Nucleic acids are important biomarkers for disease detection, monitoring, and treatment. Advances in technologies for nucleic acid analysis have enabled discovery and clinical implementation of nucleic acid biomarkers. However, challenges remain with technologies for nucleic acid analysis, thereby limiting the use of nucleic acid biomarkers in certain contexts. Here, we review single-molecule technologies for nucleic acid analysis that can be used to overcome these challenges. We first discuss the various types of nucleic acid biomarkers important for clinical applications and conventional technologies for nucleic acid analysis. We then discuss technologies for single-molecule in vitro and in situ analysis of nucleic acid biomarkers. Finally, we discuss other ultra-sensitive techniques for nucleic acid biomarker detection.
