The detection of biological molecules and their interactions is a significa
nt component of modern biomedical research. In current biosensor technologi
es, simultaneous detection is limited to a small number of analytes by the
spectral overlap of their signals. We have developed an NMR-based xenon bio
sensor that capitalizes on the enhanced signal-to-noise, spectral simplicit
y, and chemical-shift sensitivity of laser-polarized xenon to detect specif
ic biomolecules at the level of tens of nanomoles. We present results using
xenon "functionalized" by a biotin-modified supramolecular cage to detect
biotin-avidin binding. This biosensor methodology can be extended to a mult
iplexing assay for multiple analytes.