The Almighty Xenon!
Researchers in the Wemmer Lab, in collaboration with Alex Pines’
groups at UC Berkeley, are utilizing the
natural affinity of xenon for hydrophobic cavities and the
sensitivity of laser-polarized xenon nuclear magnetic
resonance (NMR) to develop sensors capable
of detecting biological and chemical analytes of
interest. When combined
with optimized detection schemes, these so-called xenon
biosensors can be detected in sub-picomolar
concentrations—orders of magnitude below the threshold
for detecting traditional magnetic resonance (MR)
1) Development of Biosensors
Xenon biosensors typically consist of a hydrophobic xenon
host molecule attached to a targeting moiety via a
the sensitivity of xenon to its environment, it is
possible to detect the biosensors due to their unique
resonance frequency in solution as well as changes in this
resonance frequency when a sensor binds to its molecular
The biosensors used
in the Wemmer lab are synthesized in the Francis group and
the xenon MR studies are conducted with a dedicated setup
in the Pines lab.
research aims include optimizing the sensors for
solubility, detection sensitivity, targeting specificity,
sensors are being developed that utilize naturally
occurring scaffolds such as viral capsids and
bacteriophages for solubility, biocompatibility, and
significant improvements in the threshold for detection
2) Molecular Imaging with
The current clinical standard for visualizing soft tissue
in the body is proton-based MR imaging (MRI).
In spite of its superiority in
resolving anatomical structures, MRI has not enjoyed the
same success as a method for localizing functionality;
e.g., localizing tumor-specific molecules within the body
for early cancer detection.
these events, the spatial resolution of proton-based MRI
is typically sacrificed for increased detection
sensitivity by using radioactive agents with positron
emission tomography (PET) and single photon emission
computed tomography (SPECT).
of an MR technique that offers the sensitivity of PET and
SPECT without radioisotopes would be invaluable in
expanding the use of MRI for molecular imaging.
Xenon-based sensors targeting an array of biological and
chemical markers are being developed to push the detection
threshold of MR contrast agents towards that of PET and
SPECT. Hyperpolarized xenon gas is either bubbled into
solutions containing the sensors or dissolved into
solution using hydrophobic membranes.
A method developed in the Wemmer and Pines labs is
used to take advantage of the exchange of xenon in and out
of the cage that dramatically increases the sensitivity
for detecting sensors in significantly less time compared
to directly looking at the xenon-cage resonance frequency.
This technique, termed
Hyper-CEST (chemical exchange saturation transfer of
hyperpolarized nuclei, ), combined with standard
imaging pulse sequences can be used to selectively image
the presence of the sensors.
Because the exchange kinetics of xenon with sensor
molecules and the chemical shift of xenon bound in sensor
molecules are both highly temperature dependent,
additional information can be gained by controlling the
temperature of the system being studied.
In doing so, it is possible to tune the detection
of sensors via their chemical shift dependence on this
detecting sensors with the Hyper-CEST technique is
improved at increased temperatures.
Applications here include using the sensors for MR
3) Remote detection of
Development of lab-on-a-chip techniques has exploded in
the past decade due to low reagent costs, small sample
size requirements, and the potential to multiplex on one
In combination with
Hyper-CEST and optimization of the detected signal via
remote detection NMR , xenon-based molecular sensors
could provide a powerful tool for analysis of chemical,
environmental, and biological processes on a microfluidic
Current work involves
development of the hardware required to detect xenon-based
molecular sensors remotely, with the long-term goal of
creating a platform compatible with microfluidic devices
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 Lowery, TJ, et al. Optimization of xenon biosensors
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 Meldrum, T, et al. A Xenon-Based Molecular Sensor
Assembled on an MS2 Viral Capsid Scaffold, J. Am. Chem.
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 Schröder, L, et al. Molecular Imaging using a Targeted
Magnetic Resonance Hyperpolized Biosensor, Science 314,
 Schröder, L, et al. Temperature-Controlled Molecular
Depolarization Gates in Nuclear Magnetic Resonance, Phys.
Rev. Lett. 100(25), 257603 (2008).
 Schröder, L, et al. Temperature response of 129
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unltra-sensitive NMR detection, Angew. Chem. Int. Ed. 47,
 Schilling, F, et al. MRI Thermometry Based on
Encapsulated Hyperpolarized Xenon, ChemPhysChem 11(16),
 Granwehr, J, et al. Time-of-Flight Flow Imaging Using
NMR Remote Detection. PRL. 95:075503 (2005).