TEMIS: A temperature-controlled microwave irradiation system for enhancing extracellular vesicle secretion

Extracellular vesicles (EVs) secreted by cells and tissues are promising tools for disease biomarkers and regenerative medicine, necessitating the establishment of technologies to efficiently enhance their secretion. Here, we investigated the effects of a temperature-controlled microwave irradiation system (TEMIS) on EV secretion from HEK293T cells. Unlike conventional microwave (MW) irradiation devices, TEMIS incorporates an active cooling mechanism that maintains the culture medium temperature at 37 °C during irradiation, thereby avoiding cell death associated with temperature elevation. Although cell viability remained unchanged, the amount of EV secretion in the MW-irradiated group increased by 2- to 3-fold compared to the non-irradiated control group, peaking approximately 3 h after irradiation began. No significant differences were observed between the irradiated and control groups in particle size distribution, proteome analysis, or miRNA expression analysis of the isolated EVs. These results indicate that MW irradiation can enhance EV secretion under temperature-controlled conditions, while preserving the molecular characteristics of the EVs. TEMIS enables MW irradiation without damaging cells, potentially making it a practical method for enhancing EV production from cells.