Development of VSSI-probe technology for in situ probing biological systems using mass spectrometry

开发使用质谱法原位探测生物系统的 VSSI 探针技术

• 批准号: 10021677
• 负责人: Peng Li
• 金额: $ 34.2万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021677
• 关键词: Address; Adopted; Adoption; Biological; Biological Assay; Biological Process; Biomedical Research; Cell Culture Techniques; Cells; Chemicals; Chemistry; Communities; Complex; Detection; Development; Diagnosis; Diagnostic; Environment; Enzymatic Biochemistry; Frequencies; Gases; Geometry; Glass; Human; Huntington Disease; Image; Immobilized Enzymes; In Situ; Ions; Kinetics; Knowledge; Lasers; Lead; Lipid Bilayers; Lipids; Liquid substance; Maps; Mass Spectrum Analysis; Mechanics; Methods; Microbe; Microscope; Monitor; Nebulizer; Organism; Oxidative Stress; Performance; Phase; Preparation; Procedures; Proteins; Proteomics; Reaction; Research; Resolution; Sampling; Slice; Slide; Solid; Solvents; Source; Spectrum Analysis; Speed; Surface; System; Techniques; Technology; Time; Tissue Sample; Tissues; Transducers; Work; base; biological systems; biomaterial compatibility; clinical diagnostics; cost; design; detector; direct application; experimental study; flexibility; high sensitivity probe; imaging platform; improved; in vivo; instrument; ionization; ionization technique; mass analyzer; metabolomics; monolayer; operation; protein aggregation; structural biology; temporal measurement; tool; voltage

Project Summary Mass spectrometry (MS) is a powerful tool for biological studies, which has found a wide range of applications including proteomics, metabolomics, glycomics, lipidomics, and structural biology. While most of the existing MS applications are extraction-based batch analysis, using MS for in situ or in vivo analysis of biological samples has become increasingly important to enable new biological discoveries. The past decade has witnessed the rapid development of interfacing methods for direct MS analysis of various biological samples from tissue slices to single cells. However, existing methods still have difficulties in studying living and dynamic biological systems in a non-invasive manner and in situ MS experiments are primarily performed by MS research groups due to the involvement of complex instrument setups. As a result, these limitations significantly hinder the progress of using direct MS for biological discoveries. To address the unmet need for in situ MS analysis of biological systems, our objective is to develop a direct MS method, vibrating sharp-edge spray ionization probe (VSSI-probe), that is simple, easy to use, biocompatible, and amenable to high speed sampling. Compared to existing methods, the proposed VSSI-probe is amenable to fast sampling, highly biocompatible, voltage-free, easy to operate, and substantially less expensive. Therefore, we expect that once demonstrated, the proposed VSSI-probe will enable new MS applications as well as improve the adoption of direct MS analysis in the biological community. In particular, we will (1) optimize the performance of the VSSI-probe for high sensitivity MS detection;(2) demonstrate a high-throughput VSSI-probe platform for studying fast biological reactions;(3) demonstrate the utility of VSSI-probe in studying a delicate and dynamic biological system of lipid/protein aggregates interaction. (4) demonstrate the high spatial resolution sampling capability of VSSI-probe for studying metabolites directly from bacterial colony. With the unprecedented capability and flexibility of probing biological samples, the proposed VSSI-probe will enable a broad range of biological applications that requires fast and biocompatible sampling including enzymology, cell monitoring, lipid bilayer chemistry, and real time intraoperative diagnosis. The simplicity, low cost, and compatibility with existing mass analyzers of the proposed system will also greatly reduce the technical barrier for adopting this technology by non-MS groups thereby expanding applications of direct MS to more diverse biological problems.

项目总结