Integration of Lateral Filter Arrays with Immunoaffinity for Circulating-Tumor-Cell Isolation
Integration of Lateral Filter Arrays with Immunoaffinity for Circulating-Tumor-Cell Isolation
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DOI：
10.1002/anie.201901412
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发表时间：
2019-06-03
影响因子：
16.6
通讯作者：
Fan, Z. Hugh
中科院分区：
文献类型：
--
作者：
Chen, Kangfu;Dopico, Pablo;Fan, Z. Hugh
循环肿瘤细胞（CTC）是癌症预后和治疗监测的重要生物标志物。然而，CTC的物理和生物学性质的异质性限制了用于从数十亿正常血细胞中分离少量CTC的各种方法的效率。为了应对这一挑战，我们开发了一种横向过滤器阵列微流体（LFAM）装置，将基于尺寸的分离与基于免疫亲和性的CTC分离相结合。LFAM装置由蛇形主通道和用于CTC分离的侧向过滤器阵列组成，大部分样品通过该蛇形主通道。独特的装置设计产生二维流动，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装置通过固定对靶细胞特异性的抗体进一步功能化。由此产生的装置以（98.7 +/-1.2）%的效率捕获血液样品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。
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.