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

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Abstract

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.

Schematic illustration of the principle and configuration of interference-free high-throughput QCM chip to evaluate and screen drugs based on cell viscoelasticity.

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Acknowledgements

We thank Beijing Chenjing Electronic Co., Ltd. who provided the quartz crystal resonators and fabricated the eight HQCM chips used for this study; particularly, Mr. Lijun Zhao’s technical help is greatly appreciated. We also thank Prof. Dazhong Shen, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, who lent us the Agilent 4395A impedance analyzer. Finally, we would like to thank Mr. Shuyue Zhou, Houston Methodist Hospital, USA, for proofreading the manuscript.

Funding

This work was supported in part by grants from the Key Project of Hunan Provincial Science & Technology Department (2013TT1009) and the National Natural Science Foundation of China (21275048).

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Authors and Affiliations

  1. Cell Mechanics and Biosensing Institute, Hunan Agricultural University, 405 Life Sciences Building, Furong District, Changsha, Hunan, 410128, China

    Haibo Shen, Tiean Zhou & Jiajin Hu

  2. College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, 410128, China

    Haibo Shen, Tiean Zhou & Jiajin Hu

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  1. Haibo Shen
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  2. Tiean Zhou
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Correspondence to Tiean Zhou.

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Shen, H., Zhou, T. & Hu, J. A high-throughput QCM chip configuration for the study of living cells and cell-drug interactions. Anal Bioanal Chem 409, 6463–6473 (2017). https://doi.org/10.1007/s00216-017-0591-4

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  • DOI: https://doi.org/10.1007/s00216-017-0591-4

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