Cell Magnifier: Peeling the "painted skin" of cancer cells
November 20, 2018 Source: Science and Technology Daily
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Recently, public figures have suddenly passed away due to cancer. It is also a hot topic: how can we discover cancer earlier and get an early treatment opportunity?
According to the Global Cancer Report, there are an estimated 18.1 million new cancer cases worldwide in 2018, with a death toll of 9.6 million. In China, cancer has become the number one killer of Chinese urban residents. At present, the incidence of cancer in China is close to the world average, but the mortality rate is higher than the world level. World Health Organization experts believe that early diagnosis and early treatment is the key.
Recently, the academician of the Chinese Academy of Sciences and the team of Professor Chen Hongyuan from the College of Chemistry and Chemical Engineering of Nanjing University have taken the lead in the international analysis of the biochemical reaction process of biomolecules in a single living cell at the nanosecond and nanometer scales, which can accurately measure the dynamics of molecules in a single cell. Variety. In other words, it is expected to detect early diseased cells and peel off the “painted skin†of cancer cells to help the clinical doctors diagnose and treat. Related research was published in a series of internationally leading publications such as the Proceedings of the National Academy of Sciences.
"see through" subtle changes in intracellular molecules
If you compare the cells in the human body to many people in the square, they seem to be normal on the surface, but some of them have changed their minds, just like a group of "latent". Once the time is ripe, they will make waves. .
In the early stage of cancer and other diseases, the human body will not have any symptoms. If it is based on general detection methods, it is equivalent to seeing or amplifying human tissues and organs from the perspective of appearance. It is difficult to "see through" the subtle changes of intracellular molecules.
Scientists have long struggled to find effective ways to identify these "latents" at an early stage. Since the 1980s, relying on scientific instruments to accurately detect the molecular changes in cells, and to use chemical analysis methods to obtain judgment results, has gradually become a new means of detection.
"Like a person, we must not only understand his appearance, height, weight, but also his personality." One of the main members of the research team, Professor Jiang Dechen of Nanjing University, made an analogy.
"Humans are made up of cells, and there are complex processes of change. We hope to investigate various chemical reactions in the cells from the source." Chen Hongyuan said that cancer cells are good at disguising themselves. This instrument can be used in the earliest stages of cytopathic, Effective identification of normal and diseased cells to make some valuable judgments.
The basic principle of this method is to use a nano-sized probe to penetrate into a single living cell and use the identifier of the probe surface or the detection reagent sent in to find a specific molecule, "like looking for a red color among a group of people. The person in clothes," Jiang Dechen said.
In the State Key Laboratory of Life Analytical Chemistry of Nanjing University, Science and Technology Daily reporter saw that this set of "single-cell high-time-space-resolved molecular dynamic analysis system" is composed of many analysis modules, occupying a whole laboratory of about 120 square meters. . “Our measurement system can detect chemical changes in cells by means of integrated electrochemical, optical and mass spectrometry. You can think of it as a 'chemical microscope' 'cell magnifier', which can attach molecules to various cells. Label." Chen Hongyuan introduced, we have to observe the results from the experiment, trying to peel off the "painting skin" of cancer cells, in order to help the clinical doctor to diagnose.
One billionth of a small water droplet flows through a nanotube
Scientific research has found that any substance is composed of tiny particles and molecules, and cells are no exception. These tiny particles are divided into organelles, vesicles and molecules. Among them, the chemical changes in the organelles dominate many activities of the cells.
In general, cells have an average diameter between 10 and 30 microns, while an organelle has a diameter of only 50 to 100 nanometers. It is extremely difficult to detect the chemical reaction of the molecules contained in such a small scale.
“The nanoprobes we designed will modify different identifiers on the probes according to the detection target, and can identify some molecules characteristically.†Chen Hongyuan said that this can obtain more detailed detection intervals. Molecular information.
In order to achieve detection of complex biomolecules, researchers send the corresponding detection reagents to the cells. Accurate and quantitative material transport to such a small space within a cell is a difficult problem, and there is no mature technology for reference.
After many discussions, the project team used the principle that “the solution can flow in the nanotube under the action of the electric fieldâ€, and realized the targeted transport of these reagents through the probe to the designated position in the cell.
Since the volume of the transport solution is only "flying up", that is, only one billionth of a drop of water, how much voltage should it use? How to observe such tiny droplets? On the basis of designing the experimental scheme, the research team also consulted a large amount of data. Through repeated experimental demonstrations, the liquid accurately discharged from the nanocapillary was finally obtained stably after repeated experiments. On this basis, the experimental parameters are further optimized so as not to interfere with the activity of the cells themselves during the analysis.
Equivalent to doing a chemical experiment in the cell
At present, internationally relevant tests usually perform observations at 200 nm resolution. The Chen Hongyuan team realized the analysis of the 50 nm molecular chemical reaction.
"We have successfully implemented the transport of the 'flying' volume of the analytical solution to the target area, and internationally took the lead in achieving quantitative electrochemical analysis of protein activity in a single organelle." Jiang Dechen said that the research is advanced. It is to improve the spatial recognition ability of single-cell analysis, just like the original photo taken is 512 × 512 pixels, and now invented a tool that can shoot higher pixels (such as 2048 × 2048), you can see more clearly.
In the 1980s, Chen Hongyuan began to explore methods, techniques and devices for spatial and temporal resolution of life analysis. After entering the 21st century, the team he led began to explore the molecular content and changes in the course of life activities on the basis of the previous ones, and explore new areas of life analysis chemistry research.
"A cell is a small universe." In the eyes of ordinary people, the cell is small to the extreme, the universe is the most extreme, and in Chen Hongyuan's view, small and big is a dialectical concept. After seeing the cell as a big thing, all the macro tools can be used here. All you have to do is to make the tool small and match the cells.
At present, humans are increasingly enriching the detection methods of cell molecules. In addition to this "single-cell high-time-space-resolved molecular dynamic analysis system", there is also a super-resolution microscope that has also made great progress.
“Both can distinguish between good and bad cells. The molecular information in cells contains physical information (such as distribution and its content) and chemical information (such as oxidation/reduction activity and kinetic parameters). It is an important parameter for evaluating cells. Super-resolution microscopy is based on fluorescence or other optical detection methods, mainly to read the physical information such as the distribution and content of biomolecules, and the spatial resolution has reached 10nm (nm). Our instrument is characterized by Acquisition of chemical information about intracellular molecules. At the same time, we synthesize information on electrochemistry, optics, and mass spectrometry, and the amount of information obtained is much richer than that of super-resolution microscopy." Chen Hongyuan said that our instruments and super-resolution microscopes have their own Directors, complement each other.
At present, the research of the Chen Hongyuan team is still exploring and deepening. According to reports, the team is currently studying the molecular measurement system to obtain a variety of "markers" dynamic changes in a single living cell by instrument, to achieve detection of multiple cancer "markers" in a single circulating tumor cell, to solve the current single "marker" "The problem of low credibility.
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