From Simulation to Application: Droplet-Based Microfluidics for Thermal Targeting of Cancer Cells.

This paper presents the development, fabrication, and characterization of a droplet-based microfluidic platform designed for precise local thermal treatment of cancer cells, with prospective chemical targeting as a future application. The workflow begins with a finite element model (FEM) using COMSOL Multiphysics 6.0 to characterize coupled hydrodynamic and thermal behavior, specifically analyzing temperature distributions across single-phase and three-phase regimes. Following the simulation, work has progressed to the fabrication of a microfluidic device and the characterization of its platinum heat source and temperature detector to ensure precise thermal control. To replicate realistic biochemical conditions, experiments have employed a three-phase configuration of oil, water, and fluorescent BSA solution. In the final stage, DX5-GFP MES-SA cancer cells have replaced the BSA solution to complete the measurements. To ensure reagent homogenization and consistent cellular exposure, a serpentine channel design was utilized to induce Dean vortices, which significantly enhanced internal mixing within the droplets. Fluorescence-loss experiments demonstrated that localized heating above ~60 °C induces irreversible thermal damage in both model proteins (fluorescent BSA) and cancer cells, establishing a proof-of-concept basis for precise thermal regulation at the single-droplet level. By deactivating specific thermo-sensitive proteins responsible for drug resistance, this integrated approach to thermal and hydrodynamic optimization enhances the efficacy of chemical stimuli and provides a robust platform for investigating the modulation of cellular defense mechanisms in future biotechnological applications. The platform holds significant potential for advancing precision oncology by enabling systematic, single-cell-level investigation of heat-shock-mediated drug sensitization, with long-term implications for overcoming multidrug resistance in aggressive cancer therapies.