Dufresne M, Patterson N H, Lauzon N, Chaurand P
Université de Montréal, Montreal, QC, Canada.
Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, United States.
Adv Cancer Res. 2017;134:67-84. doi: 10.1016/bs.acr.2016.11.003. Epub 2016 Dec 27.
In the last decade, imaging mass spectrometry (IMS) has been the primary tool for biomolecular imaging. While it is possible to map a wide range of biomolecules using matrix-assisted laser desorption/ionization IMS ranging from high-molecular-weight proteins to small metabolites, more often than not only the most abundant easily ionisable species are detected. To better understand complex diseases such as cancer more specific and sensitive methods need to be developed to enable the detection of lower abundance molecules but also molecules that have yet to be imaged by IMS. In recent years, a big shift has occurred in the imaging community from developing wide reaching methods to developing targeted ones which increases sensitivity through the use of more specific sample preparations. This has been primarily marked by the advent of solvent-free matrix deposition methods for polar lipids, chemical derivatization for hormones and metabolites, and the use of alternative ionization agents for neutral lipids. In this chapter, we discuss two of the latest sample preparations which exploit the use of alternative ionization agents to enable the detection of certain classes of neutral lipids along with free fatty acids by high-sensitivity IMS as demonstrated within our lab.
在过去十年中,成像质谱(IMS)一直是生物分子成像的主要工具。虽然使用基质辅助激光解吸/电离IMS可以对从高分子量蛋白质到小代谢物的广泛生物分子进行成像,但通常检测到的往往只是最丰富、最容易电离的物种。为了更好地理解诸如癌症等复杂疾病,需要开发更特异、更灵敏的方法,以便能够检测到丰度较低的分子,以及尚未通过IMS成像的分子。近年来,成像领域发生了重大转变,从开发广泛适用的方法转向开发靶向方法,通过使用更特异的样品制备方法来提高灵敏度。这主要体现在用于极性脂质的无溶剂基质沉积方法、用于激素和代谢物的化学衍生化方法以及用于中性脂质的替代电离剂的使用等方面。在本章中,我们将讨论两种最新的样品制备方法,这些方法利用替代电离剂,通过高灵敏度IMS检测特定类别的中性脂质以及游离脂肪酸,这在我们实验室中已得到证明。