WAVEsystem

Creoptix GCI technology

Dive into our world of label-free interaction analysis

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The WAVEsystem, a Creoptix GCI
technology – innovation at your fingertips

WAVEsystem, a Creoptix GCI technology
Next-generation bioanalytical instruments for drug discovery - the wave of the future
in kinetics.
Modern label-free technology meets no-clog microfluidics and automated software toprovide superior affinity and kinetic data quality and challenging sample compatibility.

The WAVEsystem, a Creoptix GCI technology, pushes the boundaries of affinity
range, sample compatibility and sensitivity to deliver a breakthrough level of kinetics
analysis. The system’s exceptionally high data quality and automated software
facilitate drug discovery, enabling you to make new inroads into R&D.

Four complementary components
High signal-to-noise
ratio for high sensitivity

Temperature controlled
autosampler• Work with low
immobilization levels• No sample evaporation

WAVEchipNo-clog microfluidic biosensor chips for every need.
Experience a new level of flexibility in assay development.

• 120 hours of unattended
operation• Compatible with large
ligand-to-analyte molecularweight (MW) ratios• Sample capacity of
96 or 384 well plates

WAVEcontrol
Software for label-free analysis: fast and automated.
Complete control of your analysis from start to finish.

WAVEdelta system with autosampler and WAVEcontrol software.

Innovative microfluidic cartridge

Automated and intuitive software• No-clogging with crude samples• waveRAPID - full kinetics ( ka, kd, KD
and Rmax) from a single well

• Fast transitions enabling widest kd range• Compatible with harsh solvents• Direct Kinetics - automated, evidence
based data evaluation

WAVEcare• intuitive Wizards for biologics applications- Ligand Screening and CFCA

Service and maintenance for smooth operations.
Carefree or basic support for high-quality kinetic data and unparalleled performance.

Highlights• Crude samples, harsh chemicals, and particles up to 1000 nm• Self-contained, compact, disposable cartridge• Ultra-fast transition times for weak binding interactions• Superior signal-to-noise ratios (0.01 pg/mm2 at 1 Hz)• Reliable kinetics and binding affinities (KD) from low pM to low mM with signals below 1 pg/mm2• Up to 120 hours of unattended operation

CFCA - calibration-free concentration analysis

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GCI technology
GCI is a method developed by Creoptix® tomonitor and characterize molecular interactions
and to determine kinetic rate parameters, affinity
constants and concentrations of analyte moleculesinteracting with an immobilized ligand.

Evanescent field
An electromagnetic field, in particular near an opticalor waveguide interface, which decays exponentially as
the distance to the sensor surface increases.

A fresh take on waveguide interferometry
Based on waveguide interferometry, GCI – like otheroptical label-free methods – measures changes
in refractive index within an evanescent fieldnear a sensor surface, which are caused by thedisplacement of buffer by analyte molecules binding
to the ligand immobilized on the sensor surface.
The refractive index changes occurring within theevanescent field of a waveguide result in a change ofthe light phase, which is read out interferometrically.

Unlike other optical label-free techniques, the lighttravels throughout the waveguide, creating anevanescent wave that spans the entire length of thesensor surface. This allows more binding events tocontribute to the overall signal, giving waveguideinterferometry an intrinsically higher primarysensitivity for label-free interaction analysis.

Grating

Grating

Waveguide
Phase Modulator

Powered by GCI technology
The WAVEsystem is engineered around the patented
GCI technology. GCI is a label-free detection technology
based on waveguide interferometry that measuresmolecular binding affinity and kinetics with superior
resolution in both signal and time compared to otherforms of label-free detection.

Learn more about the system’s components:(Creoptix WAVE: Explore the system’s components - YouTube)

GCI - Grating-Coupled Interferometry

Together with a temperature-controlled autosampler that
can handle 2x 48-vial racks, 96- or 384-well plates – ora combination of your choosing – the WAVEsystem issensitive enough to work with low immobilization levels
and large ligand-to-analyte MW ratios.

