NER: Charge Writing for Nano-Assembly of Bio-Molecules on Artificial Surfaces

对亚微米分子结构的尺寸、形状和组成的操纵和识别的科学和商业兴趣正在增加。在医疗诊断、化学识别和表面催化等领域，对纳米级组装和制造的需求是显而易见的。人造表面的性质决定了医疗植入物的生物相容性、生物反应器的化学反应动力学以及生物传感器响应的分子识别和特异性。表面研究仪器的发展，特别是扫描探针显微镜（SPM）技术的发明，现在已经有可能收集不仅是形态学信息，而且表面蛋白质或配体受体结合反应的热力学数据。目前，扫描探针显微镜在生物学中的广泛应用似乎受到了在扫描过程中将有机分子固定在平坦基底上的困难的阻碍。此外，如果分子纳米组装在未来变得普遍，将需要纳米机械相当于一个夹子。本提案旨在探索自上而下和自下而上的方法相结合的目的是“证明一个概念”制造纳米尺度的分子结构。首先，分子组装的靶位点将被定义（自上而下阶段），然后分子自组装到这些位点上（自下而上阶段）。靶位点将由使用SPM探针的称为“电荷写入”的技术的局部注入电荷组成。由于静电力为许多化学和生物反应提供了“对接点”，因此可以合理地假设这种自然过程的模拟可以用于纳米组装。将电荷图案“写入”到衬底上的想法是纳米组装的一种明显的初始方法，最容易通过扫描探针显微镜实现。具体而言，本研究将（1）证明使用表面（界面）带电模板进行纳米级组装和制造的可行性。 （2）确定表面电荷分布对目标大分子结合和构象的影响。(3)量化有序效应，并将实验数据与电荷-大分子相互作用的理论模型相关联。（4）研究基于电子束光刻的组装工艺的放大。 概述的研究将积极涉及两名研究生，并将PI（NSF CAREER）现有的微尺度静电组装研究扩展到纳米尺度。研究结果将在部门间生物传感器课程中传播，该课程目前正在由PI和Co-PI开发。该补助金还将为女性，美洲原住民或西班牙裔等代表性不足的少数民族工程专业学生提供研究机会，占授予的MS和博士学位总数的15.6%。所概述的研究的跨学科性质将通过参与样品制备和数据分析为高年级本科生提供教育机会。最后但并非最不重要的是，将通过PI与当地高科技材料研究公司（www.mercorp.com）的持续合作探索商业化机会。

Scientific and commercial interest in the manipulation and identification of size, shape, and composition of sub-micrometer molecular structures is increasing. The need for nano-scale assembly and manufacturing is apparent in areas such as medical diagnostics, chemical recognition, and surface catalysis. The properties of man-made surfaces determine the biocompatibility of medical implants, the kinetics of chemical reactions of bioreactors, and the molecular recognition and specificity of the response of biosensors. Advances in the development of instrumentation for surface studies, and especially the invention of scanning-probe microscopy (SPM) techniques, have now made it possible to gather not only morphological information but also thermodynamic data on surface-protein or ligand-receptor binding reactions. At present the widespread use of scanning-probe microscopy in biology seems to be hindered by the difficulty of holding organic molecules onto a flat substrate during scanning. Further, if molecular nano-assembly is to become widespread in the future, the nano-mechanical equivalent of a clamp will be needed.This proposal is aimed at exploring a combination of the top-down and bottom-up approaches for the purpose of "proving a concept" for manufacturing nano-scale molecular structures. First, target sites for molecular assembly will be defined (top-down phase), followed by molecular self-assembly onto these sites (bottom-up phase). The target sites will consist of a locally injected charge using a technique known as "charge writing" with SPM probes. Since electrostatic forces provide "docking sites" for many chemical and biological reactions, it is reasonable to assume that simulation of this natural process could be used for nano-assembly. The idea of 'writing' a charge pattern onto a substrate is an obvious initial approach to nano-assembly, most easily accomplished via scanning-probe microscopy. Specifically, this study will (1) Demonstrate the feasibility of using surface (interfacial) charged templates for nano-scale assembly and manufacturing. (2)Determine the effect of the surface charge distribution on the binding and conformation of the target macromolecules. (3) Quantify the ordering effects and correlate the experimental data with theoretical models of the charge-macromolecule interactions.(4)Investigate a scale-up of the assembly process based on e-beam lithography. The outlined research will actively involve two graduate students and will extend the existing micro-scale electrostatic assembly research of the PI (NSF CAREER) to the nanometer scale. The results of the research will be disseminated in the interdepartmental curriculum on bio-sensors, currently under development by the PI and the Co-PI. This grant will also provide research opportunities to under-represented minority engineering students such as female, Native Americans or Hispanics, constituting 15.6% of the total number of MS and PhD degrees awarded. The interdisciplinary nature of the outlined research will provide educational opportunities for senior-year undergraduate students through participation in sample preparation and data analysis. Finally but not least commercialization opportunities will be explored through the ongoing collaboration of the PI with a local high-tech materials research company (www.mercorp.com).