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 Ca 2+ 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.

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.

Digital microfluidics based on sessile droplets has emerged as a promising technology for various applications including biochemical assays, clinical diagnostics, and drug screening. Digital microfluidic platforms provide an isolated microenvironment to prevent cross-contamination and require reduced sample volume. Despite these advantages, the droplet-based technology has the inherent limitation of the quiescent flow conditions at low Reynolds number, which causes mixing samples confined within the droplets to be challenging. Recently, solutal Marangoni flows induced by volatile liquids have been utilized for sessile droplet mixing to address the above-mentioned limitation. The volatile liquid vaporized near a sessile droplet induces a surface tension gradient throughout the droplet interface, leading to vortical flows inside a droplet. This Marangoni flow-based droplet mixing method does not require an external energy source and is easy to operate. However, this passive method requires a comparably long time of a few tens of seconds for complete mixing since it depends on the natural evaporation of the volatile liquid. Here, we propose an improved ultrasound-induced heating method based on a nature-inspired ultrasound-absorbing layer and apply it to enhance solutal Marangoni effect. The heater consists of an interdigital transducer deposited on a piezoelectric substrate and a silver nanowire-polydimethylsiloxane composite as an ultrasound-absorbing layer. When the transducer is electrically actuated, surface acoustic waves are produced and immediately absorbed in the composite layer by viscoelastic wave attenuation. The conversion from acoustic to thermal energy occurs, leading to rapid heating. The heating-mediated enhanced vaporization of a volatile liquid accelerates the solutal Marangoni flows and thus enables mixing high-viscosity droplets, which is unachievable by the passive solutal Marangoni effect. We theoretically and experimentally investigated the enhanced Marangoni flow and confirmed that rapid droplet mixing can be achieved within a few seconds. The proposed heater-embedded sessile droplet mixing platform can be fabricated in small size and easily integrated with other digital microfluidic platforms. Therefore, we expect that the proposed sample mixing method can be utilized for various applications in digital microfluidics and contribute to the advancements in the medical and biochemical fields.

No abstract

Acoustofluidic Stimulation of Functional Immune Cells In article number 2105809, Jinsoo Park, Hyung Jin Sung, Jessie S. Jeon, and co‐workers employ surface acoustic waves to agitate fluid in a microreactor capable of dynamic cell culture in a controllable and contact‐free manner. This microreactor prevents cellular damages that can be seen in the acoustic vortex by adjusting the duty cycle and applied power of the acoustical actuation. Using the microreactor, the functional changes of natural killer cells are observed upon the acoustical stimulation, namely, Ca2+ influx to the cells and their enhanced cell‐mediated cytotoxicity to the tumor cells in the copresence of protein kinase C activator.