Mass spectrometers are a type of instrument that separates and detects differences in the mass of charged substances. The ionization process is crucial for mass spectrometric detection; only when analytes are converted into charged ions and transferred into the gas phase can they be detected by mass spectrometers. Current ionization methods include ESI, MALDI, APCI, and APPI. A mass spectrometer typically consists of an ion source, a vacuum interface, a mass analyzer, and a detector. 1. Mass Spectrometers and Mass Spectrometry Analysis A mass spectrometer is an instrument that separates and detects the composition of substances based on the differences in mass of atomic, molecular, or molecular fragments, following the principle that charged particles can be deflected in electromagnetic fields. Mass spectrometry analysis is an analytical method that first ionizes substances, separates ions by their mass-to-charge ratio, and then measures the intensity of various ion spectral peaks to achieve analytical purposes. Working principle: The ion source of a mass spectrometer ionizes sample molecules under high vacuum conditions. After ionization, the molecules, having received excessive energy, further fragment into various smaller mass fragment ions and neutral particles. These ions acquire average kinetic energy with the same energy under the action of an accelerating electric field and enter the mass analyzer. The mass analyzer separates ions of different masses that enter it simultaneously according to their mass-to-charge ratio (m/e). The separated ions then enter the ion detector one after another, where the ion signals are collected and amplified. After computer processing, a mass spectrum is generated. 2. Structure and Function A mass spectrometer generally includes a sample introduction system, an ion source, a mass analyzer, an ion detector, a vacuum system, and a data processing system, among which the ion source, mass analyzer, and ion detector are the core components. 1. Sample introduction system: Introduces the sample into the mass spectrometer. It can be divided into two methods: direct injection and injection through an interface. 1) Direct injection: At room temperature and atmospheric pressure, gaseous or liquid samples can be introduced into the ion source in the form of a neutral flow through an adjustable nozzle device. 2) Injection through interface technology: Currently, the rapidly developing area in mass spectrometer sample introduction systems is various chromatography-mass spectrometry interface technologies, which introduce chromatographic effluents into the mass spectrometer for ionization and subsequent mass spectrometric analysis. 2. Ion source: A device that ionizes the sample to generate a beam of charged particles. The ion source is the heart of the mass spectrometer. Since the energy required for ionization varies greatly among different molecules, different ionization methods should be selected for different molecules. Generally, ionization methods that provide large amounts of energy to the sample are called hard ionization methods, while those that provide small amounts of energy are called soft ionization methods. Soft ionization methods are suitable for samples that are easily fragmented or ionized. 3. Mass analyzer: Positive ions with different kinetic energies generated in the ion source are accelerated in the accelerator to increase their energy, and then the mass analyzer separates the charged ions according to their mass-to-charge ratio. 4. Ion detector: The detector receives and detects the separated ions and amplifies their output signals. 5. Data processing system: Uses workstation software to control the sample determination process, collect data and calculate results, analyze and judge results, display and output mass spectra, store and retrieve data, etc. 6. Vacuum system: In a mass spectrometer, all areas where sample molecules and ions exist must be in a vacuum state to reduce background interference and minimize interference caused by collisions between ions or between ions and molecules. Additionally, oxygen in the residual air can burn out the filament of the ion source. 3. Accuracy of Domestic Mass Spectrometers Matches the International "Gold Standard" In September 2022, good news came for domestic mass spectrometers. The "liquid chromatography-tandem mass spectrometry system" developed under the leadership of Fang Xiang, president of the National Institute of Metrology, was approved for China's medical device registration certificate. The system mainly consists of a liquid chromatograph, a quadrupole-linear ion trap tandem mass spectrometer, and supporting software. It is also China's first independently innovative mass spectrometric instrument based on ion trap mass spectrometry to achieve medical device registration. A mass spectrometer is a precise, efficient, and multifunctional analytical instrument that separates and analyzes different charged particles according to their mass-to-charge ratios. Based on the principle that charged particles can be deflected in electromagnetic fields, it separates substances and detects their components according to the mass differences of atoms, molecules, or molecular fragments. Mass spectrometers have an extremely wide range of applications. In fields such as food, environment, clinical medicine, pharmaceuticals, and national security, they are highly favored for their accurate qualitative and quantitative capabilities in analytical detection processes. In recent years, the global market demand for mass spectrometers has grown by more than 10%, and the demand growth rate in the Chinese market is much higher than this figure. However, for a long time, China's mass spectrometers have suffered from insufficient core technologies and a "hollowing out" phenomenon. "Facing the needs of China's economic and social development, there is an urgent need to develop mass spectrometric instruments with independent intellectual property rights," said Fang Xiang. Fang Xiang has long been engaged in research on mass spectrometry theory, instrument engineering technology, and chemical and biological measurement technologies. He is well aware that the key to developing independently controllable mass spectrometers lies in independently developing high-level mass analyzers, efficient ion sources, and other core components, as well as stable system integration. With nearly 20 years of dedicated research, the R&D team has achieved multiple innovations. Focusing on innovation in core mass spectrometry technologies and whole-machine engineering, the team has successively overcome key components and core technologies such as high-level quadrupole mass analyzers, ion trap mass analyzers, efficient ion sources, high-performance radio frequency high-voltage power supplies, and dedicated modular measurement and control systems. They have also broken through engineering and technical challenges in reliability, electromagnetic compatibility, electrical safety, environmental adaptability, and software intelligence, realizing the engineering and industrialization of a series of highly reliable key component modules and whole mass spectrometers, with overall performance indicators reaching the leading level in China. Especially in terms of high-accuracy quantification with ion traps, the team proposed new technologies of quadrupole field pre-separation and gas-phase ion selective enrichment, realizing directional enrichment of target product ions, effectively reducing the space charge effect in the ion trap, and bringing the quantitative accuracy of ion trap mass spectrometers to the same level as the international "gold standard" triple quadrupole tandem mass spectrometry. At the same time, it maintains the significant advantages of ion separation and enrichment, with both excellent accuracy and sensitivity. "To put it simply, the ion trap is small in size, like a trap that confines ions, thereby achieving simultaneous capture, enrichment, and fragmentation of ions. It can also perform multi-stage fragmentation to improve measurement accuracy," explained Fang Xiang. Currently, this instrument has been successfully applied to the accurate measurement of a series of biomarkers and was selected as an excellent scientific research instrument case by the China Association for Science and Technology in 2022. The industry generally believes that the approval of this instrument has advanced the comprehensive localization process of high-end chromatographic mass spectrometry instruments by a large step, opening up a new situation for the overall strength of independent R&D and leapfrog development of localization of mass spectrometric instruments in China. Article sources: CRI Online, Chumen's Research, Yuexu Technology (Shanghai) Co., Ltd.