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High Throughput, Polymeric Aqueous Two-Phase Printing of Tumor Spheroids

机译：肿瘤球体的高通量聚合物水两相印刷

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摘要

This paper presents a new 3D culture microtechnology for high throughput production of tumor spheroids and validates its utility for screening anti-cancer drugs. Two immiscible polymeric aqueous solutions are used and a submicroliter drop of the "patterning" phase containing cells is microprinted into a bath of the "immersion" phase. Selecting proper formulations of biphasic systems using a panel of biocompatible polymers results in the formation of a round drop that confines cells to facilitate spontaneous formation of a spheroid without any external stimuli. Adapting this approach to robotic tools enables straightforward generation and maintenance of spheroids of well-defined size in standard microwell plates and biochemical analysis of spheroids in situ, which is not possible with existing techniques for spheroid culture. To enable high throughput screening, a phase diagram is established to identify minimum cell densities within specific volumes of the patterning drop to result in a single spheroid. Spheroids show normal growth over long-term incubation and dose-dependent decrease in cellular viability when treated with drug compounds, but present significant resistance compared to monolayer cultures. The unprecedented ease of implementing this microtechnology and its robust performance will benefit high throughput studies of drug screening against cancer cells with physiologically relevant 3D tumor models.
机译：本文介绍了一种新的3D培养微技术，用于高通量生产肿瘤球体，并验证了其在筛选抗癌药物中的实用性。使用两种不混溶的聚合物水溶液，并将亚微升的包含“图案化”相的细胞微滴滴到“浸入”相的浴中。使用一组生物相容性聚合物选择合适的双相系统配方会导致形成圆形液滴，从而限制细胞以促进自发形成球体而无任何外部刺激。使这种方法适应机器人工具，可以在标准微孔板中直接生成和维护大小明确的球体，并就地对球体进行生化分析，这对于现有的球体培养技术是不可能的。为了实现高通量筛选，建立了一个相图来识别图案下降的特定体积内的最小细胞密度，从而得到单个球体。当用药物化合物处理时，球体在长期温育下显示正常生长，并且细胞存活率呈剂量依赖性降低，但与单层培养相比具有明显的耐药性。实施该微技术的前所未有的简便性及其强大的性能，将有助于对具有生理相关3D肿瘤模型的癌细胞进行药物筛选的高通量研究。

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  • 来源
    《Advanced Functional Materials》 |2014年第41期|6509-6515|共7页
  • 作者

    Ehsan Atefi; Stephanie Lemmo; Darcy Fyffe; Gary D. Luker; Hossein Tavana;

  • 作者单位

    Department of Biomedical Engineering The University of Akron Akron, OH 44325, USA;

    Department of Biomedical Engineering The University of Akron Akron, OH 44325, USA;

    Department of Biomedical Engineering The University of Akron Akron, OH 44325, USA;

    Department of Radiology University of Michigan Ann Arbor, MI 48105, USA ,Department of Microbiology and Immunology University of Michigan Ann Arbor, MI 48105, USA ,Department of Biomedical Engineering University of Michigan Ann Arbor, MI 48105, USA;

    Department of Biomedical Engineering The University of Akron Akron, OH 44325, USA;

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