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Dual-channel six-step linear concentration gradient microfluidic chip for orthogonal combination drug screening in head and neck tumor cells

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机构: [1]Department of Pulmonary and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Med+X Center for Manufacturing, West China Hospital, Sichuan University, No.17, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, China. [3]Department of Stomatology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [4]State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [5]X Multidisciplinary Research Institute, School of Instrument Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China. [6]Department of Stomatology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital& Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China. [7]School of Mechanical Engineering, Sichuan University, Chengdu 610065, China.
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摘要:
Head and neck cancer, as the seventh most common cancer worldwide, is in urgent need of an efficient drug screening platform due to tumor heterogeneity and the lack of objective markers for conventional chemotherapy resulting in limited efficacy. In this study, we developed a dual-channel microfluidic chip integrating organoid technology and hydrodynamic modulation, and realized six-chamber linear drug concentration gradient generation (<3% fluctuation at a flow rate of 10-100 μL min-1, stable for 24 hours) through a three-layer PDMS structure and serpentine microchannel design. After 24 h of treatment with four drugs, CAL-27 cell viability in the chip decreased with increasing drug concentration, showing no significant difference from conventional assays. Using a Matrigel 3D scaffold, the culture time of spheroids was reduced by 24 h compared with monolayer cells, and the organoid morphology remained unchanged before and after drug addition (P > 0.05). Fluorescence staining revealed distinct responses to the four drugs near their IC50 concentrations (P < 0.01). The platform integrates fluorescence imaging and CFD simulation, which has the advantages of automation, high mimicry and low consumables compared with the off-chip method, providing a reliable tool for the optimization of the precision treatment plan for head and neck cancer.

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出版当年[2025]版:
大类 | 2 区 工程技术
小类 | 1 区 生化研究方法 1 区 分析化学 2 区 化学:综合 2 区 仪器仪表 3 区 纳米科技
最新[2025]版:
大类 | 2 区 工程技术
小类 | 1 区 生化研究方法 1 区 分析化学 2 区 化学:综合 2 区 仪器仪表 3 区 纳米科技
第一作者:
第一作者机构: [1]Department of Pulmonary and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Med+X Center for Manufacturing, West China Hospital, Sichuan University, No.17, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, China.
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通讯作者:
通讯机构: [2]Med+X Center for Manufacturing, West China Hospital, Sichuan University, No.17, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, China. [7]School of Mechanical Engineering, Sichuan University, Chengdu 610065, China.
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