@article {256, title = {Relaxivity of Gadolinium Complexes Detected by Atomic Magnetometry}, journal = {Magnetic Resonance in Medicine}, volume = {66}, year = {2011}, note = {Magn Reson Med799AVTimes Cited:1Cited References Count:23}, month = {Aug}, pages = {605-608}, abstract = {

Laser atomic magnetomeby is a portable and low-cost yet highly sensitive method for low magnetic field detection. In this work, the atomic magnetometer was used in a remote-detection geometry to measure the relaxivity of aqueous gadolinium-diethylenetriamine pentaacetic acid Gd(DTPA) at the Earth\&$\#$39;s magnetic field (40 mu T). The measured relaxivity of 9.7 +/- 2.0 s(-1) mM(-1) is consistent with field-cycling experiments measured at slightly higher magnetic fields, but no cryogens or strong and homogeneous magnetic field were required for this experiment. The field-independent sensitivity of 80 fT Hz(-1/2) allowed an in vitro detection limit of similar to 10 mu M Gd(DTPA) to be measured in aqueous buffer solution. The low detection limit and enhanced relaxivity of Gd-containing complexes at Earth\&$\#$39;s field motivate continued development of atomic magnetometry toward medical applications. Magn Reson Med 66:605-608, 2011. (C) 2011 Wiley-Liss, Inc.

}, keywords = {nmr}, isbn = {0740-3194}, doi = {Doi 10.1002/Mrm.22811}, url = {://WOS:000293256800033}, author = {Michalak, D. J. and Xu, S. J. and Lowery, T. J. and Crawford, C. W. and Ledbetter, M. and Bouchard, L. S. and Wemmer, D. E. and Budker, D. and Pines, A.} } @article {276, title = {Temperature response of (129)Xe depolarization transfer and its application for ultrasensitive NMR detection}, journal = {Physical Review Letters}, volume = {100}, year = {2008}, note = {Phys Rev Lett320JWTimes Cited:12Cited References Count:8}, month = {Jun 27}, abstract = {

Trapping xenon in functionalized cryptophane cages makes the sensitivity of hyperpolarized (HP) (129)Xe available for specific NMR detection of biomolecules. Here, we study the signal transfer onto a reservoir of unbound HP xenon by gating the residence time of the nuclei in the cage through the temperature-dependant exchange rate. Temperature changes larger than similar to 0.6 K are detectable as an altered reservoir signal. The temperature response is adjustable with lower concentrations of caged xenon providing more sensitivity at higher temperatures. Ultrasensitive detection of functionalized cryptophane at 310 K is demonstrated with a concentration of 10 nM, corresponding to a similar to 4000-fold sensitivity enhancement compared to conventional detection. This makes HPNMR capable of detecting such constructs in concentrations far below the detection limit of benchtop uv-visible light absorbance.

}, keywords = {biosensors}, isbn = {0031-9007}, doi = {Doi 10.1103/Physrevlett.100.257603}, url = {://WOS:000257230500066}, author = {Schroeder, L. and Meldrum, T. and Smith, M. and Lowery, T. J. and Wemmer, D. E. and Pines, A.} } @article {277, title = {Temperature-controlled molecular depolarization gates in nuclear magnetic resonance}, journal = {Angewandte Chemie-International Edition}, volume = {47}, year = {2008}, note = {Angew Chem Int Edit308BXTimes Cited:13Cited References Count:19}, pages = {4316-4320}, keywords = {mri}, isbn = {1433-7851}, doi = {Doi 10.1002/Anie.200800382}, url = {://WOS:000256364400007}, author = {Schroder, L. and Chavez, L. and Meldrum, T. and Smith, M. and Lowery, T. J. and Wemmer, D. E. and Pines, A.} } @article {289, title = {Sensitivity enhancement by exchange mediated magnetization transfer of the xenon biosensor signal}, journal = {Journal of Magnetic Resonance}, volume = {184}, year = {2007}, note = {J Magn Reson127EUTimes Cited:7Cited References Count:18}, month = {Jan}, pages = {72-77}, abstract = {

