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

Szomor, Zsombor and Leelőssyné Tóth, Eszter and Bozorádi, János Márk and Pardy, Tamás and Jõemaa, Rauno and Fürjes, Péter (2026) From Simulation to Application: Droplet-Based Microfluidics for Thermal Targeting of Cancer Cells. MICROMACHINES, 17. No. 782. ISSN 2072-666X

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Abstract

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.

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