Size-amplified acoustofluidic separation of circulating tumor cells with removable microbeads

Size-amplified acoustofluidic separation of circulating tumor cells with removable microbeads
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使用可拆卸微珠对循环肿瘤细胞进行尺寸放大声流分离

DOI:
10.1088/2399-1984/aabf50
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发表时间:
2018-06-01
期刊:
影响因子:
2.1
通讯作者:
Guo, Feng
Guo, Feng
中科院分区:
材料科学3区
文献类型:
--
作者:
Liu, Huiqin;Ao, Zheng;Guo, Feng

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罕见循环肿瘤细胞(CTCs)的分离和分析对肿瘤的诊断、预后和治疗效果评价具有重要意义。声流分离因其无接触、无创、简单、通用等特点而成为一种极具吸引力的分离方法。然而,ctc与正常血细胞之间不明显的物理差异限制了使用当前声学方法检测ctc的纯度。在这里,我们展示了一个大小放大声分离和释放ctc与可移动的微珠。与正常血细胞相比,选择性结合到尺寸放大器(40 μ m直径的抗epcam /明胶涂层SiO2微珠)的ctc具有显着的物理差异(尺寸和力学),导致声辐射力的放大约为裸ctc或正常血细胞的100倍。因此,在行表面声波微流控装置中,ctc可以通过尺寸放大器有效地分离出来,并通过酶降解从尺寸放大器中释放出来,用于进一步纯化或下游分析。我们展示了从血液样本中分离出的细胞,在从大小放大器中释放细胞后,总效率(E-total)接近77%,纯度(P)接近96%,活力(V)接近83%。我们的方法大大提高了稀有细胞纯化在转化医学中的新兴应用。
Isolation and analysis of rare circulating tumor cells (CTCs) is of great interest in cancer diagnosis, prognosis, and treatment efficacy evaluation. Acoustofluidic cell separation becomes an attractive method due to its contactless, noninvasive, simple, and versatile features. However, the indistinctive physical difference between CTCs and normal blood cells limits the purity of CTCs using current acoustic methods. Herein, we demonstrate a size-amplified acoustic separation and release of CTCs with removable microbeads. CTCs selectively bound to size-amplifiers (40 mu m-diameter anti-EpCAM/gelatin-coated SiO2 microbeads) have significant physical differences (size and mechanics) compared to normal blood cells, resulting in an amplification of acoustic radiation force approximately a hundredfold over that of bare CTCs or normal blood cells. Therefore, CTCs can be efficiently sorted out with size-amplifiers in a traveling surface acoustic wave microfluidic device and released from size-amplifiers by enzymatic degradation for further purification or downstream analysis. We demonstrate a cell separation from blood samples with a total efficiency (E-total) of similar to 77%, purity (P) of similar to 96%, and viability (V) of similar to 83% after releasing cells from size-amplifiers. Our method substantially improves the emerging application of rare cell purification for translational medicine.