<h3 id="h-a-stellar-way-to-overcome-barriers-for-discovery-verification-part-1" data-uw-rm-heading="level" role="heading" aria-level="2">A stellar way to overcome barriers for discovery verification – Part 1</h3>This is the first in a multi-part blog series highlighting the key pillars and impressive benefits of the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Stellar mass spectrometer</a>-the first-of-its-kind solution purpose-built for discovery verification. Stay tuned for more blog posts in the series. &nbsp;<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_You_Need_a_Verification_class_Mass_Spectrometer_45a584008f.jpg" alt="Thermo Fisher Scientific: Why You Need a Verification-class Mass Spectrometer." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_You_Need_a_Verification_class_Mass_Spectrometer_45a584008f.jpg 207w," sizes="100vw" width="1024" height="773">If you were a handyman, you wouldn’t dream of using a wrench as a hammer, or a screwdriver as a chisel. You always need the right tool for the job. Same is true for clinical and translational researchers, who depend on having the right solution to maximize their productivity while advancing their research.<h3 id="h-the-challenge-a-missing-tool-in-the-discovery-to-validation-workflow">The challenge: A missing tool in the discovery-to-validation workflow</h3>For decades, clinical and translational researchers have struggled with biomarker verification workflows due to a technology gap. There’s no current technology that simultaneously addresses the scale, sensitivity and throughput demands without some serious drawbacks. You know this well.Triple quad technology performing multiple reaction monitoring (MRM) is challenged to keep up with limited capacity to handle massive target lists while quantifying at lower limits using faster LC gradients.HRAM MS technology performing parallel reaction monitoring (PRM) are challenged to maintain high sensitivity with high acquisition speeds to function with high throughput at experimental scale.<h3 id="h-the-breakthrough-solution-the-first-of-its-kind-verification-class-ms">The breakthrough solution: The first-of-its kind verification-class MS</h3>Researchers struggling to fill the technology gap need not struggle any more. The first-to-market <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer</a> expertly addresses the shortcomings of both ends of the existing verification-based mass spectrometer spectrum with its:&nbsp;<ul><li>Expanded scale – The Stellar MS expands biomarker candidate verification per unit time while covering a wider range of compound classes.&nbsp; For proteomics and metabolomics, the expanded scale enables researchers to include more stable isotope labeled standards (SIS) without having to drop endogenous targets, enabling absolute quantitation for better statistical analysis, plus method standardization.</li><li>Higher sensitivity – It generates data incredibly fast, but still maintains excellent sensitivity to enable accurate measurements and better putative biomarker stratification. With its impressive quantitative performance, this mass spectrometer minimizes the risk of false negatives. The sensitivity of quantitation extends dynamic range in association with the expanded scale to provide both breadth and depth of sample analysis.</li><li>Greater specificity – The Stellar mass spectrometer’s ability to acquire full scan MS2 and MS3 enables greater specificity by measuring all product ions associated with the precursor analyte, ensuring quantitative confidence in your targets of interest. It can detect smaller signal changes between donor groups (e.g., diseased and healthy), which ensures your measured expression levels are attributed to your target compound and not to background isomeric/isobaric interferences.</li><li>Massive throughput – It provides the capacity to process all the samples in a study faster, which increases the laboratory capacity for more projects or expand the study size which increases statistical power for more confidence. Combined with the Thermo Scientific Vanquish Neo UHPLC system that delivers chromatographic performance from 0.1 to 100 µL/min, the Stellar MS has the acquisition speed to improve throughput 3-5X compared to methods using existing QQQ and HRAM instrumentation.</li><li>Unrivaled quantitative productivity – Measuring a large number of targets is one thing, but how do researchers build these highly multiplexed methods? Traditionally, this process has been slow, painful and costly, requiring either direct infusion or many replicate injections followed by manual data evaluation. With the Stellar MS, researchers can go from building a method to completing an entire study faster while maintaining high data quality and confidence in results. &nbsp;&nbsp;</li></ul><h3 id="h-bridging-the-gap-between-discovery-and-clinical-validation">Bridging the gap between discovery and clinical validation</h3>Not only does the Stellar MS represent a new class of instrument, it serves as the perfect “companion” product between the upstream HRAM instruments doing discovery and the triple-quad systems performing the downstream validation processes.After discovery, the Stellar MS becomes invaluable for the verification phase—using quantitative accuracy to narrow the broad list of candidates with the highest potential down to the best set of markers to move into clinical validation. It can process a large list of potential candidates with the added benefits of higher sensitivity and quantitative accuracy.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_You_Need_a_Verification_class_Mass_Spectrometer_2_891de5ae8d.jpg" alt="Thermo Fisher Scientific: Why You Need a Verification-class Mass Spectrometer." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_You_Need_a_Verification_class_Mass_Spectrometer_2_891de5ae8d.jpg 245w," sizes="100vw" width="1024" height="576">Transitioning from verification to validation may deliver a narrowed set of biomarker candidates that have the greatest potential for specific and sensitive sample classification.&nbsp; Based on the Stellar mass spectrometer’s work, researchers now know the sample preparation steps, LC methods, retention times, detection range (LLOD/LLOQ) and method robustness that can be carried over to streamline validation.&nbsp;In addition, researchers also have the option to directly transition the LC-MS/MS method to&nbsp;the Thermo Scientific TSQ Altis Plus triple quadrupole mass spectrometer if expanded laboratory capacity is needed. The ESI source, ion source settings, and Thermo Scientific Xcalibur software provide direct overlap to minimize additional method refinement.&nbsp;The TSQ Altis Plus MS also has the same robustness to ensure maximum uptime to complete studies with higher throughput. &nbsp;<h3 id="h-no-longer-stuck-in-discovery-expanded-capability-across-the-entire-workflow">No longer stuck in discovery: expanded capability across the entire workflow</h3>Many translational researchers have avoided the move to targeted verification methods due to the complexity, as well as the lack of experience operating triple quadrupole systems to create, refine and implement these highly multiplexed methods. The introduction of the Stellar MS workflow streamlines the process while delivering quantitative performance.Therefore, researchers can expand their laboratory capacity and advance their research work in house, without the need to add people, learn new skills or devote months to this work. Researchers can cover more of the workflow process themselves—all the way to the validation phase—enabling them to maintain better control, reduce costs and increase confidence in the results.&nbsp;&nbsp;&nbsp;&nbsp;<blockquote>For more information, explore the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Stellar Mass Spectrometer MS</a> web page or reach out to your Thermo Fisher sales representative.Intrigued to learn more about the Stellar mass spectrometer and how to streamline your verification process? Watch for more blogs in this series soon.</blockquote><blockquote><h5>Visit our&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/chromatography-&amp;-mass-spectrometry/posts/?feedView=all">LinkedIn page</a>: #StellarMassSpec #MassSpectrometry</h5><section><h4>Dr. Scott Peterman</h4><div itemprop="description">Scott Peterman, Ph.D., is Senior Product Marketing Manager for Life Science Mass Spectrometry of the Chromatography and Mass Spectrometry Division of Thermo Fisher Scientific.</div></section></blockquote>&nbsp;

