Biomolecule Nanoarray Fabrication Methods and Apparatus

描述（由申请人提供）：本研究的目标是开发新型的生物功能纳米结构，大大提高基于芯片的测定的再现性，灵敏度和空间密度。这些纳米结构将改善从护理点诊断到基础研究中使用的基因组阵列的应用，使下一代筛选技术的开发更快，更灵敏，更可靠，并且可能比目前生命科学市场上的技术更具成本效益。为了实现上述目标，Nanolnk将开发一种基于蘸笔纳米光刻（DPN（tm））技术的图案化方法，以在固体表面上生成亚微米尺寸的特征。基于原子力显微镜（AFM）技术的DPN方法允许以纳米级空间精度在表面上以直写方式均匀地存款材料。这种策略提供了显着的优势，目前的微阵列打印技术，从穷人的点到点的大小，形状和寡核苷酸密度方面的再现性，以及跨微阵列载玻片的再现性。在第一阶段，Nanolnk通过在玻璃表面上生成亚微米尺度的DNA纳米结构，证明了基于DPN技术的方法的可行性。使用现有的荧光探针技术分析所得的纳米结构，以提供与常规微阵列测定进行比较的基准标准。与墨水开发和图案优化同时，开发了微制造的平行多笔阵列作为更快地同时写入多种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，该平台由纳米阵列仪、具有集成微流体墨水系统的平行多笔阵列以及适当的笔和表面改性化学物质组成，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在第一阶段的成功，并产生一个灵活的，纳米阵列制造“系统”，具有短期和长期的商业潜力。已为第三阶段确定了商业化合作伙伴。该研究项目将开发一种制造生物芯片微阵列的系统，为医学研究小组提供更灵敏和可靠的工具，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.