There are no two identical leaves in the world, and the cells are also. However, when scientists conduct modern biological research, most of the time they are examining cell populations, ignoring cellular heterogeneity. Take nerve cells, there are hundreds of millions of nerve cells in the brain, these nerve cells are highly diverse in cell morphology, synaptic connections, cell structure, electrophysiology and physiological functions. In different kinds of nerve cells, their genome, proteome, chemical molecular composition, content, and metabolism are also very different. In a small brain area less than 1 mm in diameter, there may be dozens or even hundreds of completely different neurons and glial cell types. Even in many cases, even two neurons adjacent to each other physically may be two different neuron types. Therefore, the analysis of the genome, proteome and metabolome of individual neurons in the brain has important biological value. Single-cell technology has developed very rapidly in recent years, such as single-cell sequencing, and has been widely used in various life sciences. The annual special report published in Nature Methods in January 2014 listed the application of "Singled out for sequencing" as the most important methodological advancement in 2013. Single-cell technology has not only made great progress in sequencing, but single-cell mass spectrometry is gradually gaining more attention. Unlike single-cell sequencing, which is used to analyze single-cell genomes, single-cell mass spectrometry is primarily a study of metabolites in individual cells, such as the composition, content, and metabolism of chemical small molecules. Single cell mass spectrometry has the advantage of high-throughput detection of small molecule compounds that are currently undetectable by other single-cell techniques, as well as their metabolic processes. At the same time, due to the advantages of the mass spectrometer itself, it is possible to accurately analyze the detected chemical substance information without using external means such as sequencing or specific antibodies, which can be said to be "good quality and low price". However, due to the limitations of mass spectrometry itself, large-scale measurements like single-cell sequencing are not currently available. Multidisciplinary cross-cooperation to develop single neuron mass spectrometry In 2013, Professor Xiong Wei completed his postdoctoral research work at the National Institutes of Health. After returning to China, he joined the School of Life Sciences of the University of Science and Technology of China. In the application for the “Youth Thousand Talents Programâ€, Professor Xiong Wei met another professor of “Qing Qian†Huang Guangming from the School of Chemistry of the Chinese University of Science and Technology. At that time, Professor Huang Guangming’s research group was developing a small sample (pL level). Mass spectrometry technology. After many discussions, they decided to combine the superior technologies of the two laboratories to develop a new technology called single nerve cell mass spectrometry. At present, the application of mass spectrometry in neuroscience mainly uses samples after homogenization of a large number of tissue cells. In single-cell assays, mass spectrometry is increasingly being used for single-cell cellular metabolism analysis because of its high sensitivity, large linear range, and high-throughput analytical chemical molecules. However, the current method requires the use of a large amount of organic reagents to treat the cells, and the activity of the cells at the time of sampling cannot be maintained; the lengthy processing and separation process also leads to a slower analysis speed, and it is impossible to complete a large number of single cell analyses in a short time; The electrophysiological signal of the cells; ultimately, mass spectrometry analysis of single cell metabolites cannot be used on a large scale for the analysis of nerve cells. New technology allows mass spectrometry to analyze living single neurons into reality On January 26, 2017, Prof. Xiong Wei and Prof. Huang Guangming and others published a study entitled “Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry†on PNAS. In this new study, the research team relied on electrophysiological patch clamps and electrospray ion source technology to establish a stable single-neuron intracellular component sampling and mass spectrometry component analysis technique. Analysis of single nerve cells by patch clamp and single cell mass spectrometry Electrophysiological patch clamp can contact and adsorb the glass microelectrode on the cell membrane, penetrate the membrane into a hole after high-impedance sealing, and record the ion current of the whole cell membrane outside the membrane. The electrospray technology mainly uses a high-voltage alternating current to ionize the analyte and then be detected by mass spectrometry, which has strong anti-interference ability. Compared with traditional mass spectrometry methods, the biggest advantage of this new method is that it can sample living cells in situ and collect information on cell position, electrophysiological activity and intracellular chemical composition. 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