New Publication: Accelerating Binding Kinetics with SpyBLI & eProtein Discovery™
Design is fast. Kinetics aren’t.
Computational design and NGS generate large pools of binders, but purifying each one to measure KD, kon, koff, is slow and costly, so only a fraction gets characterized. Teams need accurate kinetics from unpurified material to keep iteration moving at the pace of discovery. Traditional SPR/BLI and solution methods (MST/ITC) are proven, but requirements for purity, immobilisation, and quantitation add days to weeks, especially when screening dozens to hundreds of variants.
Innovation by Sormanni: SpyBLI × eProtein Discovery™
A recent peer-reviewed, open-access study in RSC Chemical Biology couples Nuclera’s eProtein Discovery™ (cell-free expression) with SpyBLI, a BLI workflow that covalently captures binders via SpyCatcher003–SpyTag003, to deliver robust binding kinetics from crude samples in <24 hours, no purification required. The workflow compresses the clone-purify-measure loop to a single, day-scale cycle.
What the team actually did
- Linear DNA to on-instrument expression: ran parallel screens (e.g., solubility tags, oxidative environments) to maximize usable protein yield.
- Crude to kinetics: loaded a small volume of crude cell-free mix onto BLI using SpyBLI capture chemistry for KD, kon, koff, no purification required.
- Standard hardware: executed on familiar BLI systems, enabling rapid adoption
The result?
Day-scale kinetics, without purification. SpyBLI eliminates purification and concentration determination while preserving precision through ordered sensor immobilisation, enabling accurate kinetics directly from crude cell-free blends. Paired with linear gene fragments on eProtein Discovery™, teams go from DNA to data in <24 hours across VHH and scFvs spanning six orders of magnitude, unlocking truly good-throughput screening.
Who Gains the Most?
- Biopharma discovery: faster triage of VHH, scFvs, and multispecifics before costly purification
- Diagnostics & biosensors: early validation of binder performance without purification bottlenecks.
- Computational protein design & binder optimization: rapid, accurate experimental feedback to refine designs.
- Academic cores/CROs: higher throughput and better utilization across diverse projects.
Dive Into the Study
Read the open-access paper: The SpyBLI cell-free pipeline for the rapid quantification of binding kinetics from crude samples (RSC Chemical Biology, 2025)