Why You Need a Verification-class Mass Spectrometer

<h3>Using Artificial Intelligence to Drive MS Workflow Productivity</h3>This is the second in a multi-part blog series highlighting the key attributes and impressive benefits of the Stellar mass spectrometer—the first-of-its-kind instrument designed and optimized for highly multiplexed targeted quantitation, ideally suited—for discovery verification. See Part 1 <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5077" aria-label="This is the second in a multi-part blog series highlighting the key attributes and impressive benefits of the Stellar mass spectrometer—the first-of-its-kind instrument designed and optimized for highly multiplexed targeted quantitation, ideally suited—for discovery verification" uw-rm-vague-link-id="https://www.thermofisher.com/blog/analyteguru/why-you-need-a-verification-class-mass-spectrometer/$here" data-uw-rm-vglnk="">here</a> and stay tuned for more blog posts in the series.&nbsp;As artificial intelligence (AI) continues to take the modern world by storm, a similar concept in the scientific world called “automated intelligence” is revolutionizing work for research scientists in their transition from discovery to clinical validation. This version of AI enables you to leverage empirical data, user-defined guidance and instrument performance metrics to manage experiments and dramatically improve productivity.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_You_Need_a_Verification_class_Mass_Spectrometer_45a584008f.jpg" alt="Thermo Fisher Scientific: Why you need a verification-class mass spectrometer – Part 2" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_You_Need_a_Verification_class_Mass_Spectrometer_45a584008f.jpg 207w," sizes="100vw" width="1024" height="773">It’s possible with an all-new instrument—the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer</a> (MS)—which uses AI to transform the process of building methods, data acquisition management and data processing for interpretation and planning next steps.&nbsp; Combined with the unique instrument performance, the Stellar mass spectrometer creates a new paradigm for targeted quantitation.<h3 id="h-garbage-in-garbage-out">Garbage in, garbage out</h3>Scientific research is all about data, and just like with any computational work, poor-quality input will always produce faulty or unusable output. This idea is especially true for clinical and translational researchers who perform biomarker verification. The quality of your method development and research will always be determined by several things: (1) your existing data (e.g., compound databases, empirical data, in silico predictive models), (2) your guidance (e.g., real-time decision-making parameters) and (3) the experimental capabilities of your instrument platform.<h3 id="h-another-challenge-limitations-in-the-discovery-to-validation-workflow">Another challenge: limitations in the discovery-to-validation workflow</h3>Poor quality input for method development is one challenge, but it’s not the only one. As we discussed in our <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5077">first blog post </a>researchers have long struggled with a technology gap in available instrument platforms. Until recently, there were no single-vendor solutions that offered excellent performance for both discovery and targeted verification. This was a serious limitation that impacted how much researchers could rely on AI for method-building. The old process still required a lot more hands-on optimization, which seriously limited productivity.<h3 id="h-finally-automated-intelligence-without-the-drawbacks">Finally: automated intelligence without the drawbacks</h3>With the advent of automated intelligence available on Stellar MS to build targeted methods and manage data acquisition, it’s a whole new ball game. Stellar MS software leverage automated intelligence to boost laboratory productivity, capacity, and lab reputation for high-quality data with faster turnaround times. As a researcher, you can now use automated intelligence to “feed in” your previous work and provide instructions about how to use that information to make decisions and generate new data. Here’s how it works:<h3 id="h-how-ai-speeds-method-creation-and-optimization">How AI speeds method creation and optimization</h3>Stellar MS come with the Thermo Scientific software tool PRM Conductor in Skyline software for automated method building. It uses automated intelligence to build highly effective, targeted acquisition methods from your discovery data (from either<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?instrumentationItems=33&amp;manufacturerItems=3&amp;search=Thermo+Scientific+Orbitrap"> Thermo Scientific Orbitrap</a>-based MS systems or the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Stellar MS</a>).PRM Conductor aids in the generation of targeted-MS2 and MS3 assays. The creation of an assay is broken into three main parts:<ol><li>Skyline metadata describing precursor-to-product transitions is used to filter transitions against a set of thresholds. The filters are based on integrated peak area, relative area, signal-to-background, correlation to median transition, LC base peak width, and retention time. Precursors are filtered by whether they have at least a certain number of qualifying transitions, typically three for peptides and two for small molecules.</li><li>Targeted assays are created with a visualization that depicts the concurrency of the assay in terms of how long the instrument would take to acquire data for the precursors as a function of retention time. Given a desired number of acquired points per LC peak and corresponding cycle time, you can see how various experimental parameters affect the feasibility of acquiring data for the qualifying precursors, such as linear ion trap scan rate and acquisition window width.</li><li>Finally, you can decide whether to create multiple assays for all qualifying precursors, or a single assay with a “balanced load” that picks the best N peptides per protein. Instrument methods for the final assay(s) can then be exported, based on a user-defined template method.</li></ol>In addition, Stellar MS solutions use <a target="_blank" rel="noreferrer noopener" aria-label="Normalized Collision Energy - open in a new tab" data-uw-rm-ext-link="" uw-rm-external-link-id="https://assets.thermofisher.com/tfs-assets/cmd/warranties/psb104-normalized-collision-energy-technology-en.pdf$normalizedcollisionenergy"><a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/Warranties/PSB104-Normalized-Collision-Energy-Technology-EN.pdf">Normalized Collision Energy</a></a> (NCE) – a well-established principle that automatically compensates for mass dependency by automatically estimating all of the collision energies. NCE bypasses the need for optimization per precursor-to-product ion transition performed by a triple quadrupole mass spectrometer which takes much longer to perform, multiplies the experimental cost due to replicate injections of standards and dedicated research staff time.&nbsp;<h3 id="h-how-ai-streamlines-data-acquisition">How AI streamlines data acquisition</h3>With the Stellar MS automated intelligence capabilities, scientists can also speed data acquisition with these tools:Dynamic AGC (automated gain control) helps the system maintain constant ion count and high data quality regardless of ion flux. Essentially, the Stellar MS regulates the number of charges or ions per spectrum by employing a hyper-fast ion gate managing ion accumulation to pass an ideally constant number of ions per spectrum.<figure class="image"><img style="aspect-ratio:400/443;" src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_you_need_a_verification_class_mass_spectrometer_Part_2_2db3d7d0df.jpg" alt="Thermo Fisher Scientific: Figure 1: a) Theoretical depiction of how AGC expands the accessible quantitative range of concentrations. b) Assessment of active targets at the start of a cycle, with their minimum acquisition times on the y-axis, and where more intense precursors are white. 