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instrumentOnline R&D News】On August 12th, Professor Zhao Weisong and his team, led by Academician Tan Jiubin from the School of Instrument Science and Engineering at our university, collaborated with Professor Feng Jiandong from Zhejiang University to achieve breakthrough progress in the field of super-resolution microscopy imaging technology. The research results were published in Nature under the title "Luminescent reaction enabled super resolution imaging". The research team has developed a new super-resolution imaging technology that does not require external light excitation. It uses the light signals generated during chemical reactions as imaging light sources to obtain super-resolution information through the inherent fluctuation characteristics of chemical reactions. For the first time internationally, chemical reaction luminescence specific super-resolution imaging has been achieved. This method fundamentally breaks through the limitations of phototoxicity, photodamage, and self fluorescence interference, achieving zero background and ultra long duration continuous dynamic in vivo super-resolution imaging. It provides a new scientific observation method for studying subcellular structural evolution and interactions, micro molecule super-resolution detection, and other life science and biomedical research across time scales.
The emergence of fluorescence super-resolution imaging technology has broken through the traditional optical diffraction limit, providing an important tool for analyzing the nanoscale structures and dynamic life processes inside cells. However, existing super-resolution imaging methods are based on the technical framework of "light source illumination signal response". While obtaining high spatial resolution, they inevitably introduce problems such as phototoxicity, photobleaching, and background signal interference, which pose serious challenges to long-term, high fidelity, and low disturbance continuous observation of live cell dynamics. How to break through the classic super-resolution imaging mode and achieve more biocompatible, sustainable, and high-quality super-resolution observations has become an important scientific problem that urgently needs to be solved.
In response to the above issues, the research team proposed a new super-resolution imaging method based on chemiluminescence (Luminescent Reaction enabled super solution Imaging via Entropy weighted correlation combined with Deconvolution, RIED). Unlike traditional fluorescence super-resolution techniques that rely on external light excitation for imaging, RIED uses chemiluminescent molecules to specifically label the internal structure of cells. Based on the photon fluctuation characteristics and information entropy distribution during the chemical reaction process, an efficient information extraction and reconstruction algorithm has been designed, achieving the world's first chemiluminescent specific super-resolution imaging. In addition, RIED breaks through the limitations of phototoxicity and self fluorescence interference in traditional fluorescence imaging, achieving three-dimensional super-resolution subcellular structure network imaging with near zero background. The research team further developed a multi-mode and efficient reaction luminescence imaging system, covering electrochemiluminescence (ECL), chemiluminescence (CL), and bioluminescence (BL). Based on different imaging requirements, various reaction system advantages are utilized to achieve multi scene applications from high-sensitivity molecular detection to continuous dynamic observation of live cells, bringing new breakthrough opportunities for life science research.
The research team applied RIED to dynamic imaging of live cell mitochondria, achieving continuous and stable super-resolution imaging without bleaching for over 41 hours with a spatial resolution of 100 nanometers. The long-term movement and migration process of intracellular mitochondria were fully observed, and the dynamic characteristics of mitochondrial cross cell migration were quantitatively analyzed at the single mitochondrial level, providing an important technical means for revealing the dynamic changes of mitochondria at long-term scales. Meanwhile, RIED also provides a new imaging tool for continuous dynamic observation of organelle and molecular behavior and evolution patterns in complex life processes without external light interference.
Professors Zhao Weisong and Feng Jiandong are co corresponding authors of the paper, while postdoctoral fellow Zhu Wenxin from Zhejiang University, doctoral student Zhang Chi, and doctoral student Gui Jiahui from the School of Instrumentation at our university are co first authors of the paper. The co authors of the paper also include Associate Researcher Qu Liying and PhD student Han Zhenqian from the School of Instrumentation at our university.
This work is supported by the National Natural Science Foundation of China, the National Key Research and Development Program, and the Young Scientists Studio project of our university.