Al-Doped CuS Colloidal Nanocrystals as a Highly Efficient Electrochemiluminescence Emitter for the Ultrasensitive Detection of Circulating Tumor DNA

Herein, CuS colloidal nanocrystals (NCs) with adjustable band gap and good film forming ability have been synthesized as new ECL materials. Furthermore, the band gap and oxygen vacancy (O_V) content of CuS NCs are regulated by Al³⁺ doping, which significantly improves the ECL response of CuS NCs. First, the band gap of CuS-Al NCs decreases after doping with Al³⁺, which makes it easier for electrons to transition across the band gap. At the same time, the oxygen vacancy of CuS-Al NCs increases, which is conducive to improving the conductivity and promoting charge transfer, thus improving the ECL performance of CuS-Al NCs. Circulating tumor DNA (ctDNA) is an important tumor marker, and its sensitive monitoring is of great significance for tumor diagnosis, treatment, and prognosis detection. Therefore, an ECL biosensor for ultrasensitive detection of circulating tumor DNA (ctDNA) was prepared by using CuS-Al NCs as luminescent material and combining multiple antidromic hybrid chain reaction (anti-HCR) strategy mediated by the target. Compared with the process of target-induced HCR generation, this strategy first forms multiple HCR products and then destroys the already formed HCR products by target-induced destruction, which enhances the sensitivity of target response and improves the reaction efficiency. The constructed biosensor has good detection performance, and the detection limit is as low as 2.74 aM. This work puts forward the luminescence phenomenon of colloidal nanocrystals as new ECL materials, which broadens the application of ECL technology in ultrasensitive biochemical detection.