靶向药物浓度筛选微流控器件的设计与制作

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关键词：微流控;细胞微环境；靶向药物浓度筛选；平行共培养中图分类号：TP394.1;TH691.9 文献标识码：Adoi：10.37188/OPE.20253308.1228 CSTR：32169.14.OPE.20253308.1228

Abstract：To screen the concentrations of targeted drugs，a cellco-culture microfluidic device with an integrated concentration gradient generator was designed and fabricated. The principles of concentration gradient generation，theconcentration fields，the velocity fields，and the abilityofcell co-culture within the device were studied. A microchannel model capable of generating a concentration gradient was designed based on the equivalent circuit principle，using a series-paralel structure to integrate the concentration gradient unit with thecellco-culture unit. The velocity and concentration fields were simulated and validated using the laminar flow and masstransfer modules in the finite element simulation software Comsol.The microfluidic device was fabricated using soft ithography techniques，and fluorescein sodium solution and polystyrene suspension with a 1{μm diameter were used to simulate drug concentration distribution. Co-culture of Hela cells and A549 cels was performed within the device，and the growth curves and folate receptor targeting of both celltypes were analyzed. Simulation and experimental results indicate that the designed microfluidic device could generate the desired concentration gradient （5：1： O ratio），with concentration variation within each branch cell culture unit below 0.1% . The velocity distribution in the cell culture unit is uniform，with an average flow velocity of （7.1±0.3）μm/s under an inlet flow rate of 925 μm/s . The growth of both celltypes follows an S-shaped growth curve，and membrane staining experiments demonstrate the successful parallel co-culture of two cell types within the microfluidic device. These findings demonstrate that microfluidic device could simulate the in vivo fluidic environment of cells and provide a technological platform for targeted drug concentration screening and personalized therapy.

Key words： microfluidics；cell microenvironment；targeted drugs concentration screening； parallel coculture

1引言

肿瘤靶向药物具有靶向性、药物用量少、全身毒副作用低等特点，是抗癌药物发展的一个重要方向[1-3]。（剩余14386字）