June 2016 // Actionable Intelligence – HPMS & On-board Analytics / Slide 1 ZipChip TM Microfluidic CE-ESI Utility Life Sciences CE-ESI-MS Applications Please visit us at http://www.908devices.com/
June 2016// Actionable Intelligence – HPMS & On-board Analytics / Slide 1
ZipChipTM
Microfluidic CE-ESI Utility
Life Sciences CE-ESI-MS Applications
Please visit us at
http://www.908devices.com/
June 2016// Actionable Intelligence – HPMS & On-board Analytics / Slide 2
// Presentation Overview
1. 908 Devices Company Overview
2. 908 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 3 June 2016
//
• 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
Company Overview
// Actionable Intelligence – HPMS & On-board Analytics / Slide 4 June 2016
// 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-to-
run 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 5 June 2016
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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
ZipChip Interface to the Mass Spec Microfluidic ZipChip (Inside the Interface)
ZipChip Microfluidic CE-ESI Components
• 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)
// Actionable Intelligence – HPMS & On-board Analytics / Slide 6 June 2016
// 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 7 June 2016
// Microfluidics ZipChip CE-ESI MS: How Does it Work?
MS Inlet: 0 kV
Injection
Cross
Separation
Channel
Waste
BGE
Background Electrolyte
(ESI-Compatible)
On-Line Desalting
Highly uniform and stable
surface coating – efficient
separations with reduced
electroosmotic flow
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
ZipChip developed by the J. Michael Ramsey Group
at University of North Carolina over the last 10 years
ESI
// Actionable Intelligence – HPMS & On-board Analytics / Slide 8 June 2016
//
Head Pressure
Voltage Off
Sample
Head Pressure
Voltage Off
Sample
Voltage On
+HV
Head Pressure
2 psi
3 seconds 0.5 seconds
Microfluidic ZipChip CE - High Pressure Injection Sample
Loading
Duration of Run
2 psi
1. Load 2. Clear 3. Run
// Actionable Intelligence – HPMS & On-board Analytics / Slide 9 June 2016
// Microfluidic ZipChip CE-ESI – Stable Surface Modification
N.G. Batz et al., Anal. Chem. 2014, 86, 3493-3500.
E.A. Redman et al., Anal. Chem. 2015, 87, 2264-2272.
// Actionable Intelligence – HPMS & On-board Analytics / Slide 10 June 2016
// ZipChip CE-ESI Analysis and Separation Details
• Full Integrated Microfluidic Device
• No Dead Volume
• No Inter-Component Junctions
MS Inlet: 0 kV
• 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)
Waste
BGE
ESI
CE Migration Times Significantly Slower on Non-Microfluidic Sciex and Agilent Standalone CE Systems.
// Actionable Intelligence – HPMS & On-board Analytics / Slide 11 June 2016
// ZipChip HS and ZipChip HR Available
+15 kV
+1 kV
ZipChip HRZipChip HSZip Chip HS Zip Chip HR
Separation channel length /cm 10 22
On Chip De-salting Yes Yes
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
Intact Protein Analysis
Recommended useFast injection,
relatively pure samplesHigh Resolution Separations
Analysis time < 1min ~3 minutes
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)HS – High Speed HR – High Resolution
// Actionable Intelligence – HPMS & On-board Analytics / Slide 12 June 2016
// ZipChip Autosampler Overview
12
Autosampler
ZipChip Interface AS
transfer line
Thermo Xcalibur
Mass Spec
The autosampler is acting as an auto-pipetter,
delivering rinse BGE, or samples from well-
plates. Injections, separation control are
managed from the ZipChip Interface;
Thermo AS platform
// Actionable Intelligence – HPMS & On-board Analytics / Slide 13 June 2016
// ZipChip Autosampler Overview
13
AutosamplerZipChip Interface AStransfer line
~ 50 uL internal volume
1 m @ 250 um ID
waste
ZC sample
well
BGE (rinse,
consumption
approx. 0.5
mL per
sample)
96 well plate
20 uL
minimum
(sample &
rinsate)
vacuumZCI contains
stock of BGE
internal for non-
sample well
supply
// Actionable Intelligence – HPMS & On-board Analytics / Slide 14 June 2016
// ZipChip Autosampler - Anticipated Timing Diagram
14
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
// Actionable Intelligence – HPMS & On-board Analytics / Slide 15 June 2016
//
908 Devices is
headquartered
in Boston’s
Innovation
District.
Thank You