3D bioelectronic interface: capturing circulating tumor cells onto conducting polymer-based micro/nanorod arrays with chemical and topographical control.

3D bioelectronic interface: capturing circulating tumor cells onto conducting polymer-based micro/nanorod arrays with chemical and topographical control.
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DOI:
10.1002/smll.201400429
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发表时间:
2014-08-13
期刊:
影响因子:
13.3
通讯作者:
Chen, Peilin
Chen, Peilin
中科院分区:
材料科学1区
文献类型:
--
作者:
Hsiao, Yu-Sheng;Luo, Shyh-Chyang;Hou, Shuang;Zhu, Bo;Sekine, Jun;Kuo, Chiung-Wen;Chueh, Di-Yen;Yu, Hsiao-hua;Tseng, Hsian-Rong;Chen, Peilin

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生物界面的化学和物理控制因其在细胞和组织调节以及诊断和治疗应用中的灵活性和有效性而备受关注。[1-7]当将生化信号引入细胞时,可以在其生物界面操纵各种细胞活动(例如,黏附、扩散形态、增殖)。[5-7]例如,在干细胞疗法的发展中,用合成肽修饰的表面可以用于支持干细胞的自我更新和分化。[4]值得注意的是,在三维(3D)微/纳米结构上观察到的特定的细胞-基质相互作用可以提供调节神经元细胞扩散形态的拓扑学线索,[8,9]从而促进干细胞的细胞分化水平,[10-12]提高靶基因表达细胞的转染效率,[13-15]并提高循环肿瘤细胞(CTCs)的捕获效率,用于非侵入性血液活检。[16-21]除了这些生物应用外,将额外的电功能集成到生物接口中最近引起了人们对生物电子中生物信号的数字转换的极大兴趣。生物电子接口(BEIS)是一种很有前途的中间层,可以增强电子和生物系统之间的通信;它们可以操作来耦合双向的电子和离子流动。因此,BEIS在电信号、[22,23]刺激、[24-28]和电触发响应释放和泵送小分子方面具有巨大的潜力。在BEIS的开发中,有机导电聚合物[CPS;例如,聚吡咯或聚(3,4-乙二氧基噻吩基)(PEDOT)]因其出色的电传输性能、固有的生物兼容性和高度的制造灵活性而被广泛应用。事实上,CPS可以用不同的化学设计来合成,例如加入各种阴离子掺杂剂[例如,聚苯磺酸钠(PSS),对甲苯磺酸盐(TOS)][34-36]和/或呈现各种功能侧链,[20,37-39],从而扩大了它们的适用性。例如,TOS掺杂的PEDOT(PEDOT:TOS)材料是目前最有前途的Beis材料,因为它们具有高的电稳定性和生物相容性,允许长期细胞培养或植入;[36]或者,羧酸接枝的PEDOT(PEDOTAc)材料可以连接到特定的细胞捕捉剂,用于CTC分析。[20]简而言之,这种生物结合过程包括使用N-羟基琥珀酰亚胺(NHS)和1-乙基-3-[3-二甲氨基丙基]碳二亚胺盐酸盐(EDC)激活羧酸基,然后与链霉亲和素结合。然后将链霉亲和素接枝的PEDOT膜与生物素标记的抗EpCAM孵育以
Chemical and physical control of biointerfaces is attractive because of its flexibility and effectiveness in cell and tissue regulation, as well as in diagnostic and therapeutic applications.[1–7] When introducing biochemical cues to cells, various cell activities (eg, adhesion, spreading morphologies, proliferation) can be manipulated at their biointerfaces.[5–7] For example, in the development of stem cell therapies, surfaces modified with synthetic peptides can be used to support the self-renewal and differentiation of stem cells.[4] Notably, specific cell–substrate interactions observed on three-dimensional (3D) micro/nanostructures can provide the topographic cues regulating the cell spreading morphology of neurons,[8, 9] thereby promoting the level of cell differentiation for stem cells,[10–12] enhancing the transfection efficiency of cells with targeted gene expression,[13–15] and improving the capturing efficiency of circulating tumor cells (CTCs) for noninvasive blood biopsies.[16–21] In addition to these biological applications, integrating additional electrical functionality into biointerfaces has recently attracted significant interest for the digital transformation of biological signals within bioelectronics.[22, 23]Bioelectronic interfaces (BEIs) are promising intermediate layers that can enhance communication between electronics and biological systems; they can be operated to couple the flows of electrons and ions in dual directions. Accordingly, BEIs have great potential for use in electrical signaling,[22, 23] stimulation,[24–28] and electrically triggered-response toward the release and pumping of small molecules.[29–33] In the development of BEIs, organic conducting polymers [CPs; eg, polypyrrole or poly (3, 4-ethylenedioxythiophene)(PEDOT)] have been applied widely for their outstanding electrical transport properties, inherent biocompatibility, and high manufacturing flexibility. Indeed, CPs can be synthesized with a diverse array of chemical designs, such as the incorporation of various anionic dopants [eg, poly (sodium styrene sulfonate)(PSS), tosylate (TOS)][34–36] and/or the presenting of various functional side chains,[20, 37–39] thereby extending their applicability. For instance, TOS-doped PEDOT (PEDOT: TOS) materials are currently the most promising BEIs because of their high electrical stability and biocompatibility, allowing long-term cell culturing or implantation;[36] alternatively, carboxylic acid–grafted PEDOT (PEDOTAc) materials can be conjugated to a specific cell capturing agent for CTC assays.[20] Briefly, this bioconjugation process involves initial activation of the carboxylic acid groups, using N-hydroxysuccinimide (NHS) and 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC), and subsequent conjugation with streptavidin. The streptavidin-grafted PEDOT films are then incubated with biotinylated anti-EpCAM to
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