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Journal of Proteome Research Oct 2023We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data-independent acquisition, the Thermo Scientific...
We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data-independent acquisition, the Thermo Scientific Orbitrap Astral mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific Orbitrap mass spectrometers, which have long been the gold standard for high-resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high-quality quantitative measurements across a wide dynamic range. We also use a newly developed extracellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5000 plasma proteins in a 60 min gradient with the Orbitrap Astral mass spectrometer.
Topics: Proteomics; Mass Spectrometry; Peptides; Proteome; Blood Proteins
PubMed: 37683181
DOI: 10.1021/acs.jproteome.3c00357 -
Analytical Chemistry Oct 2022In this work, we have developed a paper-based microfluidic device capable of remote biofluid collection followed by an analysis of the dried clinical samples using a...
In this work, we have developed a paper-based microfluidic device capable of remote biofluid collection followed by an analysis of the dried clinical samples using a miniature mass spectrometer. We have evaluated a portable mass spectrometer as a possible surveillance platform by analyzing the clinical malaria samples (whole blood) collected from Ghana. We synthesized pH-sensitive ionic probes and coupled them with monoclonal antibodies specific to the histidine-rich protein 2 (HRP2) malaria antigen. We then used the antibody-ionic probe conjugates in a paper-based immunoassay to capture HRP2 antigen from untreated whole blood. After the immunoassay, the bound ionic probes were cleaved, and the released mass tags were analyzed through an on-chip paper spray mass spectrometry strategy. During process optimization, we determined the detection limit for HRP2 in untreated human serum to be 0.216 nmol/L when using the miniature mass spectrometer. This sensitivity is comparable to the World Health Organization's suggested threshold of 0.227 nmol/L for HRP2, proving that our method will be applicable to diagnose symptomatic malaria infection (≥200 parasites per μL blood). The paper device can be stored at room temperature for at least 25 days without affecting the clinical outcome, with each stored paper chip offering good repeatability and reproducibility (RSD = 4-12%). The stability and sensitivity of the developed paper-based immunoassay platform will allow miniature mass spectrometers to be used for point-of-care malaria detection as well as in large-scale surveillance screening to aid eradication programs.
Topics: Antibodies, Monoclonal; Antigens, Protozoan; Histidine; Humans; Immunoassay; Malaria; Malaria, Falciparum; Mass Spectrometry; Plasmodium falciparum; Protozoan Proteins; Reproducibility of Results
PubMed: 36195476
DOI: 10.1021/acs.analchem.2c03105 -
Advances in Chronic Kidney Disease Nov 2010Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass... (Review)
Review
Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass spectrometer and its application in analyzing biological samples. Our need to understand both the identity of proteins and their abundance has led to improvements in the ability of mass spectrometers (such as with the use of the LTQ-Orbitrap mass spectrometer) to analyze complex (tryptic) peptide mixtures with high sensitivity and high mass accuracy in a high-throughput manner. Unsurprisingly, this occurred coincidentally with dramatic improvements in our understanding of CKD, the mechanisms through which CKD progresses, and the development of candidate CKD biomarkers. This review attempts to present a basic framework for the operational components of mass spectrometers, basic insight into how they are used in renal research, and a discussion on CKD research related to mass spectrometry.
Topics: Biomarkers; Chromatography, Liquid; Humans; Mass Spectrometry; Proteins; Renal Insufficiency, Chronic
PubMed: 21044768
DOI: 10.1053/j.ackd.2010.09.003 -
Analytical Chemistry Sep 2020Photoactivation and photodissociation have long proven to be useful tools in tandem mass spectrometry, but implementation often involves cumbersome and potentially...
Photoactivation and photodissociation have long proven to be useful tools in tandem mass spectrometry, but implementation often involves cumbersome and potentially dangerous configurations. Here, we redress this problem by using a fiber-optic cable to couple an infrared (IR) laser to a mass spectrometer for robust, efficient, and safe photoactivation experiments. Transmitting 10.6 μm IR photons through a hollow-core fiber, we show that such fiber-assisted activated ion-electron transfer dissociation (AI-ETD) and IR multiphoton dissociation (IRMPD) experiments can be carried out as effectively as traditional mirror-based implementations. We report on the transmission efficiency of the hollow-core fiber for conducting photoactivation experiments and perform various intact protein and peptide analyses to illustrate the benefits of fiber-assisted AI-ETD, namely, a simplified system for irradiating the two-dimensional linear ion trap volume concurrent with ETD reactions to limit uninformative nondissociative events and thereby amplify sequence coverage. We also describe a calibration scheme for the routine analysis of IR laser alignment and power through the fiber and into the dual cell quadrupolar linear ion trap. In all, these advances allow for a more robust, straightforward, and safe instrumentation platform, permitting implementation of AI-ETD and IRMPD on commercial mass spectrometers and broadening the accessibility of these techniques.