3) Expansion of injection times inverse-proportionally to target abundance. " srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_you_need_a_verification_class_mass_spectrometer_Part_2_2db3d7d0df.jpg 141w," sizes="100vw" width="400" height="443"></figure>As depicted in Figure 1, the ability to vary the injection time expands the dynamic range of quantitation, from a base range given by just the storage and detector saturation limits and multiplies it by the gate linearity range. In the case of the Stellar MS, the pulsed nature of ion trap mass analysis limits the intra-scan dynamic range to about three orders (from 1 to 25k ions in a peak), while the gate can give a linear response from about 3d-6 seconds up to a practical experimental limit, for example 3e-1 seconds.Another tool, Adaptive RT, dynamically manages PRM acquisition, which means you’ll nearly eliminate the risk of missing data while maximizing target capacity.&nbsp; Missing data requires you to re-run samples, costing time and money. Using the method (generated by PRM Conductor software), you can run one representative sample on the gradient and product ion distribution profiles as a function of retention time are built into the instrument editor, which combines PRM settings and Adaptive RT to manage every microsecond of sample acquisition. The system will continue to update and modify the method to adjust for any unexpected LC perturbation or manage data acquisition across multi-channel UHPLC column formats. For a more in-depth description, check out the <a target="_blank" rel="noreferrer noopener" aria-label="newly published BioRxiv paper - open in a new tab" data-uw-rm-ext-link="" uw-rm-external-link-id="https://www.biorxiv.org/content/10.1101/2024.05.31.596848v1$newlypublishedbiorxivpaper"><a target="_blank" rel="noopener noreferrer" href="https://www.biorxiv.org/content/10.1101/2024.05.31.596848v1">newly published BioRxiv paper</a></a>.<h3 id="h-conclusion-automated-intelligence-maximizes-workflow-performance">Conclusion: Automated intelligence maximizes workflow performance</h3>In order to maximize LC-MSn workflow performance for translational verification, you need solutions that streamline all steps while meeting experimental expectations—scale, sensitivity, specificity, throughput, and ease-of-use. Together, automated intelligence on the Stellar MS combined with unique instrument performance can help deliver the ultimate performance to boost your lab’s productivity and prestige.<blockquote>For more information, explore the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Stellar Mass Spectrometer MS</a> or <a target="_blank" rel="noreferrer noopener" aria-label="reach out to your Thermo Fisher Scientific sales representative - open in a new tab" data-uw-rm-ext-link="" uw-rm-external-link-id="https://www.thermofisher.com/us/en/home/global/forms/industrial/stellar-mass-spectrometer-contact.html$reachouttoyourthermofisherscientificsalesrepresentative"><a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/us/en/home/global/forms/industrial/stellar-mass-spectrometer-contact.html">reach out to your Thermo Fisher Scientific sales representative</a></a>.Intrigued to learn more about the Stellar MS and how it can improve your work? Watch for more blog posts in this series soon.<h5>Visit our&nbsp;<a target="_blank" rel="noreferrer noopener" aria-label="LinkedIn page - open in a new tab" data-uw-rm-ext-link="" uw-rm-external-link-id="https://www.linkedin.com/showcase/chromatography-&amp;-mass-spectrometry/posts/?feedview=all$linkedinpage"><a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/chromatography-&amp;-mass-spectrometry/posts/?feedView=all">LinkedIn page</a></a>: #StellarMassSpec #MassSpectrometry #TranslationalResearch</h5><h4>Dr. Scott Peterman</h4><div itemprop="description">Scott Peterman, Ph.D., is Senior Product Marketing Manager for Life Science Mass Spectrometry of the Chromatography and Mass Spectrometry Division of Thermo Fisher Scientific.</div></blockquote>

Why you need a verification-class mass spectrometer – Part 2

The analysis of intact proteins, such as therapeutic monoclonal antibodies (mAbs) under “native” (non-denaturing) conditions using mass spectrometry gives drug developers unique structural insights and allows simplified determination of some biochemical and biophysical properties.Until recently these analyses have been the domain of time-of-flight (TOF) mass spectrometers, due to the ability of this analyzer type to determine masses of very high mass-to-charge ratio (m/z).<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_TOF_vs_Orbitrap_for_Intact_Protein_Structural_Insights_a3206fa950.jpg" alt="Thermo Fisher Scientific: TOF vs. Orbitrap for Intact Protein Structural Insights." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_TOF_vs_Orbitrap_for_Intact_Protein_Structural_Insights_a3206fa950.jpg 245w," sizes="100vw" width="768" height="414">Systems conventionally required specialized configurations and conditions to ensure large ions were de-solvated efficiently in the source, transported through the mass spectrometer with adequate transmission efficiency, and detected with acceptable selectivity such that all relevant protein isoforms can be differentiated and identified.TOF systems used for this work typically required expert tuning to achieve acceptable results; however many systems suffered robustness in source de-solvation and lacked spectral resolution to separate key proteoforms. TOF-based systems could provide average intact and native mass, but features such as glycoforms were lost in the spectral noise – TOF could see the forest, but not the trees.<h3 id="toc-hId--1902366970" data-uw-rm-heading="level" role="heading" aria-level="2">See the Detail</h3>Consequently, significant efforts were made in the development of extended mass range Orbitrap-based mass spectrometers for the characterization of intact protein assemblies. In 2012, a prototype <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/order/catalog/product/iqlaaegaapfalgmbdl?ce=E.19CMD.PM102.16927.01&amp;cid=E.19CMD.PM102.16927.01">Thermo Scientific Exactive Plus EMR system</a> was used by <a target="_blank" rel="noopener noreferrer" href="https://www.ncbi.nlm.nih.gov/pubmed/23064518">Rose et al.</a>, to determine measurement of various protein assemblies with “outstanding mass-spectral resolution.”Data on the Orbitrap-based system represented a “notable improvement over those obtained with TOF instrumentation.” TOF data was only able to determine an average m/z result for large m/w proteins; whereas data obtained using orbitrap-based MS was baseline resolved; which even allowed determination of binding events on these large proteins. The improvements in spectral resolution on Orbitrap meant a new level of structural insight could be gained, even to the level of studying small molecule interactions with megadalton proteins – studies that were previously unimaginable using TOF.High mass analysis Orbitrap-based MS development didn’t stop there; in 2017 Thermo Fisher Scientific launched a <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/order/catalog/product/0726055?ce=E.19CMD.PM102.16927.01&amp;cid=E.19CMD.PM102.16927.01">BioPharma Option</a> for the <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/uk/en/home/industrial/mass-spectrometry/liquid-chromatography-mass-spectrometry-lc-ms/lc-ms-systems/orbitrap-lc-ms/orbitrap-hybrid-mass-spectrometer-comparison.html?ce=E.19CMD.PM102.16927.01&amp;cid=E.19CMD.PM102.16927.01">Thermo Scientific Q Exactive range of mass spectrometers</a>. This enabled a high mass mode for determinations up to 8,000 m/z, opening the door for simple, robust, and high spectral quality intact mass analyses of mAbs. Not only did this provide exceptional data to drug developers, it also came with a simple and robust set-up procedure that made acquisition of data under native-like conditions as simple as acquiring a peptide map.Drug researchers like <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/cs_72645_native_ms_protein_characterization_omass_cs72645_en_d12100345a/cs-72645-native-ms-protein-characterization-omass-cs72645-en.pdf">OMass</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/cs_72665_ms_therapeutic_proteins_lifearc_cs72665_en_cfa26cdc5d/cs-72665-ms-therapeutic-proteins-lifearc-cs72665-en.pdf">LifeArc</a> and <a target="_blank" rel="noopener noreferrer" href="http://analyteguru.com/how-to-make-cancer-face-the-music/">Symphogen</a> were quick to adopt this technology in routine.