Mass Spectrometry Reviews最新文献

One of the great triumphs of mass spectrometry-based peptide and protein characterization is the characterization of their modifications as most modifications have a characteristic mass shift. What happens when the modification does not change the mass of the peptide? Here, the characterization of several peptide and proteins modifications that do not involve a mass shift are highlighted. Protein and peptide synthesis on ribosomes involves L-amino acids; however, posttranslational modifications (PTMs) can convert these L-amino acids into their D-isomers. As another example, nonenzymatic PTM of aspartate leads to the formation of three different isomers, with isoaspartate being the most prevalent. Both modifications do not alter the mass of the peptide and yet can have profound impact on the physicochemical characteristics of the peptide. Several MS and ion mobility techniques are highlighted, as are other methods such as chromatography, enzymatic enrichment, and labeling. The challenges inherent to these analytical methods and prospective developments in bioinformatics and computational strategies are discussed for these zero-dalton PTMs.

Mass spectrometry imaging (MSI) technologies are widely used today to study the in situ spatial distributions for a variety of analytes. As these technologies advance, the pursuit of higher resolution in MSI has intensified. The limitation of direct desorption/ionization is its insufficient ionization, posing a constraint on the advancement of high-resolution MSI technologies. The introduction of postionization process compensates the low ionization efficiency caused by sacrificing the desorption area while pursuing high spatial resolution, resolving the conflict between high spatial resolution and high sensitivity in direct desorption/ionization method. Here, we discuss the sampling and ionization steps of MSI separately, and review the postionization methods in MSI according to three different sampling modes: laser sampling, probe sampling, and ion beam sampling. Postionization technology excels in enhancing ionization efficiency, boosting sensitivity, mitigating discrimination effect, simplifying sample preparation, and expanding the scope of applicability. These advantages position postionization technology as a promising tool for biomedical sciences, materials sciences, forensic analysis and other fields.

This review delves into the efficacy of utilizing bubbles to extract analytes into the gas phase, offering a faster and greener alternative to traditional sample preparation methods for mass spectrometry. Generating numerous bubbles in liquids rapidly transfers volatile and surface-active species to the gas phase. Recently, effervescence has found application in chemical laboratories for swiftly extracting volatile organic compounds, facilitating instantaneous analysis. In the so-called fizzy extraction, liquid matrices are pressurized with gas and then subjected to sudden decompression to induce effervescence. Alternatively, specifically designed effervescent tablets are introduced into the liquid samples. In situ bubble generation has also enhanced dispersion of extractant in microextraction techniques. Furthermore, droplets from bursting bubbles are collected to analyze non-volatile species. Various methods exist to induce bubbling for sample preparation. The polydispersity of generated bubbles and the limited control of bubble size pose critical challenges in the stability of the bubble-liquid interface and the ability to quantify analytes using bubble-based sample preparation techniques. This review covers different bubble-assisted sample preparation methods and gives practical guidance on their implementation in mass spectrometry workflows. Traditional, offline, and online approaches for sample preparation relying on bubbles are discussed. Unconventional bubbling techniques for sample preparation are also covered.

Time-of-flight mass spectrometry (TOF MS) excels in rapid and high-sensitivity analysis, making it a cornerstone of analytical chemistry. But as sample complexity explodes in omics studies, so does the need for higher resolving power to ensure accurate results. Traditional TOF instruments face a challenge: achieving high resolution often requires a very large instrument. To overcome this limitation, scientists developed alternative designs for TOF analyzers called multi-pass TOF analyzers (MPT). These MPT analyzers come in two main configurations: multi-turn (MTT) and multi-reflecting (MRT). Drawing on the authors' extensive experience, this review describes two decades of MPT advancements. It highlights the critical development of optimized analyzer designs, tracing the evolution towards mirror-based MRT instruments, generally providing superior resolution and spatial acceptance compared to MTT. While the manuscript attempts to overview MTT advances, it primarily focuses on MRT technology. Additionally, the review explores the role of orthogonal accelerators and trap pulse converters, comparing their efficiency and the dynamic range limits imposed by space charge effects. By comparing various MRT configurations and commercially available instruments, the review sets out to inform and empower researchers so they can make informed decisions about MRT mass spectrometers.

Some cancers such as glioblastoma (GBM), show minimal response to medical interventions, often only capable of mitigating tumor growth or alleviating symptoms. High metabolic activity in the tumor microenvironment marked by immune responses and hypoxia, is a crucial factor driving tumor progression. The many developments in mass spectrometry (MS) over the last decades have provided a pivotal tool for studying proteins, along with their posttranslational modifications. It is known that the proteomic landscape of GBM comprises a wide range of proteins involved in cell proliferation, survival, migration, and immune evasion. Combination of MS imaging and microscopy has potential to reveal the spatial and molecular characteristics of pathological tissue sections. Moreover, integration of MS in the surgical process in form of techniques such as DESI-MS or rapid evaporative ionization MS has been shown as an effective tool for rapid measurement of metabolite profiles, providing detailed information within seconds. In immunotherapy-related research, MS plays an indispensable role in detection and targeting of cancer antigens which serve as a base for antigen-specific therapies. In this review, we aim to provide detailed information on molecular profile in GBM and to discuss recent MS advances and their clinical benefits for targeting this aggressive disease.

