Writing with Lightning (Resubmission)

我们已经习惯了计算能力的快速发展，这是由于制造技术的不断进步，使得集成电路中电子元件的尺寸逐年减少，四十年来一直没有减弱。然而，这种计算机化的进步可能不仅限于计算机，而且可能涉及生活的许多领域，包括医学。例如，最近完成了人类基因组的测定，人类基因组是用来描述人类的一整套遗传词汇。虽然这是一个伟大的成就，但我们不理解这些单词所说的语言/它们如何指导细胞以它们的方式行事，以产生具有特定结构和功能的蛋白质？它们与疾病和衰老有什么关系？基于智能设备的新技术在推进我们的理解方面发挥着至关重要的作用。这种设备可以为查询大量数据集提供快速方法。我们的目标之一是开发一个zepto阵列，一个基于生物分子纳米级斑点阵列的系统，可以用来分析生物样本，灵敏度超过600个分子，比任何现有技术都要好100万倍。已经开发的用于电子器件制造的有效图案化技术更难应用于分子材料。在所有这样的结晶技术中的主要挑战是缺乏能够从单个分子的水平控制分子结构直到大约商业器件制造方法的当前限制100 nm的技术。在这个临界长度尺度上，没有技术能够以与单个大分子的分辨率相当的分辨率常规地操纵分子结构。该项目的目标就是开发这样一种技术。我们将通过结合利用几项最新进展并将其与新的复杂化学相结合来实现这一雄心勃勃的目标。当光线被迫通过非常小的孔时，它会发生衍射，不再形成明确的照明。然而，通过在近场工作，孔非常接近固体表面，可以避免这个问题。最近，我们表明，我们可以写非常小的结构，通过使用近场光源和合适的光敏材料。这些结构几乎和单个蛋白质分子一样小。最近人们发现，用一个金属针尖非常靠近物体表面照射，就可以照亮非常小的光点，其照射面积甚至比用孔径时还要小。然而，这还没有被探索为用于图案化分子的工具。我们将在这里测试它。光是由光子，微小的粒子组成的。有些光学过程需要同时吸收两个光子，而这对光强有很强的依赖性。通过将这些过程与金属尖端的使用相结合以引起样品的照射，我们相信我们可以进一步限制图案化过程。如果我们成功了，我们将开发出一种新的化学方法，既有精致的化学选择性，又有无与伦比的空间分辨率。

We have become accustomed to rapid advancements in computing power, and these have resulted from relentless advances in manufacturing technology that have enabled year-on-year reductions in the sizes of electronic components in integrated circuits to continue unabated for forty years. However, such advances in miniaturisation are potentially not restricted simply to computers, but may reach into many areas of life, including medicine. For example, the determination of the human genome, the complete set of genetic words from which the description of a human being is written, has recently been completed. While this is a great achievement, we do not understand the language that these words speak / how do they instruct cells to behave the way they do, to produce proteins with particular structures and functions? How are they related to disease and ageing? New technologies based on miniaturised devices have a critical role to plan in advancing our understanding. Such devices can provide rapid methods for the interrogation of huge sets of data. One of our goals is to develop a zepto-array , a system based on an array of nanoscale spots of biological molecules that could be used to analyse biological specimens with a sensitivity of better than 600 molecules, a million times better than any existing technology.The extension of miniaturisation into such areas, loosely described as molecular nanoscience, raises new and demanding challenges. The patterning techniques that have been developed so effectively for electronic device manufacture are harder to apply to molecular materials. A major challenge in all such miniaturisation techniques is the lack of techniques that enable the control of molecular structure from the level of a single molecule up to about the current limit of commercial device fabrication methods, 100 nm. In this critical length scale there is no technique capable of routinely manipulating molecular structure with a resolution comparable to that of a single macromolecule. The objective of this project is to develop just such a technique.We will achieve this ambitious objective by exploiting, in combination, several recent advances and integrating them with new and sophisticated chemistries. When light is forced to go through very small holes, it diffracts, no longer forming a well-defined illumination. However, by working in the near-field , with the hole very close to a solid surface, this problem can be avoided. Recently we showed that we could write very small structures by using near-field light sources and a suitable photosensitive material. These structures were nearly as small as a single protein molecule. It has recently been found that very small spots may be illuminated by using a metal tip held very close to a surface and shining light on it. The illuminated area may be even smaller than when an aperture is used. However, this has not been explored as a tool for patterning molecules. We will test this here. Light is made up of photons, tiny particles. Some optical processes require the absorption of two photons at once, and these have a very sharp dependence on the light intensity. By combining these processes with the use of a metal tip to cause the illumination of the sample, we believe that we can confine the patterning process even further still. If we are successful, we will have developed a new method for doing chemistry with both exquisite chemical selectivity and unparalleled spatial resolution.