Optical Manipulation of Whispering Gallery Mode Microlasers for Controlled Cellular Delivery

Whispering gallery mode (WGM) microlasers combine high Q factors with remote spectral readout and sensitivity to their microenvironment through refractive index changes. This intrinsic responsiveness, together with the ability of various cell types to internalize such microlasers, has enabled unique opportunities in advanced biological studies, including single cell tracking and intracellular sensing. However, precise delivery of microlasers to cells remains challenging, as conventional approaches such as microinjection often induce cellular stress or damage. In this study, we demonstrate optical trapping as a placement tool to steer individual microlasers onto non‑phagocytic mammalian cells and, critically, to uniquely monitor the entire uptake process from plasma‑membrane contact to internalization. Real‑time spectral signatures, supported by complementary imaging, reveal distinct interaction stages through characteristic shifts, broadening, and mode splitting. By positioning microlasers directly at defined membrane sites, this method also ensures consistent particle-cell encounters, resulting in markedly more reliable uptake events than stochastic approaches. This approach enables single‑cell, single‑microlaser measurements that reveal heterogeneity in membrane remodeling and uptake behavior, even across a modest number of cells. These capabilities expand the utility of biointegrated microlasers and provide a foundation for mechanistic studies of membrane dynamics, uptake pathways, and intracellular sensing, while supporting comparisons of surface coatings and cell‑type responses.