MS SIEVE-Pushing the Limits for Biomolecular Mass Spectrometry

Electrospray mass spectrometry has become indispensable in many disciplines including the classic "omics" techniques such as proteomics or lipidomics, as well as other life science applications in molecular, cellular, and structural biology. However, a limiting factor that often arises for the detection of biomolecular analytes is their poor ionization efficiency in the ion source. Here, we present an add-on device for the electrospray source, termed MS SIEVE (MS Spectral Impurity Eliminator & Value Enhancer), which is placed between the electrospray needle and the cone of the mass spectrometer. We probed the application of MS SIEVE for various biomolecules including proteins, peptides, lipids, glycans and DNA oligonucleotides and even synthetic polymers such as polyethylene glycol and found that MS SIEVE selectively improves the signal intensity, while suppressing the spectral contribution of contaminants such as NaCl. Importantly, MS SIEVE can, in principle, be adapted for any electrospray ion source and, therefore, represents a promising alternative for routine "omics" methods as well as special applications on challenging analytes.