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

Area of Science:

• Biotechnology
• Microfluidics
• Oncology

Background:

• Cancer cells exhibit drug resistance, necessitating novel therapeutic strategies.
• Precise control over cellular microenvironments is crucial for understanding treatment efficacy.
• Microfluidic platforms offer advanced tools for single-cell analysis and targeted interventions.

Purpose of the Study:

• To develop and characterize a droplet-based microfluidic platform for precise local thermal treatment of cancer cells.
• To investigate the effects of localized hyperthermia on cancer cell viability and drug resistance mechanisms.
• To establish a proof-of-concept for thermal and hydrodynamic optimization in precision oncology.

Main Methods:

• Finite element modeling (FEM) to simulate coupled hydrodynamic and thermal behavior.
• Fabrication and characterization of a microfluidic device with integrated platinum heating and sensing elements.
• Utilized a serpentine channel design to induce Dean vortices for enhanced droplet mixing.
• Performed fluorescence-loss experiments on model proteins and cancer cells under localized thermal stress.

Main Results:

• FEM simulations accurately predicted temperature distributions in single-phase and three-phase flow regimes.
• Localized heating above approximately 60°C induced irreversible thermal damage in both fluorescent BSA and DX5-GFP MES-SA cancer cells.
• Demonstrated precise thermal regulation at the single-droplet level, confirming the platform's efficacy.
• Showcased enhanced reagent homogenization and consistent cellular exposure through Dean vortex-induced mixing.

Conclusions:

• The developed microfluidic platform enables precise, localized thermal treatment of individual cancer cells.
• Localized hyperthermia can be a viable strategy to induce cancer cell death and potentially overcome drug resistance.
• This platform provides a robust foundation for future applications in precision oncology, drug sensitization, and modulation of cellular defense mechanisms.