Grating-Coupled Interferometry

Grating-Coupled Interferometry

Benefit from the revolution in the studies of biomolecular interactions

Unrivalled flexibility and high sensitivity

Engineered around a proprietary Grating-Coupled Interferometry (GCI) technology to deliver improved data quality from label-free biomolecular interaction analysis, the Creoptix® WAVEsystem builds on Waveguide Interferometry to achieve superior resolution in signal and time compared to traditional Surface Plasmon Resonance. This allows researchers to quickly and accurately measure kinetic rates, determine affinity constants, and monitor the concentrations of even low abundance interacting analytes in crude samples such as biofluids. With unrivalled flexibility and high sensitivity, the Creoptix™ WAVEsystem brings label-free analysis to a whole new world of applications, revolutionizing the study of biomolecular interactions.

GCI is Creoptix’ cutting-edge biophysical characterization method commercially available since 2015 in the WAVE family of laboratory devices.

GCI CX weblandscape

Benefit from GCI technology

Technology comparison table

Grating-Coupled Interferometry (GCI)
Surface Plasmon Resonance (SPR)
Biolayer Interferometry (BLI)
Broadest application range
Suitable for a variety of molecules ranging from low to high molecular weights, purified or crude.
Grating-Coupled Interferometry (GCI)
Yes
Suitable for Fragments, Small Molecules, Peptides, Proteins, Viruses, Cell Culture Supernatants, Serums, Cell lysates
Surface Plasmon Resonance (SPR)
No
Suitable for Small Molecules, Peptides (limited suitability for Fragments, Viruses, Cell Culture Supernatants, Serums, Cell lysates)
Biolayer Interferometry (BLI)
No
Suitable for Cell Culture Supernatants, Serums, Cell lysates (limited suitability for Peptides, Proteins, Viruses)
Measure weakest binders
Ability to measure kinetics with fast off-rates thanks to fast fluidics and high acquisition rates.
Grating-Coupled Interferometry (GCI)
Yes
Off-rates up to
kd=10 s-1
Surface Plasmon Resonance (SPR)
No
Off-rates up to
kd=1 s-1
Biolayer Interferometry (BLI)
No
Off-rates up to
kd=0.1 s-1
Measure tightest binders
Ability to accurately measure kinetics even for tight binders and fast on-rates.
Grating-Coupled Interferometry (GCI)
Yes
Measurement under flow conditions
Surface Plasmon Resonance (SPR)
Yes
Measurement under flow conditions
Biolayer Interferometry (BLI)
No
Measurement under diffusion-limited conditions (no microfluidics)
Low system maintenance
Little downtime due to service or unexpected repairs.
Grating-Coupled Interferometry (GCI)
Yes
No-clog microfluidics
Surface Plasmon Resonance (SPR)
No
Traditional microfluidics
Biolayer Interferometry (BLI)
Yes
No microfluidics

GCI vs Waveguide Interferometry and SPR

Our patented Grating-Coupled Interferometry design leverages and enhances the intrinsic benefits of Waveguide Interferometry to exceed the sensitivity levels of Surface Plasmon Resonance. Like Waveguide Interferometry, the evanescent field penetrates less deep into the sample and extends the light-to-sample interaction length for improved signal-to-noise ratios (<0.01 pg/mm2). However, our GCI readout scheme has the advantage that the interferogram is created in the time-domain and within the waveguide, instead of being projected onto a CCD camera. Measuring refractive index changes on the sensor surface as time-dependent phase-shift signals therefore provides a more robust readout compared to classical Waveguide Interferometry or Surface Plasmon Resonance, regardless of temperature drifts or vibrations, translating to superior resolution in signal and time.

  • More about traditional Surface Plasmon Resonance

    • Surface Plasmon Resonance is a label-free, optical biosensing technology that measures changes in refractive index close to a sensor surface. Traditional Surface Plasmon Resonance sensors consist of an electrically conducting metal film (gold) upon which the ligand of interest is immobilized. When polarized light at a defined angle (the incidence angle) hits the metal film, it excites collective oscillations of free electrons (surface plasmons), with an electromagnetic field extending beyond the metal surface. This so-called evanescent wave is used to probe the refractive index near to the sensor surface. When the immobilized ligand binds an analyte in solution, this local refractive index increases in direct proportion to the number of molecules bound to the sensor, making the refractive index shift equivalent to a change in mass. Reading out the refractive index shift by monitoring the incidence angle change allows researchers to use Surface Plasmon Resonance to determine the concentrations of interacting analytes (affinity) or to study real-time binding kinetics (association and dissociation rates) without the need to use labels.

