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<p>The emergence of ultrasensitive and selective biosensing technologies is pivotal to advancing early disease diagnosis and molecular detection. This research introduces a label-free surface-enhanced Raman scattering (SERS) biosensing platform based on DNA-programmed assembly of gold nanoparticle (AuNP) dimers with sub-5&#xa0;nm plasmonic nanogaps. By thiolating single-stranded DNA (ssDNA) and conjugating it to colloidal AuNPs, we established precise, programmable hybridization, yielding controlled dimerization. UV-Vis spectroscopy identified a plasmonic redshift from 520&#xa0;nm (naked AuNPs) to 538&#xa0;nm (dimers), while transmission electron microscopy (TEM) identified the formation of uniform nanogap structures with interparticle distances in the range of 2–5&#xa0;nm. Dynamic light scattering and zeta potential analyses verified the successful DNA functionalization. Numerical analysis demonstrates a high degree of electromagnetic field confinement in the nanogap with field enhancement factors of approximately 10⁶, which adds to significant SERS signal amplification. Taking miRNA-21 as a model biomarker, the platform was found to be highly sensitive with a limit of detection of ~ 100 femtomolar and a six-order-of-magnitude linear dynamic range. The proposed platform demonstrates ultrasensitive SERS detection down to femtomolar concentrations, indicating strong potential for low-abundance biomolecule sensing. Control assays showed high sequence specificity, and stable SERS signals across samples proved it to be a reproducible system. The construct’s flexibility allows for straightforward adaptation to monitor other nucleic acid targets. The platform proposed demonstrates the possibility of future development into point-of-care diagnostic systems, but it has not been validated under the conditions of real biology and integration of devices yet.</p> Graphical abstract <p></p>

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Engineering plasmonic hot spots with DNA-directed assembly for single-molecule surface-enhanced Raman scattering (SERS) biosensing

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • M. Thillai Rani,
  • C. Sheeja Herobin Rani,
  • R. Barona,
  • K. Maharajan,
  • S. Ahamed Ali,
  • N. Phani Kumar

摘要

The emergence of ultrasensitive and selective biosensing technologies is pivotal to advancing early disease diagnosis and molecular detection. This research introduces a label-free surface-enhanced Raman scattering (SERS) biosensing platform based on DNA-programmed assembly of gold nanoparticle (AuNP) dimers with sub-5 nm plasmonic nanogaps. By thiolating single-stranded DNA (ssDNA) and conjugating it to colloidal AuNPs, we established precise, programmable hybridization, yielding controlled dimerization. UV-Vis spectroscopy identified a plasmonic redshift from 520 nm (naked AuNPs) to 538 nm (dimers), while transmission electron microscopy (TEM) identified the formation of uniform nanogap structures with interparticle distances in the range of 2–5 nm. Dynamic light scattering and zeta potential analyses verified the successful DNA functionalization. Numerical analysis demonstrates a high degree of electromagnetic field confinement in the nanogap with field enhancement factors of approximately 10⁶, which adds to significant SERS signal amplification. Taking miRNA-21 as a model biomarker, the platform was found to be highly sensitive with a limit of detection of ~ 100 femtomolar and a six-order-of-magnitude linear dynamic range. The proposed platform demonstrates ultrasensitive SERS detection down to femtomolar concentrations, indicating strong potential for low-abundance biomolecule sensing. Control assays showed high sequence specificity, and stable SERS signals across samples proved it to be a reproducible system. The construct’s flexibility allows for straightforward adaptation to monitor other nucleic acid targets. The platform proposed demonstrates the possibility of future development into point-of-care diagnostic systems, but it has not been validated under the conditions of real biology and integration of devices yet.

Graphical abstract