Linear Ligand-Regulated Coordination Aggregation-Induced Electrochemiluminescence for Circulating Tumor DNA Measurement Combined with a Cruciform Tripedal DNA Walker Output Strategy

The regulation of the aggregation degree plays a crucial role in the aggregation-induced electrochemiluminescence (AIECL) induced by coordination aggregation. Herein, 1,3,5-tri(4-carboxyphenyl) benzene (H₃BTB), 1,4-di(pyridin-4-yl) benzene (DPB), and Zn²⁺ were first employed to synthesize the Zn-DPB-BTB coordination polymers (Zn-DPB-BTB CPs) with extraordinary AIECL performance as the rotation and vibration of luminescent H₃BTB were restricted. Notably, besides the coordination-induced ECL enhancement, DPB, a functional linear molecule, could effectively adjust the parallel π-π stacking pattern and the aggregation degree of Zn-BTB, enabling Zn-DPB-BTB CPs to possess significantly improved ECL efficiency at low voltage compared to H₃BTB and Zn-BTB. Hence, using Zn-DPB-BTB CPs as efficient ECL emitters, an ECL biosensor for ultrasensitive detection of circulating tumor DNA was fabricated combined with a newly designed target cleavage-induced cruciform tripedal DNA walker output strategy. Specifically, it exhibited obvious advantages in sensitive and accurate analysis of low-concentration targets as multiple sufficient preformed cruciform tripedal DNA walkers on the three-dimensional surface of magnetic beads were released for more effective signal conversion via target cleavage compared with the traditional DNA walker that was directly triggered and formed through targets. Impressively, the proposed biosensor revealed a good linear range of 10 aM to 1 nM and an excellent detection limit as low as 8.24 aM.