One crucial unmet need in clinical diagnostics is the rapid and accurate identification of antimicrobial resistance (AMR), especially in high-burden and resource-constrained situations. In order to detect total resistant microbial populations, we present a hybrid dual-mode biosensing device that combines HCR based DNAzymes and ATP-dependent bioluminescent quantification.
The platform creates the folding-driven catalytic activation of metastable DNAzymes at the molecular level, where conformational rearrangement into catalytically competent structures is induced by target-specific recognition of resistance-associated DNA sequences. According to the folding-function paradigm formerly shown in DNAzyme-based biosensing devices, these programmable DNAzyme constructions behave as highly selective molecular switches, allowing accurate identification of AMR determinants by folding-mediated activation.