Speaking of cells, they are both familiar and unfamiliar to ordinary people, because most people know that cells are the basic constituent units of human life, but that's all. In fact, in the eyes of scientists, cells can help them find the laws and mysteries of birth, old age, sickness and death in humans.
Through analysis at the single cell level, it can not only understand the differences between cells, but also reveal the molecular mechanisms of different cell phenotypes, thereby achieving more accurate diagnosis and more effective treatment of diseases. It can also explore the pathogenesis of diseases from a microscopic level, which will help study the nature and laws of related diseases, and is of great significance to the early diagnosis, treatment of major diseases and the study of cell physiological and pathological processes.
In Guangxi Normal University, the National Key Laboratory of Chemical and Drug Molecular Engineering, the provincial and ministerial departments of the State Key Laboratory of Pharmaceutical Resources, Chemistry and Drug Molecular Engineering, in this inconspicuous laboratory building, a scientific research team engaged in life analytical chemistry research has set their sights on single cells, and has made major breakthroughs in two major international cutting-edge technology fields, nanobiosensing and imaging, and microfluidic chip electrophoresis technology . Some of the achievements have even set an international precedent and led the world.
The scientific research team started to develop microfluidic chip electrophoresis technology in 2005 and began to study cell fluorescence imaging technology in 2015. During a long period of time, the team received funding from multiple national and provincial and ministerial projects such as one major scientific instrument research project of the National Natural Science Foundation and four projects , providing technical support for the early stages of the disease and post-health diagnosis.
cells have a diameter of only a few microns to tens of microns, and their internal components such as DNA/RNA, protein , and biological small molecules are usually very low. If visual observation of the cells can be carried out, it will greatly promote the intuitive analysis of internal components of cells. Therefore, the scientific research team used nanobiosensing and fluorescence imaging technology to solve the problem of how to image cells more clearly. This is a technical means to meet the needs of multi-scale, cross-level detection at the molecular, cellular and tissue levels. The specific detection method is to combine the characteristics of biomolecules to prepare fluorescent nanoprobes with special functions, which can undergo specific recognition reactions with the target substances and be displayed through imaging technology to achieve the purpose of information quantification, functional monitoring and in-vivo detection of specific biomolecules in cells.
Among them, fluorescent probe constructed based on nanomaterials is one of the important tools for realizing cell fluorescence imaging. Nanomaterials refer to the size of a certain dimension of a material located in the nanoscale, and its size is about one ten thousandth of the diameter of the hair. When the structural unit of a material is as small as the nanometer, it will show some unique physical and chemical properties. Biosensing and imaging technology built on these characteristics of nanomaterials has a wide range of applications in the fields of life medicine research and other fields.
When a certain size of the material is reduced to the nanoscale, the physical properties it exhibits are completely different from the blocky materials seen in daily life. Taking the carbon-based nanomaterials obtained by the project as an example, the bulk carbon we see is mostly black and has no obvious glossy luminescence phenomenon, but the carbon-based nanomaterials obtained by the project team will show different colors under suitable light source irradiation conditions. Nanomaterials are a small world, and life applications are great.
fluorescent probe is a specially designed synthetic method that allows the fluorescent probe structure to contain groups that have target recognition for the target analyte. By specifically identifying the target molecule, signal changes are generated, thereby achieving qualitative and quantitative analysis of the target. Then, which nanomaterial is chosen directly related to the performance of the nanofluorescent probe. In order to obtain near-infrared ratio fluorescent probes with low toxicity, strong light stability and good biocompatible, the research team proposed a new strategy for the preparation of series of fluorescent carbon-based quantum dots, and developed fluorescent nanoprobes with higher sensitivity and better stability.
fluorescent probe is a very important part of fluorescence imaging technology and is also a signal indicator for fluorescence imaging.We can use fluorescent probes to label biomolecules or specifically identify biomolecules, and image the fluorescent signals emitted by the probes, thereby obtaining relevant information on the distribution and expression of biomolecules in cells or living organisms. The team mainly conducts research on the design and construction of near-infrared ratio fluorescent nanoprobes and their application in life analysis. Near infrared light has better biological tissue penetration ability, while ratio-type fluorescence signal design can effectively reduce interference from biological background, thereby improving fluorescence imaging performance in living cells or living organisms.
