Tuning the Cell-Microchip Interface to Control the Cellular Interaction of Silicon Oxide Microdevices

Abstract While nanotechnology has long dominated the field of drug delivery and biosensing, advances in microfabrication have enabled the precise fabrication of microchips with various geometries and sizes for intracellular biomedical applications. However, maximizing their therapeutic potential requires understanding how their surface properties influence cellular interactions. In this work, we developed a systematic approach to tailor the surface chemistry of silicon oxide microchips (SiOµC) and evaluate its impact on mammalian cells. To achieve this, SiOµC were functionalized with distinct silane chemistries to generate self-assembled monolayers featuring positively charged, negatively charged, hydrophobic, and hydrophilic terminal groups, while incorporating a non-interfering fluorescent label for characterization and visualization. Surface modifications were thoroughly validated through wafer-attached and suspension-based fluorescence characterization to ensure their stability and suitability for biological studies. Biological evaluation in HeLa and HaCaT cell lines demonstrated overall cytocompatibility (~ 80%) across most surface profiles. Quantitative flow cytometry and confocal microscopy revealed that surface charge and wettability significantly modulate the internalization efficiency of these micrometre-sized devices. Finally, pathway inhibition assays using 5-( N -ethyl- N -isopropyl)amiloride (EIPA) suggests that actin reorganization-dependent mechanisms represent the predominant internalization mechanism driving the cellular uptake of these tailored microdevices, establishing a robust chemical platform to optimize the cell–microchip interactions and intracellular delivery of silicon-based microchips.