microfluidic ce-esi utility life sciences ce-esi-ms...

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


// 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.


//

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)


// ZipChip CE-ESI Interface on a Commercial Mass Spectrometer

Very straightforward ZipChip CE-ESI Installation and De-Install


// 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


//

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


// 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.


// 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.


// 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


// 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


// 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


// 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


//

908 Devices is

headquartered

in Boston’s

Innovation

District.

Thank You

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