for the application of fluorescent nanoprobes has played a role in the study of inflammation. The scientific research team has developed a near-infrared ratio fluorescent nanoprobe that can specifically recognize inflammation markers. When inflammation occurs in living mice, the concentration of hydroxyl radicals in the cells will increase, and the developed fluorescence probe has good response performance against hydroxyl radicals, and the fluorescence intensity and hydroxyl radical concentration have a good linear relationship. Therefore, fluorescence probes can be used to fluorescent imaging of the inflammation process at the cell and the living level, thus visualizing and tracking the entire process of inflammation. This provides a micro-level monitoring method for the diagnosis and treatment of inflammation. However, fluorescence imaging technology mainly solves the problem of dynamic visual tracking of cell components, which is difficult to solve the problem of accurate determination of intracellular component content. The size of a single cell is very small, but it contains many biological molecules related to life. If the biomolecules in a single cell can be accurately quantified, it will have important physiological and pathological value. However, this not only requires the development of analytical methods with higher sensitivity, but also requires the construction of a high sensitivity research platform. In order to solve the problem of accurate measurement of biomolecules in single cells, the scientific research team overcomes difficulties based on existing achievements and develops the world's first multifunctional microfluidic chip single-cell analyzer, providing a research platform for the development of accurate quantities of disease markers in single cells.
microfluidic chip is the core component of a single-cell analyzer. It is a micro-full analysis technology developed in the 1990s. It has the advantages of high integration, high separation efficiency, rapid detection, easy portability, and low consumption of samples and reagents. At present, microfluidic chip analysis technology has been applied to the detection of various substances such as proteins, nucleic acids, biological small molecules, and has shown broad application prospects in the fields of life medicine research, clinical diagnosis, , environmental and food safety testing, etc.
microfluidic chip uses lithography technology to integrate samples in conventional chemical laboratories with experimental operations such as preparation, synthesis, reaction, separation, and detection through microchannels on a small glass or silicon plate. The team has developed three generations of single-cell analyzers. The third generation is based on microfluidic chips, using micron-scale network channels to perform single-cell manipulation and separation, and detection of substances in single cells. The feature is that it integrates many network channels, which can achieve high integration and automation, and is relatively simple to operate. It can use an integrated microscope to visualize single-cell manipulation.
However, due to the small injection volume and narrow detection window on the microfluidic chip platform, it is difficult to achieve high sensitivity detection, which greatly limits the application of microfluidic chip technology in the field of trace disease marker analysis. In order to break through the technical bottlenecks for further development and application of microfluidic chips and provide new technical support for the accurate analysis of trace disease markers and early diagnosis of diseases, the scientific research team combined nucleic acid signal amplification technology with microfluidic chip detection methods to develop signal amplification methods on the microfluidic chip platform, and overcome this problem.
We have combined some nucleic acid signal conversion and amplification methods on the microfluidic chip electrophoresis research platform we built ourselves to increase the sensitivity of analysis and detection by at least 1,000 times, and successfully used for the accurate determination of trace components in single cells.For example, in this article recently published in the American Journal of Analytical Chemistry, we achieved simultaneous quantification of two tumor-related proteins in a single cell through design and analysis research. The expression of these two proteins will be significantly higher than that of normal liver cells in liver cancer cells. This is of great significance for studying the relationship between protein and liver cancer disease. The microfluidic chip developed by the scientific research team has micron-scale electrophoretic channels that can match the size of a single cell. In addition, microfluidic chip electrophoresis can integrate basic operating units such as chemical reaction, separation and detection of target analytes into a glass sheet with micron-sized channels, and achieve rapid separation and precise detection of target substances through electrophoresis driving and specific signal output methods.
At present, the microfluidic chip technology that breaks through the technical bottleneck is relatively mature. It can be used as a core component on a single-cell analyzer and makes it an important means and platform for cell analysis, thus providing new detection methods for the accurate analysis of trace disease markers and early diagnosis of diseases. The instruments and methods developed by the team are expected to be applied to genetic screening and early diagnosis of Guangxi's high-incidence diseases such as liver cancer, nasopharyngeal carcinoma, thalassemia, etc., and improve Guangxi's technical level in the field of regional disease research, prevention and treatment.
" microchip electrophoresis and optical nanobiosensing and imaging new methods" won the first prize of the Natural Science Award in the 2021 Guangxi Science and Technology Award.
At present, the scientific research team of Guangxi Normal University has trained 3 winners of the Guangxi Natural Science Outstanding Youth Fund, and 2 won the Guangxi Youth Science and Technology Award. The research results have been published in top academic journals " Analytical Chemistry " and other academic journals. The team members were also invited to give reports at the international heavyweight Pittsburgh Analytical Chemistry Conference and the National Academic Conference on Molecular Spectroscopy. The research results achieved have been highly recognized by peers.
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