Deformability-based cell classification and enrichment using inertial microfluidics
Deformability-based cell classification and enrichment using inertial microfluidics
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DOI：
10.1039/c0lc00595a
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发表时间：
2011-01-01
期刊：
影响因子：
6.1
通讯作者：
Di Carlo, Dino
中科院分区：
文献类型：
--
作者：
Hur, Soojung Claire;Henderson-MacLennan, Nicole K.;Di Carlo, Dino
从异质样品中检测和分离稀有靶细胞的能力在细胞生物学研究、免疫学、组织工程和医学中具有很高的需求。允许无标记细胞富集或检测的技术对于降低临床应用的复杂性和成本尤其重要。单细胞变形性最近被认为是一种独特的无标记的细胞表型生物标志物，可用于评估癌症的侵袭性。在微流体系统中使用流体动力学效应的独特组合，我们展示了基于细胞大小和变形性的高通量连续无标记细胞分类和富集。该系统利用了细胞在微通道流动中移动时变形诱导的升力和惯性升力之间的平衡。由于这种力的平衡，具有不同弹性和粘度的颗粒和液滴被发现具有不同的横向动态平衡位置。我们应用该系统成功地分类各种细胞类型，使用细胞大小和变形能力作为区分标记。此外，利用动态平衡位置的差异，我们调整了系统，以基于这些标记进行被动、无标记和连续的细胞富集，从而能够在没有显著基因表达变化的情况下进行芯片外样品收集。所提出的方法具有高通量变形性测量和具有成本效益的细胞分离的实际潜力，以获得在癌症研究，免疫学和再生医学中感兴趣的活靶细胞。
The ability to detect and isolate rare target cells from heterogeneous samples is in high demand in cell biology research, immunology, tissue engineering and medicine. Techniques allowing label-free cell enrichment or detection are especially important to reduce the complexity and costs towards clinical applications. Single-cell deformability has recently been recognized as a unique label-free biomarker for cell phenotype with implications for assessment of cancer invasiveness. Using a unique combination of fluid dynamic effects in a microfluidic system, we demonstrate high-throughput continuous label-free cell classification and enrichment based on cell size and deformability. The system takes advantage of a balance between deformability-induced and inertial lift forces as cells travel in a microchannel flow. Particles and droplets with varied elasticity and viscosity were found to have separate lateral dynamic equilibrium positions due to this balance of forces. We applied this system to successfully classify various cell types using cell size and deformability as distinguishing markers. Furthermore, using differences in dynamic equilibrium positions, we adapted the system to conduct passive, label-free and continuous cell enrichment based on these markers, enabling off-chip sample collection without significant gene expression changes. The presented method has practical potential for high-throughput deformability measurements and cost-effective cell separation to obtain viable target cells of interest in cancer research, immunology, and regenerative medicine.