Research On The Preparation And Application Of Functional Microstructures On Droplet-based Microfluidic Chips

The droplet microfluidic technology can realize the droplet generation in the microchannel,and precisely control the size and frequency of the generated droplets.By designing the chip structure and controlling the external conditions,droplets can be manipulated in a variety of ways to meet the requirements of different research and application scenarios.In the field of biomedicine,the micro/nano-scaled droplets,which can be easily high-throughput operated,show great potential as an independent microreactor for the biomedical detection and analysis of large number of samples.Materials science and its application research have always been a key direction in the field of biomedicine.For example,biocompatible material and highly sensitive biosensing material-based micro/nano structures have received more and more attention in drug carrier and sensing analysis applications.However,the fabrication of biomedical micro/nano structures with different materials is often an issue,which has restricted their applications.As we all know,biosafety is the primary prerequisite for biomedical materials.Traditional preparation methods of biomedical materials inevitably introduce chemical reagents.Although the final products can be non-toxic through post processing,it is still difficult to ensure thorough removal of the toxic reagents.At the same time,these additional operations are time-consuming with high cost.For sensing applications,the precise manipulation of a large number of sensitive units on the micro scale is also a challenge for the preparation method.As an emerging microfluidic operation method,the droplet microfluidic technique can be used as a practical and efficient tool for the preparation of functional microstructures,which has begun to show great application potential in related research areas.In this dissertation,the droplet microfluidic technique is used as a method to manipulate the reactive components to construct functional microstructures.By designing the operating platform and the control method of microfluidic chips,the preparation of polyvinyl alcohol(PVA)microspheres that can be used as drug carriers and the 4-Cyano-4'-pentylbiphenyl(5CB)liquid crystal droplet sensing array for biosensor analysis were studied respectively.According to the properties and application requirements of materials,the droplet(array)operation methods were explored and optimized.Furthermore,the related application studies have also been carried out,such as experimental analysis of the detection capabilities of the liquid crystal droplet-array under different conditions.The specific research contents are as follows:(1)A chip platform for the preparation of functional microstructures is designed according to the principle of microfluidic droplet manipulation.The dynamic theories involved in the process of droplet generation and manipulation in microchannels are analyzed,and simulation software is used to analyze and study the effects of microfluidic channel network structures on the droplet preparation.For the microfluidic chip platform for droplet generation and manipulation,the commonly used SU-8-based lithography method is adopted to design the microfluidic chip structure.The corresponding silicon wafer template and PDMS structure are fabricated,and the final chip structure for experimental analysis is completed through bonding process.(2)With the Y-junction microfluidic chip,the preparation of PVA droplets and the gelation of PVA microsphere are studied.The effects of chip structures and sample flow rates on the droplet generation are explored,and an optimal droplet preparation method is obtained.The functionalization of the droplet is studied using physical cross-linking method to solidify the PVA droplets,which is not only compatible with the droplet microfluidic preparation method,but also can get PVA gel microspheres without introducing chemical reagent.The physical crosslinking mechanism of PVA droplets is studied and the results show that increasing the times of physical crosslinking could improve the gel strength.(3)A microfluidic droplet formation method is used to construct a liquid crystal droplet-based sensor array.polyvinyl alcohol/ sodium dodecyl sulfate(PVA/SDS)liquid crystal droplets are generated with a flow-focusing microchannel structure.We find that the addition of PVA can greatly improve the stability of the liquid crystal droplet.By designing the structure of the microfluidic channel and the control process,independent processes such as liquid crystal droplet generation,fixation and biosensor detection can be completed on the integrated chip.Two bile acids,cholic acid(CA)and deoxycholic acid(DCA)with different concentrations were injected into the liquid crystal droplet array to obtain the detection limit concentrations of 10 ?M(CA)and 1 ?M(DCA),respectively.By defining the response time of the array,we obtained the response time for CA and DCA were 200.7 s and 144.9 s,respectively.(4)With the array of liquid crystal droplets formed on the microfluidic chip,the regulation of sensing abilities of the liquid crystal droplet was carried out.An electric field is introduced into the array to optimize the detection capability of the liquid crystal droplet array.The microelectrode array are fabricated with indium tin oxide(ITO)glass by two methods.It is found that the laser engraving processing method can greatly simplify the preparation process of the electrode array when the requirement for processing precision is not high.The relationship between the escape configuration of the liquid crystal droplets and the electric filed was investigated,and the optimal values of amplitude and frequency of the electric filed was obtained.With the amplitude of 9Vp?p and the frequency of 50 k Hz,the detection limit concentration of CA was reduced from 10 ?M to 3 ?M and DCA was reduced from 1 ?M to 0.1 ?M,and the corresponding response time was reduced from 200.7 s to 53.6 s and from 144.9 s to29.7 s respectively,which improved the detection capability of the array.Through the combination of the microfluidic droplet formation and the control methods,the PVA microsphere-based drug carriers and liquid crystal droplet-based biosensing array were constructed,indicating that the microfluidic droplet technology has great potential in the preparation and application of functional microstructures.