Enhancing retention and recovery of particles in a standing wave chamber by modulating frequency and amplitude

Abstract

Magnetic, electric, gravitational and acoustic field forces can be used to concentrate and separate particles. Here we focus on separating cells from a feed suspension using multidimensional acoustic standing waves to trap, cluster and gravitationally settle the cells. The application is concentration of cell cultures for cell therapy manufacturing. Process efficiency depends on frequency, power and settling time. Efficiency is enhanced by frequency and amplitude modulation. The acoustic standing wave is operated at its resonance frequency. Particle concentration and temperature affect the resonator frequency and may detune the system, resulting in lower retention. Exciting the field with multiple closely spaced frequencies increased particle retention between 5%–20% by changing the modulation and central frequency of the excitation signal. At the end of the retention process, the acoustic chamber is full of clusters which are sedimented into the collector. As cell clusters settle, they start dispersing in the fluid medium which impacts recovery. Use of an amplitude modulated acoustic wave during sedimentation reduces particle loss in the supernatant. As amplitude decreases, clusters start to settle. Before cells start to disperse, amplitude is increased to re-cluster the cells. This cycle repeats multiple times and increases cell recovery by 10%–30%.