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Biomolecular structure advances in Analytical Mass Spectrometry Instrument Research

  Beijing Institute of Technology, July 6th, 2020: Three-dimensional structure analysis of biomolecules is an advanced subject in chemistry and biology. Electron microscopy and nuclear magnetic resonance (N) techniques usually rely on the purification of samples, which makes it difficult to analyze the in-situ structure of trace molecules. Mass spectrometry has powerful and complex sample analysis capabilities, and is widely used in various fields such as omics research, drug research and development, Environmental monitoring, medical testing, aerospace and counter-terrorism, but current mass spectrometry techniques are inadequate for the analysis of molecular three-dimensional structures.

  In order to break through the bottleneck of electron microscopy and mass spectrometry in the analysis of the three-dimensional structure of biomolecules, Xu Wei team group of the School of life Science of BIT was supported by the National Natural Science Foundation of China (NSFC) instrument program, the Outstanding Youth Science Foundation, etc. A series of methods and instruments based on liquid phase-transfer electrophoresis, nano-hole electrospray ionization ion source and non-variable mass spectrometry have been developed, and the rapid and high-throughput resolution of the three-dimensional geometry of biomacromolecules has been realized. Related achievements published series of articles in top journals such as ACS Central Science, Chem. Sci., Anal. Chem.

  The team first developed a highly stable and reproducible technique and instrument for liquid-phase Ion Mobility electrophoresis, which uses Laminar flow instead of conventional electroosmotic flow, by introducing Taylor diffusion, the separation, radius and effective charge of the sample molecules are measured simultaneously (Wenjing Zhang, ... Wei Xu*, Chemical Science, 2019,10,7779-7787). In order to obtain a more comprehensive three-dimensional structure of biological macromolecules, the research team further combined ion-mobility electrophoresis with non-denaturing mass spectrometry, the solution accessible surface area of the molecule was obtained by the gas phase invariant mass spectrometry, and the volume of the molecule was obtained by the liquid phase transport electrophoresis, combined with the fluid mechanics equation, finally, the 3D geometric size information of proteins and protein complexes (Haimei Wu, Rongkai Zhang, ... Ye Xiang* and Wei Xu*, Chemical Science, 2020,11,4758-4765) was obtained, this method can be applied to the study of protein-small Molecule Complex (Jie Hong, ... Muyi He* and Wei Xu*, Analytical Chemistry, 2020,92,5200-5206) . Based on the principle of ion migration in liquid phase, the research group developed the ion trap device in liquid phase, and realized ion enrichment, selective transport and sequential ejection analysis in liquid phase. With this device, not only the separation of complex samples can be achieved, but also the detection sensitivity of the mass spectrometer can be increased by more than 100 times (Jie Hong, ... Wei Xu*, Analytical Chemistry, 2020, Doi: 10.1021/acs.analchem. 0c01261).

  Next, the team proposed the concept and principle of the nanoporous electrospray ion source, by measuring the perturbation of the spray current caused by the molecules as they pass through an electrospray nozzle from micron to nanometer size, at present, the three-dimensional geometric size measurement of microorganisms and other particles has been primarily realized. Combined with mass spectrometric instruments, this method will greatly improve the ability of mass spectrometric identification and three-dimensional structure resolution (Yu Zhang, Yang Tang, ... Wei Xu*, Acs Central Science, 2020,6,6,1001 something 1008) .

  Professor Xu Wei's research group has long been devoted to the development and application of spectroscopic instruments. The laboratory focuses on miniaturized mass spectrometers and new techniques of structure-resolved mass spectrometry. In-depth studies have been carried out in the fields of basic theoretical research of ion trap mass spectrometers, large-scale parallel ion trajectory simulation of interdisciplinary subjects (fluid mechanics, electromagnetism), development of miniaturized mass spectrometers, microfluidic chips, and development of liquid-phase ion mobility electrophoresis instruments, and the application-oriented, focusing on the mass spectrometer research and aerospace, anti-terrorism, biomedicine and other fields of close integration. The team developed the world's first miniaturized electrophoresis-mass spectrometer, the world's first miniature continuous atmospheric pressure interface mass spectrometer, the development of liquid ion trap, structure analysis transfer electrophoresis and other technologies. Many of the team's patents have been industrial transformation, product services in basic scientific research, chemical defense and counter-terrorism, customs, drug regulation, power transmission, environmental monitoring and other fields.

 

News Source: School of Life Science
Translation: News Agency of BIT, Ren Qinduoriji