[ WELCOME ] 2015 Waters Corporation 1

[ WELCOME ] 2015 Waters Corporation 1

Lance Nicolaysen Senior Director Americas Mass Spectrometry Business Waters Corporation, USA 2015 Waters Corporation 2

MS-Related Job Opportunities Field Marketing Manager, Health Sciences (LC/MS MA Clinical / Forensic / Toxicology) Mass Spectrometry Sales Specialist WA Chemistry Sales Specialist NJ Field Sales Account Manager NC Field Service Engineer NJ, TX, MD, CA, PA, MD, VA, LA Inside Instrument Sales Specialist MA Inside Sales Specialist - Chemistry Consumables MA Mass Spectrometry Clinical Specialist - West District CA Mass Spectrometry Sales Specialist Brazil North District Business Development Manager MA Regional Service Manager CA Senior MS Applications Chemist MA SFC/SFE Field Service Engineer CA SFC/SFE Sales Specialist USA www.waters.com/careers 2015 Waters Corporation 3

Gordon Kearney Senior Manager Mass Spectrometry Product Management Waters Corporation, UK 2015 Waters Corporation 4

What s New from Waters: 2015 Waters Users Meeting 63rd ASMS Conference, St. Louis, MO 30 th May 2015 2015 Waters Corporation 5

Set up theme Innovation Performance Access 2015 Waters Corporation 6

Separations science Mass spectrometry Standards and reagents Informatics Chemistries 2015 Waters Corporation 7

Oasis PRiME HLB How can Oasis PRiME HLB simplify sample preparation? How does it compare to other sample preparation products? Sales Tools! Questions? 2015 Waters Corporation 8

GlycoWorks RapiFluor-MS N-Glycan Kit Come Visit to Play: 2015 Waters Corporation 9

ACQUITY UPLC Glycoprotein BEH Amide 300Å 1.7 µm 2015 Waters Corporation 10

NuGenesis LMS 2015 Waters Corporation 11

Progenesis QI v2.1 New features for ASMS 2015 More compound databases Greater choice for successful compound ID NIST LC-MS/MS libraries ChemSpider results refinement Theoretical fragmentation Elemental composition filtering Increased confidence in results Pathways analysis Placing discoveries in biological context IPA (Ingenuity / Qiagen) Breakfast Meeting Wednesday Book your place now! 2015 Waters Corporation 12

UNIFI UNIFI 1.8 Streamlined Instrument Controls Seamless Workflows Integrated Ion Mobility Tools Sophisticated Reporting UNIFI: Taking Data to Knowledge 2015 Waters Corporation 13

The Evolution of Ion Mobility MS 2015 Waters Corporation 14

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 15

Storage Region Gate Electric Field Second Transfer Region Quadrupole Mass Filter Collision Cell Lenses Pusher Detector Ions Electrospray Tip Mobility Region First Transfer Region Stacked Ring Ion Guide Reflectron 2015 Waters Corporation 16

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 17

2015 Waters Corporation 18

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 19

2015 Waters Corporation 20

The Challenge of Ion Mobility 2015 Waters Corporation 21

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 22

2015 Waters Corporation 23

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 24

2015 Waters Corporation 25

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 26

Structure Separation CCS Specificity Sensitivity 2015 Waters Corporation 27

Opportunity Measure CCS of every ion in every analysis Incorporate CCS into routine workflows 2015 Waters Corporation 28

2013 Synapt G2Si HDMS Enhancing Workflows (implementing CCS) Dedicated IMS Apps Software (UNIFI TM ), MS Compare, Intellistart TM 2015 Accessible Ion Mobility 2009 Synapt G2 HDMS 2 nd Gen TriWave & QuanTOF 2011 Synapt G2S HDMS StepWave 2010 MALDI Synapt G2 HDMS HDI Software, ETD 2007 MALDI Synapt 2003 First T-Wave IMS 2006 Synapt HDMS TriWave, DriftScope 2004 Prototype SYNAPT Q-IMS-Tof 2001 Linear Field IMS 2015 Waters Corporation 29

