Active enrichment of circulating tumor DNA by supramolecular-functionalized micromotors for ultrasensitive quantification.

Liquid biopsy of pancreatic cancer via circulating tumor DNA (ctDNA) is challenged by the extreme rarity of targets, a limitation that conventional passive biosensors cannot overcome. Here, we engineered an intelligent micromotor that actively captured, transported, and electrochemically reported ctDNA. The asymmetric flask-shaped micromotor (HPCMF) was constructed from carbonaceous micro-flasks (CMF) decorated with platinum nanoparticles (PtNPs) and supramolecular (HP5) stabilized PtNPs. The HP5 moieties served as docking sites for methylene blue-labeled assist-DNA (MB-aDNA) via host-guest interactions, creating a mobile capture interface. Propelled by PtNP-catalyzed bubble generation from H2O2, the micromotor reached an average speed of 56.16 μm s-1 (5% H2O2). Upon recognizing target DNA (tDNA) in serum, it autonomously navigated to a probe DNA-modified (pDNA) glassy carbon electrode, where a ternary complex (MB-aDNA/tDNA/pDNA) assembled and anchored, positioning MB for efficient electron transfer. This active enrichment strategy achieved a linear range of 1 pM - 10 μM, a detection limit of 0.18 pM, accurate quantification in simulated pancreatic juice and mouse serum (recoveries 76.5-106.2%), and a 52.4% reduction in assay time relative to digital PCR (dPCR). This work establishes a generic "mobile sensing" framework for next-generation autonomous diagnostic devices.