Topics: Animals; Calibration; Cattle; Horses; Lasers; Mass Spectrometry; Myoglobin; Optical Fibers; Peptides; Photochemical Processes; Ubiquitin
PubMed: 32786458
DOI: 10.1021/acs.analchem.0c02087 -
Molecules (Basel, Switzerland) Aug 2021Many of the current innovations in instrument design have been focused on making them smaller, more rugged, and eventually field transportable. The ultimate application... (Review)
Review
Many of the current innovations in instrument design have been focused on making them smaller, more rugged, and eventually field transportable. The ultimate application is obvious, carrying the instrument to the field for real time sample analysis without the need for a support laboratory. Real time data are priceless when screening either biological or environmental samples, as mitigation strategies can be initiated immediately upon the discovery that contaminant metals are present in a location they were not intended to be. Additionally, smaller "handheld" instruments generally require less sample for analysis, possibly increasing sensitivity, another advantage to instrument miniaturization. While many other instruments can be made smaller just by using available micro-technologies (e.g., eNose), shrinking an ICP-MS or AES to something someone might carry in a backpack or pocket is now closer to reality than in the past, and can be traced to its origins based on a component-by-component evaluation. While the optical and mass spectrometers continue to shrink in size, the ion/excitation source remains a challenge as a tradeoff exists between excitation capabilities and the power requirements for the plasma's generation. Other supporting elements have only recently become small enough for transport. A systematic review of both where the plasma spectrometer started and the evolution of technologies currently available may provide the roadmap necessary to miniaturize the spectrometer. We identify criteria on a component-by-component basis that need to be addressed in designing a miniaturized device and recognize components (e.g., source) that probably require further optimization. For example, the excitation/ionization source must be energetic enough to take a metal from a solid state to its ionic state. Previously, a plasma required a radio frequency generator or high-power DC source, but excitation can now be accomplished with non-thermal (cold) plasma sources. Sample introduction, for solids, liquids, and gasses, presents challenges for all sources in a field instrument. Next, the interface between source and a mass detector usually requires pressure reduction techniques to get an ion from plasma to the spectrometer. Currently, plasma mass spectrometers are field ready but not necessarily handheld. Optical emission spectrometers are already capable of getting photons to the detector but could eventually be connected to your phone. Inert plasma gas generation is close to field ready if nitrogen generators can be miniaturized. Many of these components are already commercially available or at least have been reported in the literature. Comparisons to other "handheld" elemental analysis devices that employ XRF, LIBS, and electrochemical methods (and their limitations) demonstrate that a "cold" plasma-based spectrometer can be more than competitive. Migrating the cold plasma from an emission only source to a mass spectrometer source, would allow both analyte identification and potentially source apportionment through isotopic fingerprinting, and may be the last major hurdle to overcome. Finally, we offer a possible design to aid in making the cold plasma source more applicable to a field deployment.
PubMed: 34443348
DOI: 10.3390/molecules26164761 -
Journal of Separation Science Jan 2022Capillary electrophoresis coupled online with mass detection is a modern tool for analyzing wide ranges of compounds in complex samples, including urine. Capillary... (Review)
Review
Capillary electrophoresis coupled online with mass detection is a modern tool for analyzing wide ranges of compounds in complex samples, including urine. Capillary electrophoresis with mass spectrometry allows the separation and identification of various analytes spanning from small ions to high molecular weight protein complexes. Similarly to the much more common liquid chromatography-mass spectrometry techniques, the capillary electrophoresis separation reduces the complexity of the mixture of analytes entering the mass spectrometer resulting in reduced ion suppression and a more straightforward interpretation of the mass spectrometry data. This review summarizes capillary electrophoresis with mass spectrometry studies published between the years 2017 and 2021, aiming at the determination of various compounds excreted in urine. The properties of the urine, including its diagnostical and analytical features and chemical composition, are also discussed including general protocols for the urine sample preparation. The mechanism of the electrophoretic separation and the instrumentation for capillary electrophoresis with mass spectrometry coupling is also included. This review shows the potential of the capillary electrophoresis with mass spectrometry technique for the analyses of different kinds of analytes in a complex biological matrix. The discussed applications are divided into two main groups (capillary electrophoresis with mass spectrometry for the determination of drugs and drugs of abuse in urine and capillary electrophoresis with mass spectrometry for the studies of urinary metabolome).
Topics: Animals; Electrophoresis, Capillary; Humans; Mass Spectrometry; Metabolomics; Pharmaceutical Preparations; Substance Abuse Detection; Urine
PubMed: 34538010
DOI: 10.1002/jssc.202100621 -
Journal of Chromatography. A Feb 2015Microfluidic devices offer great advantages in integrating sample processes, minimizing sample and reagent volumes, and increasing analysis speed, while mass... (Review)
Review
Microfluidic devices offer great advantages in integrating sample processes, minimizing sample and reagent volumes, and increasing analysis speed, while mass spectrometry detection provides high information content, is sensitive, and can be used in quantitative analyses. The coupling of microfluidic devices to mass spectrometers is becoming more common with the strengths of both systems being combined to analyze precious and complex samples. This review summarizes select achievements published between 2010 and July 2014 in novel coupling between microfluidic devices and mass spectrometers. The review is subdivided by the types of ionization sources employed, and the different microfluidic systems used.
