Break through the limits of measurement of ultra-trace materials, lead the independent innovation of mass spectrometry instruments

[Chinese instrument network instrument research and development] The “ultra-trace amount” in analytical chemistry refers to the extremely small amount of material in the range of 10-9 g/g or less. Single-cell components, early cancer diagnostic marker content, and impurity content in high-purity reference materials are often on the ultra-trace level. Detecting and accurately quantifying these ultra-trace substances often has the effect of “seeing what we know”. For example, the ultra-trace difference between single-cell components is likely to be the basis for distinguishing cell function and judging whether cells are pathological; ultra-trace diagnostic markers in blood may be the most effective way for early diagnosis of tumors and cardiovascular and cerebrovascular diseases. . However, "ultra-trace" is close to the detection limit of mainstream analytical testing methods, and it is even more difficult to ensure the reliability and stability of ultra-trace composition measurement with a small sample size and a complex matrix.

To this end, the China Institute of Metrology ("China Institute of Metrology"), a system solution, core technology, and key components for the accurate measurement of ultra-trace substances, has jointly launched technical research with units such as Fudan University. After nearly six years of hard work, the project team has successfully opened up new ways for the ultra-trace material precision measurement, solved the world's technical problems in key measurement links, and expanded the detection limit of target analytes to one-thousandth of mainstream methods. . The core device and measurement system independently researched and developed by the project team have successfully upgraded the independent research and development capabilities of related instruments in China to the international leading level, providing strong support for breakthroughs in major researches in China's material science and life sciences. A few days ago, the “Key Technology and Application of Precision Measurement of Ultra-trace Matter” led by China Metrology Institute won the second prize of 2017 National Science and Technology Progress Award.
According to the project leader and director of the China Metrology Institute, the researcher pointed out that the system innovation of the entire technology chain and the key points of the key links are the two major breakthroughs in the project. The project team first started with the mainstream chromatogram-mass spectrometry technology route and analyzed the basic reasons for restricting the measurement accuracy. A new measurement system model based on ion-accurate measurement technology was proposed. At the same time, the project established a multi-physics multi-physics ion motion simulation system based on super-computing, which has facilitated the rapid verification, optimization, and implementation of multiple new technologies and methods in the entire R&D process. On this basis, the project focused on the key links of the system, successfully built a multi-physics field that could be precisely regulated, invented a new field-controlled ion manipulation technology, and developed a series of key components and three types of scientific devices based on different principles. Ion selective high-efficient transmission, enrichment and precise separation, the highest ion enrichment efficiency up to 10000 times. The project also developed a highly efficient glow discharge ionization device for weakly polar, easily degradable compounds, achieving accurate depletion of all impurities in pure substances, and significantly increasing the independent research and development level of China's reference pure substances, two kinds of life science fields. The method for setting the standard substance was published as a reference method by the international community, which demonstrated the international status and level of China's chemical metrology. The project has developed a unique scientific device based on electric field induced analytical ionization and ionization for the problems of very small sample size and complex matrix in single cell analysis, successfully separating the matrix and analyte molecules in pL (10-12L) grade single cells. With detection limits up to fmol (10-15 mol), we can simultaneously observe extremely small changes in the contents of thousands of metabolites in single cells, providing reliable support for cutting-edge research and cutting-edge research in China's life sciences.
In addition to supporting leading-edge cutting-edge research such as metrology science and life sciences, the project team cooperates with related research institutes and companies to focus on the independent R&D, technology upgrading, and industrialization of new products of mass spectrometry instruments, relying on innovation to lead China’s foundational frontier research on autonomous equipment capabilities and original innovations. The key technologies and components that have been formed have been applied to the research and development of multiple companies and various mass spectrometers. They have broken foreign monopoly in some important areas and enhanced the international competitiveness of domestic mass spectrometry instruments.
(Original title: Breakthrough Ultra-trace Material Measurement Limit Leads Independent Innovation of Mass Spectrometry Scientific Instruments)