Multidimensional Infrared Spectroscopy as a Bioanalytical Technique

Since its inception at the end of the last century, 2D-IR spectroscopy has undergone continuous development into an established method for studying the structure, dynamics and intermolecular interactions of biomolecules. Thanks to parallel advances in lasers and related technology, 2D-IR data sets can now be acquired in minutes, using minimal sample quantities and under physiologically relevant conditions. This progress has opened the door for 2D-IR spectroscopy to play a role as an analytical tool, making measurements that characterize samples and inform decisions in arenas ranging from drug design to biomedical diagnostics. Here, we briefly review the pioneering developments that have brought about this scenario before discussing the current state of the art in analytical applications of 2D-IR spectroscopy. We consider the implementation of 2D-IR spectroscopy to measure label free protein structure, biomolecular interactions and the use of 2D-IR to interrogate complex mixtures and biological tissues. We include strategies that have extended the reach of 2D-IR spectroscopy through advances in measurement sensitivity and data quality and highlight the potential impact that emerging methods such as machine learning could have on the development of 2D-IR. Finally, we look ahead to the challenges and opportunities facing 2D-IR on its path toward a robust and widely used bioanalytical tool.