Femtomolar Detection of Biomarkers by Universal DNA-Based Pendulum Biosensor

This paper reports a universal aptamer-based biosensor which is capable of detecting both small molecules and large biomarkers at femtomole level concentration. The tetrahedral DNA framework (TDF)-tethered pendulant double-stranded DNA (dsDNA) configuration is proposed to obtain a high signal conversion efficiency, and the chronoamperometry detection method is adopted to measure the dynamic response with sub-millisecond accuracy, both of that contribute to such a low LOD. Meanwhile, the TDF-tethered dsDNA structure provides additional benefits of feasible deployment and replaceability, as well as excellent antifouling properties. The proposed TDF-mediated molecular pendulum biosensor holds great potential for biological detecting in vivo, especially for large proteins. Adenosine triphosphate (ATP) and carcinoembryonic antigen (CEA) were employed as test targets to validate the model, with limits of detection (LODs) of 3.96 fM and 0.22 fM, respectively. These values are nearly two orders of magnitude higher than those reported in the current state of the art.