Precision acoustofluidics for high-throughput mechanobiology in suspension cells.

Mechanomodulation, the process of altering cellular behavior through applied mechanical forces, plays a critical role in physiological processes and has substantial implications for cancer therapy, immunology, and drug development. However, precise and efficient stimulation of nonadherent cells remains a major challenge, limiting the investigation of mechanotransduction pathways and the development of targeted therapeutics. Here, we developed an acoustofluidic platform named Suspension-cell Targeted Response to Excitation via Acoustofluidic Mechanomodulation (STREAM) to enable precise, high-throughput stimulation of suspension cells. STREAM accomplishes this using 101.14-megahertz high-frequency surface acoustic waves to deliver controlled mechanical stimulation at a throughput of 500,000 cells per minute. STREAM modulates intracellular calcium ion (Ca2+) signaling by activating mechanosensitive ion channels, triggering mitochondrial membrane disruption and tunable K562 leukemia cell apoptosis rates from 5.15 to 47.1%. STREAM provides a scalable, precise tool for studying mechanotransduction in suspension cells, with broad applications in cancer research, immunotherapy, and high-throughput drug screening.