<blockquote>“The system gets tuned and calibrated once a week. It’s incredibly stable and easy to set-up.” – Dr. David Tickle, Senior Principal Scientist, LifeArc</blockquote><h3 id="toc-hId--1873737819"><a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/watch?v=xtj_JIcD9BM">Symphogen on TOF vs. Orbitrap</a></h3>Users were able to run native-MS every day, and generate data with spectral quality so superior that they are now able to achieve full intact protein glycoform determinations in 15 minutes using Orbitrap-based analysis. This was a process that conventionally required complex sample preparation and chromatographic fractionation routines when using TOF based detection.<blockquote>“The thing that struck me is the difference in quality of data when comparing TOF vs Orbitrap data.”&nbsp; – Dr. Dan Bach Kristensen, Principal Investigator, Symphogen</blockquote><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_TOF_vs_Orbitrap_for_Intact_Protein_Structural_Insights_2_98f57e9e65.jpg" alt="Thermo Fisher Scientific: TOF vs. Orbitrap for Intact Protein Structural Insights." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_TOF_vs_Orbitrap_for_Intact_Protein_Structural_Insights_2_98f57e9e65.jpg 245w," sizes="100vw" width="990" height="396"><h3 id="toc-hId--1845108668"><a target="_blank" rel="noopener noreferrer" href="https://www.youtube.com/watch?v=CE2O4a0VJaw">CV-MS for Simple Characterization of Native Variants</a></h3><h3 id="toc-hId--1816479517">We want more!</h3>When it comes to intact and native mass spectrometry average mass is no longer enough. Structural insights are only provided when isoforms are easily differentiated and can be confidently determined. Orbitrap-based mass spectrometry delivers.So much so that researchers are wanting to analyse ever-larger and more complex molecules. This led, last year, to the introduction of the new <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/us/en/home/products-and-services/promotions/industrial/q-exactive-uhmr.html?ce=E.19CMD.PM102.16927.01&amp;cid=E.19CMD.PM102.16927.01">Thermo Scientific Q Exactive UHMR</a> (Ultra High Mass Range) Hybrid Quadrupole-Orbitrap MS System. The Q Exactive UHMR systems enable analysis of intact MegaDalton assemblies and resolve small differences in masses that reveal key ligands, modifications and interactions for better understanding of biological processes.<blockquote>“Thermo Fisher has made a major contribution to native mass spectrometry in recent years. In the past we couldn’t get resolution of very large protein complexes with few charges. This was a real stumbling block for us. We have benefited from recent developments in native high-resolution mass spectrometry. We didn’t realize what we weren’t seeing before.”&nbsp; – Professor Dame Carol Robinson, Chief Scientific Consultant, OMass Technologies</blockquote>For more information on Orbitrap-based mass spectrometry for intact and native mass analysis <a target="_blank" rel="noopener noreferrer" href="http://www.thermofisher.com/nativems?ce=E.19CMD.PM102.16927.01&amp;cid=E.19CMD.PM102.16927.01">click here.</a>

TOF vs. Orbitrap for Intact Protein Structural Insights

<h3>Part 3: Solving the top 5 pain points of translational metabolomics researchers</h3>This is the third in a multi-part blog series highlighting the key attributes and impressive benefits of the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Stellar mass spectrometer</a>—the first-of-its-kind instrument designed and optimized for highly multiplexed targeted quantitation, ideally suited for discovery verification. By delivering robust analytical methods and dramatically improved turnaround time, this solution helps labs boost capacity and differentiate themselves to generate more revenue. For additional background, see blog <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5077">Part 1</a> and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5086">Part 2</a> here and stay tuned for more blogs in the series<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_You_Need_a_Verification_Class_Mass_Spectrometer_Solving_the_Top_5_Pain_Points_of_Translational_Metabolomics_Researchers_be4f53aad2.jpg" alt="Thermo Fisher Scientific: Why You Need a Verification-Class Mass Spectrometer: Solving the Top 5 Pain Points of Translational Metabolomics Researchers." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_You_Need_a_Verification_Class_Mass_Spectrometer_Solving_the_Top_5_Pain_Points_of_Translational_Metabolomics_Researchers_be4f53aad2.jpg 245w," sizes="100vw" width="1024" height="512"><article><div>Metabolomics is a powerful way to gain insights into a person’s biochemistry, microbiome, exposome and lifestyle. However, developing clinically relevant metabolomics panels using liquid chromatography coupled with tandem mass spectrometry (LC-MSn) presents significant challenges. That’s why clinical research labs and CROs continue to explore more effective solutions to expedite method creation and refinement, which can deliver targeted quantitative metabolites methods at scale that extend the dynamic range while using faster chromatographic methods.By investing in new technology, your lab can deliver faster turnaround times—boosting lab capacity and ROI—while differentiating your services to attract more customers.<h3>How new technology solves 5 key challenges for metabolomics researchers</h3>Compared to existing triple quadrupole mass spectrometers (QQQ MS), the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer (MS)</a> is the most advanced solution available today for translational metabolomics research. One significant difference between the two platforms is the Stellar mass spectrometer’s ability to acquire parallel reaction monitoring (PRM*) spectra vs selected reaction monitoring (SRM*), also known for the marketing term multiple reaction monitoring (MRM*) data.Examples of these attributes are presented in the following resources:<ul><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/an_003114_lsms_stellar_ms_t_quan_analysis_fecal_library_an003114_na_en_8bef170554.pdf">Development and implementation of a comprehensive fecal metabolites LC-MS library for dietary intervention studies using the Thermo Scientific Stellar mass spectrometer.</a></li><li><a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/po_163_high_throughput_targeted_metabolomics_novel_ms_applied_microbiome_analysis_po163_asms2024_en_764f5bf319.pdf">High throughput targeted metabolomics library generation on a novel mass spectrometer applied to microbiome analysis.</a></li></ul>Let’s take a look at five challenges the Stellar MS solves…<div><div><h3>Challenge #1: Overcoming tremendous chemical/structural metabolite diversity to create an effective quantitative method for the specified metabolite panel.</h3>Mass spectrometers must perform equally well in both positive and negative ESI polarities to maximize overall quantitative performance.<ul><li>Current state: Unfortunately, some mass spectrometers can struggle with sensitive detection in ESI mode or require two different experiments (e.g., APCI and ESI) to be performed with different solvent systems, resulting in more experiment time and money.</li><li>A better solution: The Stellar MS has an efficient ionization source and detector system to perform equally well in ionization, ion transfer and detection for both positive and negative polarity, enabling more analytes to be quantified using faster gradients.</li></ul>Mass spectrometers must also have fast polarity switching capabilities to maximize the duty cycle.<ul><li>Current state: Triple quadrupole mass spectrometers may achieve 5 ms polarity switching but also require up to 5 ms for settling times before data acquisition in the second ionization polarity. That equates to 20 ms of cycle time that cannot be devoted to metabolite/lipid data acquisition.</li><li>A better solution: The Stellar MS delivers true 5 ms polarity switching (5 ms for both polarity switching and settling times), requiring much less cycle time that can then be devoted to increasing the sensitivity of measuring targeted analytes.</li></ul>Analyte characterization requires MS-level analysis to determine in-source fragmentation, adduct formation (e.g. sodium, potassium or ammonia) or if there’s an abundant co-eluting isobar or analyte. This becomes critical to identify the optimal precursor m/z value used for tandem MS or determine if LC gradient modifications are required to meet the experimental scope.<ul><li>Current state: Triple quadrupole mass spectrometers acquire full scan data slowly and with compromised sensitivity, reducing the effectiveness, even when limiting the precursor mass range transmitted through Q1 to expand beyond protonation/deprotonation.