Innovation and Partnerships Office

CB6 for Highly Sensitive Molecular Detection Using HyperCEST NMR 2016-153


  • Medical diagnostic imaging
  • Contamination / pollutant detection
  • Screening libraries for pharmaceutical development


  • Eliminates need to use costly and difficult to functionalize xenon hosts
  • Enables detection in human bodies


Berkeley Lab’s Alex Pines and Matt Francis led a team of researchers to improve detection and disease imaging applications by finding a universal, customizable probe for an array of complex chemical environments that gives yes/no information on the presence of target molecules and that can be implemented into a broad range of systems.

The Berkeley Lab team designed, synthesized, and implemented a chemically-activated cucurbit[6]uril (CB6) platform for 129Xe hyperCEST nuclear magnetic resonance (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.

HyperCEST 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. However, a major limitation of CB6 sensors has been the difficult chemical functionalization to generalize them for diverse spectroscopic applications. The Berkeley Lab technology overcomes this limitation, opening the door to highly sensitive molecular detection.

FOR MORE INFORMATION: Finbloom, J., Slack, C., Bruns, C., Jeong, K., Wemmer, D., Pines, A., and Francis, M. “Rotaxane-mediated suppression and activation of cucurbit[6]uril for molecular detection by 129Xe hyperCEST NMR,” Chem. Commum, 2016, 52, 3119-3122.

DEVELOPMENT STAGE: Proven principle.

STATUS: Available for licensing or collaborative research.


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