Biomolecular nanopatterning by electrophoretic printing lithography.
Biomolecular nanopatterning by electrophoretic printing lithography.
复制标题
通过电泳印刷光刻进行生物分子纳米图案化。
DOI：
10.1002/smll.200800850
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Chen,Yong
中科院分区：
文献类型：
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作者：
Chang,Yu;Huang,Suxian;Chen,Yong
生物分子纳米图案可以在分子水平上诱导与病毒、细菌、细胞等生物系统的可控相互作用。[1-4]小型化生物分子微米和纳米图案还可以显着提高基因组学、蛋白质组学、临床诊断和药物开发的灵敏度、通量和效率。[5-8]已经开发了各种光刻技术来制造生物分子纳米图案：电子束（e-beam）光刻可以直接在表面上形成生物分子，[9, 10] 压印光刻可以修改抗蚀剂表面以进行蛋白质附着，[11, 12] 接触印刷光刻可以将生物分子从印模转移到反应性基材上，[13, 14] 浸笔光刻可以使用扫描探针通过溶剂弯月面将生物分子输送到表面，[15] 扫描探针可以刮擦表面和移植物上的自组装单分子层[16, 17] 虽然这些光刻技术可以生成具有亚 100 nm 特征的双分子纳米图案，但电子束、浸笔和扫描探针光刻等串行光刻技术受到其点对点低速工艺的限制。接触印刷和压印光刻等并行光刻技术可以在大面积上高速生成纳米图案，但它们很难将多个生物分子集成在印模或模具的表面上，以生成具有多个不同生物分子的异质纳米图案。在这篇通讯中，我们报道了一种纳米级平版印刷技术，即电泳印刷平版印刷（EPL），其中涂有不同生物分子的带电纳米粒子被选择性地组装到纳米电极上，通过电泳沉积在印模上形成生物分子纳米图案，然后将异质生物分子纳米图案印刷到生物相容性聚合物基板上。EPL过程如方案1所示。在相对于计数器的绝缘印模表面上的纳米电极上施加电压后电极（方案 1a）中，悬浮在电解质介质中的带电纳米粒子通过电泳沉积组装并固定到纳米电极上。电泳沉积已广泛用于通过絮凝、颗粒电荷中和、电化学颗粒凝结或电双层变形将悬浮在电解质介质中的胶体纳米颗粒组装到微电极或纳米电极上。[18-25]在我们的实验中，通过选择性地向纳米电极施加适当的电势并相应地在电解质中提供涂有不同生物分子的相应纳米颗粒，可以将不同的纳米颗粒/生物分子组装到不同的纳米电极上（方案1b）。与激光打印中彩色墨粉图案化的过程类似，涂有多种不同生物分子的纳米颗粒被组装并固定到印模表面的纳米电极上，以生成异质生物分子纳米图案。然后将印模表面浸入透明基材上的可交联聚合物中，并通过紫外线使聚合物交联并固化（方案 1c）。最后，通过从印模上剥离聚合物薄膜，纳米颗粒/生物分子纳米图案完整地从印模表面转移到聚合物基底上（方案 1d）。平均直径在 20 至 60 nm 之间的带负电的聚苯乙烯纳米粒子用不同的荧光团标记，并与不同的生物分子（如 DNA、生物素和链霉亲和素）缀合（详细描述见……
Biomolecular nanopatterns can induce controllable interactions at the molecular level with biological systems such as viruses, bacteria, cells, and so on.[1–4] Miniaturized biomolecular micro-and nanopatterns can also significantly improve sensitivity, throughput, and efficiency for genomics, proteomics, clinical diagnostics, and drug development.[5–8] Various lithographic techniques have been developed to fabricate biomolecular nanopatterns: electron-beam (e-beam) lithography can directly pattern biomolecules on surfaces,[9, 10] imprint lithography can modify a resist surface for protein attachment,[11, 12] contact printing lithography can transfer biomolecules from a stamp to a reactive substrate,[13, 14] dip-pen lithography can use a scanning probe to deliver biomolecules to a surface via a solvent meniscus,[15] and scanning probes can scrape self-assembled monolayers on surfaces and graft biomolecules to form nanopatterns.[16, 17] Although bimolecular nanopatterns with sub-100-nm features can be generated by these lithographic techniques, serial lithographic techniques such as e-beam, dip-pen, and scanning probe lithography are limited by their point-to-point low-speed processes. Parallel lithographic techniques such as contact printing and imprint lithography can generate nanopatterns at high speed over large areas, but they can hardly integrate multiple biomolecules on the surface of a stamp or mold to generate heterogeneous nanopatterns with multiple distinct biomolecules. In this Communication, we report on a nanoscale lithographic technique, electrophoretic printing lithography (EPL), in which electrically charged nanoparticles coated with distinct biomolecules are selectively assembled onto nanoelectrodes to form biomolecular nanopatterns on a stamp by electrophoretic deposition, and the heterogeneous biomolecular nanopatterns are then printed onto a biocompatible polymer substrate.The EPL process is shown in Scheme 1. After applying a voltage on a nanoelectrode on an insulating stamp surface with respect to a counter electrode (Scheme 1a), the charged nanoparticles suspended in an electrolyte medium are assembled and immobilized onto the nanoelectrodes by electrophoretic deposition. Electrophoretic deposition has been used extensively to assemble colloidal nanoparticles suspended in an electrolyte medium onto micro-or nanoelectrodes by either ffocculation, particle charge neutralization, electrochemical particle coagulation, or electrical doublelayer distortion.[18–25] In our experiment, distinct nanoparticles/biomolecules can be assembled onto different nanoelectrodes by selectively applying the appropriate electrical potential to the nanoelectrodes and supplying the corresponding nanoparticles coated with distinct biomolecules in the electrolyte accordingly (Scheme 1b). Similar to the process of patterning color toners in laser printing, nanoparticles coated with multiple distinct biomolecules are assembled and immobilized onto the nanoelectrodes on the stamp surface to generate heterogeneous biomolecular nanopatterns. The stamp surface is then immersed in a crosslinkable polymer on a transparent substrate, and the polymer is cross-linked and solidified by UV light (Scheme 1c). Finally, by peeling off the polymer film from the stamp, the nanoparticle/biomolecule nanopatterns are transferred intact from the stamp surface to the polymer substrate (Scheme 1d). Negatively charged polystyrene nanoparticles with average diameters ranged between $20 and 60nm were labeled with different ffuorophores and conjugated with distinct biomolecules such as DNA, biotin, and streptavidin (as described in detail in …