Electrochemically activated DNA circuit for the amplified and accurate biosensing of cancer cells

The detection of cancer cells not only facilitates the early diagnosis of cancers but also provides valuable support for formulating personalized treatment plans for patients. In this work, we develop a new aptamer-based electrochemical biosensing method for cancer cell detection, employing an electrochemically activated DNA circuit as a signal generation module. Specifically, target cells are captured onto the indium tin oxide electrodes through aptamer-mediated recognition of surface proteins. Then, a DNA circuit begins with the potential-driven selective bioconjugation of inherent tyrosine residues on the cell surface. This is subsequently followed by the incorporation of a facile click chemistry reaction and a netlike cascade assembly involving multiple hairpin probes. As a result, a large number of electroactive methylene blue molecules are recruited to the cell surface, thereby ensuring highly efficient electrochemical signal generation. Taking breast cancer cells MDA-MB-231 as a model, this method enables the detection of target cells in the linear range from 5 to 1 × 10⁴ cells with a limit of detection down to 4.2 cells, and also demonstrates high specificity and applicability to complex samples with good recoveries from 95.0% to 106.2%. Furthermore, the DNA circuit-based signal generation module exhibits excellent universality and signal stability, allowing the method to be adapted for detecting other cancer cells, such as HER-2-positive BT-474 and MDA-MB-453 cells through simple aptamer replacement. Therefore, this work presents a reliable new tool for cancer cell detection, which holds great promise for playing an important role in future cancer diagnostic practices.