Liu Dayu, research group of Guangzhou first people's Hospital Affiliated to South China University of Technology: active droplet array microfluidic chip system for on-site rapid diagnosis

Microfluidics technology integrates the sample preparation, reaction, separation, detection and other basic operation units in the biological, chemical and medical analysis process into a micro scale chip, and automatically completes the whole analysis process The characteristics of microfluidic chip technology come from the characteristics of microfluidics and the structural complexity brought by microfabrication technology A series of special effects of micro scale fluid, including laminar effect, surface tension and capillary effect, rapid heat conduction effect and diffusion effect, are conducive to accurate fluid control and rapid reaction; micro processing technology has the ability to process small-scale, high-density microstructure, which is conducive to flexible combination and scale integration of various operation units Therefore, the sample pretreatment, separation and analysis, detection and other experimental processes can be integrated and parallelized on the same chip, so as to achieve the goal of miniaturization, automation, low consumption and high efficiency Microfluidic chip is a favorable technology platform for in vitro diagnosis, which is shown in the following aspects: 1 The traditional inspection equipment for application scenario expansion is mostly large-scale instruments Although it has advantages in testing flux and stability, its use is limited to professional laboratories Microfluidic chip system is compact and easy to operate It can be tested in outpatient and emergency departments, basic medical units and even bedside, which greatly expands the application space of in vitro diagnosis; 2 Improvement of analysis efficiency The integrated and parallel design of microfluidic chip system has the ability to provide more abundant diagnostic information in a short period of time, thus significantly improving the analysis efficiency; 3 The decrease of test cost microfluidic chip uses micro reaction system, which can significantly reduce sample consumption and reduce test cost Recently, the laboratory of laboratory medicine of Guangzhou first people's Hospital Affiliated to South China University of technology has made new progress in microfluidic chip field diagnosis technology (chem Commun Doi: 10.1039 / c7cc09377b) introduction to Laboratory of Guangzhou first people's hospital Laboratory of Guangzhou first people's hospital was established in 2008 The research team works on the front line of clinical testing, and its members include medical, chemical, physical and engineering backgrounds After ten years of research, the research group has gradually deepened its understanding of the application value of microfluidic in vitro diagnosis technology in clinical laboratory medicine The research idea of the research group is to develop innovative diagnosis technology for the pain points in clinical tests At present, the research direction is mainly based on the microfluidic technology for on-site rapid diagnosis, pathogenic microorganism analysis and personalized accurate diagnosis of tumors Brief introduction of researcher Liu Dayu, head of academic exchange research group of laboratory photo lab, laboratory of Laboratory of laboratory medicine, Guangzhou first people's Hospital, and researcher of Guangzhou first people's Hospital Affiliated to South China University of technology He obtained his bachelor's degree in medicine from Dalian Medical University in 1995, master's degree in pathology from Dalian Medical University in 2001, and doctor's degree in analytical chemistry from University of Chinese Academy of Sciences in 2006 From 1995 to 1998, he worked as a physician in Dalian Central Hospital, and since 2009, he has worked in Guangzhou first people's Hospital, during which he worked as a postdoctoral researcher in the Department of mechanical engineering of Hong Kong University of science and technology as a micro analysis system research in 2011-2012 He is now the director of laboratory medicine research office and deputy director of Laboratory of Guangzhou first people's Hospital, visiting professor of Dalian Medical University, postgraduate supervisor of South China University of technology and Guangzhou Medical University He has presided over dozens of national and local scientific research projects, published more than 40 research papers included in SCI, including analytical chemistry, chemical communications, lab on a chip, etc., applied for more than 20 patents, and participated in the preparation of microfluidic chip laboratory Cutting edge scientific research achievements: the active droplet array microfluidic system used for on-site rapid and multiple complex analysis is the most attractive part of microfluidic chip for on-site rapid detection, which is convenient for functional integration, which is very conducive to use in the condition of lack of resources The integrated operation of microfluidic chip is realized by complex fluid operation, including fluid driving and separation The traditional solution is to integrate a series of micropumps and valves on the chip, so that a series of fluid operations can be performed sequentially Although this strategy has great