&nbsp; This often reduces LC-SRM (or MRM) strategies to be used for troubleshooting which is inefficient and often ineffective.</li><li>A better solution: The Stellar mass spectrometer can acquire fast and sensitive full scan MS spectra in either polarity enabling greater analyte characterization as well as detection of abundant co-eluting matrix interferent.</li></ul>Structural diversity requires greater instrument flexibility to generate diagnostic product ions associated with the target analyte structure. HCD* is the fastest fragmentation method and suitable for over 80% of targeted analytes; yet some require too high of a voltage drop, resulting in greater secondary and tertiary fragmentation, and ultimately, increased scatting that reduces product ion transmission, sacrificing sensitivity.<ul><li>Current state: Existing triple quadrupole mass spectrometers are limited to HCD fragmentation. Triple quadrupole mass spectrometers that have Qtrap functionality can perform collision-induced dissociation (CID*) but with compromised sensitivity and exceptionally longer acquisition times reducing its utility in higher multiplexed quantitation methods.</li><li>A better solution: The Stellar mass spectrometers’ unique instrument design expands dissociation methods incorporating both beam-type higher energy collision dissociation (HCD*) as well as resonant RF CID. (Schwartz, J. C. et al. A two-dimensional quadrupole ion trap mass spectrometer 2002; 13: 659-669).</li></ul></div></div><div><div><h3>Challenge #2: Achieving enhanced specificity in the presence of complex biological matrices to maximize data confidence.</h3><ul><li>Current state: To solve this challenge today, some researchers use alternative fragmentation mechanisms. However, existing triple quadrupole mass spectrometers are limited to HCD fragmentation, which may be insufficient for some steroids and bile acids. Additionally, triple quadrupole mass spectrometers that have Q-trap functionality can perform CID but with compromised sensitivity and exceptionally longer acquisition times (ca. 3 Hz published acquisition rates) reducing its utility for quantitative methods targeted increased numbers of analytes.</li><li>A better solution: The Stellar mass spectrometers’ unique instrument design expands dissociation methods incorporating both HCD as well as CID. (Olsen, J. V. A dual pressure linear ion trap Orbitrap instrument with very high sequencing speed Mol. Cell. Proteomics 2009; 8: 2759-2769).</li></ul>Another issue is that some analytes may require higher MSn levels to overcome background interference.<ul><li>Current state: Unfortunately, standard triple quadrupole mass spectrometers are limited to SRM/MRM*, which is MS2 acquisition. And triple quadrupole mass spectrometers that have Qtrap functionality can perform CID-based MS3 or MRM3 but with compromised performance as described above.&nbsp; References: <a target="_blank" rel="noopener noreferrer" href="https://sciex.com/content/dam/SCIEX/pdf/tech-notes/all/MRM3_Quantitation_tech_oView.pdf">MRM3 quantitation for highest selectivity in complex matrices</a> or <a target="_blank" rel="noopener noreferrer" href="https://sciex.com/content/dam/SCIEX/pdf/tech-notes/all/QTRAP-Scan-Modes.pdf">Powerful scan modes of QTRAP system technology</a></li><li>A better solution: The Stellar MS can perform fast and sensitive MS2 (at rates up to 140 Hz) and MS3 (at rates up to 40 Hz) as well as higher-order MSn (up to MS10 if needed) using either HCD or CID at any MSn level.</li></ul></div></div><div><div><h3>Challenge #3: Current translational metabolomics experiments seek to expand sample coverage beyond 500 metabolites and/or lipids in a single method while maintaining greater sample throughput.</h3>SRM/MRM acquisition strategies must acquire at least two or three sequential transitions for data confidence, thus doubling or tripling the number of scan events acquired per unit time. In addition, each SRM/MRM scan event has a switching time in addition to the dwell time that collectively reduces the duty cycle per analyte.<ul><li>Current state: Unfortunately, QQQ MS that can perform trapping are slow and have reduced sensitivity relative to its MRM acquisition methods.</li><li>A better solution: The Stellar MS acquires PRM* for MSn scan events. Therefore, one scan event is needed per analyte, which increases the duty cycle and ensures qualitative analysis for high data confidence. Coupled with synchronized, dual ion packet management, Stellar MS boosts PRM acquisition speed up to 140 Hz with fast ion, sensitive detection to almost 90% of trapped ions.</li></ul></div></div><div><div><h3>Challenge #4: Maintaining the quantitative performance at scale while addressing throughput requirements during scheduled retention time (RT) windows.</h3><ul><li>Current state: Triple quadrupole mass spectrometers do not have robust dynamic RT adjustment capabilities—requiring longer RT windows and increasing the number of concurrent SRM/MRM transitions per RT window that ultimately limit LOQ performance.</li><li>A better solution: The Stellar mass spectrometer has the unique ability to perform Adaptive RT which dynamically adjusts RT windows every 3-4 seconds enabling narrow RT window lengths (down to 18 seconds) while minimizing missing data.</li></ul></div></div><div><div><h3>Challenge #5: Expediting method building and refinement strategies.</h3>After identifying the target metabolites and lipids, researchers often struggle to determine the optimal instrument settings for the most sensitive, selective, and specific acquisition.<ul><li>Current state: Most of today’s triple quadrupole mass spectrometers have different ion sources relative to their discovery-based instrumentation. This requires additional method development, the need to optimize collision energy and dwell times per metabolite, and numerous replicate injections (when tied to online LC separation) or lengthy optimization steps (when using direct infusion of standards).</li><li>A better solution: The Stellar mass spectrometer has similar ion sources to those of the Thermo Scientific Orbitrap-based mass spectrometers performing discovery experiments. The resulting set of metabolites and corresponding empirical data form spectral libraries used to automate targeted quantitative methods with the PRM Conductor tool in Skyline MS software.</li></ul>The Stellar mass spectrometer can perform untargeted sample characterization using full scan MS. It can also perform gas phase fraction (GPF) leveraging the Stellar MS acquisition speed to create comprehensive spectral libraries using 4-5 replicate sample injections.</div></div><h3>Conclusion: A smarter way to do translational metabolomics research</h3>For more information, explore the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Stellar mass spectrometer</a> and <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/brochures/in-003331-lsms-ion-trap-stellar-ms-lc-ms-in003331-na-en.pdf">download our new infographic</a>.*Glossary:Higher-energy collisional dissociation (HCD):&nbsp;HCD is a fragmentation technique associated with Thermo Scientific Orbitrap instruments. Voltage offsets between components increase the kinetic energy of the precursor ion and dissociated in the ion routing multipole cell from collisions with neutral nitrogen molecules. After which they are transferred back to the C-trap and then injected into the Orbitrap mass analyzer for detection.&nbsp; Due to the increased kinetic energy, the resulting product ions also have increased kinetic energy and can undergo secondary and tertiary fragmentation that can result in a shift in more abundant low-mass product ions.&nbsp; HCD is associated with QQQ MS fragmentation performed in the Q2 cell or ion routing multiple cells in the Stellar mass spectrometer.Collision-induced dissociation&nbsp;(CID) is a mass spectrometry&nbsp;technique to induce fragmentation of to improve selectivity, and specificity.&nbsp; For reference associated with ion traps, CID is defined as the method performed in the high-pressure linear ion trap using resonant RF to increase the kinetic energy of the selected ion which undergoes many ion-neutral collisions with helium over 3-5 ms resulting in fragmentation.&nbsp; Once product ions are formed, their m/z value is no longer resonant with the applied RF and are collisionally cooled back to the center of the ion trap.