More Capabilities, New Possibilities in Mass Spectrometry Boston, Oct 14, 2011

Iain Mylchreest, Ph.D

San Jose, CA

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Increasing App’s in Life Sciences Research and Applied Markets

Expanding Application

Base

Metabolite ID/Profiling,pK • Accelerated drug

development and compound assessment

Proteomics • Biomarker discovery • Pathway analysis • Protein identification • PTM’s

BioPharma • Biologics discovery and

development

Metabolomics/Lipidomics • Comprehensive study of

metabolites for disease and therapeutic assessment

Environmental • Water, soil analysis

Clinical/Toxicology • Disease markers • Pain management • Drugs of abuse

Food Safety • Inspection, nutrition • Chemical contaminant,

microbial detection

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Dionex: Leading Chromatography Provider

Ion Chromatography Systems

• Leading technology and market presence, especially in environmental and food safety

Liquid Chromatography Systems

• UHPLC-ready across entire platform, comprehensive columns offering

Chromatography Data Systems

• Gold standard performance and complementary to our leading LIMS

Complements Our Leading Mass Spectrometry Offering

• Deep applications expertise for compelling, high productivity, integrated solutions

Leading technology and performance across entire portfolio

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Highest Performance LC Portfolio on the Market

For all applications & configurations, standalone HPLC to MS front end

Transcend UHPLC Solutions For multiplexed workflows

UHPLC Systems 1000 to 1250 Bar

Standard Systems Range of detectors

Dual LC Systems Two systems in one

Nano LC Solutions Flexibility and ease-of-use

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• Proteomics • Biomarker Discovery • Metabolism • Metabolomics • Lipidomics • PTM Analysis

• Proteomics • Metabolomics • Bioanalysis • Clinical / Toxicology • Environmental • Food Safety

The Industry’s Leading Portfolio of MS Solutions

Triple Quads

Quantitative Qualitative

Non-targeted Analysis

Targeted Analysis Ion Traps

Hybrid Orbitraps ESI-Orbitraps

High Resolution Accurate Mass

High Resolution Accurate Mass Fast Scanning

Fast Scanning Fast Scanning MS and MSn

Research Research Applied Markets Applied Markets

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2000 2003 2005 2008 1999 2011

Dallas Proof-of-the-principle for the Orbitrap mass analyzer

Denver Exactive benchtop LC-Orbitrap launch

Long Beach Resolving power >100,000 demonstrated on concept instrument

Orbitrap: Continually Extending MS Performance Chicago Orbitrap with external accumulation developed LTQ launch

San Antonio First Commercial LTQ Orbitrap launch

Philadelphia LTQ Orbitrap Velos

2009

Denver Orbitrap Velos Pro Orbitrap Elite Q Exactive

Original 1999 Orbitrap patent US 5,886,346

ASMS 2011: The biggest launches in Orbitrap history

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Orbitrap: Unmatched Resolution vs. TOFs 400,000

300,000

200,000

100,000

FWHM

2000 m/z 1000 m/z 200 m/z

C B A

Protein + Peptide Fragments Peptides Drugs Thermo S C I E N T I F I C

Routine Orbitrap Resolution

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• Metabolite profiling, peptide sequencing, toxicology

• Sensitivity equal to high performance triple quads

• Identify, quantify and confirm in one analysis

Strengthening Our Leading Position in Mass Spectrometry

Diverse Technology Introductions

Extending Ion Trap Leadership: Velos Pro

OT Elite Quantum Leap in Orbitrap Performance

Revolutionary Q Exactive The “Quanfirmation” Instrument

June 2011 ASMS Launches

• Metabolite ID, peptide sequencing

• Fastest and most sensitive ion trap on market

• Ideal hybrid front-end • New fragmentation capability

• Proteomics, detailed structural analysis

• High field Orbitrap most significant advance since first Orbitrap

• Resolution and scan speed 4X current Orbitrap

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Velos Pro: Raising the Bar in Ion Trap Performance

• Fastest: first ion trap with 66,000 amu/sec. scan speed, 2X improvement

• New high dynamic range detection system dramatically enhances peptide/small molecule quantitation

