Controlled manufacturing of polymeric hydrogel microparticles is crucial, yet challenging, for rapid and sensitive detection of biomacromolecules in biodiagnostics and biosensing applications. Our approach is an integrated fabrication-conjugation strategy utilizing a simple and robust micromolding technique and biofabrication with a potent aminopolysaccharide chitosan as an efficient conjugation handle for high-yield bioorthogonal conjugation reactions. We present a concise overview of our recent findings in the controlled fabrication of shape-encoded or core-shell structured microparticles consisting of poly(ethylene glycol) (PEG) and short single-stranded (ss) DNA or chitosan, and their utility in the covalent conjugation and nucleic acid hybridization-based assembly of target ssDNAs, proteins and viral nanotemplates. Particularly, two novel routes to achieve substantially improved protein conjugation capacity and kinetics are presented from our recent reports: tobacco mosaic virus (TMV) as a high capacity nanotubular template and polymerization-induced phase separation (PIPS) of pre-polymer droplets for controlled core-shell structure formation. We envision that our fabrication-conjugation approaches reported here, combined with our current and future endeavors in improved fabrication and design of controlled structures with chemical functionalities, should permit a range of manufacturing strategies for advanced functional microscale materials and platforms in a wide array of applications.

Micromolding Hydrogel Microparticles Biofabrication Biomolecular Conjugation Biosensing

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