Combining cryo-DNP and rapid temperature jumps at high magnetic field for a dramatic increase of sensitivity in liquid state NMR spectroscopy

将冷冻 DNP 与高磁场下的快速温度跃变相结合，可显着提高液态 NMR 光谱的灵敏度

• 批准号: EP/I036702/1
• 负责人: Walter Kockenberger
• 金额: $ 129.26万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI036702%2F1
• 关键词: Combining; cryo; DNP; rapid; temperature

Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI) are important tools in many scientific disciplines, including medical diagnostics, molecular biology, pharmaceutical and material sciences. However, due to the low energy of interaction between a strong magnetic field and the weak magnetic moment of certain nuclei such as hydrogen, the sensitivity of these techniques is usually low in comparison to other spectroscopic techniques.We therefore propose in this project to design, construct and test an instrument which will enable us to generate a much stronger signal (10^4 -10^5 times) than is possible with current systems. The instrument relies on exploiting the interaction between unpaired electrons, which also possess a magnetic moment, and the nuclei. Since the magnetic moment of electrons is much stronger (660 times) than that of the nuclei, the energy of the interaction of electrons with a strong magnetic field is much higher. This means that at low temperatures it is possible to produce a frozen sample in which almost all the electron magnetic moments are aligned with a strong, applied magnetic field, corresponding to nearly 100 % polarisation. It is possible to transfer this very high degree of polarisation to the nuclei using millimetre wave irradiation (94GHz) at a well defined frequency in a process known as dynamic nuclear polarisation (DNP). Under certain conditions the high polarisation of the nuclei is conserved during rapid melting of the frozen sample. It can then be used in liquid state NMR experiments generating a signal that is dramatically enhanced in comparison to that obtainable using conventional NMR systems.However, this approach is technically very challenging since it requires the generation of a very fast temperature jump within the sample space of the superconductive magnet. The manufacture of such an instrument requires the interaction of two different transmitters, with GHz and MHz frequencies, the development of a strategy to control the spatial distribution of the temperature within the sample during melting and the use of infrared lasers, microwave induced heating and the generation and control of extremely low cryogenic temperatures.In addition, stable radical molecules are required that carry the unpaired electron. The dynamics of the transfer of polarisation from the electrons to the nuclear spin ensemble depends on several physico-chemical properties of the spin systems. We will optimise this process to achieve very fast build-up of the nuclear polarisation. A fast build-up is needed to make repetition of these experiments possible on a reasonable time scale.The realisation of such a prototype instrument in conjuction with optimised dynamic nuclear polarisation will have strong impact on many applications of NMR spectroscopy since the generation of a much stronger NMR signal will enable a range of new and exciting experiments such as very fast spectroscopy of the interaction of different molecules during binding. The novel technology has a huge potential for applications in biomolecular NMR spectroscopy.

核磁共振波谱和核磁共振成像是医学诊断学、分子生物学、药学和材料科学等多个学科的重要工具。然而，由于强磁场和某些原子核(如氢)的弱磁矩之间的相互作用能量很低，与其他光谱技术相比，这些技术的灵敏度通常较低。因此，我们在这个项目中建议设计、建造和测试一台仪器，使我们能够产生比目前系统可能产生的更强的信号(104-105倍)。该仪器依赖于利用未配对电子和原子核之间的相互作用，未配对电子也具有磁矩。由于电子的磁矩比原子核的磁矩大得多(660倍)，所以电子与强磁场相互作用的能量要高得多。这意味着，在低温下，可以产生冻结的样品，其中几乎所有的电子磁矩都与强大的外加磁场对准，对应于近100%的极化。在被称为动态核极化(DNP)的过程中，使用毫米波辐射(94 GHz)以明确的频率将这种非常高程度的极化转移到原子核是可能的。在某些条件下，原子核的高极化在冷冻样品的快速熔化过程中是保守的。然后，它可以用于液态核磁共振实验，产生的信号比使用传统核磁共振系统获得的信号显著增强。然而，这种方法在技术上非常具有挑战性，因为它需要在超导磁体的样本空间内产生非常快的温度跳跃。这种仪器的制造需要两个频率为GHz和MHz的不同发射器相互作用，制定一种策略来控制熔化过程中样品内部的温度空间分布，并使用红外激光、微波感应加热以及极低低温温度的产生和控制。此外，还需要携带未配对电子的稳定自由基分子。从电子到核自旋系综的极化转移的动力学取决于自旋系统的几个物理化学性质。我们将优化这一过程，以实现非常快的核极化积累。为了在合理的时间范围内重复这些实验，需要快速的准备。结合优化的动态核极化实现这样的原型仪器将对核磁共振光谱的许多应用产生强烈的影响，因为产生更强的核磁共振信号将使一系列新的和令人兴奋的实验成为可能，例如在结合过程中不同分子之间的非常快速的光谱相互作用。这项新技术在生物分子核磁共振光谱学中具有巨大的应用潜力。