常用于检测突变的线性DNA分子，包括循环肿瘤DNA（ctDNA）的基于PCR的技术，需要在突变位点的两侧具备较大的核苷酸区域用于引物结合。这意味着位于两端较近位置的DNA片段很难被检测到。因此，能够识别具有突变位点靠近两端的线性DNA的传感器，将优于现有的技术方法。本研究开发了一种由带有Au纳米粒子标记的帽端CdS量子点和发夹形态DNA探针构成的电化学发光 - 共振能量转移（ECL-RET）生物传感器，用于检测携带关键T790M肺癌突变的表皮生长因子受体（EGFR）ctDNA。ECL-RET系统能够检测不同的DNA分子，包括单链18个核苷酸（nt）和40nt以及具有单核苷酸多态性（SNP）编码T790M位于中间或距离一端仅7nt的双链100nt。对于所有目标DNA, 传感器的检测限（LODs）在aM范围内，具有优异的选择性。当EGFR T790M SNP位于中间或末端时，100nt目标线性ctDNA片段的检测限分别为8.1 aM和3.4 aM。这些结果表明，ECL-RET系统能够探测标准技术无法检测到的DNA片段中的突变。

PCR-based techniques routinely employed for the detection of mutated linear DNA molecules, including circulating tumor DNA (ctDNA), require large nucleotide sections on both sides of the mutation for primer annealing. This means that DNA fragments with a mutation positioned closer to the extremities are unlikely to be detected. Thus, sensors capable of recognizing linear DNA with characteristic mutations closer to the ends would be advantageous over the state-of-the-art approaches. Here, an electrochemiluminescence-resonance energy transfer (ECL-RET) biosensor comprising capped CdS quantum dots and hairpin DNA probes labeled with Au nanoparticles was developed for the detection of epidermal growth factor receptor (EGFR) ctDNA carrying the critical T790M lung cancer mutation. The ECL-RET system detected different DNA molecules including single-stranded 18-nucleotides (nt) and 40-nt as well as double-stranded 100-nt with the single nucleotide polymorphism (SNP) coding for T790M located either in the middle or only 7 nt from one end. For all target DNA, the sensor's limits of detection (LODs) were in the aM range, with excellent selectivity. It was the case of 100-nt target linear ctDNA fragments with LODs of 8.1 and 3.4 aM when the EGFR T790M SNP was either in the middle or at the end, respectively. These results show that ECL-RET systems can sense mutations in DNA fragments that would remain undetected by standard techniques.