PEG-based cleavable hydrogel microparticles with controlled porosity for permiselective trafficking of biomolecular complexes in biosensing applications

Abstract

In the last decade, PEG-based hydrogels have been extensively used for the production of microparticles for biosensing applications. The biomolecule accessibility and mass transport rate represent key parameters for the realization of sensitive microparticles, therefore porous materials have been developed, mainly resorting to the use of inert porogens and copolymers with different chain lengths. However, very limited information is reported regarding the addition of cleavable crosslinkers to modulate the network porosity. In this scenario, the aim of this work is to design, synthesize and characterize hydrogel microparticles, based on the copolymerization between PEG-diacrylate and N,N′-(1,2-dihydroxyethylene)-bisacrylamide, a cleavable crosslinker that simultaneously produces pores and reactive groups for bioprobe 3D bioconjugation. The results show great accessibility of these microparticles to antibodies and their complexes, without affecting their diffusion rate. Furthermore, the presence of a well-defined number of reactive aldehydes, produced by the cleavage reaction, allows modulating biosensor sensitivity through a fine control of the conjugation degree. The antibody-conjugated microparticles can efficiently capture the analyte down to a few picograms. These novel microparticles could be used as a highly sensitive platform for biomacromolecule detection in complex fluids, exploiting the combined effects of PEG's anti-fouling properties, large network porosity and interconnections, and three-dimensional bioconjugation.