Hyperpolarized 129Xe chemical exchange saturation transfer (HyperCEST) nuclear magnetic resonance (NMR), used to detect cancer markers, small molecule analytes, and cell surface glycans, relies on the targeted delivery of xenon hosts to a region of interest or small chemical shift difference between bound and unbound xenon sensors. Cryptophane-A (CryA) xenon hosts, used in the past, are hydrophobic, costly, and difficult to functionalize. CB6 is an excellent xenon host for activated 129Xe NMR detection because it produces a distinctive signal, has better exchange parameters for HyperCEST when compared to CryA, is soluble in most buffers and biological environments, and is commercially available. One major limitation of CB6 sensors is the difficult chemical functionalization to generalize them for diverse spectroscopic applications. To address this problem, researchers at Lawrence Berkeley National Laboratory and University of California, Berkeley, have designed, synthesized, and implemented a chemically-activated cucurbituril (CB6) platform for 129Xe HyperCEST NMR that blocks 129Xe@CB6 interactions with greater control to eliminate background signals until the CB6 reaches a region of interest, where it is then released to produce a 129Xe @CB6 signal. This technology will enable detection of increasingly lower concentrations of targets as the molecular systems become more optimized.