Advancing 'omics analysis with a Sciex ZenoToF 7600 mass spectrometer

理解生物学的复杂性，以及为了我们的利益而进行的工程生物学，需要对广泛的生物分子进行高精度的分析。质谱法是为数不多的能够深入了解这种生物复杂性的技术之一，我们可以用质谱法生成的数据可以用来增加我们对生物系统如何工作的理解。然而，生物学中重要分子的范围令人困惑。它们可以很小，比如参与细胞内葡萄糖转化为能量的代谢物，也可以很大，比如催化化学反应生成其他生物分子的酶。它们也可以非常稳定，比如为我们体内的细胞提供支持的胶原蛋白或构成脂肪的一些成分，或者非常脆弱，比如添加到蛋白质中的许多结构，以控制它们在细胞中的活动或定位。该项目将提供新一代质谱仪，使我们能够进行复杂的分析，以确定复杂生物样品中存在的许多分子的结构，并测量其数量。这是基于质谱仪中分子碎片化方式的改进，以提供有关其结构的信息，能够区分结构上只有细微差异的分子，并提供准确的定量。该设备是第一个商用的飞行时间质谱仪，它具有电子激活离解（EAD），这是一种非常快的分子碎片化方法，因此比其他方法提供更多的结构信息，并且能够改变这种碎片化的能量。低能量EAD对于具有不稳定化学基团的分子特别有价值，因为碎片的速度确保它不仅仅是那些可见的，而高能量EAD允许非常稳定的分子碎片化。它还有一些改进，可以同时灵敏地测量小片段到大片段，这对于大型生物分子和快速准确地定量复杂混合物中的特定分子至关重要。该仪器将为曼彻斯特大学（UoM）在国家重要战略领域的许多研究项目以及与一些主要制药和生物技术公司的合作提供好处。这包括在生物技术方面的大量研究，例如在生物燃料生产和生物原料利用方面的研究，以及在为可持续化学生产开发清洁生物催化剂方面的研究。它还有利于健康生物科学，例如了解帕金森病中脂肪和脂质的利用如何变化以及炎症如何对生物分子产生不利影响，以及可持续农业和食品的生物科学，例如确定和了解食品加工过程中基于食物的过敏原的产生。这种新仪器将产生世界级的基础生物科学，例如，在分析技术和方法的发展方面，以更好地理解酶的工作方式和生物系统的功能，以及利用微生物制造新的化学物质的工程生物过程。

Understanding the complexity of biology, and engineering biology for our benefit, requires the analysis of a wide range of biomolecules with high accuracy and precision. Mass spectrometry is one of the few techniques capable of providing an insight into this biological complexity, and the data we can generate with mass spectrometry can be used to increase our understanding of how biological systems work. However, the range of molecules important in biology is bewildering. They can be very small, for example the metabolites involved in the conversion of glucose to energy in the cell, to very large, for example the enzymes that catalyse the chemical reactions that make all the other biomolecules. They can also be very stable, such as the collagen that provides the support for the cells in our body or some of the components that make up fats, or very fragile, such as many of the structures added to proteins to control their activity or localization in the cell.This project is to provide a new generation mass spectrometer that will allow us to perform the complex analysis required to confidently identify the structures of, and measure the amount of many of the molecules that are present in complex biological samples. This is based on improvements in the way that molecules are fragmented in the mass spectrometer to provide information on their structure, enable discrimination between molecules that are only subtly different in structure and provide accurate quantification. The equipment is the first commercial time of flight mass spectrometer that has electron activated dissociation (EAD), a way of fragmenting molecules that is very fast and so gives much more information on structure than other methods, and is able to vary the energy of this fragmentation. Low energy EAD is especially valuable for molecules which have labile chemical groups, as the speed of fragmentation ensures it is not just these that are seen, and high energy EAD allows fragmentation of very stable molecules. It also has improvements that allows small to large fragments to be measured sensitively at the same time, which is critical for large biomolecules and for fast and accurate quantification of specific molecules in complex mixtures.This instrument will provide benefit to many research programs at the University of Manchester (UoM) in important strategic areas for the country, and in collaboration with a number of major pharmaceutical and biotechnology companies. This includes substantial research in biotechnology, for example in biofuels production and bio-feedstock utilization, and in the development of clean biological catalysts for sustainable chemical production. It also benefits bioscience for health, for example in understanding how the utilization of fats and lipids changes in Parkinson's disease and how inflammation adversely affects biomolecules, and bioscience for sustainable agriculture and food, for example in identifying and understanding the generation of food-based allergens during food processing. The new instrument will generate world-class and underpinning bioscience, for example in the development of analytical technologies and methodologies to understand better the way enzymes work and how biological systems function, and engineering biological processes to use microorganisms to make new chemicals.