Gradient-free microfluidic flow labeling using thin magnetic films and remotely detected MRI.

Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) may be employed as noninvasive measurements yielding detailed information about the chemical and physical parameters that define microscale flows. Despite these advantages, magnetic resonance has been difficult to combine with microfluidics, largely due to its low sensitivity when detecting small sample volumes and the difficulty of efficiently addressing individual flow pathways for parallel measurements without utilizing large electric currents to create pulsed magnetic field gradients. Here, we demonstrate that remotely-detected MRI (RD-MRI) employing static magnetic field gradients produced by thin magnetic films can be used to encode flow and overcome some of these limitations.

Measurement of Arterial Input Function in Hyperpolarized C Studies.

Recently, hyperpolarized substrates generated through dynamic nuclear polarization have been introduced to study metabolism. Injection of hyperpolarized [1-C]pyruvate, the most widely used substrate, allows detection of time courses of [1-C]pyruvate and its metabolic products, such as [1-C]lactate and C-bicarbonate, in various organs. However, quantitative metabolic modeling of data to measure specific metabolic rates remains challenging without measuring the input function.

Compressive sampling with prior information in remotely detected MRI of microfluidic devices.

The design and operation of microfluidic analytical devices depends critically on tools to probe microscale chemistry and flow dynamics. Magnetic resonance imaging (MRI) seems ideally suited to this task, but its sensitivity is compromised because the fluid-containing channels in "lab on a chip" devices occupy only a small fraction of the enclosing detector's volume; as a result, the few microfluidic applications of NMR have required custom-designed chips harboring many detectors at specific points of interest. To overcome this limitation, we have developed remotely detected microfluidic MRI, in which an MR image is stored in the phase and intensity of each analyte's NMR signal and sensitively detected by a single, volume-matched detector at the device outflow, and combined it with compressed sensing for rapid image acquisition.

Remotely detected MRI velocimetry in microporous bead packs.

Many NMR and MRI methods probe fluid dynamics within macro- and mesoporous materials, but with few exceptions, they report on its macroscopically averaged properties. MRI methods are generally unable to localize microscopic features of flow within macroscopic samples because the fraction of the enclosing detector volume occupied by these features is so small. We have recently overcome this problem using remotely detected MRI velocimetry, a technique in which spatial, chemical, and velocity information about elements of the flow is encoded with a conventional NMR coil and detected sensitively at the sample outflow by a volume-matched microdetector.

Magnetic resonance imaging of oscillating electrical currents.

Functional MRI has become an important tool of researchers and clinicians who seek to understand patterns of neuronal activation that accompany sensory and cognitive processes. However, the interpretation of fMRI images rests on assumptions about the relationship between neuronal firing and hemodynamic response that are not firmly grounded in rigorous theory or experimental evidence. Further, the blood-oxygen-level-dependent effect, which correlates an MRI observable to neuronal firing, evolves over a period that is 2 orders of magnitude longer than the underlying processes that are thought to cause it.

High-resolution 14N-edited 1H-13C correlation NMR experiment to study biological solids.

It was recently shown that nuclear magnetic resonance (NMR) spectra of nitrogen-14 (spin I=1) can be obtained by indirect detection via spin S=1/2 nuclei in powders spinning at the magic angle. An increased number of solid-state NMR methods are now available to tailor sequences for specific purposes, e.g.

Probing amide bond nitrogens in solids using 14N NMR spectroscopy.

A novel two-dimensional nuclear magnetic resonance (NMR) experiment is proposed for indirect observation of 14N nuclei in various types of nitrogen-containing solids. In a method somewhat similar to the heteronuclear single-quantum correlation (HSQC) experiment widely used for protein structure determination in solutions, this technique correlates spin S=1/2 nuclei, e.g.

Electronic excited states of tetracyanonickelate(II).

We revisit the assignment of the absorption spectrum of tetracyanonickelate(II) by calculating energies of excitations with time-dependent density functional theory. Our results give strong evidence that the original assignment of the spectrum is only partially correct. We thus propose an alternative assignment consistent with our theoretical calculations and all available experimental evidence.

Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires.

Molecular wires comprising a Ru(II)- or Re(I)-complex head group, an aromatic tail group, and an alkane linker reversibly inhibit the activity of the copper amine oxidase from Arthrobacter globiformis (AGAO), with K(i) values between 6 muM and 37 nM. In the crystal structure of a Ru(II)-wire:AGAO conjugate, the wire occupies the AGAO active-site substrate access channel, the trihydroxyphenylalanine quinone cofactor is ordered in the "off-Cu" position with its reactive carbonyl oriented toward the inhibitor, and the "gate" residue, Tyr-296, is in the "open" position. Head groups, tail-group substituents, and linker lengths all influence wire-binding interactions with the enzyme.