&nbsp; The primary difference between CID and HCD is the mass of the neutral collision gas (N2/Ar for HCD vs. He for CID) and the number of ion-neutral collisions during the process.&nbsp; As such, CID reduces the probability of secondary fragmentation and can alter the resulting product ion distribution as compared to HCD fragmentation.Parallel reaction monitoring (PRM)&nbsp;is an ion monitoring technique based on performing either HCD or CID but measuring all resulting product ions in one scan event. The principle of this technique is comparable to SRM/MRM, but it is more convenient in assay development for absolute quantification as you can measure more signal from the targeted precusor ion and has been demonstrated to quantify down to attomole sensitivity in complex biological matrices.Selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), is an important technique for quantitative analysis in complex matrices.&nbsp;SRM utilizes Q1 to isolate the precursor m/z value generally using a 1 Th isolation window, transferring the precursor to Q2 for HCD generation.&nbsp; The resulting product ions continue into Q3 where a diagnostic product ion m/z is isolated (1-2 Th isolation window) whose ion pathway continues to the detector. The SRM/MRM technique sets the instrument Q1/Q3 parameters (transitions) creating an ion beam in which the QQQ MS measures the resulting signal for a user-defined dwell time (1 to 100 ms).&nbsp; Researchers set two to four SRM/MRM transitions per analyte to increase the specificity and qualitative analysis of the resulting data.&nbsp; The SRM/MRM technique can achieve rapid, sensitive, specific quantification of the target protein in a complex system and excellent quantitative reproducibility. SRM/MRM has been identified as the gold standard for targeted quantitation for decades.<blockquote>Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#StellarMassSpec #MassSpectrometry</blockquote></div></article><section><blockquote>Dr. Scott Peterman<div>Scott Peterman, Ph.D., is Senior Product Marketing Manager for Life Science Mass Spectrometry of the Chromatography and Mass Spectrometry Division of Thermo Fisher Scientific.</div></blockquote></section>

Why You Need a Verification-Class Mass Spectrometer: Solving the Top 5 Pain Points of Translational Metabolomics Researchers

<h3>Part 4: Going beyond 4D to improve analytical performance for targeted quantitative analysis</h3>This is the fourth in a multi-part blog series highlighting the key attributes and impressive benefits of the Thermo Scientific Stellar mass spectrometer—the first-of-its-kind instrument designed and optimized for highly multiplexed targeted quantitation, ideally suited for discovery verification. By delivering robust analytical methods and dramatically improved turnaround time, this solution helps labs boost capacity and differentiate themselves to generate more revenue. For additional background, see blog <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5077">Part 1</a>, <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5086">Part 2 </a>and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/article/5416">Part 3</a> here and stay tuned for more blogs on our website.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Why_You_Need_a_Verification_Class_Mass_Spectrometer_Going_Beyond_4d_to_Improve_Analytical_Performance_for_Targeted_Quantitative_Analysis_125258804e.jpg" alt="Thermo Fisher Scientific: Why You Need a Verification-Class Mass Spectrometer: Going Beyond 4d to Improve Analytical Performance for Targeted Quantitative Analysis." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Why_You_Need_a_Verification_Class_Mass_Spectrometer_Going_Beyond_4d_to_Improve_Analytical_Performance_for_Targeted_Quantitative_Analysis_125258804e.jpg 245w," sizes="100vw" width="1200" height="600">Analytical specificity is one of the most critical requirements for successful targeted quantitative analysis. Assigning measured data to diagnostic product ions from the analyte of interest increases the confidence in resulting measurement determining the analyte expression level, copy number, or absolute amount in each sample, as well as across an entire study. Using empirically determined values for liquid chromatography (LC) and mass spectrometry (MS) provides specific information that collectively increases data processing. This orthogonal information comes in the form of 1) chromatographic retention times and peak shapes; 2) precursor m/z value; 3) MS/MS product ions; and 4) MS/MS product ion distribution profiles, which can be stored to form spectral libraries that are used to not only process LC-MSn data but build confident targeted data acquisition methods.<h3>4D parameter determination: Sufficient or not?</h3>Previous publications touted utilization of four-dimensional (4D) parameter determination to confidently create and process untargeted and targeted data. Using LC coupled to a trapped ion mobility QTOF (timsTOF) mass spectrometer, each analyte is annotated by four empirical measurements across all study samples: 1) measured retention time; 2) ion mobility as measured by its collision cross section (CCS); 3) precursor m/z value; and 4) presence of corresponding product ions. The assumption is that the orthogonal selectivity achieved by UHPLC separation and ion mobility resolution relative to the precursor isolation is sufficient to differentiate a specific analyte from co-eluting isobaric and isomeric ions and that resulting product ions are only attributed to the isolated precursor. <a target="_blank" rel="noopener noreferrer" href="https://arxiv.org/pdf/2111.03134">Adding CCS values can help accommodate for some variability</a> but requires more work by the researcher to accurately determine the variance associated with ion mobility. <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/labrulez-bucket-strapi-h3hsga3/1885960_lcms_179_lipidomics_short_gradient_ebook_rev_01_ed630faf92/1885960-lcms-179-lipidomics-short-gradient-ebook-rev-01.pdf">At no point are the product ion ratios used as an additional dimension for verification</a>.A smart addition: product ion ratio determination Product ion ratio determination, however, has been used as the gold standard for qualitative data analysis for SRM/MRM acquisition for decades. Despite quantitative methods on triple quadrupole mass spectrometers acquiring data for only two or three product ion transitions, the inclusion of the resulting product ion ratio is used to qualitatively verify that the signal measured per SRM transition is attributed to the analyte of interest. This concept has been included in the targeted quantitative studies performed using the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer (MS)</a>, significantly increasing analytical performance for a wide range of molecules.To increase the quantitative selectivity and specificity needed for confident data acquisition, the proposed solution combines the chromatographic separation capabilities of the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=40&amp;search=vanquish">Thermo Scientific Vanquish UHPLC system </a>with the innovative PRM acquisition on the Stellar mass spectrometer to go beyond data processing confidence.&nbsp; Additionally, the proposed method leverages intelligent data acquisition to perform RT alignment reducing the need to apply additional post-acquisition data processing steps.&nbsp; This blog covers the differentiation for each of these steps while presenting an important 5th dimension—extending PRM data analysis to the MS3 level.<h3>Dimension #1: Leveraging 1,500 bar UHPLC separation to drive orthogonal selectivity</h3>Using the <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/398">Thermo Scientific Vanquish Neo</a> and <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/744">Horizon UHPLC</a> systems, researchers can harness higher backpressure capabilities covering a wide range of flow rates from nanoflow to analytical flow rates—increasing peak capacity while driving higher utilization rates than HPLC systems with only 1,000 bar of backpressure. T<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products?category=40&amp;search=vanquish">he Vanquish UHPLC systems</a> also deliver reproducible performance over the course of longer studies such as populational health.Going beyond the first dimension: Including the Adaptive RT routine enables LC mapping to assign true retention time values to each analyte with narrower retention time windows. The Adaptive RT routine works for small and large molecules, from single-cell to bulk analysis, and bridges method development between longer discovery gradients and faster targeted quantitation gradients without the need for spiked RT standards.