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Design and production of a novel microfluidic device for the capture and isolation of circulating tumor cell clusters

机译:用于捕获和分离循环肿瘤细胞簇的新型微流体装置的设计与生产

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摘要

The three main challenges of cancer treatment are metastases, recurrence, and acquired therapy resistance. These challenges have been closely linked to circulating cancer cell clusters. A detailed understanding of their genetic and morphological composition is essential. This will not only improve our knowledge of basic cancer biology but enable the successful development of much needed therapies preventing the three main challenges mentioned above. Extensive research effort is underway to isolate, capture, and analyze circulating tumor cells. However, few if any current efforts specifically target cancer cell clusters, and their much greater ability to initiate new tumors. Growing scientific consensus over the last five years has convincingly established the importance of targeting circulating cancer cell clusters verses individual CTCs to prevent the occurrence of metastatic disease. Based on the increased clinical importance of cancer cell clusters as the main driver of cancer metastasis, new and improved methods are much needed to access these larger multi-celled structures. Microfluidic devices offer a readily accessible platform for a customizable microenvironment for cell isolation and analysis. In this study, we show how a well-known passive micromixer design (staggered herringbone mixer - SHM) can be optimized to induce maximum chaotic advection within antibody-coated channels of dimensions appropriate for the capture of cancer cell clusters. The device’s principle design configuration is called: Single-Walled Staggered Herringbone (SWaSH). The preliminary empirical results of our work show that utilization of extensive simulation and modeling can accelerate the development of a working prototype that allows for target-specific cancer cell cluster isolation.
机译:癌症治疗的三种主要挑战是转移,复发和获得的治疗抵抗力。这些挑战与循环癌细胞集群密切相关。对其遗传和形态学组成的详细了解至关重要。这不仅会改善我们对基本癌症生物学的知识,而是能够成功地发展疗法,防止上述三种主要挑战。正在进行广泛的研究,以分离,捕获和分析循环肿瘤细胞。然而,很少有任何目前的努力,特别是靶向癌细胞簇,以及它们更大的启动新肿瘤的能力。过去五年的增长科学共识令人信服地建立了靶向循环癌细胞簇的重要性,以防止转移性疾病的发生。基于癌细胞簇的临床重要性增加作为癌症转移的主要驱动器,需要新的和改进的方法来获得这些较大的多纤维结构。微流体设备为可定制的微环境提供易于访问的平台,用于细胞隔离和分析。在这项研究中,我们展示了众所周知的被动微混合器设计(交错的人字形混合器 - SHM)可以优化以在适于捕获癌细胞簇的尺寸的抗体涂层通道内诱导最大混沌平面。该设备的原理设计配置被称为:单壁交错的人字形(旋转)。我们的工作的初步经验结果表明,广泛的模拟和建模的利用可以加速工作原型的开发,允许靶特异性癌细胞群集隔离。

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