Circulating tumor cell (CTC)-based liquid biopsies provide unique opportunities for cancer diagnostics, treatment selection, and response monitoring, but even with advanced microfluidic technologies for rare cell detection the very low number of CTCs in standard 10-mL peripheral blood samples limits their clinical utility. Clinical leukapheresis can concentrate mononuclear cells from almost the entire blood volume, but such large numbers and concentrations of cells are incompatible with current rare cell enrichment technologies. Here, we describe an ultrahigh-throughput microfluidic chip, ^LPCTC-iChip, that rapidly sorts through an entire leukapheresis product of over 6 billion nucleated cells, increasing CTC isolation capacity by two orders of magnitude (86% recovery with 10⁵ enrichment). Using soft iron-filled channels to act as magnetic microlenses, we intensify the field gradient within sorting channels. Increasing magnetic fields applied to inertially focused streams of cells effectively deplete massive numbers of magnetically labeled leukocytes within microfluidic channels. The negative depletion of antibody-tagged leukocytes enables isolation of potentially viable CTCs without bias for expression of specific tumor epitopes, making this platform applicable to all solid tumors. Thus, the initial enrichment by routine leukapheresis of mononuclear cells from very large blood volumes, followed by rapid flow, high-gradient magnetic sorting of untagged CTCs, provides a technology for noninvasive isolation of cancer cells in sufficient numbers for multiple clinical and experimental applications.

基于循环肿瘤细胞（CTC）的液体活检为癌症诊断，治疗选择和反应监测提供了独特的机会，但是即使使用先进的微流体技术进行稀有细胞检测，标准10 mL外周血样本中的CTC数量仍然非常低临床效用。临床白细胞分离术可以从几乎整个血液中浓缩单核细胞，但是如此大量和浓度的细胞与当前的稀有细胞富集技术不兼容。在这里，我们描述了一种超高通量微流控芯片^LP CTC-iChip，它可以快速筛选出超过60亿个有核细胞的整个白细胞分离产物，从而将CTC分离能力提高了两个数量级（86％的回收率与10 ⁵丰富）。使用软铁填充通道充当磁性微透镜，我们增强了分选通道内的场梯度。施加到惯性聚焦的细胞流上的磁场不断增加，有效地耗尽了微流体通道内大量的磁性标记白细胞。抗体标记的白细胞的阴性消耗使得能够分离潜在可行的CTC，而不会偏向于特定肿瘤表位的表达，从而使该平台适用于所有实体瘤。因此，通过常规白细胞去除从非常大的血液中富集单个核细胞，然后通过快速流动，高梯度磁化未标记的CTC进行的初始富集，提供了一种用于多种临床和实验应用的足够数量的无创分离癌细胞的技术。