Hyperpolarized xenon associated with ligand derivatized cryptophane-A cages has been developed as a NMR based biosensor. To optimize the detection sensitivity we describe use of xenon exchange between the caged and bulk dissolved xenon as an effective signal amplifier. This approach, somewhat analogous to \&$\#$39;remote detection\&$\#$39; described recently, uses the chemical exchange to repeatedly transfer spectroscopic information from caged to bulk xenon, effectively integrating the caged signal. After an optimized integration period, the signal is read out by observation of the bulk magnetization. The spectrum of the caged xenon is reconstructed through use of a variable evolution period before transfer and Fourier analysis of the bulk signal as a function of the evolution time. (c) 2006 Elsevier Inc. All rights reserved.

}, keywords = {resonance}, isbn = {1090-7807}, doi = {Doi 10.1016/J.Jmr.2006.09.010}, url = {://WOS:000243568900009}, author = {Garcia, S. and Chavez, L. and Lowery, T. J. and Han, S. I. and Wemmer, D. E. and Pines, A.} } @article {294, title = {Molecular imaging using a targeted magnetic resonance hyperpolarized biosensor}, journal = {Science}, volume = {314}, year = {2006}, note = {Science096MWTimes Cited:109Cited References Count:20}, month = {Oct 20}, pages = {446-449}, abstract = {

A magnetic resonance approach is presented that enables high-sensitivity, high-contrast molecular imaging by exploiting xenon biosensors. These sensors link xenon atoms to specific biomolecular targets, coupling the high sensitivity of hyperpolarized nuclei with the specificity of biochemical interactions. We demonstrated spatial resolution of a specific target protein in vitro at micromolar concentration, with a readout scheme that reduces the required acquisition time by \>3300-fold relative to direct detection. This technique uses the signal of free hyperpolarized xenon to dramatically amplify the sensor signal via chemical exchange saturation transfer (CEST). Because it is similar to 10,000 times more sensitive than previous CEST methods and other molecular magnetic resonance imaging techniques, it marks a critical step toward the application of xenon biosensors as selective contrast agents in biomedical applications.

}, keywords = {agents}, isbn = {0036-8075}, doi = {Doi 10.1126/Science.1131847}, url = {://WOS:000241382500036}, author = {Schroder, L. and Lowery, T. J. and Hilty, C. and Wemmer, D. E. and Pines, A.} } @article {299, title = {Optimization of xenon biosensors for detection of protein interactions}, journal = {Chembiochem}, volume = {7}, year = {2006}, note = {Chembiochem003SDTimes Cited:39Cited References Count:25}, month = {Jan}, pages = {65-73}, abstract = {

Hyperpolarized Xe-129 NMR spectroscopy can detect the presence of specific low-concentration biomolecular analytes by means of a xenon biosensor that consists of a water-soluble, targeted cryptophane-A cage that encapsulates the xenon. In this work, we use the prototypical biotinylated xenon biosensor to determine the relationship between the molecular composition of the xenon biosensor and the characteristics of protein-bound resonances. The effects of diastereomer overlap, dipole-dipole coupling, chemical-shift anisotropy, xenon exchange, and biosensor conformotional exchange on the protein-bound biosensor signal were assessed. It was found that an optimal protein-bound biosensor signal can be obtained by minimizing the number of biosensor diastereomers and using a flexible linker of appropriate length. Both the line width and sensitivity of chemical shift to protein binding of the xenon biosensor were found to be inversely proportional to linker length.