Dielectric barrier discharge ionization (DBDI) sources, employing low-temperature plasma, have emerged as sensitive and efficient ionization tools with various atmospheric pressure ionization processes. In this review, we summarize a historical overview of the development of DBDI, highlighting key principles of gas-phase ion chemistry and the mechanisms underlying the ionization processes within the DBDI source. These processes start with the formation of reagent ions or metastable atoms from the discharge gas, which depends on the nature of the gas (helium, nitrogen, air) and on the presence of water vapor or other compounds or dopants. The processes of ionizing the analyte molecules are summarized, including Penning ionization, electron transfer, proton transfer and ligand switching from secondary hydrated hydronium ions. Presently, the DBDI-MS methods face a challenge in the accurate quantification of gaseous analytes, limiting its broader application in biological, environmental, and medical realms where relative quantification using standards is inherently complex for gaseous matrices. Finally, we propose future avenues of research to enhance the analytical capabilities of DBDI-MS.

Epitranscriptomics is a rapidly evolving field that explores chemical modifications in RNA and how they contribute to dynamic and reversible regulations of gene expression. These modifications, for example, N⁶-methyladenosine (m⁶A), are crucial in various RNA metabolic processes, including splicing, stability, subcellular localization, and translation efficiency of mRNAs. Mass spectrometry-based proteomics has become an indispensable tool in unraveling the complexities of epitranscriptomics, offering high-throughput, precise protein identification, and accurate quantification of differential protein expression. Over the past two decades, advances in mass spectrometry, including the improvement of high-resolution mass spectrometers and innovative sample preparation methods, have allowed researchers to perform in-depth analyses of epitranscriptomic regulations. This review focuses on the applications of bottom-up proteomics in the field of epitranscriptomics, particularly in identifying and quantifying epitranscriptomic reader, writer, and eraser (RWE) proteins and in characterizing their functions, posttranslational modifications, and interactions with other proteins. Together, by leveraging modern proteomics, researchers can gain deep insights into the intricate regulatory networks of RNA modifications, advancing fundamental biology, and fostering potential therapeutic applications.

Complex organic mixtures are found in many areas of research, such as energy, environment, health, planetology, and cultural heritage, to name but a few. However, due to their complex chemical composition, which holds an extensive potential of information at the molecular level, their molecular characterization is challenging. In mass spectrometry, the ionization step is the key step, as it determines which species will be detected. This review presents an overview of the main ionization sources employed to characterize these kinds of samples in Fourier transform mass spectrometry (FT-MS), namely electrospray (ESI), atmospheric pressure photoionization (APPI), atmospheric pressure chemical ionization (APCI), atmospheric pressure laser ionization (APLI), and (matrix-assisted) laser desorption ionization ((MA)LDI), and their complementarity in the characterization of complex organic mixtures. First, the ionization techniques are examined in the common direct introduction (DI) usage. Second, these approaches are discussed in the context of coupling chromatographic techniques such as gas chromatography, liquid chromatography, and supercritical fluid chromatography.

Nucleic acids are fundamental biological molecules that encode and convey genetic information within living organisms. Over 150 modifications have been found in nucleic acids, which are involved in critical biological functions, including regulating gene expression, stabilizing nucleic acid structure, modulating protein translation, and so on. The dysregulation of nucleic acid modifications is correlated with many diseases such as cancers and neurological disorders. However, it is still challenging to simultaneously characterize and quantify diverse modifications using traditional genomic methods. Mass spectrometry (MS) has served as a crucial tool to solve this issue, and can directly identify the modified species through their distinct mass differences compared to the canonical ones and provide accurate quantitative information. This review surveys the history of nucleic acid modification discovery, advancements in MS-based methods, nucleic acid sample preparation, and applications in biological and medical research. We expect the high-throughput and valuable quantitative information from MS analysis will be more broadly applied to studying nucleic acid modification status in different pathological conditions, which is key to filling gaps in traditional genomics and transcriptomics research and enabling researchers to gain insights into epigenetics and epitranscriptomics.

The exploration of protein structure and function stands at the forefront of life science and represents an ever-expanding focus in the development of proteomics. As mass spectrometry (MS) offers readout of protein conformational changes at both the protein and peptide levels, MS-based structural proteomics is making significant strides in the realms of structural and molecular biology, complementing traditional structural biology techniques. This review focuses on two powerful MS-based techniques for peptide-level readout, namely limited proteolysis-mass spectrometry (LiP-MS) and cross-linking mass spectrometry (XL-MS). First, we discuss the principles, features, and different workflows of these two methods. Subsequently, we delve into the bioinformatics strategies and software tools used for interpreting data associated with these protein conformation readouts and how the data can be integrated with other computational tools. Furthermore, we provide a comprehensive summary of the noteworthy applications of LiP-MS and XL-MS in diverse areas including neurodegenerative diseases, interactome studies, membrane proteins, and artificial intelligence-based structural analysis. Finally, we discuss the factors that modulate protein conformational changes. We also highlight the remaining challenges in understanding the intricacies of protein conformational changes by LiP-MS and XL-MS technologies.