Near-Field IR Microscope For Nanoscale Chemical Imaging

描述（由申请人提供）：本项目的目标是开发一种用于扫描探针显微镜的附件，该附件能够实现高通量、无孔近场红外显微镜（ANSIM）。 该仪器的开发将使传感应用，需要表征表面上的复杂生物材料的极小区域。 拟议的近场仪器将能够执行红外吸收光谱在小于100 nm的横向空间分辨率。 ANSIM附件将被设计为小型便携式，因此该附件的复制品可能成为其他原子力显微镜（AFM）的实用附加组件。仪器开发计划有三个主要组成部分。 首先，红外（IR）量子级联激光器阵列将与用于引导IR激光进出显微镜的光学器件组装在一起。 其次，将构建多通道检测和信号处理模块，并将其与通用商用仪器集成。 第三，将测试和优化用于无孔径近场扫描红外显微镜的尖锐金属针尖的改进设计。 人造聚合物表面的红外光谱化学成像在100 nm的横向分辨率，使用无孔近场显微镜已经在初步工作中得到证明。 这项探索性建议的目标是确定是否可以获得有用的信息来成像生物分子，以及是否可以开发出其他科学家容易使用的技术。 测试测量将集中在成像肽层和它们的二级结构，主要使用IR活性酰胺带。 这将是第一次红外近场显微镜已被应用于肽和蛋白质分析，并将代表一个重要的一步，在生化成像使用扫描探针显微镜。多聚谷氨酰胺（PG）及其聚集体已被选择用于示范研究，因为1）PG具有与其二级结构相关的相对简单的IR光谱，2）PG结构与各种人体器官中不溶性蛋白质聚集体（称为原纤维）沉积相关的疾病有关。 为了治疗或预防这些疾病，需要提高观察这种不溶性聚集体的形成和沉积的能力;红外近场显微镜在这一领域可能具有相当大的影响。

DESCRIPTION (provided by applicant): The goal of this project is to develop an attachment for a scanning probe microscope that enables high throughput, apertureless, near field infrared microscopy (ANSIM). The development of this instrument will enable sensing applications that require the characterization of extremely small regions of complex biological materials on surfaces. The proposed near field instrument will be able to perform IR absorption spectroscopy at less than 100nm lateral spatial resolution. The ANSIM attachment will be designed to be small and portable, so that replicas of this attachment may become a practical add-on to other atomic force microscopes (AFMs). The instrument development program has three principal elements. First, infrared (IR) quantum cascade laser arrays will be assembled with the optics for guiding the IR laser light into and out of the microscope. Second, multi-channel detection and signal processing modules will be built and integrated with a common, commercial instrument. Third, improved designs of the sharp metal tip used in an apertureless near-field scanning infrared microscopes will be tested and optimized. IR spectroscopic chemical imaging of manmade polymeric surfaces at 100nm lateral resolution using apertureless near field microscopy has already been demonstrated in preliminary work. The goal of this exploratory proposal is to determine whether useful information can be acquired for imaging biological molecules, and whether technology that would be readily used by other scientists can be developed. The test measurements will concentrate on imaging peptide layers and their secondary structure, primarily using IR active amide bands. This would be the first time IR near field microscopy has been applied to peptide and protein analysis, and would represent a significant step forward in biochemical imaging using scanning probe microscopy. Polyglutamine (PG) and its aggregates have been chosen for demonstration studies because 1) PG has a relatively simple IR spectrum related to its secondary structure and 2) PG structures have been implicated in diseases associated with the deposition of insoluble aggregations of proteins, known as fibrils, in various human organs. To treat or to prevent such diseases, improved ability to observe the formation and the deposition of such insoluble aggregates is required; IR near field microscopy could have considerable impact in this area.