Abstract
The last two decades have seen remarkable progress and improvements in optical biosensor systems such that those are currently seen as an important and value-adding component of modern drug screening activities. In particular the introduction of microplate-based biosensor systems holds the promise to match the required throughput without compromising on data quality thus representing a sought-after complement to traditional fluidic systems. This article aims to highlight the application of the two most prominent optical biosensor technologies, namely surface plasmon resonance (SPR) and optical waveguide grating (OWG), in small-molecule screening and will present, review and discuss the advantages and disadvantages of different assay formats on these platforms. A particular focus will be on the specific advantages of the inhibition in solution assay (ISA) format in contrast to traditional direct binding assays (DBA). Furthermore we will discuss different application areas for both fluidic as well as plate-based biosensor systems by considering the individual strength of the platforms.
Highlights
Label-free optical detection systems for drug discovery and in particular for small-molecule drug screening have gained popularity during the past decade within industry and academia [1]
The adoption of surface plasmon resonance (SPR) technology was further accelerated by increasing demand in efficient fragment-based drug discovery (FBDD)
Besides other alternative optical detection systems, the use of planar waveguide systems using microplates is seen as an interesting complement to SPR systems, as it enables small-molecule screening with increased throughput without compromising on data quality
Summary
Label-free optical detection systems for drug discovery and in particular for small-molecule drug screening have gained popularity during the past decade within industry and academia [1]. The second analyte or an analogue thereof (often referred to as target definition compound or TDC) is tethered onto the biosensor surface and serves as a tool to determine the change in the free target protein concentration in the presence of the first analyte This assay format was used particular in the early days of SPR more frequently as the mass sensitivity of those first instruments was not suitable to reliably quantitate small molecule binding to macromolecular targets. In order to assess the value of the ISA format for small-molecule screening using optical detection systems, with the focus on novel high-throughput instruments as displayed by plate-based OWG systems, we conducted a comparative study using human trypsin as a model system on the SRU BIND and Corning Epic platform. The results from this practical example will guide us in discussing the usage and requirements of the ISA format in contrast to other assay formats as well as discussing some brief examples of its successful application in fragment screening
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