• New Generation II ion optics for improved robustness

• Unique Trap HCD fragmentation, gives triple quad like fragments for improved molecule structural identification

Ultimate in ion trap speed, sensitivity and flexibility

The Fastest, Most Sensitive Ion Trap in the World

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Orbitrap Elite: The New Performance Standard

• New 7 Hz HCD capability • New secondary detection system for

enhanced dynamic range • Multiple fragmentation techniques for

comprehensive peptide and protein ID; unambiguous small molecule identification

• Ultimate in top down protein analysis A quantum leap in ultra high resolution and accurate mass analysis

Unprecedented mass resolution

Technology Breakthroughs: New High Field Orbitrap Resolving power of >240,000 4X scan speed improvement Advanced signal processing

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Benefits of New High Field Orbitrap Analyzer

Ultra high resolution and fragmentation flexibility for complex analysis

High-field Orbitrap

+

• Smaller size delivers 2X improved resolution and scan speed • Advanced signal processing gives 2X improved resolution and scan speed • With multiple fragmentation capabilities, significantly enhanced performance

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IgG Analysis: Orbitrap Elite

gG e5_ 0u_ 5 _ 5e _tube e s 0_ e g ad e t _ t # 60 6 6 08T: FTMS + p ESI sid=45.00 Full ms [1000.00-4000.00]

2000 2100 2200 2300 2400 2500 2600 2700 2800 2900 3000 3100 3200m/z

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45

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85

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Rel

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bund

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2815.46

2764.32

2712.06 2865.55

2667.31

2923.732621.38

2576.95

2981.072533.99

2492.48

2452.32 3043.83

2413.38

3102.662336.652269.39

3171.552021.95 2201.192113.94 3242.36

Orbitrap Elite @15000 R

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gG e5_ 0u_ 5 _ 5e _tube e s 0_ e g ad e t _ t # 60 6 6 08T: FTMS + p ESI sid=45.00 Full ms [1000.00-4000.00]

2700 2720 2740 2760 2780 2800 2820 2840m/z

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2764.32

2812.502712.06

2818.46

2767.26

2717.81

2809.50 2821.412770.14

2758.432709.18 2720.76

2824.332772.92

2723.442827.19

2776.04 2806.652725.972706.35 2778.93 2830.23

2755.61 2781.592731.80 2833.482783.65 2837.78

2737.41 2791.22 2844.442742.66

2804.11

Orbitrap Elite: Raw Spectrum zoom-in

Glycoforms – Δm = 162 Da

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OT Elite IgG ReSpect Deconvoluted Spectrum

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Q Exactive: Redefining Qual/Quan Workflows

• New high performance quadrupole parent ion selection capability

• New S Lens ion optics 3X sensitivity • Targeted & non-targeted screening • 3 workflows in one analytical run • New data dependent scanning • Multiple ion filling capabilities > speed

Exceptional MS/MS sensitivity, speed and data quality

Trace-level metabolites, contaminants, peptides/proteins in complex mixtures

QuanfirmationTM: Simultaneously identify, quantify

and confirm in one analytical run Resolving power of >140,000

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It is a simple instrument! (Makarov)

C-trap

Central electrode

Outer electrodes

HCD collision cell

Bent Flatapole

Z-lens

Quadrupole mass filter

Injection Flatapole

S-Lens assembly

Capillary Figures and design courtesy J. Rykl, Thermo Fisher Scientific, 2011

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Exactive: Speed

Peakwidth (FWHM) = 0.8 sec Scans/peak = 21

1.75 1.80 1.85 1.90 1.95 Time (min)

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1.75 1.80 1.85 1.90 1.95 Time (min)

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Peakwidth (FWHM) = 1 sec Scans/peak = 11

Resolution Setting: 35,000 Resolution Setting: 70,000

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More Possibilities, Powered by Orbitrap

Exactive • Mass range m/z 50-4000 • Mass accuracy: <2ppm • Max resolution: 100,000

LTQ Orbitrap XL • Mass range m/z 200-4000 • Mass accuracy <1ppm • Mass Resolution >100,000

Q-Exactive • Mass range m/z 50-4000 • Mass accuracy: <2ppm • Max resolution: 140,000

