Design and Fabrication of a Three-Dimensional Multi-Electrode Array for Neuron Electrophysiology.

Neural recording and stimulation with high spatial and temporal resolution are highly desirable in the study of neurocommunication and diseases. Planar multiple microelectrode arrays (MEA) or quasi-three-dimensional (3D) MEA with fixed height have been proposed by many researchers and become commercially available. In this paper, we present the design, fabrication, and test of a novel true 3D multiple electrode array for brain slice stimulation and recording. This MEA is composed of 105 microelectrodes with 50 µm diameter and 125 µm center-to-center spacing integrated in a 1.2 × 1.2 mm2 area. This "true" 3D MEA allows us to precisely position the individual electrodes by piezoelectric-based actuators to penetrate the inactive tissue layer and to approach the active neurons so as to optimize the recording and stimulation of electrical field potential. The capability to stimulate nerve fibers and record postsynaptic field potentials was demonstrated in an experiment using mouse brain hippocampus slice.

Synthesis of Fused Pyrimidinone and Quinolone Derivatives in an Automated High-Temperature and High-Pressure Flow Reactor.

Fused pyrimidinone and quinolone derivatives that are of potential interest to pharmaceutical research were synthesized within minutes in up to 96% yield in an automated Phoenix high-temperature and high-pressure continuous flow reactor. Heterocyclic scaffolds that are either hard to synthesize or require multisteps are readily accessible using a common set of reaction conditions. The use of low-boiling solvents along with the high conversions of these reactions allowed for facile workup and isolation. The methods reported herein are highly amenable for fast and efficient heterocycle synthesis as well as compound scale-ups.

Automated library synthesis of cyclopropyl boronic esters employing diazomethane in a tube-in-tube flow reactor.

The efficient synthesis of cyclopropyl boronic esters in library format using a diazomethane flow reactor has been achieved. A pivotal component of the system is a fully automated tube-in-tube reactor allowing for safe handling of hazardous diazomethane on repeated small scale and for the generation of larger quantities of product. The setup enables the repeated execution of Pd-catalyzed cyclopropanation reactions without compromising its operation over time.

Near-infrared thermo-optical response of the localized reflectance of intact diabetic and nondiabetic human skin.

We observed a difference in the thermal response of localized reflectance signal of human skin between type 2 diabetics and nondiabetics. We investigated the use of this thermo-optical behavior as the basis for a noninvasive method for the determination of the diabetic status of a subject. We used a two-site temperature differential method, which is predicated upon the measurement of localized reflectance from two areas on the surface of the skin. Each of these areas is subjected to a different thermal perturbation. The response of localized reflectance to temperature perturbation was measured and used in a classification algorithm. We used a discriminant function to classify subjects as diabetic or nondiabetic. In a prediction set of twenty-four noninvasive tests collected from six diabetic and six nondiabetic subjects, the sensitivity ranged between 73 and 100%, and the specificity ranged between 75 and 100%, depending on the thermal conditions and the probe-skin contact time. The difference in the thermo-optical response of the skin of the two groups is explained in terms of a difference in the response of cutaneous microcirculation, which is manifested as a difference in the near-infrared light absorption. Another factor is the difference in the temperature response of the scattering coefficient between the two groups, which may be caused by cutaneous structural differences induced by nonenzymatic glycation of skin protein fibers, and possibly by the difference in blood cell aggregation.

Temperature modulation of the visible and near infrared absorption and scattering coefficients of human skin.

We determine temperature effect on the absorption and reduced scattering coefficients (mu(a) and mu(s)(')) of human forearm skin. Optical and thermal simulation data suggest that mu( a) and mu(s)(') are determined within a temperature-controlled depth of approximately 2 mm. Cutaneous mu(s)(') change linearly with temperature. Change in mu(a) was complex and irreversible above body normal temperatures. Light penetration depth (delta) in skin increased on cooling, with considerable person-to-person variations. We attribute the effect of temperature on mu(s)(') to change in refractive index mismatch, and its effect on mu(a) to perfusion changes. The reversible temperature effect on mu (s)(' ) was maintained during more than 90 min. contact between skin and the measuring probe, where temperature was modulated between 38 and 22 degrees C for multiple cycles While temperature modulated mu(s)(' ) instantaneously and reversibly, mu(a) exhibited slower response time and consistent drift. There was a statistically significant upward drift in mu(a) and a mostly downward drift in mu( s)(') over the contact period. The drift in temperature-induced fractional change in mu(s)(') was less statistically significant than the drift in mu(s)('). Deltamu( s)(') values determined under temperature modulation conditions may have less nonspecific drift than mu(s)(') which may have significance for noninvasive determination of analytes in human tissue.