In situ synthesis and dynamic simulation of molecularly imprinted polymeric nanoparticles on a micro-reactor system

Current practices in synthesizing molecularly imprinted polymers face challenges-lengthy process, low-productivity, the need for expensive and sophisticated equipment, and they cannot be controlled in situ synthesis. Herein, we present a micro-reactor for in situ and continuously synthesizing trillions of molecularly imprinted polymeric nanoparticles that contain molecular fingerprints of bovine serum albumin in a short period of time (5-30 min). Initially, we performed COMSOL simulation to analyze mixing efficiency with altering flow rates, and experimentally validated the platform for synthesizing nanoparticles with sizes ranging from 52-106 nm. Molecular interactions between monomers and protein were also examined by molecular docking and dynamics simulations. Afterwards, we benchmarked the micro-reactor parameters through dispersity and concentration of molecularly imprinted polymers using principal component analysis. Sensing assets of molecularly imprinted polymers were examined on a metamaterial sensor, resulting in 81% of precision with high selectivity (4.5 times), and three cycles of consecutive use. Overall, our micro-reactor stood out for its high productivity (48-288 times improvement in assay-time and 2 times improvement in reagent volume), enabling to produce 1.4-1.5 times more MIPs at one-single step, and continuous production compared to conventional strategy. Molecularly imprinted polymers are useful elements in sensing and biomedical research but their fabrication is challenging. Here, the authors report a micro-reactor for in situ and continuous production of molecularly imprinted polymers.

Automated summary

The current synthesis methods for molecularly imprinted polymers face challenges such as lengthy process, low productivity, the need for expensive and sophisticated equipment, and inability for in situ synthesis. In this study, a micro-reactor was developed for in situ and continuous production of molecularly imprinted polymer nanoparticles that contain specific molecular fingerprints. The micro-reactor showed significantly improved productivity compared to conventional methods.