"Now those who do biology are all staring at "Science" and "Nature", and only the best equipment is required, and there is no domestic and imported point in their eyes. Doctors absolutely do not want to delay the diagnosis and treatment of patients because of the equipment. But everyone feels that domestically-made instruments are not easy to use in traditional concepts. Domestically produced instruments are really going to replace imports, and they are facing a lot of pressure. How can this be broken?"

This question raised by Professor Wang Ping of Zhejiang University, the Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences wanted to give an answer. On December 26, the national major scientific research equipment development project "Development of the core components and systems of super-resolution microscopy optics" undertaken by the Suzhou Medical Engineering Institute passed the acceptance, marking my country's ability to develop high-end super-resolution optical microscopes.

 I don’t understand the darkness of night during the day

In today's biological and basic medical research, the role of high/super-resolution optical microscope is very important, especially the 10~100nm scale super-resolution microscopic optical imaging is an important means to obtain original research results.

For example, in microbiology research, scientists can reveal many important life phenomena through ultra-micro observation of the dynamics of microbes; in the field of neurobiology, scientists need to dynamically observe the formation and changes of nerve synapses to reveal advanced neural activities. And the subcellular structure and function of neuropathy; and in the medical field, researchers need to rely on super-resolution optical microscope to observe the mechanism of viruses invading cells, etc., to better study the mechanism of some major diseases.

However, there always seems to be an invisible gap between optical experts and biologists.

Tang Yuguo, director of the Suzhou Institute of Medical Engineering, Chinese Academy of Sciences, has a personal experience of this kind of separation. Before coming to Suzhou, he worked for many years at the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences. He said frankly, "In the past, what we did in optics was to bury our heads and do our own. We didn't understand how biologists are eager for high-end microscopes.

The Suzhou Institute of Medical Engineering of the Chinese Academy of Sciences is the only research institute of the Chinese Academy of Sciences that focuses on biomedical instruments, reagents and biological materials. After contacting a large number of experts in the biological field, Tang Yuguo realized that my country’s expertise in optical microscopes, especially high-end optical microscopes The demand is extremely strong.

But the current situation is that although my country is a major consumer of microscopes, it can only produce low-end products, and high-end instruments basically rely on imports. This has severely restricted innovative research in related frontier fields such as biology and basic medicine in my country.

How to have both fish and bear paw?

After five years of research, researchers from Suzhou Institute of Medical Engineering, Chinese Academy of Sciences have made breakthroughs in key technologies such as large numerical aperture objective lenses, special light sources, new nano-fluorescence enhancement reagents, system integration and detection. They have applied for more than 90 national invention patents, of which more than 30 have been authorized. Projects and developed high-end optical microscopes such as laser scanning confocal microscope, two-photon microscope, stimulated emission loss (STED) super-resolution microscope, and two-photon-STED microscope.

Take the two-photon-STED microscope as an example. It organically integrates two-photon microscopy and STED microscopy. It can not only perform deep imaging of thick samples, but also perform ultra-high resolution imaging of areas of interest.

"Two-photon and STED microscopes have been sold in the market, but they all have their own advantages and disadvantages. Two-photon microscopes can see the deep structure of the sample, but cannot see the detailed structure within 100 nanometers; and STED The imaging resolution of the microscope can reach 50 nanometers, but the imaging depth is very shallow." said Zhang Yunhai, a researcher at the Suzhou Institute of Medical Engineering, Chinese Academy of Sciences.

Zhang Yunhai told the reporter of "China Science News" that in some brain scientific research, it is often necessary to look at some thicker brain slice structures. If you use two microscopes to observe the deep structure and the detailed structure within 100 nanometers, you need to remove the sample from one. When the microscope is moved to another microscope, the original observation position cannot be found. "With this two-photon-STED microscope, scientists can easily observe the deep structure and the fine structure of the surface area of ​​interest."

In addition, through this project, the Institute has built a high-end microscopic optical processing, assembly, inspection, and integrated engineering platform for microscope technology. It is expected to provide customized microscope equipment for user needs and provide for the development of high-end optical microscopes in my country A system solution.

From import to export

Chai Zhifang, an academician of the Chinese Academy of Sciences, is very pleased with the birth of these high-end microscopes. He hopes that these instruments can be industrialized as soon as possible, which will not only help scientific research, but also be used clinically, and to a certain extent replace foreign products.

In fact, the super-resolution microscope or core components developed by the project have been used in many research institutions at home and abroad, and some results have been achieved.

For example, the Institute of Zoology, Chinese Academy of Sciences uses high-end optical microscopes to observe basic phenomena in developmental biology and study potential regulatory mechanisms. The Shanghai Institute of Materia Medica, Chinese Academy of Sciences applies high-end optical microscopes to observe the intracellular targeted positioning and delivery of drugs, accelerating the development of innovative new drugs. Specialized laboratories such as Stanford University, the University of Tokyo in Japan, and the Army Medical University of my country have used two-photon microscopy imaging technology to conduct research on core issues of brain science such as information recognition and behavior control, as well as animal in vivo imaging experiments, and obtain high-resolution real-time nerves. Metaactive imaging data.

In addition, some achievements of the microscope and key components have been exported and sold. For example, the two-photon microscope has been sold to many foreign research institutions such as Germany, Israel, and the United States.

The acceptance expert group believes that the four types of high-end optical microscopes completed by the project team, as well as large numerical aperture microscope objectives, special light sources and other core components, all technical indicators meet the requirements of the evaluation indicators specified in the implementation plan. Four types of super-resolution microscopy imaging systems All have reached the practical level and completed the overall goal, and agreed to pass the acceptance.

However, Tang Yuguo said bluntly that the road to localization of high-end microscopes was not achieved overnight. He revealed that in the next step, the Institute will combine engineering and achievement transformation innovation models to realize the efficient docking of scientific and technological achievements on R&D platforms, engineering platforms, industrialization platforms, and market platforms. Through serialized and combined product layout, The microscope system and core components are engineered and industrialized. "Next we have to improve the performance of the microscope by a few percentage points and get back the lost ground bit by bit."