Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor

Abstract

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.

Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications

“…While the increase, in itself, was insufficient to activate the NK cells alone, which is known to occur through calcium signaling, it was shown that the SAW mechanostimulation led to an approximate 1.5-fold enhancement in the expression of lysosomal-associated membrane protein 1 (LAMP-1)—a marker of NK cell degranulation and hence activation—when applied in conjunction with the addition of phorbol 12-myristate 13-acetate (PMA) that is commonly employed to trigger protein kinase C (PKC) signaling for initiating T-cell activation. 327 …”

Acoustic levitation as a tool for cell‐driven self‐organization of human cell spheroids during long‐term 3D culture

“…It has been shown that ultrasounds, including those of frequency approaching 2 MHz, impacted various mechanosensitive ion channels involved in self‐organization of tissues (Chu et al, 2022; Kim et al, 2022; Wu et al, 2017). In addition to the acoustic effects, cells also respond to various environmental mechanical stimuli, such as compression, substrate stiffness (Biswas, 2020) or shear‐flow (Kim et al, 2021).…”

Effect of in-plane and out-of-plane bifurcated microfluidic channels on the flow of aggregating red blood cells

“…The main channel has a round cross section with a diameter of 40 μm. To conserve the flow rate along the direction of the flow, we choose the diameter D 2 of the second-generation downstream channel to follow Murray's law: 37,38 where j is the index for the number of channels in the i + 1-th generation. In our case we only have two channels with equal diameter.…”