Single-Molecule Detection of Optical Signals Using DNA-Based Plasmonic Nanostructures

Abstract

Single-molecule optical signal detection provides high sensitivity and specificity for the detection of biomolecules and chemical substances, which is of significant importance in fields such as biomedicine, environmental monitoring, and materials science. In recent years, DNA-based plasmonic nanostructures have emerged as powerful tools for achieving single-molecule optical signal detection due to their unique self-assembly properties and excellent optical performance. In particular, DNA origami technology enables the precise construction of metallic nanostructures with specific shapes and functions, which can effectively enhance the interaction between light and matter, thereby significantly increasing signal intensity and detection sensitivity. Furthermore, the programmability of DNA not only simplifies the implementation of single-molecule operations but also allows researchers to design and optimize nanostructures according to specific detection requirements. This review will explore the applications of DNA-based plasmonic nanostructures in single-molecule optical signal detection, including surface-enhanced Raman spectroscopy and enhanced fluorescence for single-molecule signal detection. We will analyze their working principles, advantages, current research progress, and future research directions. By summarizing the work in this field, we hope to provide references and insights for researchers, contributing to the advancement of biomedicine and environmental monitoring.

Keywords: DNA nanotechnology; enhanced fluorescence; plasmonic nanostructures; single-molecule; surface-enhanced Raman spectroscopy.

Figure 2

Various configurations of DNA-based plasmonic nanostructures enabling single-molecule SERS detection. (a) Influence of the excitation wavelength, as well as the nanogap size, nanoparticle dimensions, and morphology of dumbbell-shaped plasmonic nanostructures, on single-molecule SERS signals [60]. Copyright 2012, American Chemical Society. (b) Bowtie structures enabling single-molecule SERS detection [72]. Copyright 2018, Wiley-VCH. (c) Quantitative measurement of single-molecule SERS signals using metamolecules [75]. Copyright 2019, The American Association for the Advancement of Science.

Figure 4

Various configurations of DNA-based plasmonic nanostructures enabling single-molecule fluorescence enhancement detection. (a) Detection of single fluorescent molecules using AuNP dimer nanoantennas, achieving a fluorescence enhancement of 117 times [89]. Copyright 2012, American Association for the Advancement of Science. (b) Tuning the plasmonic resonance by altering the aspect ratio of AuNRs in the dimers [98]. Copyright 2021, Tsinghua University Press. (c) Establishing a single-molecule dye walking mechanism to achieve dynamic monitoring of single-molecule fluorescence signals [99]. The blue solid line represents the change in fluorescence dynamics over time. The decay curve measured before walking (gray solid line) is shown as a reference in the panels obtained at later times. The fits used to extract the fluorescence lifetimes are shown for the last time point (t = 6.5 h) with red dotted lines. Copyright 2019, American Chemical Society.

Figure 1

DNA nanostructures. (a) Design and construction of DNA origami [30]. Copyright 2006, Springer Nature. (b) Clock-shaped DNA origami constructs rotatable chiral AuNR dimers [53]. Copyright 2019, Springer Nature.

Figure 3

Applications of single-molecule SERS detection using DNA-based plasmonic nanostructures. (a) Single-molecule SERS measurements of three dyes, cytochrome c and horseradish peroxidase proteins, enabled by a DNA origami nanofork antenna [26]. Copyright 2021, American Chemical Society. (b) AuNR dimers for single-molecule detection of streptavidin and thrombin [79]. Copyright 2023, Springer Nature. (c) A plasmonic nanoantenna based on gold bipyramids enabling single-molecule SERS detection of Thioflavin T (ThT) [80]. Copyright 2023, Royal Society of Chemistry.

Figure 5

Applications of single-molecule fluorescence enhancement detection using DNA-based plasmonic nanostructures. (a) Single-molecule fluorescent detection of specific target sequences, including Zika-specific artificial DNA and RNA [100]. Copyright 2017, American Chemical Society. (b) Detection of peridinin–chlorophyll α-protein using metallic nanoantennas [27]. Copyright 2018, American Chemical Society. (c) Dynamic observation of single-molecule fluorescence signals for the coupling processes of two proteins and the pairing and dissociation processes of DNA [103]. Exemplary fluorescence time traces (right) showing donor (blue) and acceptor (orange) fluorescence during a hybridization event at 2 μs binning. Copyright 2024, American Chemical Society.