Deformability-induced lift force in spiral microchannels for cell separation

Deformability-induced lift force in spiral microchannels for cell separation
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DOI:
10.1039/c9lc01000a
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发表时间:
2020-02-07
期刊:
影响因子:
6.1
通讯作者:
Bridle, Helen
Bridle, Helen
中科院分区:
工程技术1区
文献类型:
--
作者:
Guzniczak, Ewa;Otto, Oliver;Bridle, Helen

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从异质混合物中分离和分离细胞在细胞生物学、生物技术和医学的许多方面都是一项关键任务。最近,人们对允许根据细胞的固有属性分离细胞的方法很感兴趣,例如细胞大小和变形能力,而不需要使用生化标记。螺旋微通道中的惯性聚焦已被认为是一种极具吸引力的高通量细胞分选方法,可用于各种医疗保健和临床诊断。不同大小的颗粒与螺旋微通道内产生的流体流动模式有不同程度的相互作用,从而导致基于尺寸的颗粒排序和分离。然而,单元的可变形特性增加了其在螺旋通道内的排序的复杂性。在这篇论文中,利用细胞变形性模型(细胞的变形性使用化学处理逐渐改变细胞的变形性),首次发现、研究和报道了参与螺旋微通道内细胞聚焦机制的另一种力--变形性诱导升力(FD)。利用该模型,我们证明了螺旋微通道能够分离相同尺寸但不同变形特性的细胞,扩展了以前方法的能力。我们开发了一种独特的基于变形性的无标记纯化方法,通过将FD的效应与螺旋微通道中的惯性聚焦相结合。这种基于微流控的纯化策略,不需要修改免疫标记,允许大规模细胞处理(每分钟数百万个细胞和每分钟最高浓度的介质),高达高纯度和分离效率,而不会影响细胞质量。
Cell sorting and isolation from a heterogeneous mixture is a crucial task in many aspects of cell biology, biotechnology and medicine. Recently, there has been an interest in methods allowing cell separation upon their intrinsic properties such as cell size and deformability, without the need for use of biochemical labels. Inertial focusing in spiral microchannels has been recognised as an attractive approach for high-throughput cell sorting for myriad point of care and clinical diagnostics. Particles of different sizes interact to a different degree with the fluid flow pattern generated within the spiral microchannel and that leads to particles ordering and separation based on size. However, the deformable nature of cells adds complexity to their ordering within the spiral channels. Herein, an additional force, deformability-induced lift force (FD), involved in the cell focusing mechanism within spiral microchannels has been identified, investigated and reported for the first time, using a cellular deformability model (where the deformability of cells is gradually altered using chemical treatments). Using this model, we demonstrated that spiral microchannels are capable of separating cells of the same size but different deformability properties, extending the capability of the previous method. We have developed a unique label-free approach for deformability-based purification through coupling the effect of FD with inertial focusing in spiral microchannels. This microfluidic-based purification strategy, free of the modifying immuno-labels, allowing cell processing at a large scale (millions of cells per min and mls of medium per minute), up to high purities and separation efficiency and without compromising cell quality.