“We strive to be the technology
leader, providing the bestsolutions for the most challenging
projects. The combination of
the GCI technology, the uniquechip design and the waveRAPID
method are the cutting edge
solution for kinetics”

Kaspar Cottier

creator of the GCI technology

The GCI advantage
With classical waveguide interferometry,the perfect alignment of measurement andreference beam is challenging – and sensitive
to environmental effects such as temperature
shifts or mechanical distortions or vibrations.
Creoptix® GCI technology eliminates thesetypical alignment issues, enabling robust
implementation of waveguide interferometry.

The GCI readout scheme sees the interferogram
created in the time domain and directly within the
waveguide, instead of being projected onto a camera.
This provides a more robust and more sensitive readout
compared to classical waveguide interferometry.

67WAVEchip – the no-clog
microfluidic sensor chip
The innovative design of our patented microfluidic
cartridge supports crude samples, pathogenic samples,
harsh solvents, and large particles up to 1000 nm
normally only achieved with plate-based assays. The
WAVEchips are uniquely designed for the WAVEsystem.

Compatibility

WAVEchip sensor
Quick guide

Description of chip

Immobilisation
modality

Suggested applications• 100% serum, plasma and cell supernatant

PCP

Quasi-planar PC hydrogel

Amine coupling

Large ligands and/or analytes suchas proteo/liposomes

PCP-STA

Pre-immobilized streptavidin,
quasi-planar PC hydrogel

BiotinLarge biotinylated ligands, analytes
such as liposomes, viruses, VLPs

PCP-RST

Regenerable streptavidin surface​
Quasi-planar PC hydrogel

BiotinLarge biotinylated ligands,
ligand screening

PCP-PAG

Pre-immobilized fusion protein A/G,
quasi-planar PC hydrogel

IgG

For capturing the broadest rangeof IgG and FC-tagged proteins

PCP-NTA

Pre-immobilized NTA,
quasi-planar PC hydrogel

His-Tag

Large His-tagged ligands, analytes
such as liposomes, viruses, VLPs

PCP-LIP

Pre-immobilized lipophilic groups,
quasi-planar PC hydrogel

Lipid

Hydrophobic (large) ligands suchas liposomes, membrane vesicles

PCZ

Functionalized with a zwitterionicpolymer bearing carboxylic acids
and tertiary amines in similar
densities, quasi-planar PC hydrogel

Amine coupling

Low fouling, ideal for coupling
proteins with low isoelectric points
or polyanionic ligands

PCL

Low capacity, thick PC hydrogelwith a lower amount of negative
charges (approx. 25%)

Amine coupling

Complex matrices such as serum,
culture supernatant. Requires
sulfo-NHS for activation

PCH

Thick PC hydrogel

Amine coupling

Large ligand-to-analyte molecularweight ratio. General purpose

PCH-NTA

Pre-immobilized NTA,
thick PC hydrogel

His-Tag

His-tagged ligands.
General purpose

PCH-STA

Pre-immobilized streptavidin,
thick PC hydrogel

BiotinBiotinylated ligands.
General purpose

PCH-RST

Regenerable streptavidin surface​
thick hydrogel

BiotinBiotinylated ligands.
ligand screening

DXP

Quasi-planar DX hydrogel

Amine coupling

Large ligands and/or analytes suchas proteo/liposomes, viruses, VLPS

WAVEchips – your choice, your benefits

DXP-STA

Pre-immobilized streptavidin,
thick DX hydrogel

BiotinBiotinylated ligands.
General purpose

Besides offering unparalleled compatibility, the WAVEchips improve the performance, flexibility andeffectiveness of your work.

DXH

Thick DX hydrogel

Amine coupling

Large ligand-to-analyte molecularweight ratio. General purpose

The cartridges contain four flow cells in parallel.
Typically, one flow cell is used as a reference to accountfor bulk effects. You can configure the reference channel
freely on the four-channel WAVEdelta system. While thetwo-channel WAVE only allows the usage of two FC per
experiment (FC1 and FC4; FC2 and FC3), the choice forthe reference channel is still free.