Orbitrap Velos Pro • Mass range m/z 200-4000 • Mass accuracy <1ppm • Mass Resolution >100,000

Orbitrap Elite • Mass range m/z 200-4000 • Mass accuracy <1ppm • Mass Resolution

>240,000

Perf

orm

ance

Screening Research Affordable Flexibility

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New Software to Support Workflows

New leading edge software for challenging MS workflows

MetQuest 1.0 • For HR/AM qual/quan metabolic screening • Unbiased full-scan data reveals unexpected metabolites

Tracefinder 1.1 • Automate environmental, food safety & clinical workflows • Supports Triple Quad, Ion Trap and Exactive experiments

Xcalibur 2.1 • Core software control for all Thermo Scientific MS systems • Now supports TLX/multiplexing and Turboflow automation

Exactfinder 1.0 • Integrated HR/AM qual/quan workflow analysis • Targeted and non targeted screening

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Novel MS Technologies for Proteins: Applications Growth Drivers

Advances in Hardware, Software and Reagents Move Applications to Higher Throughput

Technology improves – applications growth follows

Quantitative Qualitative Quantitative /Multiplexed

Structural accuracy at high sensitivity results in complete protein sequence determination including PTMs

High sensitivity, accuracy, precision multiple protein quantitation in biological media

High sensitivity, accuracy, precision multiple protein quantitation in biological media – many experiments in one run

Hardware: VelosPro OrbitrapElite

Hardware: TSQVantage QExactive

Hardware: VelosPro ObitrapElite

Software Software Software

Reagents Reagents Reagents

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New Proteomics Tools

Proteome Discoverer 1.3 • Comprehensive mass informatics platform for data mining • Integrate biological information from multiple sources

SIEVE 2.0 • For label-free, semiquantitative, differential expression • Expanded to support metabolomic & lipodomic workflows

Pinpoint 1.2 • Enhances speed and confidence in targeted quantitation. • Supports multiple experimental approaches including HRAM

Thermo Scientific Pierce Enrichment Kits • Enrich, capture and identify proteins, peptides, kinases • Peptide Calibration kits and libraries, ActivX kinase probes

Easy-nLC 1000 • Split-free, nano-flow LC optimized for biomolecule separation • Effortless ultra high pressure operation (1000 bar, 15,000 psi)

Leading edge tools for proteomics research

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New Enabling Technologies

Protein Biomarker & Quantitative Immunoassay

Research Market

Life Science Researchers, Biotech / Pharma & CLIA Testing

Clinical Research

Clinical diagnostic research

Pre-MS Proteomic Research Market

Sample preparation for Life Science Researchers & Biotech / Pharma

• IBI has developed proprietary enabling technology that solves a critical bottleneck in quantitative detection of protein biomarkers. It is a simple, yet powerful, approach.

• The Mass Spec-Immuno-Assay (MSIA) tip format delivers greater sensitivity, better cost effectiveness and higher throughput compared to other available methods.

New tools for quantitative MS-based proteomics

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MSIA Platform Workflow – What we will deliver

• Combining ‘Best in Class’ enabling technologies for an integrated and automated work flow solution for reproducible, high throughput sample preparation and biomarker quantitation in normal and disease states.

biofluid (plasma,

serum, urine, CSF, tissue

lysate) Affinity Extraction

Proprietary micro-columns pipette tips for enrichment of even Low abundance proteins & variants extracted directly from biofluids

Sample Processing Target protein capture, rinse and

elution step requires multiple aspiration and dispense cycles –

enabled by Versette

Mass Spec Analysis Quantitative analysis - Ability to detect different isoforms (splice variants and post translational modifications) using

MRM technology & Pinpoint SW.

TSQ Vantage MS MSIA Pipette Tip Versette ALH

Targeted Antibodies

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Summary

• Dionex acquisition: comprehensive HPLC portfolio complements leading MS technologies

• Velos Pro Ion Trap: leadership extended with high speed quantitative capabilities

• High field Orbitrap Elite: with >240,000 resolution, the most significant advancement since first Orbitrap

• Q Exactive: Revolutionary “Quanfirmation:” screen, identify, confirm and quantify in one run

• Workflow based software: comprehensive new suites for all applications