Zippering DNA Tetrahedral Hyperlink for Ultrasensitive Electrochemical MicroRNA Detection

Pluripotency of a DNA tetrahedron (DNA^TT) has made the iconic framework a compelling keystone in biosensors and biodevices. Herein, distinct from the well-tapped applications in substrate fabrication, we focus on exploring their tracing and signaling potentials. A homologous family of four isostructural DNA^TT, i.e., DNA^{TTα/β/γ/δ}, was engineered to form a sensor circuitry, in which a target-specific monolayer of thiolated DNA^TTγ pinned down the analyte jointly with the reciprocal DNA^TTδ into a sandwich complex; the latter further rallied an in situ interdigital relay of biotinylated DNA^TTα/β into a microsized hyperlink dubbed polyDNA^TT. Its scale and growth factors were illuminated rudimentarily in transmission electron microscopy and confocal laser scanning microscopy. Using a nonsmall-cell lung cancer-related microRNA (hsa-miR-193a-3p) as the subject, a compound DNA-backboned construct was synthesized, fusing all building blocks together. Its superb tacticity and stereochemical conformality avail the templating of a horseradish peroxidase train, which boosted the paralleled catalytic surge of proton donors, resulting in an attomolar detection limit and a broad calibration range of more than seven orders of magnitude. Such oligomerization bested the conventional hybridization chain reaction laddering at both biomechanical stability and stoichiometric congruency. More significantly, it demonstrates the flexibility of DNA architectures and their multitasking ability in biosensing.