Department of Chemistry, The University of Georgia, Athens, GA 30602, USA.
School of Electrical and Computer Engineering, College of Engineering, The University of Georgia, Athens, GA 30602, USA.
Lab Chip. 2021 May 4;21(9):1706-1723. doi: 10.1039/d1lc00119a.
Methods to separate circulating tumor cells (CTCs) from blood samples were intensively researched in order to understand the metastatic process and develop corresponding clinical assays. However current methods faced challenges that stemmed from CTCs' heterogeneity in their biological markers and physical morphologies. To this end, we developed integrated ferrohydrodynamic cell separation (iFCS), a scheme that separated CTCs independent of their surface antigen expression and physical characteristics. iFCS integrated both diamagnetophoresis of CTCs and magnetophoresis of blood cells together via a magnetic liquid medium, ferrofluid, whose magnetization could be tuned by adjusting its magnetic volume concentration. In this paper, we presented the fundamental theory of iFCS and its specific application in CTC separation. Governing equations of iFCS were developed to guide its optimization process. Three critical parameters that affected iFCS's cell separation performance were determined and validated theoretically and experimentally. These parameters included the sample flow rate, the volumetric concentration of magnetic materials in the ferrofluid, and the gradient of the magnetic flux density. We determined these optimized parameters in an iFCS device that led to a high recovery CTC separation in both spiked and clinical samples.
为了深入了解肿瘤转移过程并开发相应的临床检测方法，人们对从血液样本中分离循环肿瘤细胞（CTC）的方法进行了深入研究。然而，目前的方法面临着一些挑战，这些挑战源于 CTC 在其生物标志物和物理形态上的异质性。为此，我们开发了集成铁磁流体动力学细胞分离（iFCS）技术，该技术可以独立于 CTC 的表面抗原表达和物理特性来分离 CTC。iFCS 通过磁性液体介质（铁磁流体）将 CTC 的顺磁作用和血细胞的磁泳作用结合在一起，通过调整其磁体积浓度来调节铁磁流体的磁化程度。在本文中，我们介绍了 iFCS 的基本理论及其在 CTC 分离中的具体应用。建立了 iFCS 的控制方程，以指导其优化过程。确定并从理论和实验上验证了三个影响 iFCS 细胞分离性能的关键参数，包括样品流速、铁磁流体中磁性材料的体积浓度以及磁通密度梯度。我们在 iFCS 装置中确定了这些优化参数，从而在加标和临床样本中实现了高回收率的 CTC 分离。
