LAUSR

Biophysical technologies appeared on the drug discovery scene more than two decades ago and have since provided drug discovery projects with enriched information about compound binding, thereby greatly impacting drug discovery [1]. Amongst the well-established and recently developed biophysical technologies that have been all highlighted in detail by Renaud et al. [1], optical biosensors have contributed significantly to the overall success of biophysics in drug discovery. The launch of the first commercial optical biosensor system based on surface plasmon resonance (SPR) in the early 1990s paved the way for a wide range of complementing optical biosensor platforms that shortly followed [2], with optical waveguide grating (OWG) and biolayer interferometry (BLI) being currently the most prominent and established ones alongside SPR [3,4]. In this context, either fluidicsor platebased optical biosensor platforms find frequent applications as primary screening tools using both biochemical (SPR & BLI) and cellular (OWG) hit finding approaches. Besides providing a label-free readout of compound interaction thereby reducing costs and increasing assay relevance particularly for cell-based assays, their great versatility makes them impactful tools in various other stages of small-molecule drug discovery campaigns. This can include but is not limited to support assay development prior to high-throughput screening (HTS) [5] or post-HTS for the validation of primary hits. It is often followed by extending our understanding of the molecular mode of action (MoA) and can include the assessment of compound binding kinetics and thermodynamics. Particularly the application of kinetic data appears to be a crucial factor when trying to improve drug efficacy and selectivity [6]. In this context, microfluidics-based SPR has further promoted the enhanced use of kinetic data within drug discovery, as it provides data with high precision and accuracy that goes along with good throughput.