Small tools for sweet challenges: advances in microfluidic technologies for glycan synthesis

Glycans, including oligosaccharides and glycoconjugates, play an integral role in modulating the biological functions of macromolecules. Many physiological and pathological processes are mediated by interactions between glycans, which has led to the use of glycans as biosensors for pathogen and biomarker detection. Elucidating the relationship between glycan structure and biological function is critical for advancing our understanding of the impact glycans have on human health and disease and for expanding the repertoire of glycans available for bioanalysis, especially for diagnostics. Such efforts have been limited by the difficulty in obtaining sufficient quantities of homogenous glycan samples needed to resolve the exact relationships between glycan structure and their structural or modulatory functions on a given glycoconjugate. Synthetic strategies offer a viable route for overcoming these technical hurdles. In recent years, microfluidics have emerged as powerful tools for realizing high-throughput and reproducible syntheses of homogenous glycans for the potential use in functional studies. This critical review provides readers with an overview of the microfluidic technologies that have been developed for chemical and enzymatic glycan synthesis. The advantages and limitations associated with using microreactor platforms to improve the scalability, productivity, and selectivity of glycosylation reactions will be discussed, as well as suggested future work that can address certain pitfalls.