Electrochemiluminescence Sensor Based on DNA Octahedron and Nanoclusters for M6A Analysis

N6-methyladenosine (m6A) plays a significant role in tumor regulation, and quantitatively detecting m6A-RNA methylation levels can aid in the early diagnosis of cancer. This study proposes a highly specific and sensitive electrochemiluminescence (ECL) biosensor based on a DNA octahedron combined with gold/silver nanoclusters (AuAg NCs) for detecting m6A-RNA abundance. The DNA octahedron acts as a “bridge” between the electrode and the target sequence, and its three-dimensional framework effectively transforms the two-dimensional probe capture at the electrode into a three-dimensional capture. This design enhances the target (T) capture capability by dispersing the probe across different planes, which reduces the possibility of entanglement between single strands. Additionally, the rigidity of the octahedron stabilizes its binding with the capture (CP) probe, further stabilizing and effectively improving the detection sensitivity. AuAg NCs are utilized as signal amplification elements, where Au nanoclusters covalently combine with Ag nanoclusters to achieve synergistic effects, providing more stable electroluminescence signals. When these nanoclusters are combined with the m6A antibody, the target is specifically recognized by the antibody, enhancing both the specificity and sensitivity of the sensor. Under optimal experimental conditions, the sensor demonstrated a linear range of 10–7–10–14 M and a detection limit as low as 140 aM, with good repeatability and stability. This detection strategy exhibits excellent specificity and sensitivity, offering a promising platform for m6A detection.