Mass Spectrometry Reviews最新文献

Our healthcare system provides reactive sick-care, treating patients after symptoms have appeared by prescription of generic and often suboptimal therapy. This strategy brings along high costs and high pressure which is not sustainable. Alternatively, P5 healthcare is proposed focusing on five key elements: prevention, personalization, prediction, participation, psychocognition, however, changes in current clinical care pathways are required, for which antithrombin deficiency is a prime example. Hereditary antithrombin deficiency (ATD) is a genetic disorder, for which screening is instigated after a thrombotic episode. Current diagnostic tests for ATD lack sensitivity and refinement to correctly classify patients, and generic treatments are prescribed. A molecular understanding of ATD through a molecular diagnostic test that analyzes all clinically relevant features of antithrombin is required. Here, clinically relevant molecular characteristics of antithrombin, the diversity of antithrombin (deficiency) in heath and disease, and the strengths and weaknesses of antithrombin tests are reviewed. A mass spectrometry test that molecularly characterizes a patients antithrombin proteoforms harbors the highest potential to improve the clinical pathway for ATD. Application of this MS-based test in a future enhanced clinical pathway will improve patient management and outcome through molecular characterization of antithrombin and enables the promise of P5 healthcare for ATD.

Liquid chromatography-mass spectrometry (LC-MS) has become an indispensable tool for elucidating molecular structures and quantifying diverse compounds within complex mixtures. Despite its versatility, it faces various challenges such as ion suppression, low sensitivity, analyte instability, and matrix effects, which are being overcome by different kinds of offline and online derivatization techniques to improve specificity and reduce potential interferences. In this context, considerable advancements have been made in reviewing and critically evaluating a wide range of developed methods and techniques; however, little attention has been given to post-column derivatization (PCD) in LC-MS. Therefore, this comprehensive review highlights state-of-the-art advancements in LC-MS with a specific focus on various types of chemical and physical PCD, and in-source derivatization. It also examines the latest instrumentation developments, highlights methods and influencing factors, and explores applications in food, proteomics, biology, pharmaceuticals, and environmental analysis from the past four decades. Besides, this review critically examines the role of PCD in LC-MS along with outlining its advantages and disadvantages. Furthermore, special emphasis is also made on prospects and insights for developing more versatile LC-PCD-MS techniques and in-source methodologies, to address ongoing challenges and aim to open new research avenues for analysts.

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.

Monosaccharides play a central role in metabolic networks and in the biosynthesis of glycomolecules, which perform essential functions across all domains of life. Thus, identifying and quantifying these building blocks is crucial in both research and industry. Routine methods have been established to facilitate the analysis of common monosaccharides. However, despite the presence of common metabolites, most organisms utilize distinct sets of monosaccharides and derivatives. These molecules therefore display a large diversity, potentially numbering in the hundreds or thousands, with many still unknown. This complexity presents significant challenges in the study of glycomolecules, particularly in microbes, including pathogens and those with the potential to serve as novel model organisms. This review discusses mass spectrometric techniques for the isomer-sensitive analysis of monosaccharides, their derivatives, and activated forms. Although mass spectrometry allows for untargeted analysis and sensitive detection in complex matrices, the presence of stereoisomers and extensive modifications necessitates the integration of advanced chromatographic, electrophoretic, ion mobility, or ion spectroscopic methods. Furthermore, stable-isotope incorporation studies are critical in elucidating biosynthetic routes in novel organisms.

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.

Ionization and fragmentation are at the core of mass spectrometry. But they are not necessarily separated in space, as in-source fragmentation can also occur. Here, we survey the literature published since our 2005 review on the internal energy and fragmentation in electrospray ionization sources. We present new thermometer molecules to diagnose and quantify source heating, provide tables of recommended threshold (E₀) and appearance energies (E_app) for the survival yield method, and attempt to compare the softness of a variety of ambient pressure ionization sources. The droplet size distribution and desolvation dynamics play a major role: lower average internal energies are obtained when the ions remain protected by a solvation shell and spend less time nakedly exposed to activating conditions in the transfer interface. Methods based on small droplet formation without charging can thus be softer than electrospray. New dielectric barrier discharge sources can gas-phase ionize small molecules while conferring barely more internal energy than electrospray ionization. However, the tuning of the entire source interface often has an even greater influence on ion internal energies and fragmentation than on the ionization process itself. We hope that this review will facilitate further research to control and standardize in-source ion activation conditions, and to ensure the transferability of data and research results in mass spectrometry.

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.

Chemical signaling is crucial during the insect lifespan, significantly affecting their survival, reproduction, and ecological interactions. Unfortunately, most chemical signals insects use are impossible for humans to perceive directly. Hence, mass spectrometry has become a vital tool by offering vital insight into the underlying chemical and biochemical processes in various variety of insect activities, such as communication, mate recognition, mating behavior, and adaptation (defense/attack mechanisms), among others. Here, we review different mass spectrometry-based strategies used to gain a deeper understanding of the chemicals involved in shaping the complex behaviors among insects and mass spectrometry-based research in insects that have direct impact in global economic activities.

Mass spectrometry (MS) is a powerful analytical technique that typically involves sample preparation and online analytical separation before MS detection. Traditional methods often face bottlenecks in sample preparation and analytical separation, despite the rapid detection capabilities of MS. This review explores the integration of electrokinetic manipulations directly with the ionization step to enhance MS performance, focusing on methods that eliminate or simplify sample preparation and separation processes. Techniques such as paper spray, electrophoresis in nanoelectrospray ionization (nESI) emitters, induced nESI, counterflow gradient electrofocusing, and in-syringe electrokinetics are highlighted for their ability to combine extraction and ionization in a single step, significantly improving throughput. The review delves into the use of electric fields during sample preparation and separations for these methods, demonstrating the efficiency of electrophoretic methods in driving extractions, crude separations, desalting, and enhanced sensitivity. The integration of these methods directly with MS ionization aims to enhance the analytical capabilities of mass spectrometry, while reducing costs and increasing throughput relative to traditional approaches.