DNA Framework-Programmed Micronano Hierarchy Sensor Interface for Metabolite Analysis in Whole Blood

A microsubstrate is of great value for constructing a microscale interface with highly improved sensing capabilities. What has been lacking, however, is the precisely nanoscale regulation of the probes that anchored on the interface of the microsubstrate. Here we employed tetrahedron DNA framework (TDF) to program the microscale biosensing interface for metabolite analysis. When interrogated by square wave voltammetry, the TDF-corbelled aptamer showed higher susceptibility to ATP stimulus, with approximately 2.8-fold higher signal alteration than that of single-stranded aptamer (SSA) when triggered by ATP with identical concentration. Besides, the micronano composite probes showed high stability, fast response kinetics in complex matrix, and the limit of detection for ATP was as low as 50 μM in rabbit whole blood. In consideration of the high spatial resolution of the microelectrode, we anticipate that the miniaturized micronano hierarchy complex shows great potential for achieving implantable detection for tracking the metabolism of circulating therapeutic agents in living subjects.