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Immuno-capture of cells in open microfluidics: Microfluidic probes integrated with herringbone micro-mixers

机译:免疫捕获开放式微流体中的细胞:微流体探针与人字形微混合器整合

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Effective capture of cancer cells from whole peripheral blood samples, i.e. circulating tumor cells (CTCs), is still anexisting limitation for liquid biopsy-based diagnostics. The well-established closed-channel herringbone micro-mixersare one of the widely adopted methods for isolating CTCs based on antigen-antibody interaction. However, they areknown to be associated with several drawbacks, such as limited capture areas within the channels, restricted access toisolated cells, difficulties to achieve multiplexed antibody capture assays for immuno-phenotyping, and limited postprocessingpossibilities. To tackle these issues, we developed a novel microfluidic probe (MFP) that is integrated withherringbone micro-mixers on its tip surface (HMFP). The tip surface was designed with 2-slitted apertures, one forinjecting the cell suspension and the other for performing high flow rate aspiration to confine the flow. The herringbonemixing elements were distributed in-between the apertures for micro-mixing that enhances the CTCs capture on theantibodies-coated bottom glass surface. Unlike the closed herringbone chips, the functionalized bottom glass surface waskept large given the capacity for the MFP to work in scanning mode, and so it prevented cell capture saturation effect.Our MFP design and experimental setup showed a cell capture efficiency of 59-81% with flow rates of 0.6-2.4 mL/h.The capture of CTCs in an open microfluidic system allows for easy post-process and CTC analysis, such as single celldrug testing and mechano-phenotyping using atomic force microscopy.
机译:从全周血样的有效捕获癌细胞,即循环肿瘤细胞(CTC),仍然是一个液检基于液检基诊断的存在限制。建立良好的闭路蜂窝微混合器是基于抗原 - 抗体相互作用分离CTC的广泛采用的方法之一。但是,他们是已知与若干缺点相关联,例如信道内的有限捕获区域,限制访问分离的细胞,难以实现免疫表型的多路复用抗体捕获测定,并进行有限的后处理可能性。为了解决这些问题,我们开发了一种集成的新型微流体探针(MFP)其尖端表面(HMFP)上的人字形微混频器。尖端表面设计有2型狭孔,一个用于注入电池悬浮液,另一个用于执行高流速抽吸以限制流动。人民币混合元件分布在孔之间用于微混合,可增强CTCS捕获抗体涂覆的底部玻璃表面。与封闭的人字形芯片不同,官能化的底玻璃表面是鉴于MFP在扫描模式下工作的容量保持大量,因此它防止了细胞捕获饱和效果。我们的MFP设计和实验设置显示细胞捕获效率为59-81%,流速为0.6-2.4ml / h。开放式微流体系统中CTC捕获允许易于处理后和CTC分析,例如单细胞使用原子力显微镜的药物测试和机械表型。

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