Author(s)

Jiajie Zheng

Corresponding Author

Jiajie Zheng

Abstract

This study presents the development of a novel biosensing platform based on DNA tetrahedron–gold nanoparticle (AuNP) complexes for the ultrasensitive detection of miRNA21, a critical cancer biomarker. Through the precise self-assembly of thiol-modified DNA strands, stable three-dimensional nanostructures were constructed on AuNP surfaces. The platform incorporates a hybridization chain reaction (HCR) mechanism to enable effective signal amplification, thereby achieving exceptional detection sensitivity. Under optimized conditions, the biosensor demonstrated a broad linear detection range from 100 fM to 100 pM, with a detection limit as low as 1 fM for mimicDNA21. Moreover, it exhibited high specificity and stability against interfering molecules, highlighting its significant potential for use in clinical diagnostics and point-of-care testing applications. The successful integration of the structural precision of DNA nanotechnology with the enzymatic-free amplification power of HCR presents a generic and robust sensing strategy. This platform can be readily adapted for the detection of other disease-related biomarkers by simply reprogramming the probe sequences. Furthermore, by implementing a step-wise assembly strategy and rigorous buffer optimization, this study addresses key challenges in coordinating multi-component self-assembly and minimizing non-specific interactions. Consequently, this work not only establishes a high-performance sensor for miRNA21 but also provides a versatile methodological framework for constructing next-generation DNA-based biosensors.

Keywords

DNA tetrahedron, gold nanoparticles, biosensor, miRNA21, hybridization chain reaction, ultrasensitive detection