Paper Powered Pharmaceutical Manufacturing

Abstract

Programmable multistep syntheses can be useful tools in molecule discovery and process optimization, and have recently been bolstered by advances in computational chemistry and machine learning applications to molecule design. Current approaches rely on advanced liquid handling and reactor design that can reliably create fractions and aliquots of reagents and products. Here we report on the use of non-aqueous synthesis programming of pharmaceutically relevant molecules using reconfigurable paper comprising an Ampli chemical plug and play construction set. Liquid fractions and reactions are replaced with paperfluidic membranes on blocks that can be snapped together and disconnected for real time design of experiments. Reagents are embedded into the paper membranes of each block, and reactions are synthesized by snapping together blocks and allowing solution to run through them in a sequence. We explored the use of Ampli to synthesize two pharmaceutically relevant species, gold nanoparticles and the antibiotic metronidazole. Reaction products were characterized by different spectroscopic techniques (Raman spectroscopy, optical absorption spectroscopy, dynamic light scattering). The resulting products were extracted to form functional nanoparticles used in diagnostic immunoassays, and our paper synthesized metronizadole was functional in an anti-bacterial disk diffusion assay. We investigated how to map off-the-shelf reactions onto individual Ampli blocks and how to successfully generate and extract these products. This paper based pharmaceutical synthesis was faster, significantly more affordable, and lighter than traditional methods with important implications for local and distributed manufacturing.