Writing with Lightning (Resubmission)

我们已经习惯了计算能力的快速进步，这是制造技术不断进步的结果，使得集成电路中电子元件的尺寸逐年缩小40年来一直没有减弱。然而，这种微型化方面的进步可能不仅限于计算机，还可能涉及生活的许多领域，包括医学。例如，人类基因组的确定最近已经完成，人类基因组是用来书写对人类的描述的完整的遗传词集。虽然这是一项伟大的成就，但我们并不理解这些单词所说的语言/它们如何指示细胞按照它们的方式行事，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何关系？基于微型化设备的新技术在计划推进我们的理解方面发挥着关键作用。这样的设备可以为询问海量数据提供快速方法。我们的目标之一是开发Zepto阵列，这是一种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。微型化扩展到这类领域，大致被称为分子纳米科学，提出了新的和艰巨的挑战。已经发展得如此有效地用于电子设备制造的图案化技术，更难应用于分子材料。所有这些小型化技术中的一个主要挑战是缺乏能够控制分子结构的技术，从单个分子的水平到大约当前商业器件制造方法的极限，100 nm。在这个关键的长度范围内，没有一种技术能够常规地操纵分子结构，其分辨率可与单个大分子的分辨率相媲美。这个项目的目标就是开发这样一种技术。我们将通过结合几个最新的进展并将它们与新的和复杂的化学相结合来实现这一雄心勃勃的目标。当光线被迫穿过非常小的小孔时，它就会绕射，不再形成清晰的照明。然而，通过在近场工作，在洞非常接近固体表面的情况下，这个问题可以避免。最近，我们展示了通过使用近场光源和合适的光敏材料，我们可以写出非常小的结构。这些结构几乎和单个蛋白质分子一样小。最近发现，通过使用非常靠近表面的金属尖端并在其上照射，可以照亮非常小的斑点。照明面积可能比使用光圈时更小。然而，作为构图分子的工具，这还没有被探索过。我们将在这里测试这一点。光是由光子、微小粒子组成的。有些光学过程需要一次吸收两个光子，这与光强度有很大的依赖关系。通过将这些过程与金属针尖的使用相结合来使样品发光，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，既具有精致的化学选择性，又具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.