Domainex has invested in the Creoptix WAVEdelta platform which uses the biophysical technique of Grating-Coupled Interferometry (GCI). GCI is analogous to Surface Plasmon Resonance (SPR). In both techniques, the target protein is immobilised onto specialised sensor chips and the passage of analytes over the chip surface are monitored as time-dependent changes in refractive index, which can indicate bi-molecular interactions.
Changes in refractive index are obtained from mass changes near the sensor surface when a bi-molecular interaction occurs. Where GCI and SPR differ is that SPR detects a localised area of the chip surface whereas GCI samples the entire chip surface. GCI is therefore able to detect more binding events which enhances its sensitivity relative to SPR. Additionally, because the evanescent field does not penetrate as deep into the sample with GCI, there is less disturbance by bulk refractive index changes. GCI technology has proven application in fragment screening and to support subsequent hit-to-lead and lead optimisation stages of drug discovery. As the assay is label-free, homogenous, flow-based and kinetically read, it is ideally suited to measuring compound binding kinetics. The sensitivity and versatility of the WAVE system enables a wide variety of matrices to be used.
Innovative novel fluidics
The no-clog microfluids support large particles and are compatible with a wide variety of fluids such as:
- Crude reaction mixtures, high concentrations of DMSO and uncommon organic solvents
- 100% serum and plasma
- Cell supernatants
- Cell membrane preparations, PoLiPa/SMALP, nanodisc and detergent solubilised membrane proteins
Key advantages of the WAVEdelta system
- More sensitive than SPR
- Varied pulse duration to minimise cycle time (waveRAPID® technology), increase throughput and also to allow compound titrations in one run
- Extra channel opens up the possibility of running a reference or selectivity protein in parallel to the test protein as part of the same run
- Fast and accurate measurements of kinetic rates
- Accurate determination of dissociation rates of up to 10 sec-1 – useful for studying weak binders such as fragments
- “Clog-free” and therefore suitable for analysing plasma, serum and crude cell lysates
Figure 1: a) waveRAPID kinetic data obtained using the Creoptix WAVEdelta system for G9a fragment hit, Frg331. A KD value of 499 µM was obtained. B) Microscale Thermophoresis (MST) data for the same fragment hit. A KD value of 460 µM was obtained using this technique.