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一种用于基于细胞的药物筛选并具有精确定量分析功能的全氟聚醚微流控装置。

A Perfluoropolyether Microfluidic Device for Cell-Based Drug Screening with Accurate Quantitative Analysis.

作者信息

Choi Hyun Sun, Ahn Gwang-Noh, Na Gi-Su, Cha Hyung Joon, Kim Dong-Pyo

机构信息

Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.

出版信息

ACS Biomater Sci Eng. 2022 Oct 10;8(10):4577-4585. doi: 10.1021/acsbiomaterials.2c00435. Epub 2022 Sep 11.

DOI:10.1021/acsbiomaterials.2c00435
PMID:36089741
Abstract

Microfluidic drug screening technologies have been extensively explored to evaluate the pharmacology and therapeutic implications of promising chemical compounds in multiplexed physiological microenvironments in vivo. However, conventional poly(dimethylsiloxane) microchips are susceptible to adsorption by hydrophobic molecules on channel surfaces and permeation in the matrix. These can significantly compromise the drug availability and accuracy of dose-dependent quantitative analyses. Here, we prepared a perfluorinated polyether (PFPE) microchip via digital light processing 3D printing as a quantitative drug screening platform for precise concentration-dependent pharmaceutical assays. Cells cultured on PFPE microchips exhibited excellent viability with a spread morphology as well as superior proliferative capability. Importantly, PFPE constructions with a low surface energy significantly prevented the nonspecific molecular adsorption into their surfaces or permeation into the matrix. In particular, the PFPE multibranched channel preserved the concentration of the pharmaceutical drug during the perfusion process and generated a linear concentration gradient, resulting in a dose-dependent chemotherapeutic effect. We suggest that the biocompatible and nonadsorbing PFPE microchannel can provide a cell-based drug screening platform for concentration-dependent quantitative analyses.

摘要

微流控药物筛选技术已被广泛探索,用于在体内多重生理微环境中评估有前景的化合物的药理学和治疗意义。然而,传统的聚二甲基硅氧烷微芯片容易受到通道表面疏水分子的吸附以及在基质中的渗透影响。这些会显著损害药物的可用性和剂量依赖性定量分析的准确性。在此,我们通过数字光处理3D打印制备了一种全氟聚醚(PFPE)微芯片,作为用于精确浓度依赖性药物测定的定量药物筛选平台。在PFPE微芯片上培养的细胞表现出优异的活力,具有伸展的形态以及卓越的增殖能力。重要的是,具有低表面能的PFPE结构显著防止了非特异性分子吸附到其表面或渗透到基质中。特别是,PFPE多分支通道在灌注过程中保留了药物的浓度,并产生了线性浓度梯度,从而产生了剂量依赖性的化疗效果。我们认为,生物相容性和非吸附性的PFPE微通道可为基于细胞的浓度依赖性定量分析提供药物筛选平台。

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