PDF(Pubmed)
Abstract：
The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young\'s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL-1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.
摘要：
有效分离稀有靶细胞，如循环肿瘤细胞，由于缺乏具有强靶标结合亲和力和非靶细胞抗性的捕获表面,来自全血的捕获仍然具有挑战性。在这里，我们提出了一种解决方案，利用细菌病毒（噬菌体）纳米纤维的灵活性，其侧壁显示目标循环肿瘤细胞特异性适体，其末端与磁珠相连。如此灵活的噬菌体，具有低刚度和杨氏模量，可以扭曲和适应识别细胞受体，大力增强靶细胞捕获和熵抑制非靶细胞（白细胞）吸附。与具有刚性噬菌体的磁珠相比,具有柔性噬菌体的磁珠可以分离和计数靶细胞,具有显著增加的细胞亲和力和减少的非靶细胞吸收。这区分了乳腺癌患者和健康捐赠者，在最佳检测阈值（>4个靶细胞mL-1）下具有令人印象深刻的曲线下面积（0.991）。捕获的循环肿瘤细胞的免疫染色精确确定乳腺癌亚型，诊断准确率为91.07%。我们的研究揭示了病毒机械属性在设计具有优越的目标结合和非目标抗污染表面的能力。
