Precise manipulation of fluids and objects on the micro scale is seldom a simple task, but nevertheless crucial for many applications in life sciences and chemical engineering. We present a microfluidic chip fabricated in silicon-glass, featuring one or several pairs of acoustically excited sharp edges at side channels that drive a pumping flow throughout the chip and produce a strong mixing flow in their vicinity. The chip is simultaneously capable of focusing cells and microparticles that are suspended in the flow. The multifunctional micropump provides a continuous flow across a wide range of excitation frequencies (80kHz-2MHz), with flow rates ranging from nL/min to μL/min, depending on the excitation parameters. In the low-voltage regime, the flow rate depends quadratically on the voltage applied to the piezoelectric transducer, making the pump programmable. The behaviour in the system is elucidated with finite element method simulations, which are in good agreement with experimentally observed behaviour. The acoustic radiation force arising due to a fluidic channel resonance is responsible for the focusing of cells and microparticles, while the streaming produced by the pair of sharp edges generates the pumping and the mixing flow. If cell focusing is detrimental for a certain application, it can also be avoided by exciting the system away from the resonance frequency of the fluidic channel. The device, with its unique bundle of functionalities, displays great potential for various bio-chemical applications.

The acoustic contrast factor (ACF) is calculated from the relative density and compressibility differences between a fluid and an object in the fluid. To name but one application, knowing the ACF of a biological cell represents a crucial step in the design of acoustophoretic systems, for instance to isolate cancer cells from a liquid biopsy such as blood without labels or physical contact. For biological cells the static compressibility is different from the high frequency counterpart relevant for the ACF. In this study, we started by characterizing the ACF of low vs. high metastatic cell lines with known associated differences in phenotypic static E-modulus. The change in the static E-modulus, however, was not reflected in a change of the ACF, prompting a more in depth analysis of the influences on the ACF. We demonstrate that static E-modulus increased biological cells through formaldehyde fixation have an increased ACF. Furthermore, the static E-modulus decreased biological cells treated with actin polymerization inhibitor cytochalasin D have a decreased ACF. Complementing these mechanical tests, a numerical COMSOL model was implemented and used to parametrically explore the effects of cell density, cell density ratios, dynamic compressibility and therefore the dynamic bulk modulus. Collectively the combined laboratory and numerical experiments reveal that a change in the static E-modulus alone might, but does not automatically lead to a change of the dynamic ACF for biological cells. This highlights the need for a multiparametic view of the biophysical basis of the cellular ACF, as well as the challenges in harnessing acoustophoretic systems to isolate circulating cells based on their mechanical properties alone.

Despite a long history and the vast number of applications demonstrated, very few market products incorporate acoustophoresis. Because a human operator must run and control a device during an experiment,...