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. We show how flow path and history can be selected through the use of these thin film labels and through the application of synchronized, frequency-selective pulses. This obviates the need for large electric currents to produce pulsed magnetic field gradients and may allow for further application of NMR and MRI experiments on microscale devices.

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. Here, we build upon our previous work and introduce a method that incorporates our prior knowledge of the microfluidic device geometry to further decrease acquisition times. We demonstrate its use in multidimensional velocimetric imaging of a microfluidic mixer, acquiring microscopically detailed images 128 times faster than is possible with conventional sampling. This prior information also informs our choice of sampling schedule, resulting in a scheme that is optimized for a specific flow geometry. Finally, we test our approach in synthetic data and explore potential reconstruction errors as a function of optimization and reconstruction parameters.

Measurement of Arterial Input Function in Hyperpolarized 13C Studies.

Recently, hyperpolarized substrates generated through dynamic nuclear polarization have been introduced to study in vivo metabolism. Injection of hyperpolarized [1-13C]pyruvate, the most widely used substrate, allows detection of time courses of [1-13C]pyruvate and its metabolic products, such as [1-13C]lactate and 13C-bicarbonate, in various organs. However, quantitative metabolic modeling of in vivo data to measure specific metabolic rates remains challenging without measuring the input function. In this study, we demonstrate that the input function of [1-13C]pyruvate can be measured in vivo in the rat carotid artery using an implantable coil.

Remotely detected NMR for the characterization of flow and fast chromatographic separations using organic polymer monoliths.

An application of remotely detected magnetic resonance imaging is demonstrated for the characterization of flow and the detection of fast, small molecule separations within hypercrosslinked polymer monoliths. The hyper-cross-linked monoliths exhibited excellent ruggedness, with a transit time relative standard deviation of less than 2.1%, even after more than 300 column volumes were pumped through at high pressure and flow. Magnetic resonance imaging enabled high-resolution intensity and velocity-encoded images of mobile phase flow through the monolith. The images confirm that the presence of a polymer monolith within the capillary disrupts the parabolic laminar flow profile that is characteristic of mobile phase flow within an open tube. As a result, the mobile phase and analytes are equally distributed in the radial direction throughout the monolith. Also, in-line monitoring of chromatographic separations of small molecules at high flow rates is shown. The coupling of monolithic chromatography columns and NMR provides both real-time peak detection and chemical shift information for small aromatic molecules. These experiments demonstrate the unique power of magnetic resonance, both direct and remote, in studying chromatographic processes.

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. Here, we apply this method to microporous model systems, recording MRI images that correlate local velocity, spin relaxation, and time-of-flight in microscopic resolution and three spatial dimensions. Our results illustrate that remotely detected MRI is an effective approach to elucidate flow dynamics in porous materials including bead pack microreactors and chromatography columns.

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. Here, we instead demonstrate experiments to directly image oscillating currents by MRI. The approach rests on a resonant interaction between an applied rf field and an oscillating magnetic field in the sample and, as such, permits quantitative, frequency-selective measurements of current density without spatial or temporal cancellation. We apply this method in a current loop phantom, mapping its magnetic field and achieving a detection sensitivity near the threshold required for the detection of neuronal currents. Because the contrast mechanism is under spectroscopic control, we are able to demonstrate how ramped and phase-modulated spin-lock radiation can enhance the sensitivity and robustness of the experiment. We further demonstrate the combination of these methods with remote detection, a technique in which the encoding and detection of an MRI experiment are separated by sample flow or translation. We illustrate that remotely detected MRI permits the measurement of currents in small volumes of flowing water with high sensitivity and spatial resolution.

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. In particular, we reassign the bands at 22 400 and 32 300 cm(-1) to the (1)A(1g) --> (3)A(2g) (b(2g) --> b(1g)) and (1)A(1g) --> (1)A(2g) (b(2g) --> b(1g)) excitations.

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.