ZipChip TM. Microfluidic CE-ESI Utility Life Sciences CE-ESI-MS Applications. Please visit us at

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1 ZipChip TM Microfluidic CE-ESI Utility Life Sciences CE-ESI-MS Applications Please visit us at // Actionable Intelligence HPMS & On-board Analytics / Slide 1 June 2016

2 // Presentation Overview Devices Company Overview Devices ZipChip Technique How does ZipChip CE-ESI work? Integration to Commercial Mass Spectrometers for Key Life Sciences Applications // Actionable Intelligence HPMS & On-board Analytics / Slide 2 June 2016

3 // Company Overview Founded in March 2012 creating elegant new tools for fast, unique analyte separations through CE and miniaturized mass spectrometer detection. Science Founder Prof. J. Michael Ramsey of UNC-Chapel Hill, previously science founder of Caliper (NASDAQ: CALP) later acquired by Perkin Elmer Raised $29M Series A, B & C ARCH, Razor s Edge, UTEC, Schlumberger, & Aramco The seminal IP underlying is an outgrowth of >$20M in federally funded development programs DOE, DARPA, DTRA Flagship Handheld HPMS Product Released March 2014 shipments began mid 2014 Development partnerships in place w/ In-Q-Tel, Schlumberger, & DTRA -- DTRA awarded $11.5M contract in April 2015 Customer pull for accelerated workflows disruption of centralized lab model A platform technology handheld, tiny footprint systems, & even wearables Multimarket impact Safety & Security, Oil & Gas, & Life Sciences // Actionable Intelligence HPMS & On-board Analytics / Slide 3 June 2016

4 // ZipChip CE-ESI Utility Overview FAST microfluidic CE separations developed over last 10 years by the J. Michael Ramsey Group at University of North Carolina. Cationic (+ve) CE separations currently available. nesi capability (~150 nl/min flow) on the same microfluidic chip. Q Exactive (Classic, Plus, HF) and LTQ- Orbitrap compatible. Excellent native Biotherapeutics data on Exactive Plus EMR + NEW Q Exactive Plus EMR Small and light ZipChip Interface, with fast and easy install/de-install on the MS. Inexpensive. Fast, high resolution CE separations in less than three minutes for analytes ranging from amino acids (low Da) to intact antibody-drug conjugates (>150 kda). Minimal sample preparation for complex matrices courtesy of on-chip desalting. MS-compatible CE system, the coated separation channel allows for volatile background electrolytes (BGE). Low volume nl injections advantageous for precious samples. Very low volume solvent usage. Negligible run-torun carryover. High resolution sharp CE separations. No dead volume. Optimized CE methods for small molecule, biotherapeutics and proteomics experiments, Provides MS users an easy-to-use, powerful and inexpensive orthogonal CE separation capability in addition to LC. Autosampler capability for ZipChip nearing completion. Investigation on anionic (-ve) CE separations. // Actionable Intelligence HPMS & On-board Analytics / Slide 4 June 2016

5 // ZipChip Microfluidic CE-ESI Components ZipChip Interface to the Mass Spec Microfluidic ZipChip (Inside the Interface) Easy Install/Deinstall on Commercial Mass Spectrometers Initial Interfacing to Thermo Q Exactive, Exactive, LTQ-Orbitrap, Ion Trap and QQQ Mass Spectrometers Cost Effective ($25K for the ZipChip Interface) Fast Analyses (< 3 min) and Unique CE Separations on Chip Proteins, Antibodies, ADCs - Intact and Peptide Mapping Cell Lysates, Biomarker Discovery Bottom-Up, Top-Down Amino Acids, Metabolomics, DMPK Quan/Qual Minimal Sample Prep for Analytes in Complex Matrices // Actionable Intelligence HPMS & On-board Analytics / Slide 5 June 2016

6 // ZipChip CE-ESI Interface on a Commercial Mass Spectrometer Very straightforward ZipChip CE-ESI Installation and De-Install // Actionable Intelligence HPMS & On-board Analytics / Slide 6 June 2016

