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Innovation with IntegrityNMR & Mass Spectrometry
Bru
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Powering Comprehensive Studies
Metabolomics
Power Your Metabolomics Studies
The accurate determination of changes in small molecule profiles related to a disease, therapeutic intervention, genetic modification or environmental variation is central to all metabolomics studies.
Bruker remains the leader in integrated solutions for metabolomics with its latest innovations for hyphenated NMR, LC-MS and GC-MS technologies. These systems can be used for a multitude of metabolomics studies and are very well equipped to detect, identify, and quantify metabolites across the large chemical diversity of compounds building the metabolome.
Many different pieces of information have to be linked in metabolomics experiments. Bruker provides all you need in a comprehensive, integrated system adjustable to your growing requirements.
Bruker‘s analytical systems for targeted and non-targeted metabolomics are used in:
• Clinical research
• Public health studies
• Plant science
• Nutrition & food
• Microbial research
• Environmental & ecology research
• Drug discovery & development
• Biochemistry
• Systems biology
Comprehensive Solutions
Bruker`s NMR based food screening solutions are best suited for sample classification e.g. for food quality control and can be combined with Bruker´s MS solutions for food safety studies.
impact II™ – omics knowledge generation
Equipped with the latest of Bruker’s time-of-flight technology, the impact II delivers the best of what only TOF can do: combined resolution, sensitivity, mass accuracy and dynamic range, over the full mass range.
Because biology’s diversity demands versatility …
Bruker solutions for the main Metabolomics workflows:
Non-targeted profiling
Maximum coverage of the metabolome’s chemical space can be achieved by utilizing Bruker’s high performance LC-MS, GC-MS and NMR systems in conjunction with dedicated software for data evaluation. These systems combine all necessary tools for feature extraction, statistical evaluation and compound identification. The unique hyphenationof high resolution MS and NMR, the MetabolicProfilerTM, enables rapid bio-marker detection and identification by combined statistical evaluation of MS and NMR data.
Targeted analysis - biomarker validation
Identified biomarkers can be validated in targeted metabolomics experiments, where a limited number of compounds are quantified.
For such tasks, Bruker offers both dedicated triple quadrupole MS systems with excellent sensitivity and powerful quantitation capabilities as well as more versatile ESI-UHR-QTOF MS systems that provide highly accurate data with a wide dynamic range and excellent resolu-tion for the simultaneous analysis of both high- and low-abundance metabolites.
Transform Your Data into Knowledge
Non-targeted Metabolomics – Detect and ID possible Biomarkers using ProfileAnalysis
• Increased productivity using “Find Molecular Features” – automatically extract all relevant information from complex LC-MS datasets • Ease of use for handling complex data sets – ○ Retention time alignment ○ Different scaling, normalization & filtering options• Quickly pinpoint relevant information by supervised and unsupervised statistics: PCA, t-Test, ANOVA, PLS-DA, etc.
PCA scores and loadings plot
Unsupervised statistical analysis – ProfileAnalysis™
A) Accurate mass and isotopic fidelity in MS and MS/MS spectra; B) SmartFormula3D™ - unique molecular formula generation capabilities by combining accurate mass and isotopic pattern information in MS and MS/MS spectra; C) In-silico Fragmentation via direct Link to MetFrag (IPB Halle, Germany); D) Detailed evaluation using the FragmentExplorer supports the in-silico fragments generated by MetFrag.; E) Verification of the identity with reference standard.
De novo identification of target compound X
53.0390
80.0494
96.0443
124.0392
QC_aMSMS.d: +MS2(124.0393), 20.5-30.7eV, 0.4-0.6min #67-99
53.0394
80.0496
106.0291
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Nicotinate_aMSMS.d: +MS2(124.0393), 20.5-30.7eV, 0.5-0.5min #79-870
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ID of compound X
De novo identification of target compound X
ID of compound X
• Hypothesis driven targeted data evaluation quickly turns LC-QTOF- MS data into knowledge• Rapidly screen for known metabolites• Biochemical pathway driven workflows• Deeper insights by sample batch processing and retrospective data analysis
Get twice the answers from Compass PathwayScreener.
Hypothesis generation
Full scan LC-MS data (MS/MS)
Knowledge
Unknown ID
Pathway directed targeted
data evaluationNovel hypothesis
Tailored views enable straightforward data review
Hypothesis based pathway driven analysis – PathwayScreener™
Read more:Bruker Daltonics Application Note ET-38
Combine Targeted and Non-Targeted Workflows for Deeper Insights
Non-targeted data evaluation
1) Query formula or compound name in KEGG database
2) Select relevant metabolic pathway(s)
Batch of samples
Area
Analysis
Chromatogram
MS
Analytes
Accelerate Known Target Compound Identification
• Accelerate data analysis in metabo- lomics research with this tandem mass spectrometry accurate-mass library• Increase your productivity with high- confidence identification based on manually curated MS/MS spectra
• Obtain deeper insights with links to external repositories for bringing identified molecules quickly into a biological context
Bruker HMDB Metabolite Library™
HRAM Metabolomics LC-MS/MS spectral library
“We are delighted to have collaborated with Bruker to produce a new Human Metabolite MS/MS accurate-mass library with much improved spectral quality. This library, along with an automated spectral acquisition and processing strategy, allows researchers to identify metabolites very quickly and with highest confidence.”
