Abstract：
The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.
摘要：
糖类抗原19-9(CA19-9)通常被用作胰腺癌(PC)的代表性生物标志物;然而,它缺乏早期PC诊断的敏感性和特异性。此外，一些PC患者CA19-9阴性（<37U/mL），这给他们的准确诊断和治疗带来了额外的限制。因此，有必要改进准确检测CA19-9阴性患者PC分期的方法.在这项研究中,肿瘤近端液体活检和惯性微流体技术相结合,能够实现门静脉循环肿瘤细胞(CTC)的高通量富集,并支持早期PC患者的有效诊断.所提出的惯性微流体系统显示出使用倾斜螺旋通道中的惯性聚焦和迪恩流动效应来提供基于尺寸的CTC富集。值得注意的是,与外周血(10.9个CTC/5mL)相比,门静脉血液样本的CTC(21.4个细胞/5mL)产率是外周血的两倍.外周和门静脉CTC数据以及CA19-9结果的组合显示，CA19-9阴性PC患者的平均准确性从47.1％大大提高，常规CA19-9测试高达87.1％。因此，基于门静脉CTC的微流体活检可用于诊断早期PC，具有较高的敏感性和特异性，特别是在CA19-9阴性患者中。