• Organic solvents, including highpercentages of acetonitrile and DMSO
• Viscous detergents and additives tosolubilize membrane proteins• Cell membrane preps, partiallysolubilized, unpurified material• VLPs, liposomes, or nanodisks usedas solubilization structures• Large binding partners: nanoparticles
and crude membrane preps

Section view of WAVEchip, showing microfluidics
integrated into the disposable cartridge byplacing the downstream valves instead of
microvalves near the chip.
Flow configuration of the WAVEchips, with one
possible combination among many of reference
channels/ flow cells (red) and sensing channels/
flow cells (green).

Performance

Flexibility

Effectiveness• Parallel flow channels• All-in-one solution for any
biomolecular interaction• Rapid exchange for fresh, clean
microfluidics within minutes• Broad range of sensor chip surfaces• No clogging, no downtime• Rapid, synchronizedsample transitions
Choosing your WAVEchip

Our WAVEchips are designed with your applications in mind. Choose from our range of products for small molecules,
serology, membrane proteins and biologics.
DMSO - dimethyl sulfoxide; FC - flow cell; VLP - virus-like particle

PC- = polycarboxylate
DX- = Carboxymethyldextran
DX coated sensors available upon request

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9WAVEcontrol –for flexibility and functionality
Move seamlessly from sample to data in a simple stepwise process, generating outputs
at the touch of a button. Every step – from assay setup and data evaluation to reportwriting – is simplified with an intuitive design that mirrors the way you work.

Design your experimentSet up your experiment

Evaluate your data

Report your data

Use our built-in optimizer
to simulate data and get
the design right before
you begin.

Let our wizards accelerate
your preparation – or edit
manually for full flexibility
and control.

Apply our predefinedmodels to evaluate theresults of your experiments.
Adjustments can be fully
fine-tuned.

Get access to raw dataand export your results ina customizable PDF or
Word format.

Four key benefits• Helpful wizards
Use pH scouting, support for new
WAVEchip® types, Ligand Screening,calibration-free concentration analysis andour new wizards to improve time-to-result• Smoother setup
Copy/paste and import from Excel files forlarge screens, drag and drop for full flexibility• Improved evaluation
Choose from more models for kinetics
and automated evaluation with Direct
Kinetics (1-click evaluation tool)• Save time and costs
Benefit from waveRAPID, a novel method
allowing you to obtain kinetics of aninteraction by injections from a single wellInnovative software solutions
Our robust and sensitive hardware is complemented by sophisticatedsoftware solutions to help you get the most from your analysis.
waveRAPID™ – a new way of measuring kinetics

Direct kinetics – automated, objective data evaluation

Instead of relying on a titration series, waveRAPID(Repeated Analyte Pulses of Increasing Duration) injects
a single concentration, pulsing the sample over thesensing surface at increasing durations, meaning kinetics
can be derived from a single well.

Global fitting is the most commonly used data evaluation
function in real-time biomolecular interaction analysis.
Based on non-linear least-squares fitting, this methodfinds rates and affinity constants to fit curves as close as
possible to the actual data.

waveRAPID also addresses a fundamental challenge ofrefractive index-based sensors: liquid refractive index
disturbances that need correction. This is especially
useful when dealing with molecules that significantly alter
the refractive index of the buffers used, such as DMSO.
It means there’s no need for DMSO buffer correction,
making it even easier to prepare your assay.

Global fitting needs human intervention for obtaining
best results and is driven by “what looks good”. A welltrained scientist would need 3-5 minutes to analyze one
interaction. With Direct Kinetics, instead of optimizing
the visuals, the error on the determined parameters
is minimized. Dozens of interactions are automaticallyanalyzed in 3-5 minutes.

