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基于铝纳米缝阵列的对比图像高通量及药物与细胞相互作用的动态研究。

High-Throughput and Dynamic Study of Drug and Cell Interactions Using Contrast Images in Aluminum-Based Nanoslit Arrays.

机构信息

Research Center for Applied Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.

Institute of Optoelectronic Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan.

出版信息

Anal Chem. 2020 Jul 21;92(14):9674-9681. doi: 10.1021/acs.analchem.0c00972. Epub 2020 Jul 1.

DOI:10.1021/acs.analchem.0c00972
PMID:32608970
Abstract

High-throughput and dynamic measurement for living cell activities can benefit biological research and drug development. A low-cost metallic nanostructure-based surface plasmon resonance (SPR) imaging platform, comprising multiple aluminum nanoslit arrays and a color image device, is proposed for label-free study of cell and drug interactions. The multiple nanoslit sensing arrays were fabricated using the compression-injection molding process. These sensing chips showed a detectable depth of 600 nm and refractive index resolution of ∼5 × 10 refractive index unit (RIU) by using a self-referenced two-color analysis. Two examples of kinetic studies of living cells under various doses of drugs are presented. The focal adhesion kinases inhibitor (FAKi 14) and cell interactions show exponential changes of cellular adhesion and time constants for different concentrations of antiadhesion drugs. The anticancer drug (doxorubicin (DOX))-treated cells show slow increases of SPR signals in the first 2 h due to the nucleus swelling. The DOX-treated cells further process plasma membrane disruption and become floating cells and debris in the medium, resulting in rapid drops of the SPR signals.

摘要

高通量和动态测量活细胞活动可以有益于生物研究和药物开发。提出了一种基于低成本金属纳米结构的表面等离子体共振(SPR)成像平台,该平台由多个铝纳米狭缝阵列和彩色图像设备组成,用于无标记研究细胞和药物相互作用。多个纳米狭缝传感阵列使用压缩注塑成型工艺制造。这些传感芯片通过使用自参考双色分析显示出可检测的 600nm 深度和约 5×10 折射率单位(RIU)的折射率分辨率。给出了两种在不同药物剂量下活细胞动力学研究的示例。粘着斑激酶抑制剂(FAKi 14)和细胞相互作用显示出细胞粘着的指数变化和不同浓度抗粘着药物的时间常数。用抗癌药物(阿霉素(DOX))处理的细胞由于核肿胀,在最初的 2 小时内显示出缓慢增加的 SPR 信号。DOX 处理的细胞进一步破坏质膜,并在培养基中成为漂浮的细胞和碎片,导致 SPR 信号迅速下降。

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