Meeting the Sensitivity Grand Challenges in Pulsed Electron Magnetic Resonance

该仪器开发项目旨在大幅提高电子顺磁共振(EPR)光谱仪的灵敏度、时间分辨率和能力，并展示其在生物、化学、物理和材料科学领域的重大影响。支配物质基本结构和组织的基本量子力学规则之一是电子喜欢配对。然而，在许多材料中，这种配对过程留下了未配对的电子。这样的系统被称为顺磁性，例子包括自由基、多种类型的金属原子和晶体中的缺陷。任何给定的未成对电子的反应性强烈地依赖于它的局域原子环境。有些自由基活性很强，能够从附近的任何分子中撕裂电子，引发破坏性的级联反应。事实上，正是这种自由基在体内积累的损害被认为是我们衰老过程的基础，尽管身体进化了许多防御机制。测量血液中的自由基可以作为健康指标。其他准磁网可能相对稳定且非常有益。瞬时顺磁物种在大量的生物过程中参与严格控制的反应。英国化学工业的大部分依赖于使用自由基和过渡金属来启动和促进催化反应。晶体、薄膜或界面上的顺磁缺陷可以决定或强烈影响材料的电、磁、光、化学和机械性能，在英国的材料科学和电子行业中非常重要。核磁共振或核磁共振实验的灵敏度可以通过使电子自旋与局部核相互作用而显著提高。即使在没有自然产生的未配对电子的系统中，分子生物学家也开发出了在生物分子内的特定位置常规添加自由基(电子)自旋标记的方法，这些标记可以被用作“分子间谍”，以了解反应、相互作用、大规模结构和快速动力学，这是其他技术无法达到的精度。这种结构和过程的特征可以为理解疾病背后的机制和新药的开发奠定基础。研究和理解这些系统最重要的工具是脉冲电子顺磁共振。这项技术包括将顺磁样品置于大磁场中，用精心控制的快速高功率微波脉冲序列照射样品，并监测样品的响应。直到最近，人们还普遍认为，脉冲EPR仪器的灵敏度几乎没有显著提高的余地。然而，十年前，我们证明了普通测量的浓度灵敏度显著增加了15到30倍。今天，商业票据几乎但仍未迎头赶上。这个项目现在寻求进一步提高敏感度，再提高30倍。这一增长将通过利用快速电子学的最新进展以及使用我们已经在许多原理验证实验中演示的技术来修改现有的最先进的系统来实现。这将是一个重大进步，特别是对于分子生物学，因为它将首次允许使用电子磁共振在自然(细胞内)蛋白质浓度下研究自旋标记蛋白质系统。还有许多重要的电子、材料和催化系统，这些系统涉及薄膜中的顺磁中心或灵敏度最高的界面上的顺磁中心。为了最大限度地发挥仪器开发的影响，该项目与大量的应用和方法开发计划相联系，并有广泛的当地合作者和合作研究人员。

Summary This instrument development project seeks to substantially and dramatically increase the sensitivity and time resolution and capability of electron paramagnetic resonance (EPR) spectrometers and to demonstrate a major impact across biology, chemistry, physics and materials science. One of the fundamental quantum mechanical rules governing the basic structure and organisation of matter, is that electrons like to pair up. However, in many materials there are unpaired electrons left over from this pairing process. Such systems are known as paramagnetic and examples include radicals, many types of metal atoms, and defects in crystals. The reactivity of any given unpaired electron strongly depends on its local atomic environment. Some radicals are so reactive that they are able to tear electrons from any nearby molecules and initiate a destructive cascade of reactions. Indeed, it is the accumulated damage from such free radicals within the body that is believed to underlie our aging process, despite the body evolving many defense mechanisms. Measurements of free radicals in the blood can be health indicators. Other paramagnets can be relatively stable and highly beneficial. Transient paramagnetic species are involved in closely regulated reactions in huge numbers of biological processes. Much of the UK's chemical industry depends on the use of radicals and transition metals to initiate and promote catalytic reactions. Paramagnetic defects in crystals, thin films or at interfaces can determine or strongly affect a material's electronic, magnetic, optical, chemical and mechanical properties and are hugely important in the UK's material science and electronics industries. The sensitivity of NMR or MRI experiments can be dramatically increased by making electron spins interact with local nuclei.Even in systems where there are no naturally occurring unpaired electrons, molecular biologists have developed ways to routinely add free radical (electron) spin labels at specific sites within biomolecules, which can be used as "molecular spies" to understand reactions, interactions, large-scale structure and fast dynamics with a precision not possible with other techniques. Characterisation of such structures and processes can underpin the understanding of the mechanisms behind disease and the development of new drugs. The most important tool in studying and understanding these systems is pulsed electron paramagnetic resonance. This technique involves placing a paramagnetic sample in a large magnetic field and illuminating it with a carefully controlled sequence of rapid high power microwave pulses and monitoring the response of the sample. Until relatively recently, it was widely believed there was little scope to significantly improve the sensitivity of pulsed EPR instruments. Yet ten years ago we demonstrated a significant increase by a factor of between 15 and 30 in concentration sensitivity for common measurements. Today, commercial instruments have nearly but still not caught up. This project now seeks to further increase sensitivity, by another factor of 30. This increase will be achieved by taking advantage of recent advances in fast electronics and by modifying an existing state-of-the-art system using techniques that we have already demonstrated in many proof-of-principle experiments. This would be a major advance, particularly for molecular biology, as for the first time it would allow spin-labeled protein systems to be investigated at natural (in-cell) protein concentrations using electron magnetic resonance. There are also many important electronic, materials and catalytic systems, which involve paramagnetic centres in thin films or at interfaces where sensitivity is paramount.To maximise the impact of the instrument development, the project is linked to a large number of applications and methodology development programmes, with a wide range of local collaborators and co-investigators.