Mass Spectrometry Reviews最新文献

Gas chromatography-mass spectrometry (GC-MS) with Cold electron ionization (EI) is based on interfacing the GC and MS with a supersonic molecular beam (SMB) along with electron ionization of vibrationally cold sample compounds in the SMB in a contact-free fly-through ion source (hence the name Cold EI). Cold EI improves all the central performance aspects of GC-MS, including: a significantly extended range of compounds that are amenable for analysis, enhanced molecular ions, highly improved sample identification, faster analysis (much faster), uniform response to all analytes, greater selectivity and higher signal to noise ratios and lower limits of detection, particularly for compounds that are difficult to analyze. GC-MS with Cold EI executes the analysis of the full range of standard EI applications and most with major improvements of various metrics. Furthermore, it significantly extends the range of compounds and applications amenable for GC-MS analysis. Accordingly, it is a highly superior replacement ion source. In this review article, we describe Cold EI and its main features, discuss its benefits, and demonstrate several of its unique applications including cannabinoids analysis, synthetic organic compounds analysis, whole blood analysis for medical diagnostics, isomer distribution analysis for improved fuels and oils, and explosives analysis.

An intricate network of protein assemblies and protein-protein interactions (PPIs) underlies nearly every biological process in living systems. The organization of these cellular networks is highly dynamic and intimately tied to the genomic and proteomic landscapes of a cell. Disruptions in normal PPIs can impair cellular functions and contribute to the development of human diseases. In recent years, targeting PPIs has emerged as an attractive strategy for drug discovery. Consequently, the identification and characterization of endogenous PPIs-those occurring naturally under physiological conditions-has become crucial for unraveling the molecular mechanisms driving human pathology and for laying the groundwork for novel diagnostics and therapeutics. Owing to numerous technological advancements, mass spectrometry (MS)-based proteomics has transformed the study of PPIs at the systems-level. This review focuses on proteomics approaches that enable the characterization of physiologically relevant endogenous interactions, spanning complex-centric to structure-centric analyses. Additionally, their applications to define native PPIs in the contexts of cancer and viral infectious diseases is highlighted.

With the increasing FDA approvals of glycoprotein-based biotherapeutics including monoclonal antibodies, cytokines, and enzyme treatments, the significance of glycosylation in modulating drug efficacy and safety becomes central. This review highlights the crucial role of mass spectrometry (MS) in elucidating the glycome of biotherapeutics that feature N- and O-glycosylation, directly addressing the challenges posed by glycosylation complexity and heterogeneity. We have detailed the advancements and application of MS technologies including MALDI-TOF MS, LC-MS, and tandem MS in the precise characterization of glycoprotein therapeutics. Emphasizing MS-based strategies for detecting immunogenic glycans and ensuring batch-to-batch consistency, this review highlights targeted approaches for glycoprotein, glycopeptide, and glycan analysis tailored to meet the stringent analytical and regulatory demands of biopharmaceutical development.

Mass spectrometry (MS) has become a critical tool in the characterization of covalently modified nucleic acids. Well-developed bottom-up approaches, where nucleic acids are digested with an endonuclease and the resulting oligonucleotides are separated before MS and MS/MS analysis, provide substantial insight into modified nucleotides in biological and synthetic nucleic. Top-down MS presents an alternative approach where the entire nucleic acid molecule is introduced to the mass spectrometer intact and then fragmented by MS/MS. Current top-down MS workflows have incorporated automated, on-line HPLC workflows to enable rapid desalting of nucleic acid samples for facile mass analysis without complication from adduction. Furthermore, optimization of MS/MS parameters utilizing collision, electron, or photon-based activation methods have enabled effective bond cleavage throughout the phosphodiester backbone while limiting secondary fragmentation, allowing characterization of progressively larger (~100 nt) nucleic acids and localization of covalent modifications. Development of software applications to perform automated identification of fragment ions has accelerated the broader adoption of mass spectrometry for analysis of nucleic acids. This review focuses on progress in tandem mass spectrometry for characterization of nucleic acids with particular emphasis on the software tools that have proven critical for advancing the field.

Protein tandem mass spectrometry data are most often interpreted by matching observed mass spectra to a protein database derived from the reference genome of the sample being analyzed. In many application domains, however, a relevant protein database is unavailable or incomplete, and in such settings de novo sequencing is required. Since the introduction of the DeepNovo algorithm in 2017, the field of de novo sequencing has been dominated by deep learning methods, which use large amounts of labeled mass spectrometry data to train multi-layer neural networks to translate from observed mass spectra to corresponding peptide sequences. Here, we describe these deep learning methods, outline procedures for evaluating their performance, and discuss the challenges in the field, both in terms of methods development and evaluation protocols.

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.