flexibility, it inevitably leads to the increase of chip size and control complexity, which is obviously not conducive to field analysis and application The recently developed droplet technology is a good tool for microanalysis Compared with the single-phase fluid strategy used in traditional microfluidic analysis, the multi-phase fluid strategy is used in droplet analysis With the help of the formation of water in oil droplets, liquid separation and sealing can be realized In order to realize the integrated analysis, a droplet transport mechanism is also needed to complete the series connection of multiple droplet functions, so active droplet microfluidics emerges Following this concept, the research group developed an active droplet array microfluidic system for rapid and complex field analysis Its design concept is to complete a series of energy mass transport processes required by the analysis through the spatial shift operation of the relative magnetic, thermal and optical areas of the chip, which can realize the integration and parallelization of multiple complex analysis (Figure 1) Figure 1 Schematic diagram of active droplet array microfluidic chip "T", "m", "O" represent temperature, magnetic force and optical detection module respectively, and 1 and 0 represent startup and non startup state respectively A series of energy mass transport processes are completed by means of the spatial shift operation of the relative magnetic, thermal and optical areas of the chip, and the integration and parallelization of multiple complex analysis are realized (source: chem Commun.) the microfluidic chip used in the study has a series of parallel series drain micro pools, which are connected by slit Due to surface tension, droplets containing reagents or samples are anchored to a designated micro cell Driven by the magnetic force, the magnetic beads can pass through the slit and the oil-water interface, and between the droplets Figure 2 active droplet microfluidic chip analysis system (A) Microfluidic chip analysis system physical diagram; (b) active droplet microfluidic chip analysis system structure diagram, in which temperature, magnetic force and optical detection module cooperate to complete chip analysis; (c) active droplet microfluidic chip analysis system control schematic diagram; (d) droplet microfluidic chip physical diagram (source: chem Commun.) research first used this active droplet array microfluidic chip technology to demonstrate a fully integrated approach to multiple genital tract pathogen RNA detection (Figure 3) The chip switches in the heating area, the magnetic field area and the optical detection area, and successively completes cell lysis / nucleic acid capture, magnetic bead washing, nucleic acid elution and amplification / detection Each tandem droplet array on the chip can detect one pathogen, so the parallel tandem droplet array can simultaneously detect multiple pathogens In this study, the simultaneous detection of four genital tract pathogens, including Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium and Neisseria gonorrhoeae, was realized in a fully integrated way The whole analysis process was completed within 45 minutes Fig 3 RNA analysis of four kinds of reproductive system infection pathogens on droplet array microfluidic chip (A) Reagent pre loading on the droplet chip; (b) RNA analysis flow on the droplet chip; (c) before and after amplification (I) of NG, UU, CT and Mg; (d) real-time fluorescence quantitative curve (n = 3) of NG, UU, CT and Mg; (E) CV value of real-time fluorescence quantitative analysis of NG, UU, CT and Mg; (f) correlation analysis of TT value and pathogen load (source: chem Commun.) also used this active droplet array microfluidic chip technology to realize multiple immunochemiluminescence analysis (Figure 4) Similar to nucleic acid analysis, the chip switches in the heating area, magnetic field area and optical detection area, and successively completes immunoaffinity, magnetic bead washing, and chemiluminescence reaction / detection In this study, two kinds of infection related protein markers, C-reactive protein (CRP) and procalcitonin (PCT), were detected in a fully integrated way The whole analysis process was completed in 15 minutes Figure 4 immunochemiluminescence analysis of infectious disease markers on active droplet array microfluidic chip (A) Reagent pre loading on the droplet chip; (b) immunochemiluminescence analysis process on the droplet chip; (C-D) quantitative analysis of CRP and PCT (n = 3) (source: chem Commun.) the active droplet array microfluidics technology developed in this study has the advantages of convenient operation, flexible application and strong expansibility, so it is a favorable tool to realize on-site rapid multiple complex analysis Original source: Shu, B, Li, Z, Yang, x, Xiao, F, Lin, D, Lei, x, Xu, B, and Liu, D active droplet array (ADA) microfluidics enables multiple complex bioassays for point of care, chem Commission 2018, 54 (18), 2232 ~ 2235 Today, people and scientific research are getting more and more attention in the economic life, China has ushered in the "node of the outbreak of science and technology" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeango app, chembeango official microblog, CBG wechat subscription number and other 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