The biomechanical properties of populations of diseased cells are shown to have differences from healthy populations of cells, yet the overlap of these biomechanical properties can limit their use in disease cell enrichment and detection. We report a new microfluidic cell enrichment technology that continuously fractionates cells through differences in biomechanical properties, resulting in highly pure cellular subpopulations. Cell fractionation is achieved in a microfluidic channel with an array of diagonal ridges that are designed to segregate biomechanically distinct cells to different locations in the channel. Due to the imposition of elastic and viscous forces during cellular compression, which are a function of cell biomechanical properties including size and viscoelasticity, larger, stiffer and less viscos cells migrate parallel to the diagonal ridges and exhibit positive lateral displacement. On the other hand, smaller, softer and more viscous cells migrate perpendicular to the diagonal ridges due to circulatory flow induced by the ridges and result in negative lateral displacement. Multiple outlets are then utilized to collect cells with finer gradation of differences in cell biomechanical properties. The result is that cell fractionation dramatically improves cell separation efficiency compared to binary outputs and enables the measurement of subtle biomechanical differences within a single cell type. As a proof-of-concept demonstration, we mix two different leukemia cell lines (K562 and HL60) and utilize cell fractionation to achieve over 45-fold enhancement of cell populations, with high purity cellular enrichment (90% to 99%) of each cell line. In addition, we demonstrate cell fractionation of a single cell type (K562 cells) into subpopulations and characterize the variations of biomechanical properties of the separated cells with atomic force microscopy. These results will be beneficial to obtaining label-free separation of cellular mixtures, or to better investigate the origins of biomechanical differences in a single cell type.

中文翻译：

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通过基于细胞生物力学特性的微流控分离进行细胞富集。

已显示患病细胞群体的生物力学特性与健康细胞群体具有差异，但是这些生物力学特性的重叠会限制它们在疾病细胞富集和检测中的使用。我们报告了一种新的微流控细胞富集技术，该技术通过生物力学特性的差异连续分级分离细胞，从而产生高度纯净的细胞亚群。细胞分离是在微流体通道中实现的，该通道具有一系列对角线脊，这些对角线脊用于将生物力学上不同的细胞隔离到通道中的不同位置。由于在细胞压缩过程中施加了弹性和粘性力，这是细胞生物力学特性（包括尺寸和粘弹性）的函数，因此，较硬和较少的粘膜细胞平行于对角线脊移动并表现出正的横向位移。另一方面，由于脊引起的循环流，较小，较软和较粘的细胞垂直于对角脊迁移，并导致负的横向位移。然后，利用多个出口收集细胞生物力学特性差异更细微分级的细胞。结果是，与二元输出相比，细胞分级分离显着提高了细胞分离效率，并能够测量单个细胞类型内细微的生物力学差异。作为概念证明，我们混合了两种不同的白血病细胞系（K562和HL60），并利用细胞分离技术实现了超过45倍的细胞群扩增，每个细胞系的高纯度细胞富集（90％至99％）。此外，我们展示了将单个细胞类型（K562细胞）分为亚群的细胞分级分离，并通过原子力显微镜表征了分离细胞的生物力学特性。这些结果将有利于获得无混合物的细胞混合物分离，或更好地研究单一细胞类型中生物力学差异的起源。