Nanopore-Enabled Determinations of Drug Impurities and Biomarkers Using Hydrophobically-Gated Systems and 3D-Printed Point-of-Care Assays

This work explores the usage of block copolymer – nanopore electrode arrays as hydrophobically-gated biosensors and 3D-printed microfluidic sensors as point-of-care analytical devices to detect oxidative impurities in drug formulations and clinical biomarkers in body fluids non-invasively. By combining the measurement advantages of electroanalytical chemistry with those arising from volume confinement inside nanopores, the sensitivity, selectivity, and robustness of electrochemical sensors improves significantly. The usage of thin membrane layers that exhibit hydrophobic gating properties enables potential control over mass transport and achieves effective confinement of analytes to attoliter volumes. To overcome the inherent limitation of low electrochemical selectivity, enzymes are incorporated for electrochemical signal transduction through redox mediation cascades, which are utilized to detect 4-ethyl phenol, a model environmental pollutant, and lipid degradation products in lipid nanoparticle formulations. Furthermore, direct 3D-printing techniques are deployed to realize the cost-effective, high-throughput fabrication of fully integrated microfluidic biosensors to detect biomarkers in sweat and oxidative impurities in drug formulations. The work reported here presents novel sensing modalities by combining mass-transport control on the nanoscale with electrochemical analysis under volume confinement, and the fabrication of 3D-printed microfluidic electrochemical sensors presents important improvements in electrochemical point-of-care assays that are applied toward real-time health monitoring and impurity screening in drug manufacturing.