Lipid and Phospholipid Profiling of Biological Samples Using MALDI Fourier Transform Mass Spectrometry

Here we describe a study of the feasibility of lipid and phospholipid (PL) profiling using matrix assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry (FTMS) for two different applications. In this work PL profiles of different mammalian tissues as well as those of whole cell organisms were examined. In particular, comparative analysis of lipid and PL profiles of tissues from mice fed different diets was done and, in another application, MALDI FTMS was used to analyze PL profiles of genetically modified Saccharomyces cerevisiae. Computational sorting of the observed ions was done in order to group the lipid and PL ions from complex MALDI spectra. The PL profiles of liver tissues from mice fed different diets showed a cross correlation coefficient of 0.2580, indicating significant dissimilarity, and revealed more than 30 significantly different peaks at the 99.9% confidence level. Histogram plots derived from the spectra of wild type and genetically modified yeast resulted in a cross correlation coefficient 0.8941 showing greater similarity, but still revealing a number of significantly different peaks. Based on these results, it appears possible to use MALDI FTMS to identify PLs as potential biomarkers for metabolic processes in whole cells and tissues.     

Fourier transform ion cyclotron resonance mass spectrometry at the true cyclotron frequency

Ion cyclotron resonance (ICR) cells provide stability and coherence of ion oscillations in crossed electric and magnetic fields over extended periods of time. Using the Fourier transform enables precise measurements of ion oscillation frequencies. These precisely measured frequencies are converted into highly accurate mass-to-charge ratios of the analyte ions by calibration procedures. In terms of resolution and mass accuracy, Fourier transform ICR mass spectrometry (FT-ICR MS) offers the highest performance of any MS technology. This is reflected in its wide range of applications. However, in the most challenging MS application, for example, imaging, enhancements in the mass accuracy of fluctuating ion fluxes are required to continue advancing the field. One approach is to shift the ion signal power into the peak corresponding to the true cyclotron frequency instead of the reduced cyclotron frequency peak. The benefits of measuring the true cyclotron frequency include increased tolerance to electric fields within the ICR cell, which enhances frequency measurement precision. As a result, many attempts to implement this mode of FT-ICR MS operation have occurred. Examples of true cyclotron frequency measurements include detection of magnetron inter-harmonics of the reduced cyclotron frequency (i.e., the sidebands), trapping field-free (i.e., screened) ICR cells, and hyperbolic ICR cells with quadrupolar ion detection. More recently, ICR cells with spatially distributed ion clouds have demonstrated attractive performance characteristics for true cyclotron frequency ion detection. Here, we review the corresponding developments in FT-ICR MS over the past 40 years.     

Evaluation of a Method for Nitrotyrosine Site Identification and Relative Quantitation Using a Stable Isotope-Labeled Nitrated Spike-In Standard and High Resolution Fourier Transform MS and MS/MS Analysis

The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues to form nitrotyrosine, and to date, the identification of nitrotyrosine sites in proteins continues to be a major analytical challenge. We have developed a method by which ¹⁵N-labeled nitrotyrosine groups are generated on peptide or protein standards using stable isotope-labeled peroxynitrite (O¹⁵NOO⁻), and the resulting standard is mixed with representative samples in which nitrotyrosine formation is to be measured by mass spectrometry (MS). Nitropeptide MS/MS spectra are filtered using high mass accuracy Fourier transform MS (FTMS) detection of the nitrotyrosine immonium ion. Given that the nitropeptide pair is co-isolated for MS/MS fragmentation, the nitrotyrosine immonium ions (at m/z = 181 or 182) can be used for relative quantitation with negligible isotopic interference at a mass resolution of greater than 50,000 (FWHM, full width at half-maximum). Furthermore, the standard potentially allows for the increased signal of nitrotyrosine-containing peptides, thus facilitating selection for MS/MS in a data-dependent mode of acquisition. We have evaluated the methodology in terms of nitrotyrosine site identification and relative quantitation using nitrated peptide and protein standards.     

Fourier Transform Mass Spectrometry: The Transformation of Modern Environmental Analyses

Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and complex environmental analyses. Two features of FTMS are responsible for changing the face of how complex analyses are accomplished. First is the ability to quickly and with high mass accuracy determine the presence of unknown chemical residues in samples. For years, the field has been limited by mass spectrometric methods that were based on knowing what compounds of interest were. Secondly, by utilizing the high resolution capabilities coupled with the low detection limits of FTMS, analysts also could dilute the sample sufficiently to minimize the ionization changes from varied matrices.     

人工神经网络用于FTMS准确质量的测定

FTMS中离子质量和测量频率之间的关系通常采用回归法实现经验公式的描述，由于离子频率的测定受许多因素影响，离子质量和测定频率之间的准确关系很难以一种公式来描述。采用无隐含层的BP网络建立了测定频率和质荷比的数学关系，提高了离子质量预测的准确度，并成功地在内标法和外标法准确质量测定中应用，对阿奇霉素的降解产物质量测定的相对误差均小于2×10^-6。     

零均值复杂噪声背景下二维谐波的三次非线性耦合分析

该文利用一种四阶时间平均矩谱,通过对原始数据取平方的办法,改变了原始信号中噪声的统计特性,首次对零均值独立噪声背景下的二维谐波的三次耦合问题给出了解决方法,文中给出了详细的理论分析和证明。由于该方法也适合于非零均值噪声下的谐波耦合问题,因此这种方法不再需要对噪声的均值、颜色和分布作任何限制。仿真结果表明了该方法的有效性。     

Characterization of polyisobutylene succinic anhydride chemistries using mass spectrometry

Representative Polyisobutylene succinic anhydride (PIBSA) samples have been studied by different MS techniques including Electrospray Ionization Fourier Transform Ion Cyclotron Resonance MS (ESI‐FTMS) (positive and negative modes), Atmospheric Pressure Chemical Ionization Fourier Transform Ion Cyclotron Resonance MS (negative mode), and Matrix‐Assisted Laser Desorption/Ionization Time‐of‐Flight (positive and negative modes). Negative ion ESI‐FTMS produces the best results. Differences between “mono‐succan” and “di‐succan” content can readily be observed. The source of the PIBSA (PIBSA‐I and PIBSA‐II processes) can be easily distinguished and the formation of methyl esters and amide derivatives can provide complementary data. The experiments have demonstrated the capabilities of mass spectrometry to detect and characterize such polymers samples. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

The development and application of matrix assisted laser desorption electrospray ionization: The teenage years

In the past 15 years, ambient ionization techniques have witnessed a significant incursion into the field of mass spectrometry imaging, demonstrating their ability to provide complementary information to matrix-assisted laser desorption ionization. Matrix-assisted laser desorption electrospray ionization is one such technique that has evolved since its first demonstrations with ultraviolet lasers coupled to Fourier transform-ion cyclotron resonance mass spectrometers to extensive use with infrared lasers coupled to orbitrap-based mass spectrometers. Concurrently, there have been transformative developments of this imaging platform due to the high level of control the principal group has retained over the laser technology, data acquisition software (RastirX), instrument communication, and image processing software (MSiReader). This review will discuss the developments of MALDESI since its first laboratory demonstration in 2005 to the most recent advances in 2021.