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Development of a simple static microwell array with uniform cell seeding and a chemical concentration gradient

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Abstract

For personalized screening and therapeutic inventions across many diseases, the drug–dose response for an individual patient is a major unmet need. In this work, we applied a direct strategy to generate a static microwell array for cell culture with uniform cell seeding and to create the desired chemical concentration gradient into this cell array. It is a simple, novel and easily operable device for a high-throughput drug–dose response experiment that complies with the procedures of cell-based drug screening. Only two repeated operating steps suffice for the entire cell-based drug test—an injection of cells or drug into the flow channel and then injection of air flow into the flow channel. This device comprises two PDMS layers: one side forms an air chamber; the other side forms the liquid channel with embedded cavities as the cells culture and reaction region. The concentration of the drug decreases exponentially along the microwell array; the range of the concentration gradient is varied with the rate of air flow, the volume of the drug plug and the initial concentration of the drug. Small variations of concentration were accessed across varied ranges; the IC50 value of DOX in the MDA-MB-231 cell line was thus utilized on this device, precisely and quickly. The IC50 value calculated in this work is consistent with the range published elsewhere. With this device, hundreds of data points per compound drug screening can be tested in one experiment, which will be an essential key to determine customized drug dosage and to make possible personalized medicine.

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Acknowledgements

Ministry of Science and Technology of Taiwan provided financial support of this research under contract MOST 103-2221-E-002-097-MY3.

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Authors and Affiliations

  1. Department of Mechanical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan

    S. I. Yeh, C. C. Hau, C. J. Huang & J. T. Yang

  2. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, No. 250 Kuo Kuang Road, Taichung, 40227, Taiwan

    H. C. Chang

  3. Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, No. 35 Keyan Road, Miaoli, 35053, Taiwan

    H. C. Chang & C. H. Hsu

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  1. S. I. Yeh
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  2. C. C. Hau
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  3. C. J. Huang
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  4. H. C. Chang
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  5. C. H. Hsu
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Correspondence to J. T. Yang.

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Yeh, S.I., Hau, C.C., Huang, C.J. et al. Development of a simple static microwell array with uniform cell seeding and a chemical concentration gradient. Microfluid Nanofluid 21, 80 (2017). https://doi.org/10.1007/s10404-017-1921-8

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