High-Resolution NMR Spectroscopy of Sample Volumes from 1 nL to 10 μL

Lacey, Michael E.; Subramanian, Raju; Olson, Dean L.; Webb, Andrew; Sweedler, Jonathan V.

doi:10.1021/cr980140f

Cited by 243 publications

(246 citation statements)

References 137 publications

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“…31 Similarly, the xenon spectrum for a racemic mixture of the allyl-substituted cryptophane-A cage enantiomers (15) shows only one resonance (Figure 3a). However, the spectra of the xenon biosensor exhibit multiple peaks rather than a single resonance (Figure 3c).…”

Section: Biosensor Molecule Diastereomers Detected By Functionalized mentioning

confidence: 95%

“…However, the spectra of the xenon biosensor exhibit multiple peaks rather than a single resonance (Figure 3c). This is a consequence of the formation of diastereomer biosensor molecules resulting from the addition of new chiral centers to the cage precursor (15). The first pair of diastereoisomers is formed by the introduction of chiral L amino acids Cys, Lys and Arg.…”

Section: Biosensor Molecule Diastereomers Detected By Functionalized mentioning

confidence: 99%

“…Steady progress is being made to incorporate NMR analysis into high-throughput and combinatorial chemistry applications. [13][14][15][16][17][18] Utilization of conventional NMR for high-throughput biosensor applications may be limited by the intrinsically low sensitivity and the complexity of spectra obtained from biomolecules and mixtures. Laser-polarization 19 of 129 Xe offers an increase in signal-tonoise by several orders of magnitude relative to the equilibrium nuclear-spin polarizations measured in normal NMR experiments.…”

Section: Introductionmentioning

confidence: 99%

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Development of a Functionalized Xenon Biosensor

et al. 2004

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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.

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Section: Biosensor Molecule Diastereomers Detected By Functionalized mentioning

confidence: 95%

Section: Biosensor Molecule Diastereomers Detected By Functionalized mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of a Functionalized Xenon Biosensor

et al. 2004

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“…For liquid samples at room temperature, pioneering work on fabrication of solenoids around capillary tubes (16,24) and microfabrication techniques to create planar coils on semiconductor substrates (1,25) demonstrates that miniaturization of probes is possible and substantially reduces sample quantity while retaining signal sensitivity (15). Solenoidal microcoils detect nanomole quantities with high sensitivity but have not been successfully fabricated below Ϸ300 m inner diameter (26), whereas planar coils on semiconductor substrates are scalable but show lower signal sensitivity due to inhomogeneous broadening and path loss.…”

Section: N Uclear Magnetic Resonance (Nmr) Is a Powerful Analyticalmentioning

confidence: 99%

Ultra-small-sample molecular structure detection using microslot waveguide nuclear spin resonance

