Field-free capillary vibrating sharp-edge spray ionization (cVSSI) is evaluated for its ability to conduct native mass spectrometry (MS) experiments. The charge state distributions for nine globular proteins are compared using field-free cVSSI, field-enabled cVSSI, and electrospray ionization (ESI). In general, for both positive and negative ion mode, the average charge state (q avg) increases for field-free cVSSI with increasing molecular weight similar to ESI. A clear difference is that the q avg is significantly lower for field-free conditions in both analyses. Two proteins, leptin and thioredoxin, exhibit bimodal charge state distributions (CSDs) upon the application of voltage in positive ion mode; only a monomodal distribution is observed for field-free conditions. In negative ion mode, thioredoxin exhibits a multimodal CSD upon the addition of voltage to cVSSI. Extensive molecular dynamics (MD) simulations of myoglobin and leptin in nanodroplets suggest that the multimodal CSD for leptin may originate from increased conformational “breathing” (decreased packing) and association with the droplet surface. These properties along with increased droplet charge appear to play critical roles in shifting ionization processes for some proteins. Further exploration and development of field-free cVSSI as a new ionization source for native MS especially as applied to more flexible biomolecular species is warranted.

Mass spectrometry (MS) is an information rich analytical technique and plays a key role in various 'omics studies. Standard mass spectrometers are bulky and operate at high vacuum, which hinder their adoption by the broader community and utility in field applications. Developing portable mass spectrometers can significantly expand the application scope and user groups of MS analysis. This review discusses the basics and recent advancements in the development of key components of portable mass spectrometers including ionization source, mass analyzer, detector, and vacuum system. Further, major areas where portable mass spectrometers are applied are also discussed. Finally, a perspective on the further development of portable mass spectrometers including the potential benefits for 'omics analysis is provided.

Rationale The performance of mass spectrometry (MS) analysis is often affected by the presence of salt ions. To achieve optimal MS detection results, desalting is necessary for samples with high salt concentrations. We report a rapid, low‐cost and flexible online desalting method using Nafion‐coated sponge. This method is easy to perform and can be implemented to a wide range of customized fluidic systems. Methods Nafion‐coated melamine sponge was fabricated by soaking a glass tube containing a melamine sponge in Nafion solution and then drying overnight. The online desalting workflow is comprised of three major parts: (1) Syringe pump, which provides a continuous flow for the online fluid system; (2) Nafion sponge in a glass tube, where the online desalting of sample solution happens; (3) Capillary Vibrating Sharp‐Edge Spray Ionization (cVSSI), which is an ionization technique to ionize the desalted analytes. Results Effective online desalting of a 10 mM NaCl solution was demonstrated for a wide range of molecules including small molecules, peptides, DNAs, and proteins using a flow rate of 10 μL/min. By incorporating multiple pieces of the Nafion‐coated sponge, effective desalting for ubiquitin and cytochrome c (Cyt‐c) from physiological buffers, including phosphate‐buffered saline (PBS) and tris‐buffered saline (TBS), were also achieved. For molecules that are sensitive to low pH conditions after desalting, a R‐SO3NH4‐type Nafion‐coated sponge was fabricated. Desalting of ubiquitin, oligosaccharide, and DNA oligomers from 10 mM NaCl or 10 mM KCl solutions was demonstrated. Conclusions Flexible, low‐cost, and efficient online desalting was achieved by the Nafion‐coated sponge. A variety of molecules ranging from small molecules, peptides, proteins to oligosaccharides and DNAs can be desalted for MS analysis. The desalting by Nafion sponge has great potential for desalting applications that require customized fluidic design and rapid analysis.