Fabrication And Application Of Microfabricated Counter For Micro-Nano Particles And Biological Macromolecular Analysis

In the field of biometrics,it is one of the most active areas of international metrological research to establish a clear traceability system of biomass and develop relevant measurement standards.So that the results of biomass detection can be traced to the international basic unit(SI unit).Currently,most of the biometric results are mass concentration.In order to improve the accuracy of biological sample detection,this project proposed to use the single-molecule counting technology to quantify biological macromolecules,which was planning to achieve quantitative concentration measurement of biomacromolecules,and provided an optional metering device for biomacromolecule measurement.The main work of this project was to design and manufacture microfluidic chips with submicron size channels,which combined microfluidic and nanopore technology and used MEMS processing technology.The microfluidic chips used the Coulter Counter(Resistance Pulse Sensing)principle to detect the signals of the biological macromolecules passing through the submicron channel,such as plasmids and exosomes.Moreover,it performed sample quantity concentration detection by being integrated on a microfluidic chip or an external volume-measuring device.In order to meet the needs of biomacromolecules detection and quantification,this project had studied two kinds of microfluidic chips with different structures,one was silicon-based microfluidic chip,and the other was PDMS-glass microfluidic chip.The silicon-based microfluidic chips were fabricated by the MEMS sacrificial layer process,and had the advantages of large-scale production and high production precision.In addition,the submicron channel was created by PDMS,which was bonded to a glass substrate to form a PDMS-glass microfluidic chip.And which manufacturing difficulty was less than that of the silicon-based microfluidic chip,and the manufacturing cycle was short and the manufacturing cost was low.In order to improve the signal-to-noise ratio of PDMS-glass microfluidic chip,an improved differential electrode design was proposed.Two kinds of microfluidic chips were used for the detection of biological macromolecules such as plasmid DNA and exosomes,and the experimental results have high detection sensitivity and signal to noise ratio.In addition,the photoelectric interconnect detection experiment was carried out on the PDMS-glass microfluidic chip to realize the photoelectric detection of fluorescently labeled polystyrene particles with 1 ?m diameter.