NanoESI

Nanoelectrospray ionization (nanoESI) is a variant of electrospray ionization that operates at very low liquid flow rates, typically in the nanoliter per minute range. It uses nanoscale spray emitters and is usually coupled to nano-flow liquid chromatography or direct infusion. Compared with conventional ESI, nanoESI aims to maximize ionization efficiency while minimizing sample consumption.

In nanoESI, a high electric potential drives the formation of a charged aerosol at the emitter tip, generating smaller initial droplets that desolvate more efficiently. The result is enhanced ion transmission into the mass spectrometer and often higher sensitivity, particularly for peptides, proteins, and other biomolecules. The technique is well suited for precious or limited samples due to the reduced solvent and sample requirements, and it can improve signal for low-abundance species when combined with nanoLC.

Practical considerations include the use of very small-capillary emitters, typically pulled fused-silica or metal tips, with flow rates commonly in the tens to hundreds of nanoliters per minute. Operating parameters such as spray voltage (often around 1 to 2 kV) and solvent composition (for example water/acetonitrile with additives like formic acid) are important for spray stability. NanoESI systems can be more prone to clogging and require careful maintenance and alignment, but they offer high sensitivity and low sample consumption when conditions are well controlled.

Applications of nanoESI span proteomics, peptidomics, metabolomics, and small-molecule analysis, particularly when sample volume is limited or high sensitivity is required.