Controlled Synthesis of Branched Gold Nanoparticles By Microfluidic Device For Light-Activated Biomolecular Delivery

Intracellular delivery is a method to engineer cells, that enables us to understand biology and treat diseases. However, impermeability of cell membranes to most molecules hampers the delivery. Light-activated intracellular delivery (or photoporation) mediated by photosensitive nanoparticles is a universal method, which is non-invasive, simple, and reproducible. However, non-uniformity and declined cell viability while improving the efficiency restrict the method. Hence, in this paper, we propose a unique device that can synthesize and tune the optical properties of branched gold nanoparticles (BGNPs), which act as photosensitive material to facilitate uniform, highly efficient, and low-cellular damage intracellular delivery, for the first time. To achieve the desired optical properties, the morphology of BGNPs was precisely controlled by varying the mixing efficiency inside the tiny microdroplet volume (~10 µL) that passes through serpentine and semi-spiral microchannels. ~ 99% transfection efficiency and ~100% cell viability with higher uniformity is demonstrated with BGNP-sensitized photoporation in cancer cells, which could be used as a promising platform for drug discovery, cellular therapy, and diagnosis.