Research Of Microwave Biosensor Integrated With PDMS Microfluidic Chip

With the features of high sensitivity,real-time response,multiple parameters characterization,low power consumption,the microwave biosensor shows unique advantages in the application fields of food safety detection,environmental pollution monitoring and biological health care.Compared with traditional electrode detection schemes,microwave detection has the advantages of high accuracy,multiple derivative parameters,strong penetration and non-intrusion.In addition,microfluidic chips have the advantages of small sample size,low detection cost and fast detection rate.However,key scientific and technical issues such as the cooperative mechanism of microwave sensors and microfluidic chips,the composite modeling of microwave signals and measured samples,and the rapid and sensitive detection of complex biological indicators still need to be studied.This thesis focuses on the sensing mechanism of the microwave detection module and the functional mechanism of microfluidic chips,two types of microwave sensing units and two microfluidic structures have been designed and fabricated,namely,a coupled capacitance type and a resonant split ring type microwave sensing unit design,as well as corresponding design of a quantitative microfluidic cavity and a spiral microfluidic array of microfluidic chips,which are respectively applied to glucose solution concentration detection and biological cell detection and analysis.By analyzing the changes in microwave dielectric properties of glucose solution and the under test biological cells with changes in concentration,quantity,and category,establishing a microwave electromagnetic perturbation model by selecting corresponding microwave transmission parameters,and the multivariate linear regression algorithm is used to accurately characterize the glucose solution and biological cells solution.The main design and research contents of this paper are as follows.（1）The basis of microwave biosensors is the relationship between the detection marker point and the concentration of the solution under test or the category or quantity of the measured biological cell samples.Taking the transmission zeros and poles of microwave resonance as the detection marker point,the low-frequency squared spiral coupling capacitance（SSC）and interdigital capacitance type（IDC）microwave sensing units are proposed.The working mechanism of two closely coupled microwave sensing units is analyzed by means of equivalent circuit models.In addition,by designing resonant microwave sensing units based on split ring resonator（SRR）and complementary split ring resonator（CSRR）,a high intensity electromagnetic coupling field and radiation field are constructed through full wave electromagnetic simulation.The research shows that the low frequency capacitive and high frequency resonant detection units can be formed by optimizing the coupling path between capacitive metal conductors or the critical size of the resonant split ring.In addition,the micro/nano processing process of planar microstrip microwave structures has been reviewed,providing reliable theoretical guidance and technical support for the subsequent development,fabrication,and testing of microwave sensing units.（2）Currently,the research on microwave microfluidic biosensors lacks the exploration of the cooperative mechanism between the sensitive regions of microwave devices and the control function of microfluidic chips.In addition,there is a partial gap in the research on microwave wireless detection based on the concept of radio frequency identification（RFID）.Therefore,a non-contact microwave biosensor model based on the RFID concept is proposed.This model is based on the complementary open ring resonator CSRR and the tightly wound coupling capacitive SSC microwave sensor unit described in the previous chapter,and its cooperative working mechanism is studied.At the same time,the conventional microfluidic channel is improved into a microfluidic cavity structure integrated with SSC.The CSRR structure enhances the electromagnetic radiation range and expands the detection area to include the entire internal region of the SSC sensing unit,forming a new concept of non-contact detection and RFID.In addition,the square shaped quantitative microfluidic cavity structure is made of polydimethylsiloxane（PDMS）and completely covers all SSC capacitance sensitive regions,further improving detection sensitivity.The test results show that the sensitivity based on resonant frequency can reach 10.27 k Hz/mgd L^-1,the linearity can reach 98.97%,and the response time is within 1 s.（3）In view of the shortcomings of the current microwave microfluidic sensing research in which the functions of microfluidic chips are too single,and the lack of specificity in the detection mechanism of microwave sensing,a spiral microfluidic array based microfluidic chip with cell sorting and enrichment have been proposed based on the previously defined quantitative microfluidic cavity.Utilizing the fluid inertial centrifugation effect at low Reynolds numbers to achieve real-time separation and enrichment of biological cells with different particle sizes or categories at low flow rates,and use corresponding microwave detection intervals for real-time microwave dielectric characterization.At the same time,based on two types of cells with different particle sizes or categories to be tested,a resonant symmetric open loop microwave sensing unit（DBR）with dual frequency band independent operating range was designed.In addition,based on the dielectric perturbation transmission model,analytical models for biological cell samples and species with different particle sizes were constructed using a highly sensitive microwave resonance frequency offset based on a linear regression algorithm.The test results show that the designed microwave biosensor based on spiral microfluidic array achieves real-time separation and enrichment of biological cells with different particle sizes and dielectric characterization of microwave parameters at different concentrations,with microwave dielectric sensitivities of different sensitive regions reaches 0.3431 MHz/%and 0.6327 MHz/%,respectively.This research work provides ideas for future research on the real-time screening and detection of specific molecular markers such as circulating tumor cells（CTCs）in the blood of early cancer patients using microwave biosensors based on microfluidic cell sorting in clinical practice.