Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Zhejiang, 315211, China; Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315211, China.
Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315211, China.
Biosens Bioelectron. 2023 Nov 1;239:115590. doi: 10.1016/j.bios.2023.115590. Epub 2023 Aug 10.
Breast cancer (BC) is a complex disease with high variability and no specific tumor markers available for diagnosis. Exosomes contain rich maternal tumor information and are a novel non-invasive biomarker with the potential for cancer diagnosis and prognosis. However, analysis of exosomal protein markers in blood samples is challenging due to lengthy sample workups and insufficient sensitivity. To address this difficulty, we developed a novel filter-electrochemical microfluidic chip (FEMC) to detect and classify BC directly in whole blood without requiring heavy purification methods. In our system, exosome enrichment was performed using a dual filtration system. The target was directed through a curved channel onto four screen-printed electrodes (SPEs), where it was captured by the previously modified antibodies. Simultaneously, Zr-MOFs encapsulated with a large number of methylene blue molecules (MB@UiO-66) were absorbed on the surface of exosomes due to the high affinity for phosphate groups. This process leads to the amplification of electrical signals. The approach demonstrated that the utilization of BC exosome-associated tumor biomarkers (i.e., PMSA, EGFR, CD81, and CEA), enabled the classification of various BC mouse models samples and clinical BC samples. The entire FEMC assay was completed in 1 h with a limit of detection of 1 × 10 particles/mL. Thus, the FEMC assay can provide real-time detection information, allowing timely and better-informed opportunities for clinical BC diagnosis and typing.
乳腺癌（BC）是一种具有高度变异性的复杂疾病，目前尚无特异性的肿瘤标志物可用于诊断。外泌体包含丰富的母肿瘤信息，是一种具有癌症诊断和预后潜力的新型非侵入性生物标志物。然而，由于样本处理过程冗长且灵敏度不足，分析血液样本中外泌体蛋白标志物具有一定的挑战性。为了解决这个难题，我们开发了一种新型的过滤-电化学微流控芯片（FEMC），可直接在全血中检测和分类 BC，而无需采用繁琐的纯化方法。在我们的系统中，采用双过滤系统进行外泌体富集。目标物通过弯曲通道进入四个丝网印刷电极（SPE），在那里被预先修饰的抗体捕获。同时，Zr-MOF 被大量的亚甲基蓝分子（MB@UiO-66）包裹，由于对磷酸盐基团具有高亲和力，Zr-MOF 被吸附在外泌体的表面上。这个过程导致了电信号的放大。该方法证明，利用 BC 外泌体相关肿瘤标志物（即 PMSA、EGFR、CD81 和 CEA），可以对各种 BC 小鼠模型样本和临床 BC 样本进行分类。整个 FEMC 检测在 1 小时内完成，检测限为 1×10 个颗粒/mL。因此，FEMC 检测可以提供实时检测信息，为临床 BC 诊断和分型提供及时和更好的机会。
