Research progress of single molecule sensors based on DNA platform

Deoxyribonucleic acid (DNA) is the genetic blueprint of living organisms and represents one of the most fundamental molecules across species. Recent research and development in the field of materials science indicates that DNA is not only highly programmable, but also a nanomaterial capable of precise self-assembly. Integrating diverse single-molecule detection techniques with advanced DNA nanotechnology enables direct probing of the properties of DNA as well as other molecular entities. This article aims to explain the working principles of electrical and optical detection strategies, explore system construction approaches, and evaluate their application performance. Furthermore, this review systematically summarizes the evolution of DNA-based single-molecule biosensing platforms. Electrical single-molecule sensors include single-molecule junctions (SMJs), field-effect transistors (FETs), and nanopore technologies, enabling label-free detection by monitoring electron transport, field-effect modulation, and ionic current fluctuations at the single-molecule level. Optical sensors represent another major direction and include surface-enhanced Raman scattering (SERS), fluorescence-based sensing methods, and electrochemiluminescence (ECL), enabling ultrasensitive biomolecular recognition via changes in optical signals. When DNA is employed as the recognition element, optical sensing platforms benefit from high specificity, facile programmability, and excellent signal stability. Despite remaining challenges, including stability and repeatability limitations in complex environments, integrated multimodal analysis provides a viable framework for developing robust, sensitive, and selective single-molecule sensing platforms.