Acoustofluidic microreactor: altering cellular functions with contact-free dynamic cell culture

Acoustical actuation of microfluid enables dynamic cell culture in a controllable and contact-free manner, which applies mechanical stimulations to the cells and alters cellular functions.

Article | Spring 2023

When an external stimulus is transmitted to cells in the body, cells feel mechanical forces from their surrounding microenvironment, with these forces subsequently translated into intracellular signaling pathways, resulting in the regulation of various cellular functions. As such, studying the response of cells to these external physical stimuli is an important yet intriguing research topic.

A KAIST research team lead by Jessie Sungyun Jeon, Associate Professor from the Department of Mechanical Engineering, in collaboration with Professor Hyung Jin Sung from KAIST and Assistant Professor Jinsoo Park from Chonnam National University, developed an acoustofluidic microreactor that enables a dynamic cell culture to be set up in a miniaturized system while maintaining the performance of agitating media (Figure 1a).

In the system, the Rayleigh-type surface acoustic waves (SAWs), formed by an interdigital transducer propagate along the surface of a piezoelectric substrate, encounter with membrane/fluid. The SAWs then refract into longitudinal waves in liquid media, consequently creating an acoustic streaming flow in the cylindrical microreactor as shown in Figure 1b. This chaotic vortex applies flow-induced shear stress to the cells.

The suspended Natural Killer (NK) cells are found to not be damaged by the SAW operation of the adjusted experimental setup. Suspended NK cell aggregates subjected to a SAW treatment show increased intracellular calcium ion concentrations (Figure 1c). 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.

Compared to the conventional dynamic cell culture platforms (e.g. perfusion bioreactor using peristaltic pump or magnetic stirrer), the system allows the dynamic stimulation of functional immune cells in a noncontact and rotor-free manner. This allows a number of advantages which include requiring only a small amount of cells (~ 5000 cells), the precise control of fluid flow velocity and frequency, and the high-resolution in-situ imaging for cellular status.

These results have important implications by showing that the acoustically actuated system allows dynamic cell culture without cell damages and further alters cytotoxicity-related cellular activities. Thus, this microsystem could be used to complement the available bulky platforms while maintaining the performance of agitating culture media, highlighting the potential of a novel way to achieve advanced cell culture applications, and its implications for the study of mechanosensitive immune responses.

This study was published in Advanced Science (S. Kim, H. Nam, B. Cha, J. Park, H.J. Sung & J.S. Jeon, ”Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor”, Advanced Science, 2022, 9(16), 2105809).