Microfluidic ECL and Voltammetric Arrays for Metabolite-related DNA Damage
This chapter reviews the sequential development of voltammetric and electrochemiluminescent (ECL) arrays in our laboratory, to measure metabolite-related DNA damage and help elucidate pathways of genotoxic chemistry. We describe herein the evolution of these sensor systems starting from manually operated single sensors up to a fully automated 3D-printed microfluidic multi-detection array system for estimating relative rates of metabolite-related DNA adduction and oxidation. The key features in these assay systems are layer-by-layer (LbL) films of DNA metabolic enzyme and electrochemical and ECL catalysts that produced metabolites from test chemicals that can react with DNA bases and lead to direct base-metabolite adduct formation or oxidation if coupled in redox cycles with NADPH and metal ions to produce reactive oxygen species. DNA damage array results, especially when coupled with follow up LC–MS/MS analyses, can provide significant insight into complex metabolic pathways.