Dynamics of Heparin Translocations Through Solid-State Nanopores

Abstract

Carbohydrates are one of the many biomolecular building blocks of life, with many practical applications in medicine. However, current methods for analysing these biomolecules struggle to operate at the single-molecule level. Carbohydrate sensing with solid-state nanopores has recently been explored but has proved difficult due to their structural complexity and the rapid translocation through the pores in the case of short polysaccharide chains. Among the numerous forms they can take, the best-known example is heparin, a widely used anticoagulant that has a closely related but toxic contaminant. In this work, we study the kinetics of capture and translocation of heparin molecules passing through a solid-state nanopore based on experimental results and signal simulations, seeking to understand the dynamics of passage. We examine the molecular interaction with the pore as a function of pH to elucidate the conformational dynamics of translocation. Despite using state-of-the-art electronics, we find that the durations of translocation through bare silicon nitride pores are too short to provide the resolution needed to reliably distinguish heparin from its contaminants. En route, we shed light on the physical mechanisms that govern translocation and suggest practical means by which future work might overcome these limitations.