Researchers at National Taiwan University have developed a tip-enhanced Raman spectroscopy platform that can identify tiny structural differences in oligosaccharides without fluorescent labels. The method can distinguish glycosidic linkages, estimate chain length, and even follow glycan synthesis in real time.
Carbohydrates are among the most structurally complex biomolecules in nature, but analyzing them remains challenging. Many sugars share very similar chemical compositions, and even a small change in the position of a single bond can alter their biological function. Because of this complexity, researchers have long sought a method that can read glycan structures directly, sensitively, and without relying on labels or complicated sample preparation.
A research team from National Taiwan University has now reported a new analytical platform that brings scientists closer to that goal. Their method combines tip-enhanced Raman spectroscopy, or TERS, with nanopillar-assisted glycan trapping. The study is published in Angewandte Chemie International Edition.
By mechanically confining glycans in a highly localized plasmonic region, the system generates strong and reproducible vibrational signals from extremely small amounts of sample. This allows the platform to detect rich structural information from oligosaccharides in a label-free manner.
One of the key advances of this work is its ability to resolve very subtle differences in carbohydrate structure. The team showed that the method can distinguish between closely related glycosidic linkages such as β(1→3) and β(1→4), which are difficult to separate using many conventional approaches.
The researchers also found that characteristic H–C–H deformation signals can be used to estimate chain length in a semi-quantitative way. In addition, an azido tag serves as an internal reference to improve signal normalization when only trace sample volumes are available.
Beyond static analysis, the platform can also follow carbohydrate biosynthesis dynamically. The study demonstrated real-time monitoring of enzymatic glycosylation reactions, including the appearance of α1→2 fucosylation linkages during product formation.
This means the method is not only useful for identifying glycan structures, but also for tracking how they are built over time. Such capability could be valuable for glycoscience, biomaterials, and future diagnostic technologies, where understanding both molecular identity and biosynthetic progression is important.
“This work shows that tip-enhanced Raman spectroscopy can move beyond simple detection and become a practical tool for decoding carbohydrate structures with very high specificity,” says Dr. Kien Voon Kong, co-corresponding author and professor of chemistry at National Taiwan University.
“We hope this platform will open new opportunities for studying complex glycans and their dynamic formation in biological systems.”
Prof. Kien Voon Kong's email address: kvkong@ntu.edu.tw
To see article on Asia Research News: https://www.asiaresearchnews.com/content/decoding-sugars-one-bond-time