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

毛细管振动锐边喷雾电离 (cVSSI) 天然质谱的改进方法和商业化

基本信息

批准号：
10256885
负责人：
Stephen Valentine
金额：
$ 25.65万
依托单位：
INVIBRAGEN INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10256885
关键词：
3-Dimensional Adoption Affect Amplifiers Area Benchmarking Biological Response Modifier Therapy Biopolymers Blood capillaries Buffers Clip Communicable Diseases Coupled Coupling Data Deposition Detection Deuterium Development Devices Disease Disease Progression Exhibits Future Gases Goals Growth Health Housing Human Hydrogen Industry Infusion procedures Ions Isoelectric Point Letters Liquid Chromatography Malignant Neoplasms Manufacturer Name Mass Spectrum Analysis Medicine Methods Micromanipulation Nebulizer Oligonucleotides Onset of illness Pathway interactions Performance Pharmacologic Substance Phase Positioning Attribute Power Sources Production Proliferating Protein Analysis Protein Engineering Proteins Research Research Personnel Signal Transduction Solvents Source Structure System Technology Therapeutic Universities West Virginia Work aqueous base commercialization design design and construction early onset experimental study improved instrument instrumentation interest ion source ionization ionization technique mass analyzer mass spectrometer nano-electrospray new technology novel strategies preservation protein complex protein structure prototype therapeutic gene therapeutic protein three dimensional structure tool voltage

项目摘要

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.

抽象/总结