高灵敏、可重复性好的表面增强拉曼活性基底中尺寸小于10 纳米的热点结构的可控制备及其生物检测应用研究

Surface-enhanced Raman scattering (SERS) has shown to be an ultrasensitive real-time nondestructive technique for chemical, medical and environmental analyte especially biomolecules detection. SERS has a distinct advantage over normal Raman spectroscopy in enhancing the detection sensitivity significantly because of plenty of hot spots in the active SERS substrates. Recent experimental and theoretical results indicate that the precise control of the hot spots among the nanostructures in the regime of sub-10 nm, especially 1-3 nm is critical for the preparation of the SERS substrates with high enhancement factors. Carefully designed hot spots can become much more active and even enable the possibility of single molecule spectroscopy. However, the fabrication of reliable SERS substrates with uniformly reproducible giant signal enhancement over large substrate areas at low cost remains the major challenge of much research. The precise control of 'hot junctions' on a highly SERS-active substrate in the sub-10 nm regime is extremely difficult to obtain by existing nanofabrication methods. Ultra-thin alumina marks (UTAM) surface naon-patterning has its unique advantage in controlled fabrication of smaller-sized hot spots and biomolecule detection because of its high uniformity, easy-control fabrication, ultrahighy density nanostructure, facile and low-cost protocol. In this project, based on our previous research on UTAM surface naon-patterning technique, we will prepare five types of large area，highly active, highly uniform and reproducible SERS substrates with tunable hot spots by UTAM, and further study the high sensitivity and high selectivity for the biological sensing application. We expect this UTAM surface naon-patterning technique for controllable fabrication of active substrates with tunable hot sptos may widen the scope of SERS for sensor applications.

SERS是一种超灵敏的实时无损检测技术。SERS活性基底中拉曼信号的巨大增强与金属纳米结构中的"热点"紧密相关。将纳米结构中热点尺寸控制在10 纳米以内对获得性能可靠、增强显著的SERS活性基底至关重要。精确地设计热点能使基底活性更强，从而使单分子检测更加可行。然而，"热点"的精确控制仍然是大面积、低成本、性能可靠的SERS活性基底制备研究中很难实现的问题。超薄氧化铝模板表面纳米制备技术以其高度有序、灵活可控、超高密度、简单快速的独特优势，更适合SERS活性基底中更小热点尺寸的可控制备及生物检测的需要。本课题以SERS活性基底中热点结构的可控制备为主要研究对象，提出一种灵活简便的、精确可控的SERS活性基底制备技术，筛选信号增强显著、可重复性好、均一、稳定的金属纳米结构阵列SERS活性基底，研究其对生物小分子的检测性能的影响，以期制备性能可控的高效生物检测器件。

本项目以SERS活性基底中热点结构的可控制备为基础，结合超薄氧化铝模板（UTAM）的制备方法，特别是在UTAM传统制备技术中创新性地提出了高低温两步扩孔法，从而实现了热点尺寸可精确控制在10 纳米以内甚至5 纳米以内的灵活简便、精确可控的SERS活性基底制备技术。成功实现了高度灵敏、增强显著、可重复性好的不同结构参数的各种纳米金属结构（纳米点、纳米帽、Ni/Au 双金属、中空纳米碗、嵌入式纳米点以及双金属双重星系结构）阵列SERS活性基底的大面积、低成本制备。实现了所制备基底对常用染料分子罗丹明和结晶紫的灵敏、可重复、均一、稳定的响应测试，并完成了对生物分子葡萄糖的灵敏检测及特异性检测。同时以优化的基底结构对两种乳腺癌细胞SK-BR-3和MCF-7的响应进行了有益的探索和尝试。所取得的研究成果对SERS技术在生物、化学、医学以及环境检测等领域的应用特别是生物传感器设计和构筑方面研究的发展起到了有益的促进作用。