# Glycan signal enhancement by ammonium fluoride doping and electrospray diverting

**Authors:** Seth M. Eisenberg, David C. Muddiman

PMC · DOI: 10.1039/d6an00090h · The Analyst · 2026-03-23

## TL;DR

A new method using ammonium fluoride and an electrospray diverter greatly improves the detection of N-linked glycans in mass spectrometry.

## Contribution

Combining ammonium fluoride doping with an electrospray diverter synergistically enhances glycan signals more than either method alone.

## Key findings

- Cleaved N-linked glycans from solution showed a 9-fold signal increase.
- Cleaved N-linked glycans from tissue showed a 27-fold signal increase.
- Signal enhancement was consistent across different m/z, adducts, and monosaccharides.

## Abstract

By combining ammonium fluoride electrospray doping with an electrospray diverter, signals of N-linked glycans were significantly enhanced. The addition of NH4F into the electrospray increases signal by deprotonating neutrals and creating [M − H]− ions. The electrospray diverter can prevent excess background ions from entering the mass spectrometer ion trap, reducing ion suppression. Utilizing these techniques simultaneously resulted in a synergistic effect, increasing signal more than demonstrated previously by either technique. Cleaved N-linked glycans analyzed from a solution showed an average 9-fold signal increase while cleaved N-linked glycans from tissue experienced an average 27-fold increase in signal. These increases showed no statistical differences when considering their m/z, adduct, or specific monosaccharides, suggesting that this technique is highly robust and agnostic to analyte characteristics.

By combining ammonium fluoride electrospray doping with an electrospray diverter, signals of N-linked glycans were significantly enhanced.

## Linked entities

- **Chemicals:** ammonium fluoride (PubChem CID 25516), NH4F (PubChem CID 25516)

## Full-text entities

- **Chemicals:** N-linked glycans (-), monosaccharides (MESH:D009005), ammonium fluoride (MESH:C024822), Glycan (MESH:D011134)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13037699/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC13037699/full.md

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Source: https://tomesphere.com/paper/PMC13037699