}, keywords = {complexes}, isbn = {1439-4227}, doi = {Doi 10.1002/Cbic.200500327}, url = {://WOS:000234701000012}, author = {Lowery, T. J. and Garcia, S. and Chavez, L. and Ruiz, E. J. and Wu, T. and Brotin, T. and Dutasta, J. P. and King, D. S. and Schultz, P. G. and Pines, A. and Wemmer, D. E.} } @article {301, title = {Spectrally resolved magnetic resonance imaging of a xenon biosensor}, journal = {Angewandte Chemie-International Edition}, volume = {45}, year = {2006}, note = {Angew Chem Int Edit997CZTimes Cited:48Cited References Count:14}, pages = {70-73}, keywords = {delivery}, isbn = {1433-7851}, doi = {Doi 10.1002/Anie.200502693}, url = {://WOS:000234223900007}, author = {Hilty, C. and Lowery, T. J. and Wemmer, D. E. and Pines, A.} } @article {297, title = {Xenon biosensor amplification via dendrimer-cage supramolecular constructs}, journal = {Journal of the American Chemical Society}, volume = {128}, year = {2006}, note = {J Am Chem Soc043HFTimes Cited:37Cited References Count:21}, month = {May 17}, pages = {6334-6335}, keywords = {chemistry}, isbn = {0002-7863}, doi = {Doi 10.1021/Ja061735s}, url = {://WOS:000237590400033}, author = {Mynar, J. L. and Lowery, T. J. and Wemmer, D. E. and Pines, A. and Frechet, J. M. J.} } @article {313, title = {Distinguishing multiple chemotaxis Y protein conformations with laser-polarized Xe-129 NMR}, journal = {Protein Science}, volume = {14}, year = {2005}, note = {Protein Sci907SSTimes Cited:23Cited References Count:27}, month = {Apr}, pages = {848-855}, abstract = {

The chemical shift of the Xe-129 NMR signal has been shown to be extremely sensitive to the local environment around the atom and has been used to follow processes such as ligand binding by bacterial periplasmic binding proteins. Here we show that the Xe-129 shift can sense more subtle changes: magnesium binding, BeF3- activation, and peptide binding by the Escherichia coli chemotaxis Y protein. H-1-N-15 correlation spectroscopy and X-ray crystallography were used to identify two xenon-binding cavities in CheY that are primarily responsible for the shift changes. One site is near the active site, and the other is near the peptide binding site.

}, keywords = {cavity}, isbn = {0961-8368}, doi = {Doi 10.1110/Ps.041231005}, url = {://WOS:000227738900002}, author = {Lowery, T. J. and Doucleff, M. and Ruiz, E. J. and Rubin, S. M. and Pines, A. and Wemmer, D. E.} } @article {317, title = {NMR-based biosensing with optimized delivery of polarized Xe-129 to solutions}, journal = {Analytical Chemistry}, volume = {77}, year = {2005}, note = {Anal Chem942GLTimes Cited:30Cited References Count:37}, month = {Jul 1}, pages = {4008-4012}, abstract = {

Laser-enhanced (LE) Xe-129 nuclear magnetic resonance (NMR) is an exceptional tool for sensing extremely small physical and chemical changes; however, the difficult mechanics of bringing polarized xenon and samples of interest together have limited applications, particularly to biological molecules. Here we present a method for accomplishing solution Xe-129 biosensing based on flow (bubbling) of LE Xe-129 gas through a solution in situ in the NMR probe, with pauses for data acquisition. This overcomes fundamental limitations of conventional solution-state LE Xe-129 NMR, e.g., the difficulty in transferring hydrophobic xenon into aqueous environments, and the need to handle the sample to refresh LE Xe-129 after an observation pulse depletes polarization. With this new method, we gained a factor of \> 100 in sensitivity due to improved xenon transfer to the solution and the ability to signal average by renewing the polarized xenon. Polarized xenon in biosensors was detected at very low concentrations, \<= 250 nanomolar, while retaining all the usual information from NMR. This approach can be used to simultaneously detect multiple sensors with different chemical shifts and is also capable of detecting signals from opaque, heterogeneous samples, which is a unique advantage over optical methods. This general approach is adaptable for sensing minute quantities of xenon in heterogeneous in vitro samples, in miniaturized devices and should be applicable to certain in-vivo environments.

