Capillary Vibrating Sharp-Edge Spray Ionization (cVSSI) for Voltage-Free Liquid Chromatography-Mass Spectrometry

Abstract

Here we report a continuous flow-based ionization method, capillary Vibrating Sharp-edge Spray Ionization (cVSSI), that nebulizes liquid sample directly at the outlet of a capillary without using high-speed nebulization gas or a high electrical field. cVSSI is built upon the recently reported VSSI principle which nebulizes bulk liquid using vibrating sharp-edges. By attaching a short piece of fused silica capillary on top of the vibrating glass slide in VSSI, liquid is nebulized at the outlet of the capillary as the result of the vibration. Utilizing standard 360 μm OD/100 μm ID capillary, cVSSI works with a wide range of flow rates from 1 μL/min to 1 mL/min. The power consumption is as low as 130 mW. ESI-like MS spectra are obtained for small molecules, peptides and proteins. 5 orders of magnitude linear response for acetaminophen solution is achieved with a limit of detection (LOD) of 3 nM. cVSSI is also demonstrated to be compatible with LC-MS analysis. Two LC-MS applications are demonstrated with cVSSI: 1) separation and detection of a mixture of small molecules; 2) bottom-up proteomics using a protein digest. A mixture of 9 common metabolites was appropriately separated and detected using LC-cVSSI-MS. In the bottom-up experiment, 78 peptides were detected using LC-cVSSI-MS/MS with a protein coverage of 100% for cytochrome c, which is comparable with the coverage obtained using LC-ESI-MS. cVSSI offers a means of interfacing LC or other continuous flow-based applications to mass spectrometers with the salient features of voltage-free, flexibility, small footprint and low power consumption.

Integrated sample desalting, enrichment, and ionization on an omniphobic glass slide for direct mass spectrometry analysis

“…Finally, we tested the quantification capability of the present workflow. As reported in our previous studies, 33,36 VSSI offers good linear ranges for direct spray of analytes. Here, we first confirmed that a linear range from 1 nM to 10 μM can be achieved for clarithromycin in water (Figure S4).…”

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

“…Therefore, no conclusions can be drawn with regard to the degree of membrane‐induced oligomerization. To disentangle the routes of formation for such a heterogenous mixture of oligomeric species is the subject of future, more extensive experiments employing a greater number of lipid systems as well as gas‐phase separations and reactivity studies . This process will also be examined by MD simulations where multiple peptides are examined with the membrane systems.…”

Facile Improvement of Negative Ion Mode Electrospray Ionization Using Capillary Vibrating Sharp-Edge Spray Ionization

“…Here we report a simple instrumentation method that can effectively suppress corona discharge for aqueous solutions based on capillary vibrating sharp-edge spray ionization (cVSSI). cVSSI is a process that can generate a plume of liquid droplets at the outlet of a capillary by simply attaching it to a vibrating glass slide. , By combining the cVSSI process with a bias voltage, negative ion signals of various analytes including DNA, proteins, peptides, and oligosaccharides from aqueous solutions are improved significantly. While several ultrasonic nebulization systems that can be coupled with ESI have been developed including an array of micromachined ultrasonic electrospray (AMUSE), ultrasonically assisted electrospray, single pulse nanoelectrospray, the capability of suppressing corona discharge for these methods has not been reported.…”