1. Project introduction (brief introduction of the basic situation of the project)

The project plans to develop a miniaturized high-sensitivity time-resolved fluorescent rapid quantitative detection system with independent intellectual property rights and corresponding supporting detection kits, and develop an early rapid and accurate diagnosis system for sepsis-related markers. The project plans to be based on instrument design and development and realize the development and industrialization of an early detection system for sepsis by combining supporting kits.

2. Cooperation content

(1) Brief introduction of the main related technologies involved (mainly introduce the main technical contents involved in this project and other technologies that need to be supported)

The equipment uses time-resolved fluorescence detection technology, that is, the detection optical path, signal acquisition and amplifier are designed based on the characteristics of time-resolved fluorescent dyes, as well as the overall instrument design and debugging. Time-resolved fluorescence analysis is currently the most sensitive microanalysis technology, with a sensitivity of up to 10^-12g/ml, 3 orders of magnitude higher than radioimmunoassay. The kit is a collection and detection analytical chromatographic technology designed by combining the antibody-antigen specific adsorption principle with time-resolved fluorescent labeling technology. That is, the antigen is combined with a fluorescently labeled antibody, and the fluorescence intensity is detected using a device, thereby achieving specific immunodiagnosis.

The specific research content is:

(1) Research and development and technical improvement of time-resolved fluorescence instruments: mainly aiming at the defect that the current characteristic of long fluorescence life cannot be exerted, the constant light source is converted into a flashing light source, and then the time-resolved time characteristics are determined to achieve early diagnosis of sepsis. Rapid and accurate diagnosis;

(2) Optimization of rare earth complexes: Optimize the central rare earth ion, first ligand and second ligand of different rare earth complexes respectively to screen complexes with the best luminescent efficiency;

(3) Development of time-resolved immunofluorescent microspheres: Using the copolymerization method of rare earth complexes and polymer monomers, time-resolved fluorescent signal amplifying microspheres with uniform and controllable particle size and stable properties were developed;

(4) Design and synthesis of rare earth doped luminescent nanoparticles with high luminescent efficiency:

It is proposed to design and synthesize time-resolved fluorescent nanoprobes with high stability (such as NaLuF4, NaGd/LuF4, etc.) with low photon energy and ion luminescent centers with long fluorescence lifetimes (such as Eu3 +, Tb3 +, etc.). At the same time, through the design of the core-shell structure, the luminescent efficiency of nanoparticles is further improved;

(5) Combining time-resolved fluorescence analysis technology with immunochromatography technology, and studying the proposed use of nano-surface functionalization technology to modify sepsis-related markers based on the time-resolved fluorescent nanoprobes designed and synthesized in the early stage. A time-resolved sepsis multi-marker joint detection platform achieves early rapid and accurate diagnosis of sepsis. Developed a kit for early diagnosis of sepsis.

(2) Proposed cooperation areas and cooperation objects (mainly describe the areas and recipients of cooperation in the project)

Fujian Institute of Material Structure, China Academy of Sciences

(3) Proposed cooperation model (briefly introduce the future business model of the project and the cooperation model you hope to carry out)

For technical cooperation development and transformation cooperation with the company, the Haixi Research Institute of China Academy of Sciences is mainly responsible for technical research and development support, and the company is responsible for market development and sales business.

3. Cooperation cases (if there are demonstrations, applications, etc., available)

It has cooperated with Xiamen Aode Biotechnology Co., Ltd. on technical product transformation and carried out the "R & D and Industrialization of Miniaturized Time-Resolved Fluorescence Medical Detection System" project, and has successfully developed the "Time-Resolved Fluorescence Rapid Diagnosis System" and related products. At present, a total of 12 national medical device registration certificates have been obtained, of which 6 diagnostic reagent products and detectors have been put into commercial production and clinical application, and 25 products have obtained EU CE certification. The PCT (sepsis testing) product has passed clinical sample evaluations from the General Hospital of the People's Liberation Army and Beijing Tiantan Hospital, proving that the product has reached the international leading level. At present, the total annual sales of products reach 10 million yuan.

4. Project implementation unit (brief introduction of the main undertaking unit and cooperating unit of the project)

Xiamen Rare Earth Materials Research Institute (hereinafter referred to as Xiamen Rare Earth Institute) is a research and development institution jointly established by Haixi Research Institute of China Academy of Sciences, Xiamen City Government and Xiamen Tungsten Industry Co., Ltd. The Xiamen Rare Earth Institute Park covers an area of 97 acres, with a total construction scale of about 110,000 square meters, a total investment of 430 million yuan, and a planned institute staff of 800 people. Based on the advantages of rare earth resources in Fujian Province and the foundation of Xiamen's existing rare earth enterprises (production) industry, Xiamen Rare Earth Institute is guided by the development and application of rare earth functional materials, carries out research and development of common key rare earth technologies and related functional materials, promotes the integrated development and utilization of rare earth resources in Fujian and Jiangxi, and enhances the independent innovation capabilities of the Haixi rare earth industry; Prospective layout of rare earth science and technology research and development, effectively gather rare earth scientific research forces, and jointly build a national-level rare earth material research and development base and a rare earth material application technology research and development and industrialization demonstration base. It currently has a provincial engineering technology research center-"Fujian Province Rare Earth Engineering Technology Research Center" and has established a joint medical transformation center with Mengchao Hepatobiliary Hospital of Fujian Medical University. In recent years, Xiamen Rare Earth Institute has undertaken more than 60 government projects of various types, including international cooperation from the Ministry of Science and Technology, major science and technology projects in Fujian Province, major R & D platforms in Xiamen City, National Natural Science Foundation of China and enterprise entrusted projects.

Xiamen Aode Biotechnology Co., Ltd. was established in 2014 as the medical device industrialization base of Xiamen Rare Earth Materials Institute of Haixi Research Institute of China Academy of Sciences. It specializes in the research and development, production and sales of new miniaturized in vitro diagnostic testing instruments and supporting kits, and provides third-party medical testing services. Relying on the economic and geographical advantages of beautiful Xiamen, the company has grown rapidly. In the R & D section, there is a R & D team composed of doctors and masters who have been engaged in related professional research for many years. This project currently has 36 technical backbones, 27 of whom have master's and doctoral degrees, and has successfully developed a miniaturized time-resolved fluorescence immunoassay instrument and supporting kits. At present, 12 products developed and applied for inflammation testing, tumor, heart failure and myocardial infarction testing have obtained national Class II medical device registration certificates. At the same time, 25 products have obtained CE certification from the European Union. The company covers an area of 1200 meters in Haicang Factory², of which the GMP pilot workshop is 600 meters²。Expansion factory: Jimei factory area 2000 meters²。The company has invested 8 million yuan in equipment, and it is estimated that the total equipment investment in 2020 will be 15 million yuan.