Rapid acoustofluidic mixing by ultrasonic surface acoustic wave-induced acoustic streaming flow.

Ultrasonic surface acoustic wave (SAW)-induced acoustic streaming flow (ASF) has been utilized for microfluidic flow control, patterning, and mixing. Most previous research employed cross-type SAW acousto-microfluidic mixers, in which the SAWs propagated perpendicular to the flow direction. In this configuration, the flow mixing was induced predominantly by the horizontal component of the acoustic force, which was usually much smaller than the vertical component, leading to energy inefficiency and limited controllability. Here, we propose a vertical-type ultrasonic SAW acousto-microfluidic mixer to achieve rapid flow mixing with improved efficiency and controllability. We conducted in-depth numerical and experimental investigations of the vertical-type SAW-induced ASF to elucidate the acousto-hydrodynamic phenomenon under varying conditions of total flow rate, acoustic wave amplitude, and fluid viscosity conditions. We conducted computational fluid dynamics simulations for numerical flow visualization and utilized micro-prism-embedded microchannels for experimental flow visualization for the vertical SAW-induced ASF. We found that the SAW-induced vortices served as a hydrodynamic barrier for the co-flow streams for controlled flow mixing in the proposed device. For proof-of-concept application, we performed chemical additive-free rapid red blood cell lysis and achieved rapid cell lysis with high lysis efficiency based on the physical interactions of the suspended cells with the SAW-induced acoustic vortical flows. We believe that the proposed vertical-type ultrasonic SAW-based mixer can be broadly utilized for various microfluidic applications that require rapid, controlled flow mixing.

Acoustofluidic separation of proteins from platelets in human blood plasma using aptamer-functionalized microparticles.

Microfluidic liquid biopsy has emerged as a promising clinical assay for early diagnosis. Herein, we propose acoustofluidic separation of biomarker proteins from platelets in plasma using aptamer-functionalized microparticles. As model proteins, C-reactive protein and thrombin were spiked in human platelet-rich plasma. The target proteins were selectively conjugated with their corresponding aptamer-functionalized microparticles of different sizes, and the particle complexes served as a mobile carrier for the conjugated proteins. The proposed acoustofluidic device was composed of an interdigital transducer (IDT) patterned on a piezoelectric substrate and a disposable polydimethylsiloxane (PDMS) microfluidic chip. The PDMS chip was placed in a tilted arrangement with the IDT to utilize both vertical and horizontal components of surface acoustic wave-induced acoustic radiation force (ARF) for multiplexed assay at high-throughput. The two different-sized particles experienced the ARF at different magnitudes and were separated from platelets in plasma. The IDT on the piezoelectric substrate could be reusable, while the microfluidic chip can be replaceable for repeated assays. The sample processing throughput with the separation efficiency >95% has been improved such that the volumetric flow rate and flow velocity were 1.6 ml/h and 37 mm/s, respectively. For the prevention of platelet activation and protein adsorption to the microchannel, polyethylene oxide solution was introduced as sheath flows and coating on to the walls. We conducted scanning electron microscopy, x-ray photoemission spectroscopy , and sodium dodecyl sulfate- analysis before and after the separation to confirm the protein capture and separation. We expect that the proposed approach will provide new prospects for particle-based liquid biopsy using blood.

Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor.

The cytotoxic response of natural killer (NK) cells in a microreactor to surface acoustic waves (SAWs) is investigated, where the SAWs produce an acoustic streaming flow. The Rayleigh-type SAWs form by an interdigital transducer propagated along the surface of a piezoelectric substrate in order to allow the dynamic stimulation of functional immune cells in a noncontact and rotor-free manner. The developed acoustofluidic microreactor enables a dynamic cell culture to be set up in a miniaturized system while maintaining the performance of agitating media. The present SAW system creates acoustic streaming flow in the cylindrical microreactor and applies flow-induced shear stress to the cells. The suspended NK cells are found to not be damaged by the SAW operation of the adjusted experimental setup. Suspended NK cell aggregates subjected to an SAW treatment show increased intracellular Ca2+ concentrations. Simultaneously treating the NK cells with SAWs and protein kinase C activator enhances the lysosomal protein expressions of the cells and the cell-mediated cytotoxicity against target tumor cells. These have important implications by showing that acoustically actuated system allows dynamic cell culture without cell damages and further alters cytotoxicity-related cellular activities.