Label-free technologies: Which technique to use and what to watch out for!

The number of different label-free platforms available for drug discovery and life science research has exploded in the last decade. Until the late 1990s, the field was dominated by just four technologies: mass spectrometry (MS), nuclear magnetic resonance (NMR), calorimetry, and surface plasmon resonance (SPR). Commercial systems based on these technologies were marketed as “easy to use,” with companies and review writers (including ourselves) promoting the virtues of “label-free” assays, their inherent simplicity, and direct, easy-to-interpret results. However, label-free technologies often require carefully designed experimental controls and analytical rigor in the interpretation of what at first appears to be simplistic data. As with any assay technology, label-free platforms are also affected by physical and biological artifacts, which can be erroneously interpreted to be related to drug action. In this chapter we review the fundamentals of drug action in a biological system, the physical basis of different label-free systems, and then discuss the advantages and artifacts associated with each technique. We hope that this will help guide the reader towards a rational choice of technology for their particular project. Forearmed with an awareness of the pitfalls that can lead a beguiled label-free devotee astray, label-free assays can indeed illuminate the complex biology of drug action.

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