论文标题
流速独立的多尺度液体活检，用于精确肿瘤学
Flow Rate Independent Multiscale Liquid Biopsy for Precision Oncology
论文作者
论文摘要
循环肿瘤细胞（CTC）的基于免疫亲和力的液体活检对癌症管理具有巨大的希望，但通常遭受低吞吐量，相对复杂性和后处理的限制。在这里，我们通过解耦和独立优化易于制造和操作的富集设备的纳米，微尺度和宏观尺度来同时解决这些问题。与其他基于亲和力的设备不同，我们的可扩展网格方法可以以任何流速为最佳的捕获条件，如恒定的捕获效率所证明的，超过50-200 ul/min之间的75％。当使用79名癌症患者和20个健康对照组的血液中检测CTC时，该设备的敏感性和100％的特异性达到了96％的敏感性和100％的特异性。我们证明了其后处理能力，并确定了对免疫检查点抑制疗法的潜在反应者和HER2阳性乳腺癌的检测。结果与其他测定法（包括临床标准）相比良好。这表明我们的方法克服了与基于亲和力的液体活检相关的主要限制，可以帮助改善癌症管理。
Immunoaffinity-based liquid biopsies of circulating tumor cells (CTCs) hold great promise for cancer management, but typically suffer from low throughput, relative complexity and post-processing limitations. Here we address these issues simultaneously by decoupling and independently optimizing the nano-, micro- and macro-scales of an enrichment device that is simple to fabricate and operate. Unlike other affinity-based devices, our scalable mesh approach enables optimum capture conditions at any flow rate, as demonstrated with constant capture efficiencies, above 75% between 50-200 uL/min. The device achieved 96% sensitivity and 100% specificity when used to detect CTCs in the blood of 79 cancer patients and 20 healthy controls. We demonstrate its post processing capacity with the identification of potential responders to immune checkpoint inhibition therapy and the detection of HER2 positive breast cancer. The results compare well with other assays, including clinical standards. This suggests that our approach, which overcomes major limitations associated with affinity-based liquid biopsies, could help improve cancer management.
