Universal and Flexible Signal Transduction Module Based on Overload Triggering Probe Escape for Sensitive Detection of Tau Protein

Aptamer-based methods have attracted increasing interest due to flexible engineering, but their generality is limited by the heterogeneity of signal transduction mechanisms. Given the fact that nonlinear and large molecules are more likely to make the nanosurface overloaded, we investigated a novel signal transduction process to extend the application of aptasensors. In this work, an aptamer complementary element (ACE) is designed with a primer region to serve as the signal probe, which can fully hybridize with an aptamer and be separated by magnetic beads (MBs). Upon target binding, the formed aptamer/target complex is much larger than the linear aptamer/ACE-primer dimer, causing overload of MBs on account of steric hindrance. An extra aptamer/ACE-primer can escape from the surface to the supernatant, which can be amplified by a catalytic hairpin assembly (CHA) circle. The size-dependent signal transduction and the modular design endow the method with high generality and flexibility for protein analysis. The proposed aptasensor was successfully applied to the detection of tau proteins ranging from 0.5 to 1000 ng mL–1 with a limit of detection (LOD) as low as 0.254 ng mL–1. The recovery tests in both human serum and cerebra spinal fluid confirmed the high accuracy and stability. Furthermore, a successful distinction was made between AD patients and healthy controls by the method, suggesting the possible applicability for practical analysis of tau proteins.