NANOSCOPE: looking inside a living cell with nanoscale resolution

观测仪器分辨率的提高是推动科学技术发展的主要因素之一。光学、电子和扫描显微镜促进了生物学、医学、地质学、化学、材料研究和物理领域的无数重大发现，而这些仪器现在被常规用于医院、研究和工业实验室。尽管激光的广泛应用导致了许多高分辨率非线性光学技术的发展，但这些技术仅适用于狭窄类别的样品，并且需要应用高且往往具有破坏性的光强水平。电子显微镜可以提供高分辨率，但活细胞无法在所需的真空、强电子束或有时必要的样品金属化下存活。高分辨率隧道显微镜和光学扫描显微镜(SNOM)无法在不破坏活物体的情况下看到它的内部切片--或者实际上是任何物体--它们的运行依赖于距离被成像特征几纳米处的探测器的存在。因此，到目前为止，利用低强度光的亚波长分辨率而不依赖于特定的分子吸收共振来无损地观察活细胞或微小生物物体内部是不可能的。在过去的几年里，我们见证了由教授提出的光学超分辨率的新概念的显著发展。约翰·彭德利爵士和维克多·维塞拉戈。它基于一种负折射率材质，该材质使光线以与正常介质相反的方向折射。虽然这项技术已经在原理上得到了验证，但要开发出适用于负折射率超透镜的光学负折射率材料，还需要多年的工作才能克服纳米制造工艺的局限性和损耗。在这里，我们建议开发一种替代Pendry-Veselago超级透镜的技术，使亚波长成像成为可能。我们的概念围绕着2006年发表的一项了不起的理论发现：教授。迈克尔·贝里爵士和桑杜·波佩斯库(布里斯托尔大学和惠普实验室)预测，一个设计得当的光栅结构可以产生亚波长局域光，将几个波长的光从结构传播到远场。他们将这种效应与这样一个事实相关联，即带限函数能够以任意速度比它们所包含的最高傅立叶分量更快地振荡，这种现象被称为超级振荡。这提供了一个非常重要的机会：原则上，可以创造一种分辨率远远超过波长限制的光学仪器，并且在不显影负折射率材料的情况下，使用距离透镜几十微米的样品进行操作。最近，我们团队展示了一种远场亚波长聚光器，这是一种经过适当设计的纳米孔阵列，可以产生光学超级振荡，并将相干辐射聚焦到亚瑞利分辨率的光斑中。这为我们的提议提供了基础，这将给英国科学提供一个难得的机会来开发诞生于这个国家的新技术。拟议研究的主要目标是在超振荡概念发展的基础上开发新一代非侵入性超分辨率光学技术(纳米显微镜)，并展示纳米仪器的使用，希望对活细胞内部甚至单个生物大分子进行成像。这项技术还将为捕捉和操纵极小的物体提供新的机会，例如在活细胞内或检测纳米颗粒在光学景观上的运动。除了生物应用，该项目将对所有类型的成像应用和光刻高密度组件集成产生巨大影响。

The increase in resolution of observational instruments is one of the main drivers of science and technology. Optical, electron and scanning microscopy have facilitated an uncountable number of key discoveries in biology, medicine, geology, chemistry, materials research and physics, while these instruments are now routinely used in hospitals, research and industrial laboratories. Although the wide application of lasers has led to the development of a number of high-resolution nonlinear optical techniques, these techniques only work with narrow classes of specimens and require the application of high and often destructive light intensity levels. Electron microscopy can provide high resolution, but living cells cannot survive the required vacuum, exposure to intense electron beams or sometimes necessary sample metallization. High resolution tunnelling and optical scanning microscopes (SNOM) are not capable of seeing internal sections of a living object - or indeed any object - without destroying it: their operation depends on the presence of probes a few nanometres from the feature being imaged. Therefore, it has not been possible so far to look inside a living cell or small biological object non-destructively with sub-wavelength resolution using low intensity light and without dependence on specific molecular absorption resonances.In the last few years we have witnessed the remarkable development of a new concept of optical super-resolution, proposed by Profs. Sir John Pendry and Victor Veselago. It is based on a negative-index material that refracts light in the opposite direction to normal media. Although the technology has been proved in principle, the development of a suitable optical negative index material for the negative index super-lens will require many years of work to overcome limitations of the nano-fabrication process and losses. Here we propose to develop a technology ALTERNATIVE to the Pendry-Veselago super-lens that will make possible sub-wavelength imaging. Our concept centres around a remarkable theoretical discovery published in 2006: Profs. Sir Michael Berry and Sandu Popescu (Bristol University and HP Laboratories) predicted that a properly designed grating structure could create sub-wavelength localisations of light that propagate several wavelengths away from the structure, into the far-field. They relate this effect to the fact that band-limited functions are able to oscillate arbitrarily faster than the highest Fourier components they contain, a phenomenon known as super-oscillation. This gives an opportunity of colossal importance: in principle it is possible to create an optical instrument with resolution far exceeding the wavelength limit and operating with specimens located a few tens of microns away from the lens without developing negative index materials. Recently our group demonstrated a far-field subwavelength concentrator of light, a nanolens which is an appropriately designed array of nano-holes that creates optical super-oscillations and focuses coherent radiation into a sub-Rayleigh resolution spot. This provides the foundation for our proposal that will give the UK science an exceptional opportunity to develop a new technology which was born in this country. The main goal of the proposed research is to develop a new generation of non-invasive super-resolution optical technologies (nanoscope) based on the development of the super-oscillation concept and to demonstrate the use of nanoscope instruments with the hope of imaging the inside of a living cell and perhaps a single large bio-molecule. The technique will also provide new opportunities for trapping and manipulating extremely small objects, for instance inside a living cell or detecting the motion of nanoparticles on optical landscapes. Beyond the biological applications this project will have a colossal impact on all types of imaging application and on lithography high-density component integration.