    • SPR CX weblandscape
    • Molecular interactions are detected as changes in refractive index within an evanescent field (orange) of the surface plasmon shown as energy dips at specific incidence angle.

  • Advantages of Waveguide Interferometry over Surface Plasmon Resonance

    • Like Surface Plasmon Resonance, Waveguide Interferometry also measures changes in refractive index at a sensor surface. However, in contrast to traditional Surface Plasmon Resonance, the light in Waveguide Interferometry can travel through the entire length of the sample. This allows more binding events to contribute to the overall signal, giving Waveguide Interferometry an intrinsically higher primary sensitivity for label-free interaction analysis, especially when paired with an interferometric readout to translate the phase change of the waveguide mode into an intensity pattern. A further advantage of Waveguide Interferometry over Surface Plasmon Resonance is that the evanescent field penetrates less deep into the sample, minimizing the disturbance caused by bulk refractive index changes and increasing the signal-to-noise ratio.

    • WI CX weblandscape
    • Molecular interactions are detected as changes in refractive index within an evanescent field (orange) causing a phase shift of the beam in the waveguide and hence an interference to a reference beam projected in parallel to a screen.

  • How is Grating-Coupled Interferometry (GCI) different from Bio-Layer Interferometry (BLI)?

    • Although both Grating-Coupled Interferometry (GCI) and Bio-Layer Interferometry (BLI) work by using interference to measure refractive index changes on a thin layer above the surface of the sensor, they are two completely different technologies. GCI, the technology used in the Creoptix WAVEsystem, measures the effect of refractive index changes on an evanescent wave generated by the light passing through the waveguide in the sensor. These refractive index changes affect the phase of the light traveling through the waveguide, and interference with a reference light beam (hence interferometry) is needed to measure the phase change reliably and precisely. In contrast, BLI analyzes the interference pattern of white light reflected from two surfaces: a layer of protein immobilized on the biosensor tip, and an internal reference layer. Any change in the number of molecules bound to the biosensor tip can cause a shift in the interference pattern that may be measured in real-time as an increase in optical thickness at the biosensor tip; this results in a wavelength shift in the interference pattern.

  • Can Grating-Coupled Interferometry (GCI) detect conformational changes?

    • Hypothetically, the Creoptix WAVEsystem can detect conformational changes, provided those conformational changes make sufficient contribution to a change in refractive index. The WAVEcontrol software also supports suitable interaction models which account for conformational changes. Despite this, conformational changes are difficult to infer purely based on either Creoptix WAVEsystem kinetic data or SPR data. This is because conformational changes are seldom a one-step process, meaning models that would perfectly fit the kinetic data would be far too complicated to be fully trusted. Additionally, conformational changes might generate unexpected responses (e.g. negative curves) due to the surface reorganization, which could prove extremely difficult to analyze and quantify consistently. Creoptix recommends performing orthogonal validation of any suspected conformational changes and ensuring that kinetic analysis is as simple as possible, for instance by analyzing kinetic differences between functional mutants.

  • Are the ligand capture and immobilization techniques used for Surface Plasmon Resonance (SPR)/Bio-layer Interferometry (BLI) also suitable for Grating-Coupled Interferometry (GCI)?

    • Yes, standard immobilization techniques such as amine-coupling, Ni-NTA capture and streptavidin-biotin capture are also available for the Creoptix WAVEsystem on polycarboxylate surfaces; dextran surfaces can be supplied on request. Additionally, there is a wide range of other immobilization methods, including lipidic interactions or Protein A/G capture. An overview of the available surfaces (WAVEchips) can be found here.

Advantages of GCI over Waveguide Interferometry and SPR

Grating-Coupled Interferometry

Interpretation of Waveguide Interferometry data relies on accurate alignment of the reference beam and the measurement beam. However, during classical Waveguide Interferometry, perfect alignment is extremely challenging and sensitive to environmental effects such as temperature shifts or mechanical distortions or vibrations. With our proprietary Grating-Coupled Interferometry technology, we have developed a solution to eliminate the alignment issues common to classical waveguide set-ups, thereby offering the first robust implementation of Waveguide Interferometry on the market.

Interested in the Creoptix WAVEsystem?

Customer testimonial

Dr. Nicolas Bocquet | leadXpro

Continue exploring the benefits for the software

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  • Measure interactions, not interference

    WAVEcore®

    Engineered around a proprietary Grating-Coupled Interferometry (GCI) technology, the Creoptix® WAVE system builds on waveguide interferometry to achieve superior resolution in signal and time. With low limits of detection, the WAVEsystem generates accurate kinetic rates, affinity constants, and concentrations of label-free biomolecular interactions, even at low analyte abundance, with no loss of definition.

    WAV Edelta square web landscape
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