Benefits for you waveRAPID:

Benefits for you Direct kinetics:• Run more samples: up to 500 in 24 hours• Quick decision making: rapid computation ofconfidence intervals• Faster assay development: no DMSO correction• Cost and time savings: full kinetics fromone single well (up to 7x less plates)• Fewer errors: automated, evidence-based estimation• Reproducible data: mitigate the risk of over-fitting
artifacts

Ligand Screening

CFCA

A faster, flexible way to screen andcharacterize antibodies

A calibration-free approach to quantification

Multiple analyte injection is the preferred method to screen
for binding partners. But it’s not suitable for all biologicalsystems. In kinetic analysis, for example, it’s important tomaintain the same immobilization levels for all antibodies toensure correct interpretation of the results.

CFCA stands for “calibration-free concentration analysis”.
It’s a label-free approach using the relationship between
the diffusion properties of the analyte and the absoluteanalyte concentration. It’s useful when:

The Ligand Screening Wizard:• Allows easy and intuitive assay setup by
creating a “ligand block”, where ligand samples
are cycled through the biosensor surface insequential capture/regeneration steps• Works in perfect harmony with the“target level” function• You want to determine only the“active” fraction of a sample• No satisfactory calibrant is available
for the analyte under study• There’s a mismatch between buffers or matrices• Fast quantification is required without sample
purification (e.g. antibodies in serum)• Ensures that ligands are always captured at thesame density level for correct data interpretation

Learn how Ligand Screening provides a faster, flexible
way to screen and characterize antibodies:
https://www.youtube.com/watch?v=Kn8tvSYcJeA

have a look at our one pager explaining waveRAPID
https://view.highspot.com/
viewer/65dd969ae4d7b78546991e47

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11

Small molecules and biologics

Full kinetic characterizationin complex matrix samples

Research involving small molecules and biologics comeswith specific challenges. The WAVEsystem is designed tomeet these – and deliver high-quality results whatever yourobjectives.

Kinetic characterization of interactions with the respective
crude matrix.
Profile biologic reagents in great detail in pure serum (oreven plasma).

Small molecules – no more hiding

With the industry’s fastest kinetics and utmost sensitivity,
the WAVEsystem offers a whole new level of previously
unattainable interaction data. The WAVEsystem iscompatible with the high ligand-to-analyte molecularweight ratios, providing outstanding resolution and reliablekinetics at low immobilization levels for target-to-analytemolecular weight ratios of up to >1000:1. The outcome isincreased sensitivity to accurately measure low-potency
small molecules or fragments, or targets with low activity.

BufferLigand 1: Antibody 1

Weak binders, such as those found in fragment-based
screening libraries, are typically ranked by affinity rather
than kinetics. This is because standard instrumentation
lacks the capacity to measure fast off-rates. However,measuring affinity rather than off-rates can generate large
numbers of false positive hits, extending workflows andincurring unnecessary costs.

“Employing a proprietary GCI technology, the Creoptix
WAVE provides resolution of fast off-rates up to 10 sec-1.
This enables accurate, early stage selection of true hits togreatly increase efficiencies.”

BufferWith the WAVEsystem, you measure more than just affinity,
even in the low pM range, while confirming and enriching
ELISA data. Use it to:• Run slow off-rate analysis of high-affinity binders• Detect anti-drug antibodies (ADA)
in the low ng/ml range• Identify the most effective antibody
pairs in diagnostic development

Ligand 2: Antibody 2

Biologics – characterization and quality control
Biologics – such as antibodies, nanobodies, and otherlarge molecules manufactured in living systems – are highly
complex. Characterizing them is an important task in drug
development and quality control, but it can be a challenge.

Serum (90%)

Serum (90%)• Surface: 4PCP WAVEchip (quasi planar)• Immobilization: amine-coupling• Ligand: two different IgG antibodies• Analyte: Protein antigen• Running buffer:
Learn how to determine affinity and binding kinetics of
crude samples like cell extracts, serum, plasma, viruslike particles, (in)organic nanoparticles, liposomes andnanodisks directly, reliably and easily:
https://www.youtube.com/watch?v=4Ayml3x5fcM• PBS-P+• 90% Bovine Serum• Double referencing• Globally fit with 1:1 binding modelNot all antibodies work in a serum or plasma!
No binding detected from mAb 2 when run in serum, demonstrating
the importance of antibody profiling in the respective matrix.

