SBIR Phase I: Three-Dimensional Atom Probe Imaging for Nano-Biotechnology

这个小企业创新研究第一阶段（SBIR）项目将开发必要的手段，使局部电极原子探针（LEAP）能够提供生物芯片和其他纳米级生物技术样本的三维原子分辨率成像和元素分析。在微电子和生物技术工业中使用的硬光刻技术已经产生了纳米结构，用目前的仪器很难对其进行评估。软光刻、自组装和其他方法将从生物和有机材料中产生更小的特征。生物纳米技术的结构表征已经存在问题，因为分析电子显微镜在碳和其他低原子序数元素的定量成像方面有很大的局限性。与微电子器件的简单几何形状不同，生物技术所固有的生物大分子是三维的，这一事实使问题进一步复杂化。如果没有更适合评估三维生物有机结构的分析仪器，工业界在开发复杂的纳米级生物技术时将是“盲目的”。我们的项目旨在适应和发展LEAP对生物有机生物技术标本进行原子尺度分析的方法。在适应之后，LEAP应该能够在原子（0.2-0.5 nm）分辨率下快速成像三维结构，同时为生物芯片和其他生物大分子纳米工程设备提供合成聚合物、蛋白质和核酸的量子级元素组成。本项目所开发的技术和产品的主要商业应用将作为现有分析仪器的补充，用于测定纳米生物技术设备和部件的结构和组成。在结构生物学、细胞生物学和制药领域的学术和工业研究中设想了更多的应用。

This Small Business Innovation Research Phase I (SBIR) project will develop the means necessary to adapt the Local Electrode Atom Probe (LEAP) to provide three-dimensional atomic-resolution imaging and elemental analysis of biochips and other nanoscale biotechnological specimens. Hard lithography used in the microelectronics and biotechnology industries already produces nanostructures that are extremely difficultto evaluate with current instrumentation. Soft lithography, self-assembly, and other methods will produce even smaller features from biological and organic materials. Structural characterization for bio-nanotechnology is already problematic because analytical electron microscopy has substantial limitations in the quantitative imaging of carbon and other low atomic number elements. Further compounding this problem is the fact that unlike the simpler geometries of microelectronics devices, the biomacromolecules intrinsic to biotechnology are three-dimensional. Without analytical instrumentation better suited to the evaluation of 3-D bio-organic structures, industry will be "flying blind" as it develops complex nanoscale biotechnologies. Our project is designed to adapt and develop methods for the LEAP to perform atomic-scale analysis of bio-organic biotechnological specimens. After adaptation, LEAP should be able to rapidly image 3-D structures at atomic (0.2-0.5 nm) resolution, while providing quantum-level elemental composition of synthetic polymers, proteins, and nucleic acids critical for biochips and other biomacromolecular nanoengineered devices.The primary commercial application of the technology and the product developed in this project will be as a supplement to the existing analytical instrumentation used for the determination of structure and composition of nano-biotechnology devices and components. Additional applications are envisioned in academic and industrial research in the areas of structural biology, cell biology and pharmaceutics.