Fluid nanoporous microinterface enables multiscale-enhanced affinity interaction for tumor-derived extracellular vesicle detection.
Fluid nanoporous microinterface enables multiscale-enhanced affinity interaction for tumor-derived extracellular vesicle detection.
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流体纳米多孔微界面能够实现多尺度增强的亲和力相互作用，用于肿瘤源性细胞外囊泡检测
DOI：
10.1073/pnas.2213236119
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发表时间：
2022-11
影响因子：
11.1
通讯作者：
Yang, Chaoyong
中科院分区：
文献类型：
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作者：
Niu, Qi;Gao, Jiafeng;Zhao, Kaifeng;Chen, Xiaofeng;Lin, Xiaolin;Huang, Chen;An, Yu;Xiao, Xiuying;Wu, Qiaoyi;Cui, Liang;Zhang, Peng;Wu, Lingling;Yang, Chaoyong
肿瘤来源的细胞外囊泡 (T-EV) 的有效捕获和灵敏检测具有诊断、免疫治疗预测和癌症复发监测的潜力。 T-EV 的亲和分离依赖于界面亲和反应，其效率由界面物理化学性质决定。在这里，微流控芯片中的流体纳米多孔微界面（FluidporeFace）是通过在纳米多孔人字形微结构上装饰支撑脂质双层来设计的，以同时增强传质、界面接触和结合亲和力。与解决界面亲和反应部分基本限制的现有方法相比，FluidporeFace 将 T-EV 的捕获效率提高了 1.4 至 1.6 倍，检测灵敏度提高了 1 至 2 个数量级。总体而言，这项工作为疾病生物标志物的分离和检测中的界面工程开辟了途径。肿瘤源性细胞外囊泡（T-EV）是肿瘤诊断和治疗指导的重要标志物。然而，T-EV 的纳米级尺寸和低丰度的标记蛋白限制了界面亲和反应，导致分离效率和检测灵敏度低。在这里，我们通过多尺度增强亲和反应在纳米多孔人字形微结构上装饰支撑脂质双层（SLB），在微流控芯片中设计了流体纳米多孔微界面（FluidporeFace），以有效分离T-EV。在微观层面上，人字形微图案促进 T-EV 的质量转移到表面。在纳米级水平上，纳米孔隙可以克服 T-EV 与界面之间紧密接触的边界效应。在分子水平上，流体 SLB 在结合位点提供识别分子的聚集，从而实现多价结合，与非流体界面相比，亲和力增加约 83 倍。凭借协同增强的传质、界面接触和结合亲和力，FluidporeFace 可以对 T-EV 进行超灵敏检测，检测限为 10 个 T-EV μL−1，其 PD-L1 表达水平成功区分癌症患者和健康供体。我们预计这种多尺度增强的界面反应策略将激发生物传感器的设计并扩大液体活检的应用，特别是对于临床样本中的低丰度目标。
Efficient capture and sensitive detection of tumor-derived extracellular vesicles (T-EVs) hold potential for diagnosis, immunotherapy prediction, and recurrence monitoring of cancers. Affinity isolation of T-EVs relies on interfacial affinity reaction, whose efficiency is dominated by interfacial physicochemical properties. Here, a fluid nanoporous microinterface (FluidporeFace) in a microfluidic chip was engineered by decorating supported lipid bilayers on nanoporous herringbone microstructures to simultaneously enhance mass transfer, interface contact, and binding affinity. FluidporeFace improved the capture efficiency toward T-EVs by 1.4- to 1.6-fold and the detection sensitivity by 1 to 2 orders of magnitude compared with existing methods that address partial fundamental limits in interfacial affinity reaction. Overall, this work opens avenues for interface engineering in isolation and detection of disease biomarkers. Tumor-derived extracellular vesicles (T-EVs) represent valuable markers for tumor diagnosis and treatment guidance. However, nanoscale sizes and the low abundance of marker proteins of T-EVs restrict interfacial affinity reaction, leading to low isolation efficiency and detection sensitivity. Here, we engineer a fluid nanoporous microinterface (FluidporeFace) in a microfluidic chip by decorating supported lipid bilayers (SLBs) on nanoporous herringbone microstructures with a multiscale-enhanced affinity reaction for efficient isolation of T-EVs. At the microscale level, the herringbone micropattern promotes the mass transfer of T-EVs to the surface. At the nanoscale level, nanoporousity can overcome boundary effects for close contact between T-EVs and the interface. At the molecular level, fluid SLBs afford clustering of recognition molecules at the binding site, enabling multivalent binding with an ∼83-fold increase of affinity compared with the nonfluid interface. With the synergetic enhanced mass transfer, interface contact, and binding affinity, FluidporeFace affords ultrasensitive detection of T-EVs with a limit of detection of 10 T-EVs μL−1, whose PD-L1 expression levels successfully distinguish cancer patients from healthy donors. We expect this multiscale enhanced interfacial reaction strategy will inspire the biosensor design and expand liquid biopsy applications, especially for low-abundant targets in clinical samples.
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