We discuss advanced optical and nanophotonic techniques for detecting single biomolecules with extremely high sensitivity, down to single-molecule levels. We describe and show how modern optical methods — including fluorescence imaging, plasmonics, and nanostructure-enhanced sensing — can be used to visualize single molecules, detect ultra-low analyte concentrations directly in complex samples (e.g., biological fluids), and even enable optical sequencing of DNA molecules without the need for bulk amplification. We also examines the physical limitations of these optical detection methods and their impact on practical applications in biology, medicine, and genetics. By summarizing the state of the art in optical sensorics and single-molecule visualization, the article highlights both the capabilities and challenges of current technologies for ultra-sensitive biomolecular detection.
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