Proximity binding-triggered multipedal DNA walker for the electrochemiluminescence detection of telomerase activity

The sensitive detection of telomerase activity is of great significance for the early diagnosis and treatment of cancer. Here, an innovative electrochemiluminescence resonance energy transfer (ECL-RET) sensor was explored to reliably detect telomerase activity based on proximity binding-triggered multipedal DNA walker. In this system, CdS quantum dots (CdS QDs) and silver nanoclusters (Ag NCs) were applied as ECL donor and acceptor, respectively. By ingeniously introducing a repetitive bases sequence (TTAGGG) along the telomerase primer, multiple same DNA "legs" were formed, leading to the activation of proximity binding-triggered multipedal DNA walker. Unlike the traditional unipedal DNA walker, one walking step of multipedal DNA walker concurrently initiated the responsivity of multiple signals, resulting in the shortening of the walking time and improvement of the signal amplification efficiency. Thus, under optimal conditions, the designed ECL-RET sensor exhibited a wide dynamic correlation of HeLa cells' telomerase activity from 1 × 10² to 1 × 10⁶ cells/mL and a low detection limit of 16 cells/mL. Moreover, this sensor realized the general and reliable analysis of telomerase activity in different cell lines. Due to the outstanding application potential in real samples, it is believed that the ECL-RET sensing system provides a new approach for the application of telomerase activity assays in cancer diagnostics.