Distance-dependent spatial analysis of micropattern-generated shockwave for cell-type specific intracellular delivery

Intracellular delivery of therapeutic materials remains challenging, with conventional micropattern-assisted optoporation methods making it difficult to analyze the spatial effects of individual laser pulses. Here, we show that pigmented SU-8 microdisks enable precise analysis of distance-dependent shockwave effects on cell membrane permeabilization, achieving delivery yields up to 60% in optimized conditions. Using 20 μm and 50 μm microdisks irradiated by nanosecond laser pulses, we discovered that larger patterns generate more extensive shockwaves leading to increased cell damage over broader ranges, while smaller patterns maintain high delivery efficiency with minimal cellular disruption. Furthermore, cellular adhesion strength critically influences treatment outcomes: strongly adherent SAOS-2 cells showed remarkable resilience while weakly adherent HEK-293 cells experienced extensive damage at greater distances. Our results demonstrate how micropattern size and cell-specific properties determine the spatial extent and efficiency of shockwave-mediated delivery, providing a framework for optimizing intracellular delivery strategies while preserving cell viability.