Technical analysis: Why is the microfluidic chip so powerful?

From 1990, Manz et al. first proposed the concept of micro-full analysis system. By 2003, Forbes magazine ranked microfluidic technology as one of the 15 most important inventions affecting the future of human beings. Microfluidic technology has developed rapidly. Among them, microfluidic chip technology plays an important role in the fields of biology, chemistry and medicine, and has become a "core" in the hands of scientists.

Microfluidic chip technology

Microfluidic is a technique for precisely controlling and manipulating microscale fluids, especially submicron structures. Through the control of fluids at microscales, in the 1980s, microfluidic technology began to emerge, and in the direction of DNA chips, chip labs, micro-injection technology, micro-thermodynamics technology, etc.

The microfluidic analysis chip was originally called "lab-on-a-chip" in the United States and called "micrototal analytic chip" in Europe. It is a microfluidic technology ( Microfluidics) is the main platform for integrating the basic operations of sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a micron-scale chip to automate the entire analysis process. Microfluidic chips with small volume, small sample and reagents, fast reaction speed, large amount of parallel processing and ready-to-use, have great potential in biology, chemistry, medicine, etc. Developed into a new research field where biology, chemistry, medicine, fluids, electronics, materials, machinery and other disciplines intersect.

Principle of microfluidic chip

Technical analysis: Why is the microfluidic chip so powerful?

The microfluidic chip uses a semiconductor-like microelectromechanical processing technology to build a microfluidic system on a chip, and transfer the experimental and analytical processes to a chip structure consisting of a path and a liquid phase chamber that are connected to each other, and after loading the biological sample and the reaction solution. , using a micro mechanical pump. The electric hydraulic pump and electroosmotic flow drive the flow of the buffer in the chip to form a micro flow path, and perform one or a plurality of continuous reactions on the chip. Laser-induced fluorescence, electrochemical and chemical detection systems, as well as many detection methods combined with mass spectrometry and other analytical methods have been used in microfluidic chips for fast, accurate and high-throughput analysis of samples. The biggest feature of the microfluidic chip is the micro-full analysis system that can form a multi-functional integrated system and a large number of composite systems on one chip. Microreactors are structures commonly used in microarray laboratories for biochemical reactions, such as capillary electrophoresis, polymerase chain reaction, enzymatic reactions, and microreactors for DNA hybridization reactions. Among them, voltage-driven capillary electrophoresis (CE) is easier to implement on a microfluidic chip, and thus it is the fastest growing technology. It etches the capillary channel on the chip, and the sample liquid moves in the channel under the action of electroosmotic flow, and completes the detection and analysis of the sample. If a capillary array is built on the chip, hundreds of samples can be completed in a few minutes. Parallel analysis. Since the first report of the microfluidic chip CE in 1992, has it made rapid progress? The first commercial instrument is a microfluidic chip CE (Biochemical Analyzer, Aglient) that provides microfluidic chip products for nucleic acid and protein analysis.

Development of microfluidic chips

The concept of the micro-analysis system was first proposed by Manz and Widmer of Ciba2Geigy in Switzerland in 1990. At that time, the emphasis was placed on the "micro" and "full" of the analysis system, and the MEMS processing method of the micro-pipeline network was not clear. Its appearance characteristics. The following year, Manz et al. realized capillary electrophoresis and flow on a flat microchip. The current development front of the micro total analysis system. The microfluidic analysis system has evolved from capillary electrophoresis separation to core analysis technology to liquid-liquid extraction, filtration, and membrane-free diffusion. The multi-phase laminar flow separation microfluidic system has a simple structure and a plurality of separation functions, and has wide application prospects. A number of reports have reported the use of multi-phase laminar flow technology to achieve film-free filtration, membrane dialysis and extraction separation on the chip. At the same time, there are reports on the pre-treatment of the sample before mass spectrometry using a micromachined membrane microdialyser. The flow control analysis system develops from electroosmotic flow as the main flow drive means to fluid power, air pressure, gravity, centrifugal force, shear force and other means.

To this day, scientists from all over the world have made even more remarkable achievements in this field. As the important development front of current analytical science, microfluidic technology has achieved rapid development in research and application.

Microfluidic chip features

The chip integrates more and more unit components, and the scale of integration is also larger, which makes the microfluidic chip have strong integration. At the same time, a large number of samples can be processed in parallel, with high flux characteristics, fast analysis speed, low consumption, low material consumption, low pollution, and the amount of reagent required for analyzing the sample is only a few microliters to several tens of microliters, the substance to be analyzed The volume is even upgraded or upgraded.

Cheap and safe, therefore, the microfluidic analysis system is miniaturized. The advantages of integrated integration and portability provide extremely broad prospects for applications in biomedical research, drug synthesis screening, environmental monitoring and protection, health quarantine, forensic identification, and detection of biological reagents.

Prospects of microfluidic chips

The microfluidic analysis chip was originally only a supplement to the nanotechnology revolution. After experiencing a lot of publicity and neglect, it finally realized commercial production. Microfluidic analysis chips were originally called "lab-on-a-chip" in the United States, and called "micrototal analytic systems" in Europe, along with materials science, micro-nano The breakthrough in processing technology and microelectronics, microfluidic chips have also developed rapidly, but still far less than the speed of semiconductor development predicted by "Moore's Law".

In principle, microfluidic chips can be used in various analytical fields such as biomedicine, synthesis and screening of new drugs, and other important applications such as food and commodity inspection, environmental monitoring, criminal science, military science and aerospace science. Analysis is a hot spot. At present, its applications mainly focus on nucleic acid isolation and quantification, DNA sequencing, gene mutation and gene differential expression analysis. In addition, protein sieving has also been reported in microfluidic chips for the characteristic fragments of the pathogenic microbial genome and the sequence polymorphism of chromosomal DNA. The location and characteristics of gene mutations, design and selection of appropriate nucleic acid probes, after PCR amplification, can obtain pathogenic microbes, subtypes, virulence, drug resistance, pathogenicity, homology, and more Information such as morphology, variation and expression provides a good entry point for the diagnosis and treatment of diseases.

There are five methods for internationally recognized PCR product detection, which are arranged in order of sensitivity: capillary electrophoresis, solid phase hybridization, liquid phase hybridization, high pressure liquid phase hybridization and gel electrophoresis (not recommended for clinical use). The microfluidic chip CE uses capillary electrophoresis as the main body of the chip, and no probe hybridization is required, and the signal acquisition rate of the sample to be tested is close to one hundred percent. The microfluidic chip CE can detect PCR products ranging from 15 to 7500 bp with a resolution of up to 20 bp. The sample densification further reduces the diffusion and the separation effect is excellent. Each well can be used for simultaneous analysis of multiple different PCR products.

Although China's research on microfluidic analysis started four to five years later than foreign countries, it has sufficient accumulation and advantages in many related disciplines. China has the world's largest microfluidic chip market, using China. The occupation of this market by chip products is the mission of Chinese scientists. On March 26, several experts in the field of microfluidics will also participate in the 2015 (3rd) Advanced In Vitro Diagnostic Technology Summit held in Shanghai to jointly summarize and analyze the advanced technologies of microfluidics, and microfluidics in China. More interpretation in the field of chip research. It is believed that through unremitting efforts, the vigorous development of microfluidic chips will soon come in China.

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