Research On High-throughput Microfluidic Drug Screening Platform Based On Photolithography

With high sensitivity,low cost and high accuracy,microfluidic chips provide stable and confined culture environment,precise fluid control,automated data analysis,and are widely used in medical diagnostics,drug screening and microfluidic analysis.However,how to improve the drug screening throughput of microfluidic chips while maintaining their features of miniaturization and automation is still a technical challenge.The technical challenge in improving throughput is how to arrange tens of thousands of individual cell culture chambers in an area the size of a "palm of your hand".In this paper,we propose a high-throughput microfluidic chip that integrates 19,800 independent culture chambers in a 7 cm × 5 cm area through a multilayer stacked,bypass design.The chip can be applied to the construction of organoid and the screening of multiple combinatorial drug sequences.In addition,this paper investigates automated methods for culturing large scale biological samples in medical applications.The details of the study are as follows:(1)Microfluidic chip template preparation and chip fabrication : In this study,the chip template is processed using a UV exposure machine combined with a contact lithography process,and a multi-layer nesting method is used to produce the chip template and integrate the functional structure with a minimum structure of 10 μm into the chip.After that,this study completed the fabrication of multilayer chip by soft etching process of polydimethylsiloxane(PDMS),infusion of flow layer by positive molding method,control layer by homogenization method,optical alignment of the two layers,bonding to the bottom of the package.(2)Construction of high-throughput drug screening chip : This study aims to meet the function of high-throughput drug screening by combining different functional units to realize the mutual independence and individual control of each culture chamber,completes the integrated design of flow control valves,micro-peristaltic pumps,fluid channels,bypass channels and culture chambers.The single-layer contains 6,752 flow control valves,enabling independent controllability of 6,600 culture chambers.It improves the detection throughput by 415.6% compared to previous reports.(3)Automatic chip control: The microfluidic chip proposed in this study applies hydraulic pressure to the microfluidic valve through a software-controlled digital solenoid valve to accomplish automated fluid manipulation(fluid mixing accuracy of 10 nl and valve response time of 2 ms).Meanwhile,a microfluidic platform for automatic liquid exchange in 96-well plates was constructed in this study.The platform has an overall height of 4.8 cm,an area of 8 cm × 9 cm,and a complete feeding time of 4.6 minutes for a single culture chamber,which has contributed to the automation process of well plate culture models in clinical medicine.