A digital microfluidic droplet generator produces self-assembled supramolecularnanoparticles for targeted cell imaging

Abstract

Controlling the size distribution of polymer-based nanoparticles is a challenging task due totheir flexible core and surface structures. To accomplish such as task requires very precisecontrol at the molecular level. Here we demonstrate a new approach whereby uniform-sizedsupramolecular nanoparticles (SNPs) can be reliably generated using a digitalmicrofluidic droplet generator (DMDG) chip. A microfluidic environment enabledprecise control over the processing parameters, and therefore high batch-to-batchreproducibility and robust production of SNPs with a very narrow size distributioncould be realized. Digitally adjustment of the mixing ratios of the building blockson the DMDG chip allowed us to rapidly scan a variety of synthesis conditionswithout consuming significant amounts of reagents. Nearly uniform SNPs with sizesranging from 35 to 350 nm were obtained and characterized by transmission electronmicroscopy and dynamic light scattering. In addition, we could fine-tune the surfacechemistry of the SNPs by incorporating an additional building block functionalizedwith specific ligands for targeting cells. The sizes and surface properties of theseSNPs correlated strongly with their cell uptake efficiencies. This study showed afeasible method for microfluidic-assisted SNP production and provided a greatmeans for preparing size-controlled SNPs with desired surface ligand coverage.