations and experimental results are discussed. The acoustic fluidized bed has been shown to give final purities of 99 + % of TCR- cells from a starting purity of 60%–70%, with 70 + % recoveries of TCR- cells.

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Acoustic standing wave fields are widely used in MEMS applications to manipulate micron sized particles in fluids with typical fluid channel dimensions of half a wavelength. This report presents three novel acoustofluidic platforms for particle separation and/or manipulation at macroscale, i.e., tens to hundreds of wavelengths. The first platform uses multidimensional standing waves which generate lateral radiation forces that trap and tightly cluster suspended fluid or particulate, enhancing the gravitational settling effect that results in continuous, macroscale separation. The second platform employs acoustic radiation forces generated near the edge of an acoustic standing wave to hold back particles and generate a wall type separation effect. The third platform uses the acoustic radiation forces generated by a macroscale, angled standing wave to deflect particles in a controlled fashion for particle manipulation and/or differentiation. Applications are focused in biopharmacy and cellular and gene therapy: mammalian cell clarification, continuous perfusion of bioreactors, cell concentration and washing, cell sorting and differentiation, fractionation, microcarrier-cell separation, and affinity acoustic separation. A commercial cell clarification device has been introduced. The key physics principles related to acoustic radiation force and low Reynolds number multi-phase flows are discussed. Experimental results of cell clarification, perfusion, and manipulation are shown.