Immunoaffinity-based liquid biopsies of circulating tumor cells (CTCs) hold great promise for cancer management but typically suffer from low throughput, relative complexity, and postprocessing 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 and 200 μL min^–1. 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 postprocessing capacity with the identification of potential responders to immune checkpoint inhibition (ICI) 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.

中文翻译：

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用于精准肿瘤学的不依赖于流速的多尺度液体活检

基于免疫亲和力的循环肿瘤细胞 (CTC) 液体活检为癌症管理带来了巨大希望，但通常存在通量低、相对复杂和后处理限制等问题。在这里，我们通过分离和独立优化易于制造和操作的浓缩装置的纳米、微米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在任何流速下实现最佳捕获条件，正如恒定捕获效率所证明的那样，在 50 至 200 μL min –1 之间，捕获效率高于 75 ^%. 当用于检测 79 名癌症患者和 20 名健康对照者血液中的 CTC 时，该设备实现了 96% 的灵敏度和 100% 的特异性。我们通过识别免疫检查点抑制 (ICI) 疗法的潜在反应者和 HER2 阳性乳腺癌的检测来证明其后处理能力。结果与其他检测方法（包括临床标准）相比效果很好。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局限性，可以帮助改善癌症管理。