Beyond Resolution 2015 Waters Corporation 30

2015 Waters Corporation 31

QuanTof2 Detector Dual Channel 7.2GHz (up-sampled) 10-bit ADC Amplifier ADC From MS x 1 x 0.03 ADC High Gain Channel ADC Low Gain Channel Peak Processing Peak processing Apply calibration Combine ADC Test signal 2015 Waters Corporation 32

Benefits of QuanTof2 2015 Waters Corporation 33

Intensity High Selectivity (HS) MS/MS m/z RT DT m/z m/z DT DT 2015 Waters Corporation 34

Routine ion mobility Seamlessly from sample to answers Just press START Simply Acquire Get to the Answers 2015 Waters Corporation 35

Benefits of Routine Ion Mobility Clarity cleaner mass spectra Confidence valuable CCS information for every ion System Productivity with UNIFI analytical workflows 2015 Waters Corporation 36

Benefits of Routine Ion Mobility Clarity 617.3076 m/z 236.6 Å 2 Verapamil 441.2758 m/z Unlimited Product ion HDMS E 289.1923 m/z 518.2235 m/z 2015 Waters Corporation 37

Vion measured CCS(N 2 ) values <2% time after time Reserpine - 609.28 m/z : 252 Å 2-0.10 % RSD LueEnk 556.27 m/z : 230 Å 2-0.15 % RSD Terfenadine 472.32 m/z : 230 Å 2-0.12 % RSD Verapamil 455.29 m/z : 211 Å 2-0.17 % RSD Sulphadimethoxine 311.08 m/z : 168 Å 2-0.15 % RSD Caffine 195.08 m/z : 136 Å 2-0.22 % RSD Data from 400 injections over 33 hours 2015 Waters Corporation 38

Acetamiprid Azoxystrobin Bromuconazole II Carbetamide Carbofuran Chlorbromuron Chloridazon (Pyrazon) Clethodim I Clethodim I fgt Clethodim II Clethodim II fgt Cyromazine DEET Demeton-S-methyl-sulfone Dichlorvos Diethofencarb fgt Disulfoton-sulfone Diuron Ethoprophos Fenamiphos sulphone Fenoxycarb Fenoxycarb fgt Fenpropimorph Fenpyroximat Flutriafol Formetanate Fosthiazate Furathiocarb Heptenophos Hexazinone Indoxacarb Isoxaben Linuron Mesotrione Metalaxyl Methabenzthiazuron Metobromuron Metolachlor Metribuzin Mevinphos trans Nitenpyram Oxadiazon pethoxamid phenthoate Pirimicarb Primicarb-desmethyl fgt* Propamocarb propargite Prosulfocarb Pymetrozine Pyraclostrobin Pyridaben Pyridaben fgt 1 Pyridate Pyriproxifen Simazine Spinosad Spirodiclofen Spiroxamine II Tebuconazole tepraloxydim Thiacloprid Thiodicarb Thiophanate-methyl Triasulfuron Triflumuron Trinexapac-ethyl Triticonazole Vamidothion % CCS Difference WIV ISP Study: SYNAPT/Vion Comparison for Pesticides Confidence 5 Synapt WIV ISP/Vion IMS Q ToF Comparison April 2015 4 3 2 1 0 Pesticide -1-2 -3-4 -5 Dr Severine Goscinny, Scientific Institute of Public Health, Belgium Axis Title At Waters user meeting 2015 Waters Corporation 39

Benefits of Routine Ion Mobility Confidence 2015 Waters Corporation 40

153 Coeluting Components Resolved with Vion Mobility System Productivity 2015 Waters Corporation 41

2015 Waters Corporation 42

Mike Wilson 30 th May 2015 2015 Waters Corporation 43

What if...