Topics: Mass Spectrometry; Microfluidic Analytical Techniques; Microfluidics
PubMed: 25458901
DOI: 10.1016/j.chroma.2014.10.039 -
The Journal of Venomous Animals and... 2022The word venomics was coined to acknowledge the studies that use omics to investigate venom proteins and peptides. Venomics has evolved considerably over the last 20...
The word venomics was coined to acknowledge the studies that use omics to investigate venom proteins and peptides. Venomics has evolved considerably over the last 20 years. The first works on scorpion or spider venomics were published in the early 2000's. Such studies relied on peptide mass fingerprinting (PMF) to characterize venom complexity. After the introduction of new mass spectrometers with higher resolution, sensitivity and mass accuracy, and the next-generation nucleotide sequencing, the complexity of data reported in research on scorpion and spider venomics increased exponentially, which allowed more comprehensive studies. In the present review article, we covered key publications on scorpion venomics and spider venomics, presenting historical grounds and implemented technologies over the last years. The literature presented in this review was selected after searching the PubMed database using the terms "(scorpion venom) AND (proteome)" for scorpion venomics, and "(spider venom) AND (proteome)" for publications on spider venomics. We presented the key aspects related to proteomics in the covered papers including, but not restricted to, the employed proteomic strategy (i.e., PMF, two-dimensional gel electrophoresis, shotgun/bottom-up and/or top-down/peptidome), and the type of mass spectrometer used. Some conclusions can be drawn from the present study. For example, the scorpion genus is the most studied concerning venomics, followed by ; whereas for spiders the studied genera were found more equally distributed. Another interesting conclusion is the lack of high throughput studies on post-translational modifications (PTMs) of scorpion and spider proteins. In our opinion, PTMs should be more studied as they can modulate the activity of scorpion and spider toxins.
PubMed: 35291269
DOI: 10.1590/1678-9199-JVATITD-2021-0034 -
Bioengineering (Basel, Switzerland) Sep 2023Quadrupole mass spectrometers (QMS) are widely used for clinical diagnosis and chemical analysis. To obtain the best experimental results, mass spectrometers must be...
Quadrupole mass spectrometers (QMS) are widely used for clinical diagnosis and chemical analysis. To obtain the best experimental results, mass spectrometers must be calibrated to an ideal setting before use. However, tuning the current QMS is challenging. Traditional tuning techniques possess low automation levels and rely primarily on skilled engineers. Therefore, in this study, we propose an innovative auto-tuning algorithm for QMS based on the improved particle swarm optimization (PSO) algorithm to automatically find the optimal solution of QMS parameters and make the QMS reach the optimal state. The improved PSO algorithm is combined with simulated annealing, multiple inertia weights, dynamic boundaries, and other methods to prevent the traditional PSO algorithm from the issue of a local optimal solution and premature convergence. According to the characteristics of the mass spectrum peaks, a termination function is proposed to simplify the termination conditions of the PSO algorithm and further improve the automation level of the mass spectrometer. The results of auto-calibration testing of resolution and mass axis show that both resolution and mass axis calibration could effectively meet the requirements of mass spectrometry experiments. By the experiment of auto-optimization testing of lens and ion source parameters, these parameters were all in the vicinity of the optimal solution, which achieved the expected performance. Through numerous experiments, the reproducibility of the algorithm was established as meeting the auto-tuning function of the QMS. The proposed method can automatically tune the mass spectrometer from its non-optimal condition to the optimal one, which can effectively reduce the tuning difficulty of QMS.
PubMed: 37760181
DOI: 10.3390/bioengineering10091079 -
Journal of the American Society For... Feb 2008Mass spectrometers that use different types of analyzers for the first and second stages of mass analysis in tandem mass spectrometry (MS/MS) experiments are often... (Review)
Review
Mass spectrometers that use different types of analyzers for the first and second stages of mass analysis in tandem mass spectrometry (MS/MS) experiments are often referred to as "hybrid" mass spectrometers. The general goal in the design of a hybrid instrument is to combine different performance characteristics offered by various types of analyzers into one mass spectrometer. These performance characteristics may include mass resolving power, the ion kinetic energy for collision-induced dissociation, and speed of analysis. This paper provides a review of the development of hybrid instruments over the last 30 years for analytical applications.
Topics: Awards and Prizes; Equipment Design; Tandem Mass Spectrometry; Tetraethylammonium
PubMed: 18187337
DOI: 10.1016/j.jasms.2007.11.013