Interdisciplinary Microsystems Group (IMG), Department of Mechanical and Aerospace Engineering, University of Florida, P.O. BOX 116250, Gainesville, FL, 32611, USA.
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32611, USA.
Angew Chem Int Ed Engl. 2019 Jun 3;58(23):7606-7610. doi: 10.1002/anie.201901412. Epub 2019 May 9.
Circulating tumor cells (CTCs) are an important biomarker for cancer prognosis and treatment monitoring. However, the heterogeneity of the physical and biological properties of CTCs limits the efficiency of various approaches used to isolate small numbers of CTCs from billions of normal blood cells. To address this challenge, we developed a lateral filter array microfluidic (LFAM) device to integrate size-based separation with immunoaffinity-based CTC isolation. The LFAM device consists of a serpentine main channel, through which most of a sample passes, and an array of lateral filters for CTC isolation. The unique device design produces a two-dimensional flow, which reduces nonspecific, geometric capture of normal cells as typically observed in vertical filters. The LFAM device was further functionalized by immobilizing antibodies that are specific to the target cells. The resulting devices captured pancreatic cancer cells spiked in blood samples with (98.7±1.2) % efficiency and were used to isolate CTCs from patients with metastatic colorectal cancer.
循环肿瘤细胞(CTCs)是癌症预后和治疗监测的重要生物标志物。然而,CTC 的物理和生物学特性的异质性限制了从数十亿个正常血细胞中分离少量 CTC 所使用的各种方法的效率。为了解决这一挑战,我们开发了一种侧向过滤阵列微流控(LFAM)装置,将基于大小的分离与基于免疫亲和的 CTC 分离相结合。LFAM 装置由蛇形主通道组成,大部分样品通过该通道,以及用于 CTC 分离的侧向过滤阵列。独特的装置设计产生二维流,这减少了通常在垂直过滤器中观察到的正常细胞的非特异性、几何捕获。LFAM 装置通过固定针对靶细胞的抗体进一步功能化。所得到的装置以(98.7±1.2)%的效率捕获了血液样本中掺入的胰腺癌细胞,并用于从转移性结直肠癌患者中分离 CTC。