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具有自组装并四苯纳米纤维阵列的多功能有机电化学晶体管用于循环肿瘤细胞的分离与检测及细胞外囊泡分泌增强

Versatile Organic Electrochemical Transistors with Self-Assembled Coronene Nanofiber Arrays for the Isolation and Detection of Circulating Tumor Cells and Enhanced Secretion of Extracellular Vesicles.

作者信息

Quiñones Edgar Daniel, Yu Jiashing, Liu Rou-Zhen, Li Yi-Shiuan, Lu Yu-Chuan, Hsiao Yu-Sheng

机构信息

Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 106335, Taiwan.

Taiwan International Graduate Program, Sustainable Chemical Science & Technology, Academia Sinica, Institute of Chemistry, Taipei, 115, Taiwan.

出版信息

ACS Appl Mater Interfaces. 2025 Jun 11;17(23):33592-33605. doi: 10.1021/acsami.5c05442. Epub 2025 May 30.

DOI:10.1021/acsami.5c05442
PMID:40444994
Abstract

The integration of organic bioelectronic interfaces has opened new avenues for merging biological systems with electronics, offering transformative solutions to challenges in both fields. In this study, we present a novel hybrid organic electrochemical transistor (OECT) featuring self-assembled three-dimensional (3D) nanofiber arrays (NFAs) of small-molecule semiconductors grown on poly(3,4-ethylenedioxythiophene):polystyrenesulfonate active-layer channels. The hybrid OECT was further evaluated for its potential to capture, recover, and biosense circulating tumor cells (CTCs), as well as to enhance extracellular vesicle (EV) secretion through electrical stimulation (ES). Using template-free self-assembly via standard thermal evaporation, out-of-plane coronene (CR)-based NFAs were fabricated and surface-engineered with 1-pyrenebutyric acid through π-π interactions, enabling bioaffinity coatings on OECTs for advanced biological applications. The device demonstrated efficient CTC isolation, achieving an isolation rate exceeding 90% for MCF-7 breast cancer cells spiked into THP-1 monocytic cells (10 cells mL), with minimal nonspecific binding by incorporating a specific antibody-coated CR-based NFA layer. Moreover, over 80% of the captured CTCs were released from CR-based NFAs during cyclic voltammetry sweeps in phosphate-buffered saline. The device also enhanced EV secretion by incorporating a collagen-coated CR-based NFA layer, which supported cell attachment and proliferation under sustained ES at 20 V, 0.5 Hz, with 5 ms pulses for 24-72 h periods. EV production increased by approximately 12.4-fold in MCF-7 cells and 8.0-fold in immortalized bone marrow stromal cells without significantly altering the EV size or requiring additional cellular modifications. This dual-functionality platform, enabled by a surface-engineered 3D-hybrid OECT, is a powerful tool for selective CTC isolation, liquid biopsy purification, and enhanced EV production. This versatility highlights the potential of this approach for advanced bioelectronic applications and paves the way for innovations in diagnostics and therapeutic research.

摘要

有机生物电子界面的整合为生物系统与电子学的融合开辟了新途径,为这两个领域的挑战提供了变革性解决方案。在本研究中,我们展示了一种新型混合有机电化学晶体管(OECT),其具有在聚(3,4 - 乙撑二氧噻吩):聚苯乙烯磺酸盐活性层通道上生长的小分子半导体自组装三维(3D)纳米纤维阵列(NFA)。对该混合OECT捕获、回收和生物传感循环肿瘤细胞(CTC)的潜力,以及通过电刺激(ES)增强细胞外囊泡(EV)分泌的潜力进行了进一步评估。通过标准热蒸发的无模板自组装方法,制备了基于平面外并五苯(CR)的NFA,并通过π - π相互作用用1 - 芘丁酸进行表面工程处理,从而在OECT上实现生物亲和涂层以用于先进的生物应用。该器件展示了高效的CTC分离,对于掺入THP - 1单核细胞(10个细胞/毫升)中的MCF - 7乳腺癌细胞,分离率超过90%,通过掺入特定抗体包被的基于CR的NFA层实现了最小的非特异性结合。此外,在磷酸盐缓冲盐水中进行循环伏安扫描期间,超过80%捕获的CTC从基于CR的NFA中释放出来。该器件还通过掺入胶原包被的基于CR的NFA层增强了EV分泌,该层在20 V、0.5 Hz、5 ms脉冲的持续ES下支持细胞附着和增殖24 - 72小时。在MCF - 7细胞中EV产量增加了约12.4倍,在永生化骨髓基质细胞中增加了8.0倍,而没有显著改变EV大小或需要额外的细胞修饰。这个由表面工程化的3D混合OECT实现的双功能平台,是用于选择性CTC分离、液体活检纯化和增强EV产生的强大工具。这种多功能性突出了这种方法在先进生物电子应用中的潜力,并为诊断和治疗研究的创新铺平了道路。

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