2015 Waters Corporation 57

What is REIMS? Rapid Evaporative Ionization Mass Spectrometry iknife Hand-held sampling device Diathermy Generator Informatics System Sample REIMS Source 2015 Waters Corporation 58

How does it work? 2015 Waters Corporation 59

How does it work? 2015 Waters Corporation 60

Product Availability 2015 Waters Corporation 61

Workflow o Fast, direct ionization o No sample prep required o No chromatography required Acquire Import Analyze Identify Review 2015 Waters Corporation 62

Workflow Acquire Import Analyze Identify Review o Easily manage large datasets o Handle multiple replicates o Enhance data quality 2015 Waters Corporation 63

Workflow o Easy to use multivariate statistics o Differentiate sample groups o Highlight significant features Acquire Import Analyze Identify Review 2015 Waters Corporation 64

Workflow Acquire Import Analyze Identify Review Flexible compound search methods o Compatible with popular databases o Confident assignments o 2015 Waters Corporation 65

Workflow Effective visualization tools o Integrate with other informatics o Employ pathway analysis o Acquire Import Analyze Identify Review 2015 Waters Corporation 66

Applications Food Research 2015 Waters Corporation 67

Applications Food Research 2015 Waters Corporation 68

Applications Health Sciences Research 2015 Waters Corporation 69

Applications Health Sciences Research The REIMS Research System with iknife Sampling is intended for research use only, and is not intended for diagnostic or therapeutic use 2015 Waters Corporation 70

Find out more Waters Hospitality Suite Renaissance Grand Hotel, Ballroom E Mon Wed, 8pm 11pm 2015 Waters Corporation 71

Find out more Visit us at the Waters Hospitality Suite Renaissance Grand Hotel, Ballroom E Mon Wed, 8pm 11pm 2015 Waters Corporation 72

Find out more www.waters.com/reims 2015 Waters Corporation 73

2015 Waters Corporation 74

Ambient Ionisation Mass Spectrometry Mike Morris Waters Users Meeting ASMS St Louis 30 th May 2015 2015 Waters Corporation 75

Newborn Screening Inherited metabolic disorders 2015 Waters Corporation 76

Acylcarnitine analysis Duke University RCOO H (CH 3 ) 3 N CH 2 CH CH COOH Butylation RCOO H Charlie Roe (CH 3 ) 3 N CH 2 CH CH COOC 4 H 8 H Dave Millington CID - RCOOH -(CH 3 ) 3 N -C 4 H 8 [ CH 2 CH CH COOH ] + (m/z 85) Don Chace 2015 Waters Corporation 77

Amino Acids & Acylcarnitines Neutral and acidic amino acids Neutral Loss 102Da 2-minute measurement Up to 50 metabolic disorders Acylcarnitines Precursors of m/z85 2015 Waters Corporation 78

Adoption of MS/MS in the US North Carolina, 1997 New England, 1998 California, 2004 New York, 2005 Texas, 2006 It ll never catch on, you know! 2015 Waters Corporation 79

MS/MS in Neonatal Screening Laboratories In the US: All states have Tandem MS programs >80% use Waters instruments In the UK: Leeds, Manchester, Birmingham, Newcastle, Sheffield, North London, South London, Glasgow, Portsmouth, Glasgow In Europe: Belgium, Germany, Netherlands, Sweden, Hungary, Italy, Norway, Switzerland, Russia, UK, Denmark RoW: Australia, Saudi Arabia, Brazil, Argentina, China, Canada, Hong Kong, Korea, Turkey, Kuwait, Taiwan, Japan, Costa Rica, Malaysia, Thailand, Oman, Philippines, Vietnam. In 2015, between 12,000,000 and 15,000,000 babies will be screened using tandem mass spectrometry. 2015 Waters Corporation 80

REIMS and DESI Plenary Speakers Ambient MS in clinical diagnostics from microbiology to MS-guided surgery Professor Zoltan Takats, Imperial College London Addressing complex and critical food integrity issues using the latest analytical technologies Professor Chris Elliott, Queen s University Belfast 2015 Waters Corporation 81

[ THANKS ] 2015 Waters Corporation 82