Nanoelectrospray

Nanoelectrospray is a form of electrospray ionization optimized for extremely low liquid flow rates and small-capillary emitters. It is used in mass spectrometry to generate gas-phase ions from liquid samples with high efficiency and sensitivity while minimizing sample consumption.

The technique relies on applying an electric field to a liquid at the tip of a narrow emitter to form a Taylor cone. As solvent is sprayed, droplets desolvate and undergo Coulombic fission, producing multiply charged gas-phase ions that enter the mass spectrometer. The reduced flow rate and smaller emitter size improve ionization efficiency, particularly for large biomolecules, and can enhance tolerance to salts and other matrix components.

Instrumentation typically includes a nanoelectrospray emitter, often a pulled glass capillary or a microfabricated device, connected to a sample reservoir and a high-voltage supply to initiate spraying. Nanoelectrospray operates at flow rates from tens of nanoliters per minute up to about 1 microliter per minute, with spray voltages roughly in the 0.6–2.5 kV range. It is commonly coupled to liquid chromatography–mass spectrometry systems, and sheathless interfaces are used to reduce dead volume and improve sensitivity.

Advantages of nanoelectrospray include heightened sensitivity, lower sample consumption, and, in some cases, improved tolerance to salts. Limitations include emitter clogging or instability, sensitivity to solvent composition and viscosity, and reduced robustness for high-throughput workflows.

Applications span proteomics, especially for limited or precious samples, as well as metabolomics, lipidomics, and intact-protein analysis.