DNA nanotechnology for next-generation biosensors: Principles, strategies, and challenges

The unique structural and functional properties of nucleic acids make DNA nanotechnology a powerful platform for constructing programmable nanostructures with precise control over size, shape, and biorecognition. This review highlights how DNA-based biosensors achieve unparalleled sensitivity (e.g., attomolar detection via CRISPR systems) and multiplexing capabilities, overcoming limitations of conventional methods like PCR and ELISA. We critically evaluate design strategies, including aptamers, DNAzymes, DNA origami, and CRISPR integration, for detecting diverse analytes (nucleic acids, proteins, pathogens) in clinical, environmental, and food safety applications. While challenges such as nuclease susceptibility and scalability persist, emerging solutions like backbone modifications and microfluidic automation are discussed. By synthesizing recent advances, this review underscores DNA nanotechnology's transformative potential in next-generation diagnostics, offering a roadmap for bridging lab-scale innovations to real-world deployment.