# Improved Methods and Commercialization of Native Mass Spectrometry by Capillary Vibrating Sharp-edge Spray Ionization (cVSSI)

> **NIH NIH R41** · INVIBRAGEN INC. · 2021 · $256,452

## Abstract

Abstract/Summary
Over the last 20 years, mass spectrometry (MS) instrumentation has advanced at a remarkable
clip. Improvements in ion focusing, mass analyzer, and ion detection regions have greatly
enabled the study of protein molecules in their native state (native MS). One area that has
remained relatively constant is the ionization source where nanoelectrospray ionization (nESI)
has remained the most sensitive means to produce the large biomolecules of interest. A severe
drawback of nESI for native MS is that it suffers from stability issues when operated in negative
ion mode. This primarily results from the earlier onset of the corona discharge in negative ion
mode which abrogates ion production. The result of this limitation is to drastically reduce the
utility of native MS as >104 proteins exhibit PI values below 6. This has implications for the
study of protein structures important to human health ranging from therapeutic molecules to
those associated with disease onset and progression. Recently, the research group of Prof.
Peng Li at West Virginia University developed a new ionization technique termed Vibrating
Sharp-edge Spray Ionization (VSSI). The approach has recently been demonstrated to provide
a 10× to 100× boost in ionization performance compared with state-of-the-art approaches
operated in negative ion mode. Here, we will leverage the power of the new approach to
provide a prototype ionization source which will consistently provide 100× signal enhancements
in negative ion mode and 10× improvement in positive ion mode. These leaps in ionization
efficiency will unlock the door to high-efficiency native MS experiments especially in negative
ion mode. The result will be to enable human health researchers to characterize the structures
of many important proteins that have heretofore remained largely inaccessible.

## Key facts

- **NIH application ID:** 10256885
- **Project number:** 1R41GM142379-01
- **Recipient organization:** INVIBRAGEN INC.
- **Principal Investigator:** Stephen Valentine
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $256,452
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256885

## Citation

> US National Institutes of Health, RePORTER application 10256885, Improved Methods and Commercialization of Native Mass Spectrometry by Capillary Vibrating Sharp-edge Spray Ionization (cVSSI) (1R41GM142379-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10256885. Licensed CC0.

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