&nbsp; The advantage is that the retention time alignment for the study is reliably performed during data acquisition, not processing.<h3>Dimension #2: Introduction of targeted analytes</h3>Following UHPLC separation and ionization, targeted analytes (precursors) are introduced into the MS and moved through the ion flight path to the detector. The quadrupole mass filter (termed isolating quadrupole or Q1) has an RF/DC offset to transmit a narrow m/z range centered on the target precursor m/z value. The mass range used for precursor ion filtering is ca. 1 to 2 Th depending on the mass spectrometer. Leveraging precursor isolation following chromatographic separation increases the target analyte selectivity relative to co-eluting compounds.Going beyond the second dimension: The Stellar mass spectrometer’s QR5 Plus quadrupole mass filter uses hyperbolic-surfaced quadrupole rods that improve ion transmission efficiency across a wider precursor m/z range. Unit resolution settings are 0.7 Th at the baseline—significantly better than other quadrupole mass spectrometers using 1.2 to 2 Th (almost 2-3x wider), which can compromise quantitative performance.<h3>Dimension #3: Acquiring PRM data from more product ions</h3>The<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149"> Stellar mass spectrometer </a>acquires PRM data which is comprised of full scan MS2 spectra per scan event relative to SRM/MRM acquisition. Acquiring data for many more product ions per unit time increases the specificity of the resulting measurement. It also enables post-acquisition data processing methods to determine specific product ions used for quantitation without having to update the experimental method and re-analyze samples.Going beyond the third dimension:&nbsp; The Stellar mass spectrometer combines the unique capabilities of dual ion packet management with ion accumulation outside of the ion trap to boost quantitative performance.&nbsp; Simultaneously managing two different ion packets enables longer accumulation times without significantly compromising the PRM acquisition rates which becomes imperative when performing quantitative measurements at the LOD and LOQ levels.<h3>Dimension #4: Leveraging the full scan MS2 spectrum and multiple product ions to evaluate the product ion ratios compared to a reference spectrum</h3>As mentioned above, ion ratio calculations are used in validated quantitative methods to ensure selectivity relative to the matrix or background interference per product ion.Going beyond the fourth dimension: What, where and how you perform ion accumulation differentiates the effectiveness of each mass spectrometer. The Stellar MS first filters for the targeted precursor m/z value, then accumulates product ions in an ion-routing multipole (as has been done on Thermo Scientific Orbitrap mass spectrometers for over a decade).&nbsp; Performing tandem MS in this order maximizes sensitivity for low-level product ions to maintain accurate ion ratio analysis. Finally, incorporating dynamic AGC automates the accumulation time regardless of precursor ion flux. (Reference: <a target="_blank" rel="noopener noreferrer" href="https://doi.org/10.1101/2024.06.04.597431">Plubell et al. BioRxiv</a>)<h3>Dimension #5: Addressing sensitivity disrupters</h3>Targeted quantitation for specific analytes using MS2 acquisition may have co-eluting isomeric/isobaric ions potentially disrupting quantitative sensitivity (signal-to-noise limitation).&nbsp; Two options to pursue would be modifying LC gradients or increasing the tandem MS level to MS3. Elongating the LC gradient decreases sample throughput yet still may not remove all background interferences. The Stellar MS, on the other hand, can implement MS3 acquisition with exceptionally fast acquisition speeds (up to 40 Hz) to maintain target capacity and the number of data points per LC peak.Going beyond the fifth dimension:&nbsp;In addition to the unique MS3 acquisition speed, the Stellar MS implements dynamic AGC to maximize spectral quality across a wider dynamic range, as well as the ability to perform either HCD or CID at each MSn level. Finally, introduction of Adaptive RT to confidently manage scheduled retention time windows ensures tMS3 methods can succeed for increased target capacity using faster LC gradients.<blockquote>For more information, explore the <a target="_blank" rel="noopener noreferrer" href="https://www.thermofisher.com/content/lifetech/global/en/home/industrial/mass-spectrometry/liquid-chromatography-mass-spectrometry-lc-ms/lc-ms-systems/orbitrap-lc-ms/stellar-mass-spectrometer.html">Stellar mass spectrometer</a> and <a target="_blank" rel="noopener noreferrer" href="https://assets.thermofisher.com/TFS-Assets/CMD/brochures/eb-003672-lsms-stellar-2024-year-in-review-eb003672-na-en.pdf">download our new 2024 year in review ebook</a>.Visit us on <a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a> #StellarMassSpectrometer #Vanquish #UHPLC</blockquote><section><blockquote><h5>Dr. Scott Peterman</h5><div>Scott Peterman, Ph.D., is Senior Product Marketing Manager for Life Science Mass Spectrometry of the Chromatography and Mass Spectrometry Division of Thermo Fisher Scientific.</div></blockquote></section>

Why You Need a Verification-Class Mass Spectrometer: Going Beyond 4d to Improve Analytical Performance for Targeted Quantitative Analysis

In the intricate world of metabolomics, understanding the complete set of metabolites within a biological sample is key to unlocking insights into metabolic pathways and the physiological state of an organism. The <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149">Thermo Scientific Stellar mass spectrometer</a> from Thermo Fisher Scientific is revolutionizing this field with its advanced capabilities, making it an indispensable tool for researchers. Let’s delve into how the Stellar MS is transforming metabolomics research.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Unveiling_the_Power_of_the_Stellar_Mass_Spectrometer_in_Metabolomics_6923cbceb2.jpg" alt="Thermo Fisher Scientific: Unveiling the Power of the Stellar Mass Spectrometer in Metabolomics" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Unveiling_the_Power_of_the_Stellar_Mass_Spectrometer_in_Metabolomics_6923cbceb2.jpg 245w," sizes="100vw" width="1024" height="536"><article><div><h3>The importance of metabolomics</h3>Metabolomics is the comprehensive study of small molecules, or metabolites, within cells, tissues, or organisms. These metabolites are the end products of cellular processes and provide a snapshot of the physiological state of an organism. By analyzing these metabolites, researchers can gain valuable insights into metabolic pathways, disease mechanisms, and potential therapeutic targets.<h3>Why the Stellar mass spectrometer?</h3>The Thermo Scientific Stellar MS stands out as an ideal instrument for metabolomics due to its high sensitivity, specificity, and throughput. Here are some key features that make it a game-changer in this field:<ol><li>High sensitivity and specificity:<ul><li>The dual-pressure linear ion trap technology of the Stellar MS enhances both sensitivity and specificity. This is crucial for detecting and quantifying low-abundance metabolites in complex biological matrices, where accurate measurement is often challenging.</li></ul></li><li>Wide dynamic range:<ul><li>The Stellar MS can reproducibly quantify metabolites across a broad dynamic range. This ensures accurate measurement of both high and low-abundance compounds, providing a comprehensive metabolic profile.</li></ul></li><li>Rapid data acquisition:<ul><li>With hyper-fast acquisition rates, the Stellar MS can quickly acquire detailed data, making it ideal for high-throughput metabolomics studies. This capability allows researchers to process large numbers of samples in a short amount of time.</li></ul></li><li>Reduced matrix effects:<ul><li>Complex biological samples often contain various interfering substances. The Stellar MS minimizes these matrix effects, ensuring reliable quantification of metabolites even in complex samples, which is essential for accurate metabolomics analysis.