Maguire

Chuang

Zhang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

102

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We here report on the design of a planar microslot waveguide NMR probe with an induction element that can be fabricated at scales from centimeters to nanometers to allow analysis of biomolecules at nano-or picomole quantities, reducing the required amount of materials by several orders of magnitude. This device demonstrates the highest signal-to-noise ratio for a planar detector to date, measured by using the anomeric proton signal from a 15.6-nmol sample of sucrose. This probe had a linewidth of 1.1 Hz for pure water without susceptibility matching. Analysis of 1.57 nmol of ribonuclease-A shows high sensitivity in one-and twodimensional NMR spectra. Along with reducing required sample volumes, this integrated geometry can be packed in parallel arrays and combined with microfluidic systems. Further development of this device may have broad implications not only for advancing our understanding of many intractable protein structures and their folding, molecular interactions, and dynamic behaviors, but also for high-sensitivity diagnosis of a number of protein conformational diseases.inductive microslot ͉ miniature probe fabrication ͉ nanomole RNAase-A structural detection ͉ nuclear magnetic resonance scaling ͉ ultra-sensitivity N uclear magnetic resonance (NMR) is a powerful analytical tool not only for determining complex biomolecular structures (1-4) but also for monitoring molecular dynamics (5-7). Despite its versatility, NMR protein and large-molecule structural analyses currently require large quantities of protein material at high concentration and purity (8-10), and timeconsuming data gathering (11-13). Furthermore, it has been difficult to obtain adequate amounts of proteins with high molecular weight, many protein complexes, and especially membrane proteins for structural analysis because they can form insoluble aggregates (14). We here report design and fabrication of a microdevice that can analyze nanomole quantities of proteins (15)(16)(17)(18)(19), and that can be integrated in microfabricated systems.The ultimate sensitivity limit is a single spin. Single-electron spins have been detected by using mechanical oscillations (20) and by single nuclear spins using optical methods (21,22). For a volume on the order of Ϸ10 8 spins, a report of a novel semiconductor detection mechanism shows electronic detection of small quantities of spin 3/2 nuclei at the nanoscale (23). However, all of these techniques require low temperatures. For liquid samples at room temperature, pioneering work on fabrication of solenoids around capillary tubes (16, 24) and microfabrication techniques to create planar coils on semiconductor substrates (1, 25) demonstrates that miniaturization of probes is possible and substantially reduces sample quantity while retaining signal sensitivity (15). Solenoidal microcoils detect nanomole quantities with high sensitivity but have not been successfully fabricated below Ϸ300 m inner diameter (26), whereas planar coils on semiconductor substrates are scalable but show lower signal sensitivit...

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“…This is the motivation for the second component of this research, and it utilizes the development of µ-coils for NMR detection. In recent years significant advances in the development and fabrication of µ-coils (size < 1 mm) for NMR have continued [15][16][17]. Both planar surface µ-coils and solenoid µ-coils have been developed for a wide range of applications [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Bioagent detection using miniaturized NMR and nanoparticle amplification : final LDRD report.

Clewett¹,

Adams²,

Fan³

et al. 2006

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This LDRD program was directed towards the development of a portable micro-nuclear magnetic resonance (µ-NMR) spectrometer for the detection of bioagents via induced amplification of solvent relaxation based on superparamagnetic nanoparticles. The first component of this research was the fabrication and testing of two different micro-coil (µ-coil) platforms: namely a planar spiral NMR µ-coil and a cylindrical solenoid NMR µ-coil. These fabrication techniques are described along with the testing of the NMR performance for the individual coils. The NMR relaxivity for a series of water soluble FeMn oxide nanoparticles was also determined to explore the influence of the nanoparticle size on the observed NMR relaxation properties. In addition, The use of commercially produced superparamagnetic iron oxide nanoparticles (SPIONs) for amplification via NMR based relaxation mechanisms was also demonstrated, with the lower detection limit in number of SPIONs per nanoliter (nL) being determined.* Author to whom correspondence should be addressed: tmalam@sandia.gov 4 AcknowledgementsThe progress made in this LDRD project is the result of contributions from a number of team members both here at Sandia National Laboratories, at the University of New Mexico and the company New Mexico Resonance. These members include C. The development and testing of two different µ-coil platforms for nuclear magnetic resonance (NMR) detection were completed under this LDRD project. The performance of these NMR µ-coils allowed the demonstration of SPION (superparamagnetic iron oxide nanoparticle) amplification via induced changes in the NMR relaxation rates of the carrier solvent water. A detection limit of 10 particles/nL was experimentally measured for the first prototype solenoid µ-coil design. These results clearly show that nanoparticle amplification for µ-NMR can be used for detection of bioagents. List of Tables

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High-Resolution NMR Spectroscopy of Sample Volumes from 1 nL to 10 μL

Cited by 243 publications

References 137 publications

Development of a Functionalized Xenon Biosensor

Development of a Functionalized Xenon Biosensor

Ultra-small-sample molecular structure detection using microslot waveguide nuclear spin resonance

Bioagent detection using miniaturized NMR and nanoparticle amplification : final LDRD report.

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