Carbon Nanomaze for Biomolecular Detection with Zeptomolar Sensitivity

Despite numerous efforts, the accurate determination of trace biomolecules with zeptomolar sensitivity remains elusive. Here, a 3D carbon nanomaze (CAM) electrode for the ultrasensitive detection of trace biomolecules such as nucleic acids, proteins, and extracellular vesicles is reported. The CAM electrode consists of an interlaced carbon fiber array on which intercrossed graphene sheets are vertically tethered in situ, permitting local confinement of trace molecules to increase molecular hybridization efficiency. Furthermore, a self-assembled DNA tetrahedron array adopts a rigid spatial conformation to guarantee the controllable arrangement of immobilized biological probes, facilitating analytical sensitivity and reproducibility. In a proof-of-concept experiment on detecting microRNA-155, a linearity of 0.1 aM to 100 nM and a sensitivity of 0.023 aM (23 zM) are achieved. With the optimal parameters, the proposed nanoelectrode demonstrates encouraging consistency with quantitative real-time polymerase chain reaction during clinical sample detection. Through simple functionalization by appending various biomolecular probes of interest, the developed CAM platform with ultrahigh sensitivity can be exploited as a versatile tool in environmental, chemistry, biology, and healthcare fields.