用于研究活细胞和细胞-药物相互作用的高通量QCM芯片配置。,Analytical and Bioanalytical Chemistry

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用于研究活细胞和细胞-药物相互作用的高通量QCM芯片配置。
Analytical and Bioanalytical Chemistry ( IF 3.8 ) Pub Date : 2017-09-11 , DOI: 10.1007/s00216-017-0591-4
Haibo Shen _{1,

2} , Tiean Zhou _{1,

2} , Jiajin Hu _{1,

2}

Affiliation

在这项研究中，我们提出了一种无干扰，安装引起的应力可忽略不计的新颖设计，适用于制造高通量石英晶体微天平（HQCM）芯片。这种新颖的HQCM芯片配置是在一个普通玻璃基板中使用八个独立但相同批次的石英晶体谐振器制造的，该谐振器的八个通孔的直径略大于石英谐振器的直径。每个石英谐振器的边缘都通过硅酮胶粘附到通孔的内部，形成刚性（石英）-软（硅酮）-刚性（玻璃）结构（RSRS），从而有效消除了不同谐振器之间的声耦合。减轻安装引起的应力。通过非常相似的等效电路参数以及对液体密度和粘度的非常接近的响应斜率，验证了八个谐振器的一致性。然后，将HQCM芯片用于实时连续监测H9C2心肌母细胞的粘附和由两种药物的治疗引起的粘弹性变化：两种药物影响细胞骨架，包括诺考达唑，紫杉醇和Y-27632，以及影响细胞骨架的药物。细胞的收缩特性：维拉帕米和不同剂量的异丙肾上腺素。同时，我们比较了影响药物诱导的H9C2粘弹性变化的细胞骨架和人脐静脉内皮细胞（HUVEC）的骨架。此处描述的结果提供了制造HQCM芯片的第一种解决方案，该芯片不受谐振器数量，安装引起的应力，

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A high-throughput QCM chip configuration for the study of living cells and cell-drug interactions.

In this study, we present a novel design of interference-free, negligible installation-induced stress, suitable for the fabrication of high-throughput quartz crystal microbalance (HQCM) chips. This novel HQCM chip configuration was fabricated using eight independent yet same-batch quartz crystal resonators within a common glass substrate with eight through-holes of diameter slightly larger than that of the quartz resonator. Each quartz resonator's rim was adhered to the inner part of the through-hole via silicone glue to form the rigid (quartz)-soft (silicone)-rigid (glass) structure (RSRS) which effectively eliminates the acoustic couplings among different resonators and largely alleviates the installation-induced stresses. The consistence of the eight resonators was verified by very similar equivalent circuit parameters and very close response slopes to liquid density and viscosity. The HQCM chip was then employed for real-time and continuous monitoring of H9C2 cardiomyoblast adhesions and viscoelastic changes induced by the treatments of two types of drugs: drugs that affect the cytoskeletons, including nocodazole, paclitaxel, and Y-27632, and drugs that affect the contractile properties of the cells: verapamil and different dosages of isoprenaline. Meanwhile, we compared the cytoskeleton affecting drug-induced viscoelastic changes of H9C2 with those of human umbilical vein endothelial cells (HUVECs). The results described here provide the first solution to fabricate HQCM chips that are free from the limitation of resonator number, installation-induced stress, and acoustic interferences among resonators, which should find wide applications in areas of cell phenotype assay, cytotoxicity test, drug evaluation and screening, etc. Graphical abstract Schematic illustration of the principle and configuration of interference-free high-throughput QCM chip to evaluate and screen drugs based on cell viscoelasticity.

更新日期：2017-09-09

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