Mammalian cell culture and analysis in digital microfluidic platforms

Digital microfluidics has emerged as a promising platform for cell culture, offering precise control over droplet-based microenvironments while enabling automation and miniaturization. This review examines the integration of DMF with various cell culture substrates, including hydrogels and synthetic polymers, and evaluates their advantages and limitations for supporting cellular growth, adhesion, and viability. The influence of AC and DC actuation modes on droplet handling, as well as their effects on cell behavior, are also discussed. I elaborate how DMF systems can be designed to deliver and modulate physical and biochemical stimuli, such as shear stress, temperature, and gradients of signaling molecules, to better mimic in vivo conditions and study cell behavior in dynamic environments. Next, I highlight the incorporation of analytical tools and sorting techniques in DMF-based cell culture and explore its potential applications in organ-on-chip systems. While DMF presents unique opportunities for cell-based research, challenges such as material compatibility, cell viability, and system stability remain. This review provides a critical assessment of current developments and future directions for DMF in cell culture applications.