7 // Microfluidics ZipChip CE-ESI MS: How Does it Work? Injection Cross BGE Background Electrolyte (ESI-Compatible) Waste On-Line Desalting Separation Channel Highly uniform and stable surface coating efficient separations with reduced electroosmotic flow ESI MS Inlet: 0 kv ZipChip developed by the J. Michael Ramsey Group at University of North Carolina over the last 10 years CE separation achieved through differences in electrophoretic mobility which is governed by charge and size of analyte Batz, Mellors, Alarie, Ramsey, Anal Chem, 2014, 86, 3493 // Actionable Intelligence HPMS & On-board Analytics / Slide 7 June 2016

8 // Microfluidic ZipChip CE - High Pressure Injection Sample Loading 2 psi 1. Load 2. Clear 3. Run Head Pressure 2 psi Head Pressure +HV Head Pressure Sample Sample Voltage Off Voltage Off 3 seconds 0.5 seconds Voltage On Duration of Run // Actionable Intelligence HPMS & On-board Analytics / Slide 8 June 2016

9 // Microfluidic ZipChip CE-ESI Stable Surface Modification N.G. Batz et al., Anal. Chem. 2014, 86, E.A. Redman et al., Anal. Chem. 2015, 87, // Actionable Intelligence HPMS & On-board Analytics / Slide 9 June 2016

10 // ZipChip CE-ESI Analysis and Separation Details BGE Waste ESI MS Inlet: 0 kv Full Integrated Microfluidic Device No Dead Volume No Inter-Component Junctions FAST CE Analysis Often less than 3 minutes Optimal Peak Sharpness and Resolution Flow Rate ~150 nl/min (can go as low as 50 nl/min) CE Migration Times Significantly Slower on Non-Microfluidic Sciex and Agilent Standalone CE Systems. // Actionable Intelligence HPMS & On-board Analytics / Slide 10 June 2016

11 // ZipChip HS and ZipChip HR Available Zip Chip HS Zip Chip HR Separation channel length /cm On Chip De-salting Yes Yes ZipChip HS +15 kv ZipChip HR Integrated ESI Yes Yes Metabolite and Small Molecule Analysis Recommended use High Resolution Separations Ultimate Resolution Analysis time (typical) ~ 2 minutes ~ 9 minutes Peptide Mapping Recommended use High Resolution Separations Ultimate Resolution Analysis time ~ 3 minutes ~ 12 minutes +1 kv Intact Protein Analysis Recommended use Fast injection, relatively pure samples High Resolution Separations Analysis time < 1min ~3 minutes HS High Speed HR High Resolution Typically Small Molecule and Peptide Digests 1 HS Chip Good for 100+ Samples ($300) Typically Intact Proteins, IgGs and ADCs 1 HR Chip Good for 100+ Samples ($400) // Actionable Intelligence HPMS & On-board Analytics / Slide 11 June 2016

12 ZipChip Interface AS // ZipChip Autosampler Overview transfer line Autosampler Thermo Xcalibur The autosampler is acting as an auto-pipetter, delivering rinse BGE, or samples from wellplates. Injections, separation control are managed from the ZipChip Interface; Thermo AS platform Mass Spec 12 // Actionable Intelligence HPMS & On-board Analytics / Slide 12 June 2016

13 // ZipChip Autosampler Overview ZipChip Interface AS transfer line ~ 50 ul internal volume um ID Autosampler ZCI contains stock of BGE internal for nonsample well supply 13 vacuum waste (sample & rinsate) ZC sample well BGE (rinse, consumption approx. 0.5 ml per sample) 96 well plate 20 ul minimum // Actionable Intelligence HPMS & On-board Analytics / Slide 13 June 2016

14 // ZipChip Autosampler - Anticipated Timing Diagram Rinse (20 sec): Evacuate sample in reservoir (2 sec) 500 ul rinse with BGE (15 sec) CE-MS (2-3 min): Deliver Sample (10 sec): 5 ul minimum in microwell plate 14 // Actionable Intelligence HPMS & On-board Analytics / Slide 14 June 2016

15 // Thank You 908 Devices is headquartered in Boston s Innovation District. // Actionable Intelligence HPMS & On-board Analytics / Slide 15 June 2016