ADA - anti-drug antibodies

12

13

Specifications WAVE

Specifications WAVEdelta

GeneralGeneralNoise (RMS)<0.01 pg/mm @ 1 Hz

Noise (RMS)<0.01 pg/mm2 @ 1 Hz

Drift<0.3 pg/mm2/min

Drift<0.3 pg/mm2/min

Readout Frequency

1 Hz, 10 Hz or 40 Hz

Readout Frequency

1 Hz, 10 Hz or 40 Hz

2

ka = 10 – 5x10 M sec (small molecules)
2

Association Const. Range

7

-1

–1

ka = 102 – 3x109 M-1 sec–1 (large molecules)

Association Const. Rangeka = 102 – 5x107 M-1 sec–1 (small molecules)
ka = 102 – 3x109 M-1 sec–1 (large molecules)

Dissociation Const. Range

kd = 10–6 – 10 sec–1

Dissociation Const. Range

kd = 10–6 – 10 sec–1

Analysis temperature range

15°C – 40°C

Analysis temperature range

4°C – 45°C (max 15°C below ambient)

Molecular Weight Limit

No lower limit

Molecular Weight Limit

No lower limit

Fluidics

Fluidics

Flow Channels / Path2, parallel

Flow Channels / Path4, parallel

Channel Referencing

1–4 and 4–1 or 2–3 and 3–2

Channel Referencing

Any combination of the 4 channels

Flow Cells

Sealed, disposable, integrated into
disposable WAVEchip

Flow Cells

Sealed, disposable, integrated into
disposable WAVEchip

Flow Rate

1 – 400 μl/min

Flow Rate

1 – 400 μl/min

Crude Sample Robustness

Yes

Crude Sample Robustness

Yes

Sample handling

Sample handling

Sample Capacity

2x microtiter plates(96 or 384 well, standard or deep well)or vial racks (48 positions of 1.5 ml)

Sample Capacity

2x microtiter plates(96 or 384 well, standard or deep well)or vial racks (48 positions of 1.5 ml)

Buffer

1 buffer

BufferAutomatic switching between 4 buffers

Degasser

Built-inDegasser

Built-in

Injection Volume< 450 µl, 100 µl typicalInjection Volume< 450 µl, 100 µl typicalSample Volume Required

Injection volume plus 15-50 µl(application dependent)

Sample Volume Required

Injection volume plus 15-50 µl (application
dependent)

Sample Storage Temperature

Ambient or 4°C – 20°C regulated

Sample Storage Temperature

Ambient or 4°C – 20°C regulated

Sample Recovery

Yes

Sample Recovery

Yes

Automation

120 hours of unattended operation

Automation

120 hours of unattended operation

Data treatment

Data treatment

Information Provided

Kinetic affinity (ka, kd, KD)

Information Provided

Kinetic affinity (ka, kd, KD)

Graphs

Real-time curves, multiple curve overlays, fit,
report point plots

Graphs

Real-time curves, multiple curve overlays, fit,
report point plots

Data Extraction

Curves, ka, kd, KD tables, graphs, reports

Data Extraction

Curves, ka, kd, KD tables, graphs, reports

Data Analysis

Fully automated data evaluation

Data Analysis

Fully automated data evaluation

Kinetic Models

Predefined models including 1:1 interaction,
mass transport, heterogenous ligand,conformational change and bivalent

Kinetic Models

Predefined models including 1:1 interaction,
mass transport, heterogenous ligand,conformational change and bivalent

