Biomolecule Nanoarray Fabrication Methods and Apparatus

描述(申请人提供)：这项研究的目标是开发新颖的、具有生物功能的纳米结构，显著提高基于芯片的分析的重复性、灵敏度和空间密度。这些纳米结构将通过开发比目前生命科学市场上可用的技术更快、更灵敏、更可靠、可能更具成本效益的下一代筛查技术，来改进从护理点诊断到基础研究中使用的基因组阵列的各种应用。为了实现规定的目标，Nanolnk将开发一种基于Dip Pen Nanolithography(Tm)(DPN(Tm))技术的图案化方法，在固体表面生成亚微米尺寸的特征。DPN方法建立在原子力显微镜(AFM)技术的基础上，可以在纳米级的空间精度的表面上以直接写入的方式均匀地沉积材料。与当前的微阵列打印技术相比，该策略提供了显著的优势，目前的微阵列打印技术在大小、形状和寡核苷酸密度以及跨微阵列载玻片的重复性方面存在点对点重现性差的问题。在第一阶段，Nanolnk通过在玻璃表面生成亚微米级的DNA纳米结构，证明了一种基于DPN技术的方法的可行性。使用现有的荧光探针技术对得到的纳米结构进行分析，以提供基准标准，以便与传统的微阵列分析进行比较。在墨水开发和图案化优化的同时，微细制造的并行多笔阵列被开发为一种更快、同时写入多个DNA墨水的手段。在第二阶段，Nanolnk将开发一个纳米阵列制造平台，包括纳米阵列仪器、具有集成微流控墨水系统的并行多笔阵列以及适当的笔和表面修饰化学，以允许使用各种生物分子进行图案化。第二阶段的工作将建立在我们第一阶段的成功基础上，并产生一种具有近期和长期商业潜力的灵活的纳米阵列制造“系统”。第三阶段的商业化合作伙伴已经确定。该研究项目将开发一种制造生物芯片微阵列的系统，该系统将为医学研究小组提供更敏感和可靠的工具，帮助他们更好地了解基因和蛋白质在人类健康中的作用。诊断和治疗疾病的方法将得到改进。

DESCRIPTION (provided by applicant): The goal of this research is to develop novel, biologically functional nanostructures that dramatically enhance the reproducibility, sensitivity, and spatial density of chip based assays. These nanostructures will improve applications ranging from point-of-care diagnosis to genomic arrays used in basic research by enabling the development of next generation screening technologies that are faster, more sensitive, more reliable, and possibly more cost effective than those presently available in the life sciences market. To accomplish the stated goals, Nanolnk will develop a patterning methodology based on Dip Pen Nanolithography (tm)(DPN(tm)) technology to generate sub-micron sized features on solid surfaces. The DPN method, built upon the technique of Atomic Force Microscopy (AFM), allows one to deposit materials uniformly in a direct-write fashion on surfaces with nanoscale spatial precision. This strategy offers significant advantages over current microarray printing technologies that suffer from poor spot to spot reproducibility in terms of size, shape, and oligonucleotide density, as well as reproducibility across microarray slides. In Phase I, Nanolnk demonstrated the feasibility of an approach based on DPN technology by generating sub-micron scale DNA nanostructures on glass surfaces. The resulting nanostructures were analyzed using existing fluorescence probe technology to provide benchmarking standards for comparison to conventional microarray assays. Concurrent with ink development and patterning optimization, microfabricated parallel multipen arrays were developed as a means for faster, simultaneous writing of multiple DNA inks. In Phase II, Nanolnk will develop a nanoarray fabrication platform consisting of a nanoarrayer instrument, parallel multipen arrays with integrated microfluidic inking systems and appropriate pen and surface modification chemistry to allow patterning with a variety of biomolecules. The Phase II effort will build on our success in Phase I and yield a flexible, nanoarray fabrication "system" with both near term and long term commercial potential. A commercialization partner has been identified for Phase III. This research project will develop a system for fabricating biochip microarrays that will offer more sensitive and reliable tools for medical research groups helping them to better understand the role of genes and proteins in human health. Improved methods of diagnosing and treating disease will result.