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Transitioning from multi-phase to single-phase microfluidics for long-term culture and treatment of multicellular spheroids

机译:从多相微流控到单相微流控的过渡,以长期培养和治疗多细胞球体

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摘要

When compared to methodologies based on low adhesion or hanging drop plates, droplet microfluidics offers several advantages for the formation and culture of multicellular spheroids, such as the potential for higher throughput screening and the use of reduced cell numbers, whilst providing increased stability for plate handling. However, a drawback of the technology is its characteristic compartmentalisation which limits the nutrients available to cells within an emulsion and poses challenges to the exchange of the encapsulated solution, often resulting in short-term cell culture and/or viability issues. The aim of this study was to develop a multi-purpose microfluidic platform that combines the high-throughput characteristics of multi-phase flows with that of ease of perfusion typical of single-phase microfluidics. We developed a versatile system to upscale the formation and long-term culture of multicellular spheroids for testing anticancer treatments, creating and array of fluidically addressable, compact spheroids that could be cultured in either medium or within a gel scaffold. The work provides proof-of-concept results for using this system to test both chemo- and radio-therapeutic protocols using in vitro 3D cancer models.
机译:与基于低粘附力或悬滴板的方法相比,液滴微流控技术为多细胞球体的形成和培养提供了多个优势,例如具有更高的通量筛选潜力和减少的细胞数量,同时为板处理提供了更高的稳定性。然而,该技术的一个缺点是其特有的分隔性,这限制了乳剂中的细胞可利用的营养,并对封装溶液的交换提出了挑战,通常会导致短期细胞培养和/或生存能力问题。这项研究的目的是开发一种多用途的微流控平台,该平台将多相流的高通量特性与单相微流控典型的易于灌注特性相结合。我们开发了一种通用的系统,可以扩展多细胞球体的形成和长期培养,以测试抗癌治疗,创建和排列可寻址液体的紧凑球体,并可以在培养基或凝胶支架中进行培养。这项工作为使用该系统使用体外3D癌症模型测试化学疗法和放射疗法方案提供了概念验证结果。

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