Microfluidics‐Driven Manufacturing and Multiscale Analytical Characterization of Nanoparticle‐Vesicle Hybrids

Coating synthetic nanoparticles (NPs) with lipid membranes is a promising approach to enhance the performance of nanomaterials in various biological applications, including therapeutic delivery to target organs. Current methods for achieving this coating often rely on bulk approaches which can result in low efficiency and poor reproducibility. Continuous processes coupled with quality control represent an attractive strategy to manufacture products with consistent attributes and high yields. Here, this concept is implemented by developing an acoustic microfluidic device together with an analytical platform to prepare nanoparticle-vesicle hybrids and quantitatively characterize the nanoparticle coverage using fluorescence-based techniques at different levels of resolution. With this approach polymethyl methacrylate (PMMA) nanoparticles are successfully coated with liposomes and extracellular vesicles (EVs), achieving a high encapsulation efficiency of 70%. Moreover, the approach enables the identification of design rules to control the efficiency of encapsulation by tuning various operational parameters and material properties, including buffer composition, nanoparticle/vesicle ratio, and vesicle rigidity.