Effect of Nanoemitters on Suppressing the Formation of Metal Adduct Ions in Electrospray Ionization Mass Spectrometry

Abstract

In the work, we showed that the use of nanoemitters (tip dimension <1 μm, typically ∼100 nm) could dramatically reduce the nonspecific metal adduction to peptide or protein ions as well as improve the matrix tolerance of electrospray ionization mass spectrometry (ESI-MS). The proton-enriched smaller initial droplets are supposed to have played a significant role in suppressing the formation of metal adduct ions in nanoemitters. The proton-enrichment effect in the nanoemitters is related to both the exclusion-enrichment effect (EEE) and the ion concentration polarization effect (ICP effect), which permit the molecular ions to be regulated to protonated ones. Smaller initial charged droplets generated from nanoemitters need less fission steps to release the gas-phase ions; thus, the enrichment effect of salt was not as significant as that of microemitters (tip dimension >1 μm), resulting in the disappearing of salt cluster peaks in high mass-to-charge (m/z) region. The use of nanoemitters demonstrates a novel method for tuning the distribution of the metal-adducted ions to be in a controlled manner. This method is also characterized by ease of use and high efficiency in eliminating the formation of adduct ions, and no pretreatment such as desalting is needed even in the presence of salt at millimole concentration.

Confined Nanopipette Sensing: From Single Molecules, Single Nanoparticles, to Single Cells

“…[80] It has been proved that nanopipettes can be used for sample collection and effective enhancement of the signal intensity of peptides and proteins. [81] Moreover,b yi ntegrating nano-ESI pipettes in the patch clamp platform, single living neurons have been profiled rapidly using only nanoliter-scale samples. [82] As aconsequence of the sample collection features,nanopipettes were further used in matrix-assisted laser-desorption/ionization mass spectrometry (MALDI-MS).…”

Native Mass Spectrometry from Common Buffers with Salts That Mimic the Extracellular Environment

“…Reagents that desalt protein ions in the ESI process or in the gaseous phase can be used for solutions containing up to 25 m m NaCl . Nanoelectrospray (nano‐ESI) emitters with tip diameters of about 1 μm or smaller produce ions that have less sodium ion adduction than do those formed using larger tips . This method has been demonstrated for solutions containing organic solvents and acid in which proteins are denatured and from aqueous solutions with up to 25 m m NaCl .…”

“…Nanoelectrospray (nano‐ESI) emitters with tip diameters of about 1 μm or smaller produce ions that have less sodium ion adduction than do those formed using larger tips . This method has been demonstrated for solutions containing organic solvents and acid in which proteins are denatured and from aqueous solutions with up to 25 m m NaCl . It has been proposed that the droplets from the smaller emitter tips undergo more solvent acidification and less solvent evaporation and fission events than larger droplets .…”

“…This method has been demonstrated for solutions containing organic solvents and acid in which proteins are denatured and from aqueous solutions with up to 25 m m NaCl . It has been proposed that the droplets from the smaller emitter tips undergo more solvent acidification and less solvent evaporation and fission events than larger droplets . Recently, submicrometer tips were used to produce resolved charge‐state distributions of proteins and protein complexes from a 150 m m KCl 25 m m Tris‐HCl pH 7 buffer that mimics the intracellular environment …”

“…The much larger salt cluster ions observed with the larger tips than with the smaller tips (for example, Figure e vs. j) is consistent with this mechanism. The charge‐state distributions of the protein and protein complexes from all six buffers with the submicrometer emitter tips are nearly identical to those from aqueous ammonium acetate with the larger emitter tips, indicating that any effects of acidification and proton‐enrichment of the smaller droplets are negligible.…”