}, keywords = {blood}, isbn = {0003-2700}, doi = {Doi 10.1021/Ac0500479}, url = {://WOS:000230270800035}, author = {Han, S. I. and Garcia, S. and Lowery, T. J. and Ruiz, E. J. and Seeley, J. A. and Chavez, L. and King, D. S. and Wemmer, D. E. and Pines, A.} } @article {320, title = {Xenon NMR as a probe for microporous and mesoporous solids, polymers, liquid crystals, solutions, flames, proteins, imaging}, journal = {Actualite Chimique}, year = {2005}, note = {Actual ChimiqueSuppl. 287952GHTimes Cited:3Cited References Count:89}, month = {Jun}, pages = {16-34}, abstract = {

We present in this paper some examples of the applications of the Nuclear Magnetic Resonance (NMR) of xenon used as a probe in the study of different chemical environments: determination of the porosity of micro-and mesoporous solids, evaluation of the concentrations and sizes of amorphous domains in solid polymers, characterization of liquid crystals, study of combustion processes at high temperature, determination of the structure and dynamics of organic systems and proteins in solution, assessment of cerebral blood flow.

}, keywords = {silica-gels}, isbn = {0151-9093}, url = {://WOS:000230991500005}, author = {Bartik, K. and Choquet, P. and Constantinesco, A. and Duhamel, G. and Fraissard, J. and Hyacinthe, J. N. and Jokisaari, J. and Locci, E. and Lowery, T. J. and Luhmer, M. and Meersmann, T. and Moudrakovski, I. L. and Pavlovskaya, G. E. and Pierce, K. L. and Pines, A. and Ripmeester, J. A. and Telkki, V. V. and Veeman, W. S.} } @article {333, title = {Design of a conformation-sensitive xenon-binding cavity in the ribose-binding protein}, journal = {Angewandte Chemie-International Edition}, volume = {43}, year = {2004}, note = {Angew Chem Int Edit877MVTimes Cited:10Cited References Count:20}, pages = {6320-6322}, keywords = {probe}, isbn = {1433-7851}, doi = {Doi 10.1002/Anie.200460629}, url = {://WOS:000225575600015}, author = {Lowery, T. J. and Rubin, S. M. and Ruiz, E. J. and Pines, A. and Wemmer, D. E.} } @article {325, title = {Development of a functionalized xenon biosensor}, journal = {Journal of the American Chemical Society}, volume = {126}, year = {2004}, note = {J Am Chem Soc872UHTimes Cited:60Cited References Count:76}, month = {Nov 24}, pages = {15287-15294}, abstract = {

NMR-based biosensors that utilize laser-polarized xenon offer potential advantages beyond current sensing technologies. These advantages include the capacity to simultaneously detect multiple analytes, the applicability to in vivo spectroscopy and imaging, and the possibility of \"remote\" amplified detection. Here, we present a detailed NMR characterization of the binding of a biotin-derivatized caged-xenon sensor to avidin. Binding of \"functionalized\" xenon to avidin leads to a change in the chemical shift of the encapsulated xenon in addition to a broadening of the resonance, both of which serve as NMR markers of ligand-target interaction. A control experiment in which the biotin-binding site of avidin was blocked with native biotin showed no such spectral changes, confirming that only specific binding, rather than nonspecific contact, between avidin and functionalized xenon leads to the effects on the xenon NMR spectrum. The exchange rate of xenon (between solution and cage) and the xenon spin-lattice relaxation rate were not changed significantly upon binding. We describe two methods for enhancing the signal from functionalized xenon by exploiting the laser-polarized xenon magnetization reservoir. We also show that the xenon chemical shifts are distinct for xenon encapsulated in different diastereomeric cage molecules. This demonstrates the potential for tuning the encapsulated xenon chemical shift, which is a key requirement for being able to multiplex the biosensor.

}, keywords = {drug discovery}, isbn = {0002-7863}, doi = {Doi 10.1021/Ja0483037}, url = {://WOS:000225233600051}, author = {Spence, M. M. and Ruiz, E. J. and Rubin, S. M. and Lowery, T. J. and Winssinger, N. and Schultz, P. G. and Wemmer, D. E. and Pines, A.} }