Development of a Novel MALDI Mass Spectrometer and Technology for the Generation of Multiply Charged Ions at High Sensitivity

开发新型 MALDI 质谱仪和高灵敏度多电荷离子生成技术

基本信息

批准号：
EP/L006227/1
负责人：
Rainer Cramer
金额：
$ 80.45万
依托单位：
University of Reading
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FL006227%2F1
关键词：
Development Novel MALDI Mass Spectrometer

项目摘要

Modern mass spectrometry (MS) can be compared to microscopy with its impact on analysing nature and materials down to the molecular (individual molecule) level, including the analysis of the cellular processes of life and the structure of molecules. These analytical tools have frequently been the key to major breakthroughs in science. MS in particular, has been at the forefront of recent advances in areas like biomedicine and healthcare. In this project we will develop a new instrument and the associated methodologies for another major step forward in MS and its application.MS requires the production of gas phase ions. The two major ionisation techniques in modern MS are electrospray ionisation (ESI) and matrix-assisted laser desorption/ionisation (MALDI). There are fundamental differences between these two techniques. ESI enables ion formation exclusively out of a liquid while MALDI uses predominantly solid samples. Another significant difference can be found in their ability to produce multiply charged ions. For peptides, MALDI typically generates singly charged while ESI easily provides multiply charged ions.Importantly, the production of highly charged ions is desirable as it allows the use of high-performance mass spectrometers, which typically cannot analyse the larger singly charged ions. It also facilitates more informative controlled fragmentation of the ions, thus helping to obtain further information such as their molecular structure. Consequently, there is a clear advantage of using ESI. Nonetheless, MALDI with its higher tolerance to contaminants, ease-of-operation, potential for high-speed automated analysis as well as its MS imaging capabilities makes it an ionisation technique that can cover (bio)analytical areas where ESI is less suitable. If these strengths could be combined with the analytical power of multiply charged ions, new instrumental configurations and new large-scale (bio)analyses using MALDI MS would become feasible.The proposed instrument and method development will lead to a new technology that will enable the production of stable and high yields of multiply charged MALDI ions at high sensitivity, i.e. low analyte concentration and low sample consumption. It is based on a new ion source design, using a heated ion transfer tube to transfer the produced ions into the analyser of the mass spectrometer, and novel liquid sample preparation methods, ensuring stable and high yields of ESI-like multiply charged ions. Thus, the two main disadvantages of MALDI (no/low yield of multiply charged ions and highly variable ion yield and signal quality) will be addressed within this project. Ultimately, the newly developed technology should not only become a real competitor for ESI but also open up new areas of analysis that have previously been inaccessible.In short, this project will develop a new MS technology that will significantly widen the application range of MALDI MS and thus MS in general, enabling new and more powerful analytical strategies. The project will result in a prototype instrument and methodology that can easily be commercialised. As MALDI MS is already making great strides within the (bio)analytical field it can be anticipated that this project will have significant impact in many areas from academia and industry to the public health sector and thus society at large.

可以将现代质谱（MS）与显微镜进行比较，其对分析性质和材料的影响，直至分子（单个分子）水平，包括分析生命的细胞过程和分子的结构。这些分析工具通常是科学领域重大突破的关键。特别是MS，在生物医学和医疗保健等领域的最新进展一直处于最前沿。在这个项目中，我们将开发一种新的工具，以及在MS及其应用中向前又向前迈的相关方法。MS需要生产气相离子。现代MS中的两种主要电离技术是电喷雾电离（ESI）和基质辅助激光解吸/离子化（MALDI）。这两种技术之间存在根本差异。 ESI仅由液体形成离子，而Maldi则主要使用固体样品。在产生乘电离子的能力方面可以找到另一个显着差异。对于肽，MALDI通常会单独产生充电，而ESI很容易提供带电的离子。事实上的是，高电荷离子的产生是可取的，因为它允许使用高性能的质谱仪，通常无法分析较大的单人单位离子。它还促进了更信息的离子碎片化，从而有助于获得进一步的信息，例如它们的分子结构。因此，使用ESI具有明显的优势。尽管如此，MALDI对污染物的耐受性较高，易于操作，高速自动分析的潜力以及其MS成像功能，使其成为一种电离技术，可以覆盖ESI不太合适的（BIO）分析区域。如果这些优势可以与带电离子的分析能力相结合，那么使用MALDI MS的新仪器配置和新的大规模分析（BIO）分析将变得可行。拟议的工具和方法开发将导致一种新技术，将导致一种稳定和高收益的乘积和高产量的多重型Maldi Inions以高浓度的浓缩率，即浓度低的分析，即eo.ee。它基于一种新的离子源设计，使用加热的离子转移管将产生的离子转移到质谱仪的分析仪中，并采用新型的液体样品制备方法，以确保ESI样型多重离子的稳定和高产量。因此，在本项目中将解决MALDI的两个主要缺点（无电荷离子的无/低收益率和高度可变的离子产量和信号质量）。最终，新开发的技术不仅应该成为ESI的真正竞争对手，而且还应该开放以前无法访问的新分析领域。简而言之，该项目将开发一种新的MS技术，该技术将大大扩大MALDI MS的应用范围，从而大大扩大MS的应用范围，从而实现新的和更强大的分析策略。该项目将产生一种原型工具和方法，可以轻松商业化。由于Maldi MS已经在（生物）分析领域取得了长足的进步，因此可以预见，该项目将在从学术界和行业到公共卫生部门，因此社会上的许多领域产生重大影响。