Direct Kinetic

Yes

Direct Kinetics

Yes

waveRAPID Functionality

No

CFCA and Ligand Screening

Yes

waveRAPID Functionality

Yes

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15

Product overview / Order info
Name

Discover more

Description

Product code

Includes WAVEcore (2-channel device), WAVEsampler (autosampler), WAVEcontrol (2perpetual software licenses) and warranty coverage for the first 12 months

9005002

DevicesWAVE* Warranty extension to be purchased with device

WAVEdelta

Includes WAVEcore (4-channel device), WAVEsampler (autosampler), WAVEcontrol(2 perpetual software licenses with waveRAPID functionality, ligand screening and
CFCA wizards) and warranty coverage for the first 12 months

This brochure is designed to offer you an overview of our products andsolutions. To learn more, scan the QR codes on the relevant pages or visit our
website for the latest updates: About Creoptix | Malvern PanalyticalWe’ve also put together a list of further resources that
may be of interest to you:

9005004* Warranty extension to be purchased with device

Sensor surfaces
PCP

Quasi-planar PC hydrogel

9060001

PCP-STA

Pre-immobilized streptavidin, quasi-planar PC hydrogel

9060002

PCP-RST
PCH-RST

Regenerable streptavidin surface, quasi-planar PC hydrogel. 50 cycles (includes
sensorchip, RST capture solution and regeneration solution)
Regenerable streptavidin surface, thick hydrogel. 50 cycles (includes sensorchip, RST
capture solution and regeneration solution

90600199060020

PCP-PAG

Pre-immobilized fusion protein A/G, quasi-planar PC hydrogel

9060003

PCP-NTA

Pre-immobilized NTA, quasi-planar PC hydrogel

9060004

PCP-LIP

Pre-immobilized lipophilic groups, quasi-planar PC hydrogel

9060005

PCZ

Functionalized with a zwitterionic polymer bearing carboxylic acids and tertiary amines insimilar densities, quasi-planar PC hydrogel

9060006

PCL

Low capacity, thick PC hydrogel with a lower amount of negative charges (approx. 25%)9060007

PCH

Thick PC hydrogel

9060008

PCH-NTA

Pre-immobilized NTA, thick PC hydrogel

9060009

PCH-STA

Pre-immobilized streptavidin, thick PC hydrogel

9060010

DXP

Quasi-planar DX hydrogel. Available upon request

9060012

DXP-STA

Pre-immobilized streptavidin, thick DX hydrogel. Available upon request

9060013

DXH

Thick DX hydrogel. Available upon request

9060014

Our Kinetics Guide
Kinetics Guide - Binding Kinetics with the WAVEsystem | Malvern Panalytical

How the Creoptix WAVEsystem drove real-time kinetic and affinity analysis for faster andbetter characterization of candidates – from fragments to biologics:
https://www.malvernpanalytical.com/en/learn/knowledge-center/customer-stories/CS220810Creoptix-drug-discovery-WAVE

Software• Enjoy all options for a full year.
WAVEcontrol
1 Year License• Includes software updates with bug fixes, stability and usability improvements.
• Exclude software version upgrades.

9270014* In addition to licenses included with system• Pay once, use as long as you want.
WAVEcontrol
Perpetuallicense• Includes software updates with bug fixes, stability and usability improvements.
• Excludes software version upgrades.

9270013* In addition to licenses included with system

Services
Creoptix offers a wide range of service agreements, trainings and maintenance. Please reach out to your contact todecide which solution suits you best.

Antibody characterization from COVID-19 patient plasma binding to SARS-COV-2 antigens:
https://www.malvernpanalytical.com/en/learn/knowledge-center/technical-notes/TN201124Creoptix-antibody-characterization-plasma-bindingWe draw on the power of our analytical instruments
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We partner with many of the world’s biggest companies,
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employees and customers think about their part increating a healthier, cleaner, and more productive world.

Service & Support
Malvern Panalytical provides the global training, service
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grow, we are there to support you.
Our worldwide team of specialists adds value to yourbusiness processes by ensuring applications expertise,
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Malvern Panalytical. We’re BIG on small™

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