Target-Induced DNA Nanodevice as Efficient Signal Amplification Strategy Coupled with a Regenerable SERS Substrate HOF@Au for Ultrasensitive Detection of Roxithromycin

Currently, surface-enhanced Raman scattering (SERS) biosensors face practical challenges, including SERS substrate waste and unsatisfactory detection results. Accordingly, the highly efficient and regenerable SERS substrate HOF@Au was collaborated with a target-triggered identifying-cleaving-rolling-assembly cycling nanodevice (ICRACN) as a cascade signal amplification system to achieve an ultrasensitive detection of roxithromycin (RXM). In this system, abundant Au nanoparticles (NPs) were reduced in situ on the surface of alkali-resistant HOF-102 to form a uniform and high-enhancement SERS substrate HOF@Au, thereby enhancing the accuracy and stability of the sensor. Furthermore, aptamer-mediated specific recognition, efficient cleavage activity of DNA nanorollers, and a pH-responsive DNA triplex structure were engineered to construct ICRACN. In the presence of the target, it was specifically recognized by the aptamer, leading to the activation of the DNAzyme. Meanwhile, the dynamic nanorollers were triggered to initiate cleavage of a specific site along a defined pathway, enabling highly efficient signal amplification. Concurrently, the triplex structure formed by the two single-stranded DNA atoms on the SERS substrate was opened, allowing the capture of the SERS tag and generating a pronounced SERS signal. The proposed strategy achieved the sensitive detection of RXM with a low limit of detection of 3.97 × 10–14 mol/L. Moreover, modulation of pH induced reversible folding and unfolding of the triplex structure to facilitate regeneration of the SERS substrate, which simplified operational procedures and reduced detection costs. As a result, this work presents a novel, regenerable SERS biosensor and offers valuable insights into the design of multifunctional sensing platforms for analytical applications.