FloDesign (United States)

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.

A three-dimensional model is developed to describe an acoustic field excited by a piezoelectric plate of finite size in a fluid filled resonator. First, the eigenfunctions (modes) of a bare plate are derived using general piezoelectric equations considering the elastic and electric properties of the plate. Then, the piezoelectric plate is placed into a fluid media such that only one plate side is in fluid and an acoustic field generated by the plate in the fluid is estimated. Finally, a reflector is placed to be parallel to the piezoelectric plate and acoustic field in a resonator is evaluated. The solution for a piezoelectric plate of finite size is obtained using Singular Value Decomposition (SVD) method. Equations for acoustic and electric variables are presented. Radiation force on spherical particles in the standing wave field is derived and discussed. Numerical results are presented to show the three-dimensional modal displacement and electrical characteristics of the plate at various frequencies and aspect ratio. Finally, the analytical results are compared with two-dimensional and three-dimensional finite element results using COMSOL Multiphysics commercial software.

Large scale acoustophoretic separation of particles in a flow field can be accomplished by trapping the particles, i.e., remain in a stationary position, in ultrasonic standing waves. The particles are collected in a column pattern, separated by half a wavelength. Within each nodal plane, the particles are trapped in the minima of the acoustic radiation potential. The axial component of the acoustic radiation force drives the particles to their stable axial position. The radial or lateral component of the acoustic radiation force is the force that traps the particle. It must be larger than the combined effect of fluid drag force, i.e., Stokes drag, and gravitational force. There is a need for a better understanding of the lateral acoustic radiation force in realistic acoustophoretic separation devices. COMSOL Multiphysics® software was used to predict the acoustic field in two and three dimensional models of acoustophoretic separation devices driven by piezoelectric transducers. The resulting acoustic field was then used to calculate the acoustic radiation force acting on a suspended particle in two and three dimensions by applying Gor’kov’s equation. Measurements of trapped particles in standing waves indicate accurate calculations of acoustic field and radiation force. [Work supported by NSF PFI:BIC 1237723.]

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