DNA-Fueled Molecule Machine-Mediated Atom Transfer Radical Polymerization Amplification for 17β-Estradiol Assay in Clinical Samples

17β-Estradiol (E2) is crucial for the development of the genital system and sexual maturation in females, but it is still challenging to monitor E2 because of its low concentrations in bodily fluids. This study demonstrates an efficient electrochemical sensor based on a DNA-fueled molecule machine-mediated atom transfer radical polymerization amplification for the sensitive detection of E2 in clinical samples. The involved toehold-mediated strand displacement leads to the attachment of azido group-modified probes on the sensing electrode, with Cu(I)-catalyzed azide-alkyne cycloaddition to facilitate the introduction of electrochemically mediated atom transfer radical polymerization (eATRP) initiators onto the electrode. The following eATRP reaction further creates lengthy electroactive polymers (poly-FcMMA) to generate a significantly amplified current response for the quantitative determination of E2. By harnessing the considerably increased current, the sensor exhibits outstanding specificity over other interferents, a small detection limit of 35 fM, and a wide linear range from 100 fM to 80 nM. The effectiveness of the reported sensor to analyze complex samples is demonstrated to accurately detect E2 in clinical serum samples from different menstrual cycle phases and weeks of pregnancy, providing an effective prediction of pregnancy outcomes and the endocrine system.