</li></ul></li><li>Streamlined method development:<ul><li>The Stellar MS simplifies method development, allowing researchers to quickly set up and optimize experiments for metabolite analysis. This is particularly beneficial when transitioning from method development to large-scale studies.</li></ul></li></ol><h3>Application example: metabolic profiling in disease research</h3>Let’s consider a practical example of how the Stellar MS can be used in metabolomics, specifically in disease research.A research team is investigating metabolic changes associated with a specific disease. Using the Stellar MS, they can:<ul><li>Method development: Quickly develop and optimize methods for detecting and quantifying a wide range of metabolites, including both primary and secondary metabolites. The system’s PRM Conductor software aids in automating method creation, enhancing productivity.</li><li>Data acquisition: Leverage the system’s rapid full-scan MSn acquisition to gather comprehensive data on metabolites, providing a detailed metabolic profile of the samples. This detailed data helps identify key metabolic changes associated with the disease.</li><li>Quantification: Accurately quantify metabolites across a wide dynamic range, ensuring that both high and low-abundance metabolites are measured reliably. This is crucial for identifying subtle metabolic changes that may be indicative of disease.</li><li>High throughput: Process large numbers of samples efficiently, enabling the team to conduct extensive metabolic profiling studies in a short amount of time. The ability to process 96-well plates in just nine hours accelerates the research process.</li></ul>The Stellar MS’s capabilities allow the research team to generate detailed metabolic profiles, providing insights into metabolic pathways and identifying potential biomarkers for the disease. This information can be used to understand disease mechanisms, identify therapeutic targets, and develop diagnostic tools.<h3>Conclusion</h3>The Stellar mass spectrometer is a powerful tool for metabolomics, offering high sensitivity, wide dynamic range, rapid data acquisition, reduced matrix effects, and streamlined method development. These features make it an ideal instrument for comprehensive metabolic profiling, enabling researchers to gain deeper insights into metabolic pathways and the physiological state of organisms. Invest in the Stellar MS to enhance your metabolomics research and accelerate discoveries in disease mechanisms, biomarkers, and therapeutic targets. With the Stellar MS, the future of metabolomics is brighter than ever.<blockquote>Explore the capabilities of the Stellar mass spectrometer and see how it can transform your metabolomics research. Contact us for more information or to schedule a demo. Let’s revolutionize metabolomics together.Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#MassSpectrometry #Metabolomics #BiomarkerDiscovery #StellarMS</blockquote></div></article><section><blockquote><h4>Dane Walker</h4>Dane Walker is Regional Marketing Manager at Thermo Fisher Scientific, focused on LC-MS systems across EMEA. With a PhD in Surface Science and a background in scientific instrumentation, he blends technical expertise with strategic marketing to drive data-led campaigns. Passionate about communicating science and enabling innovation, Dane enjoys powerboating, cycling, stargazing, and talking endlessly about mass spectrometry.</blockquote></section>

Unveiling the Power of the Stellar Mass Spectrometer in Metabolomics

<h3>Celebrating innovation in mass spectrometry</h3>We are delighted to announce that Thermo Fisher Scientific has been awarded the prestigious Lab Innovation Award for the Thermo Scientific Stellar mass spectrometer (MS) in the category of Best Technology Innovation. This recognition was bestowed upon us at the annual award ceremony hosted by Lab Innovations and Laboratory News, which celebrates the outstanding achievements and innovations within the lab community.<img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Thermo_Fisher_Scientific_Thermo_Fisher_Wins_Award_for_Stellar_Mass_Spectrometer_f772ae1c5b.jpg" alt="Thermo Fisher Scientific: Thermo Fisher Wins Award for Stellar Mass Spectrometer" srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Thermo_Fisher_Scientific_Thermo_Fisher_Wins_Award_for_Stellar_Mass_Spectrometer_f772ae1c5b.jpg 245w," sizes="100vw" width="1024" height="536"><article><div><h3>Introducing the Stellar mass spectrometer</h3>First introduced during the 2024 American Society for Mass Spectrometry (ASMS) conference, the<a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/1149"> Thermo Scientific Stellar MS</a> is a groundbreaking advancement in the field of mass spectrometry. This state-of-the-art system empowers researchers to advance translational omics research* on an unprecedented scale, facilitating breakthrough discoveries with greater efficiency than ever before.<h3>A key piece in translational research</h3>The Stellar MS completes a critical component of the translational research workflow. It complements our <a target="_blank" rel="noopener noreferrer" href="https://lcms.labrulez.com/products/836">Thermo Scientific Orbitrap Astral MS</a>, which excels in discovering new biomarkers. The Stellar MS plays a pivotal role by connecting these discoveries to clinical research, providing verification of all biomarkers that matter, including peptides, metabolites, and lipids. By equipping researchers with powerful tools like the Stellar MS, Thermo Fisher is enabling faster, more accurate scientific discoveries that will ultimately improve patient outcomes.<h3>Recognizing excellence in innovation</h3>At this year’s Lab Innovations award ceremony, Thermo Fisher received a total of three nominations. In addition to the Stellar MS’s win in the Best Technology Innovation category, our Thermo Scientific Heratherm Environmental Chambers were also nominated in the same category, and our Thermo Scientific TSX Universal Series ultra-low temperature freezers received a nomination in the Best Sustainable Innovation category.<h3>Celebrating our team’s success</h3>We extend our heartfelt congratulations to the entire team on this exciting win! This achievement is a testament to the dedication, hard work, and ingenuity of our scientists, engineers, and collaborators.“Stellar MS delivers a more straightforward routine to create robust quantitative methods for clinical research and [measure] once right, always right,” said Jennifer Van Eyk, Ph.D., Director of Advanced Clinical Biosystems Institute, Cedars-Sinai Medical Center.Peter Morrish, Senior Commercial Manager, EMEA, accepted the Lab Innovation award on behalf of Thermo Fisher Scientific.<h3>Looking forward</h3>As we celebrate this recognition, we remain committed to pushing the boundaries of mass spectrometry and supporting the scientific community with innovative solutions. The Stellar MS is just one example of how we are shaping the future of scientific research and improving human health.Stay tuned for more updates on our latest advancements and how we continue to drive progress in the field of mass spectrometry!*Omics describes the field of large-scale data-rich biology, including genomics (investigating thousands of DNA sequences), proteomics (examining large numbers of proteins), metabolomics (studying large samples of small molecules like tissues and cells), and more. Translational omics research refers to the scientific approach that aims to apply discoveries in the omics field to practical use cases that will improve human health.<blockquote>Visit us on&nbsp;<a target="_blank" rel="noopener noreferrer" href="https://www.linkedin.com/showcase/72003132/admin/dashboard/">LinkedIn:</a>&nbsp;#MassSpectrometry #StellarMS #NextGenMS #FutureOfScience</blockquote></div></article><section><blockquote><h4>Dane Walker</h4>Dane Walker is Regional Marketing Manager at Thermo Fisher Scientific, focused on LC-MS systems across EMEA. With a PhD in Surface Science and a background in scientific instrumentation, he blends technical expertise with strategic marketing to drive data-led campaigns. Passionate about communicating science and enabling innovation, Dane enjoys powerboating, cycling, stargazing, and talking endlessly about mass spectrometry.</blockquote></section>

Thermo Fisher Wins Award for Stellar Mass Spectrometer

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