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Nanoscale Chemical Imaging of Functionalized Monosaccharides Via Click-Chemistry by Tip-Enhanced Raman Spectroscopy
Nana Li1, Yida Han2, Jie Wang2
1State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
The Journal of Physical Chemistry Letters
|June 26, 2026
Summary
This study introduces a new method using tip-enhanced Raman spectroscopy (TERS) to image individual sugars at the nanoscale. This advance allows for detailed mapping of sugar molecules, crucial for understanding their biological roles.
Area of Science:
- Chemical Imaging
- Spectroscopy
- Nanotechnology
Background:
- Direct molecular imaging of sugars is vital for understanding their structure and function.
- Tip-enhanced Raman spectroscopy (TERS) provides nanoscale resolution but faces challenges with weak Raman scattering and surface adsorption of native monosaccharides.
Purpose of the Study:
- To develop a surface-anchored TERS strategy for imaging functionalized monosaccharides.
- To overcome limitations of TERS for native sugar imaging by enhancing surface binding and signal.
Main Methods:
- Azido sugars were functionalized with an alkyne-thiol reporter (4-EBMT) via click chemistry for gold surface chemisorption.
- Reproducible TERS mapping was performed on six functionalized monosaccharides (Gal, Neu5Ac, ManNAc, GlcNAc, Glc, Xyl).
- Density functional theory (DFT) calculations were used to assign sugar-backbone vibrations, and t-SNE analysis identified spectral clusters.
Main Results:
- TERS successfully mapped six functionalized monosaccharides with high reproducibility.
- Distinct spectral clusters corresponding to different sugars were identified using t-SNE analysis.
- TERS imaging resolved nanoscale chemical heterogeneity in mixed monolayers, distinguishing between specific sugar-enriched regions with ~5 nm resolution.
Conclusions:
- A robust surface-anchored TERS method was established for probing local monosaccharide heterogeneity.
- This technique enables high-resolution imaging of individual sugars in model glycan systems.
- The findings advance the capability for molecular-level analysis of carbohydrate structures.