Dr. Liang Li, Professor of Chemistry, University of Alberta,(co-PI of the Human Metabolome Database (HMDB) project) explained.
Novel GC-APCI II source for
• Improved LLQQ and dynamic range by optimized source chamber design • Revealing more significantly regulated metabolites• Improved unknown ID capabilities by automated calibration routines• Increased ease of use by tool free switching between GC and LC mode
HRAM Metabolomics LC-MS/MS spectral library
“GC-APCI II is expected to reveal more significantly regulated metabolites in metabolic fingerprinting and subsequently to enable their sensitive quantification.”
Dr. Katja Dettmer, Institute of Functional Genomics, Regensburg University, Germany
Enhanced Metabolite Profiling by GC-MS
GC-APCI-MS: Identification by accurate mass and isotopic pattern
... use the same QTOF MS for LC and GC analysis
Metabolomics studies based on gas chromatography-mass spectrometry (GC-MS) are well-established and typically employ electron impact (EI) ionisation. Unfortunately, many possible biomarkers detected in these experi-ments cannot be identified due to the lack of EI reference spectra for a majority of biologically relevant compounds.
Hyphenating GC with HRAM TOF-MS technology by soft atmospheric pres-sure ionisation (APCI) can preserve the molecular ion information and deliver accurate mass and isotopic pattern infor-mation. This data enables identification of possible biomarkers which remained “unknowns” up until now.
Read more:Bruker Daltonics Application Note ET-22
Read more: „Enhanced metabolite profiling using a redesigned atmospheric pressure chemical ionization source for gas chro-matography coupled to high-resolution time-of-flight mass spectrometry”
Christian J. Wachsmuth, Thomas A. Hahn, Peter J. Oefner, Katja DettmerAnalytical and Bioanalytical Chemistry 2015 in press
C9H24NO2Si2
eXtreme Resolution for Deeper Insights
In this rat testis dataset, the two displayed lipid signals have a mass difference of only 3 mDa. The signal shown in green is found in the seminiferous tubules, the one in red is seen in the interstitial space. At a resolving power of 470k the signals are clearly resolved.
solariX XR™ FT-ICR-MS
™
Spatial Metabolomics by MALDI Imaging
• Direct localization of lipids, metabo- lites, drugs, and peptides• High selectivity using extreme resolution• High specificity through unparalleled mass accuracy
• Full statistical analysis package (SCiLS) for true non-targeted discovery
Elemental composition by IFS – Isotopic Fine Structure
• Read out elemental compositions based on eXtreme Resolution• Create powerful streamlined workflows to efficiently discover and ID new metabolites
Rapid profiling by USP – Ultra Fast Statistical Profiling
• Rapid profiling of complex metabolic extracts • Automated data acquisition by ESI or MALDI• Increased sample throughput 10-100x
eXtreme resolution reveals IFS
Read more: Bruker Daltonics Application Note FTMS-43
Read more: Bruker Daltonics Application Note FTMS-51
Verify Your Small Molecule Structures
Fully integrated and automated NMR and HRAM-MS
• Generate complementary metabo- lomics data for statistical analysis as well as for the identification of un- known compounds• Combine the structural capabilities and highest reproducibility of NMR with mass accuracy and sensitivity of MS - enabling identification and quan- tification of metabolites for biomarker discovery
“Mass spectrometry and NMR are the two major platforms used for unknown identification in metabolomics research because they provide complementary information for de novo identification”
Professor Kazuki SaitoGroup Director of the Metabolomics Research Group, RIKEN Center for Sustainable Resource Science, Yokohama, Japan, Professor of the Graduate School of Pharmaceutical Sciences Chiba Univesity, Japan
Read more:Bruker Daltonics Application Note LCMS-85
Read more:Bruker Daltonics FUSION-SV Flyer
The Bruker FUSION-SV™ software solution for rapid automatic structure verification allows scientists to easily integrate and combine high resolution accurate mass (HRAM) mass spectrometry and complementary NMR data.
Bruker FUSION-SV Features
• Fully automatic structure verification for small organic molecules synergizing NMR and MS data into one result• Structure centric workflow which guides chemists straight to a clear and meaningful report• Bruker FUSION-SV’s intuitive operation enables the rapid deployment of structure verification workflows
Configurable Workbench layout
Unambiguously Identify Unknown Compounds by MS + NMR
Boost Your Metabolomics Impact
MetabolicProfilerFully integrated and automated NMR and HRAM-MS generate complementary metabolomics data for statistical analysis as well as for the identification of unknown compounds.
Meta-bolomics
GC-APCI SourceUnique combination of high-resolution accurate mass MS with GC enables identification of unknowns in GC-MS based metabolomics.
Triple Quadrupole Mass SpectrometersDeliver exceptional sensitivity, precision, accuracy, linearity, and a wide dynamic range for targeted metabolomics.
ESI–QTOF mass spectrometers featuring Instant Expertise™High performance ESI-TOF-MS Instruments for full sensitivity and resolution at fast scan speeds to detect, resolve, identify and quan-tify even low-level metabolites.
solariX XR FT-ICR-MSProviding eXtreme Resolution (XR™) to reveal the fine struc-ture (IFS-MS) in isotopic pat-terns that are uniquely specific to the exact molecular formulae of the detected compounds. Gain unique insights into highly complex samples.
Recommended Metabolomics Publications
Plant Metabolomics
Combination of liquid chromatography-Fourier transform ion cyclotron resonance-mass spectrometry with 13C-labeling for chemical assignment of sulfur-containing metabolites in onion bulbs.
Nakabayashi R, et al.: Anal Chem. 2013, 5;85(3): 1310-1315.
Annotating unknown components from GC/EI-MS-based metabolite profiling experiments using GC/APCI(+)-QTOFMS
Strehmel N. et al.:, Metabolomics 2014, 10(2): 324-336
Bacterial Metabolomics
Microbial strain prioritization using meta-bolomics tools for the discovery of natural products
Hou Y. et al.: Anal Chem. 2012, 15; 84(10): 4277–4283.
Myxoprincomide, a novel natural product from myxococcus xanthus discovered by a comprehensive secondary metabolome mining approach
Cortina N. et al.: Angewandte Chemie International Edition 2012, 51(3), 811–816
Clinical Metabolomics
Development of a universal metabolome-standard method for long-term LC−MS metabolome profiling and its application for bladder cancer urine-metabolite-bio-marker discovery
Peng J. et al.: Anal Chem. 2014, 1;86(13): 6540-7
Molecular cartography in acute chlamydia pneumoniae infections – a non-targeted metabolomics approach.
Müller C. et al.: Anal Bioanal Chem 2013, 405: 5119–5131
Food & Environmental
Apple peels, from seven cultivars, have lipase-inhibitory activity and contain numerous ursenoic acids as identified by LC-ESI-QTOF-HRMS
McGhie T. et al.: J. Agric.Food Chem. 2012, 60, 482−491
Ultra high performance liquid chromatogra-phy-time of flight mass spectrometry for analysis of avocado fruit metabolites: Method evaluation and applicability to the analysis of ripening degrees
Hurtado-Fernández E. et al.: J Chrom A 2011, 1218, 42(21): 7723–7738
Lipidomics
Optimizing a ultrahigh pressure liquid chro-matography-time of flight-mass spectrometry approach using a novel sub-2μm core-shell particle for in depth lipidomic profiling of caenorhabditis elegans.
Witting M. et al.: J Chrom A 2014, 1359: 91–99
Invertebrate Metabolomics
Metabolomic changes in caenorhabditis elegans lifespan mutantsas evident from GC–EI–MS and GC–APCI–TOF–MS profiling
Jaeger C. et al.: Metabolomics 2014, 10(5): 859-876
A novel ion pairing LC/MS metabolomics protocol for study of a variety of biologically relevant polar metabolites
Knee J. et al.: J Chrom B 2013, 936: 63-73
Spatial Metabolomics
Molecular cartography of the human skin surface in 3D
Bouslimani A. et al.: PNAS 2015, 112(17): 2120-2129
Bru
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“We are pushing the boundaries of metabolite identification in our lab with Bruker´s hyphenated UHPLC-UV-MS-SPE-NMR system. A combination of complementary MS and NMR technology will be used to accelerate identification of unknown compounds.”
Professor Lloyd W. SumnerSamuel Roberts Noble Foundation Ardmore, OK, USA
Bruker Daltonik GmbH
Bremen · GermanyPhone +49 (0)421-2205-0 Fax +49 (0)421-2205-103
Bruker Daltonics Inc.
Billerica, MA · USA Phone +1 (978) 663-3660 Fax +1 (978) 667-5993
[email protected] - www.bruker.com
For research use only. Not for use in diagnostic procedures.
Think Biology!
Gain Deeper Insights
In the past decade modern metabolomics has quickly grown and become widely adopted. The growing number of detect-able and identifiable substances increase the need for comprehensive workflows. Bruker remains the leader in integrated solutions for metabolomics with its latest innovations for hyphenated NMR, LC-MS and GC-MS technologie.
