Thermal effects on neurons during stimulation of the brain.

All electric and magnetic stimulation of the brain deposits thermal energy in the brain. This occurs through either Joule heating of the conductors carrying current through electrodes and magnetic coils, or through dissipation of energy in the conductive brain.Objective.Although electrical interaction with brain tissue is inseparable from thermal effects when electrodes are used, magnetic induction enables us to separate Joule heating from induction effects by contrasting AC and DC driving of magnetic coils using the same energy deposition within the conductors. Since mammalian cortical neurons have no known sensitivity to static magnetic fields, and if there is no evidence of effect on spike timing to oscillating magnetic fields, we can presume that the induced electrical currents within the brain are below the molecular shot noise where any interaction with tissue is purely thermal.Approach.In this study, we examined a range of frequencies produced from micromagnetic coils operating below the molecular shot noise threshold for electrical interaction with single neurons.Main results.We found that small temperature increases and decreases of 1∘C caused consistent transient suppression and excitation of neurons during temperature change. Numerical modeling of the biophysics demonstrated that the Na-K pump, and to a lesser extent the Nernst potential, could account for these transient effects. Such effects are dependent upon compartmental ion fluxes and the rate of temperature change.Significance.A new bifurcation is described in the model dynamics that accounts for the transient suppression and excitation; in addition, we note the remarkable similarity of this bifurcation's rate dependency with other thermal rate-dependent tipping points in planetary warming dynamics. These experimental and theoretical findings demonstrate that stimulation of the brain must take into account small thermal effects that are ubiquitously present in electrical and magnetic stimulation. More sophisticated models of electrical current interaction with neurons combined with thermal effects will lead to more accurate modulation of neuronal activity.

Enhanced thermoelectric efficiency in nanocrystalline bismuth telluride nanotubes.

We report on the thermal and thermoelectric properties of individual nanocrystalline Bi2 Te3 nanotubes synthesized by the solution phase method using 3ω method and a microfabricated testbench. Measurements show that the nanotubes offer improved ZT compared to bulk Bi2Te3 near room temperature due to an enhanced Seebeck coefficient and suppressed thermal conductivity. This improvement in ZT originates from the nanocrystalline nature and low dimensionality of the nanotubes. Domain boundary filtering of low-energy electrons provides an enhanced Seebeck coefficient. The scattering of phonons at the surface of the nanotube leads to suppressed thermal conductivity. These have been theoretically analyzed using the Boltzmann equation based on the relaxation time approximation and Landauer approach. This work clearly demonstrates the possibility of achieving enhancement in thermoelectric efficiency by combining nanocrystalline and low-dimensional systems.

Robust visibility of graphene monolayer on patterned plasmonic substrates.

Single and few-layer graphene flakes, while visible on a dielectric surface with customized thickness, cannot be optically imaged when exfoliated directly on semiconductors or metal substrates with arbitrary thickness. In this paper, we show that such graphene flakes become visible through a conventional microscope on a substrate patterned with a submicron sized, hexagonally packed array of gold disks. The interaction of the metal pattern with the incident light generates surface plasmon polaritons (SPPs) and results in enhanced reflectivity for certain angles and wavelengths. In the areas where graphene flakes are present, the interaction of the SPP with incident radiation is altered and consequently decreases the reflectivity in this region and increases the contrast, which accounts for the visibility of the graphene flakes on such substrates. We validate the observed contrast in visibility utilizing an in-house developed modified form of rigorous coupled wave analysis algorithm to appropriately incorporate the optical properties of two-dimensional materials. We present a parametric study of the contrast of graphene flakes on the patterned substrate to demonstrate the robustness of the visibility.

Detection of bacterial metabolism in lag-phase using impedance spectroscopy of agar-integrated 3D microelectrodes.

Traditional methods for detection of metabolically-active bacterial cells, while effective, require several days to complete. Development of sensitive electrical biosensors is highly desirable for rapid detection and counting of pathogens in food, water, or clinical samples. Herein, we develop a highly-sensitive non-Faradaic impedance sensor which detects metabolic activity of E. coli cells in a mere 1 µl of sample volume and without any sample filtration/purification. The three dimensional (3D) interdigitated electrodes (IDEs) along with self-assembled gold-nickel (Au-Ni) nanostructures significantly amplify the sensitivity by increasing the sensing area almost three-fold. The developed microsystem is integrated with an agar-based growth medium and monitors the metabolism of bacterial cells, enabling bacterial detection in approximately one hour after inoculation, i.e. in the lag-phase. Incorporation of a secondary agar layer as a biocompatible passivation layer protects the IDEs from potential Faradaic reactions and enhances sensitivity to modulation of the non-Faradaic impedance due to cellular metabolism. The resultant label-free sensor is capable of selective identification of metabolizing cells (vs. dead cells) across a wide linear range (10-1000 cells/µl). These results help pave the way for rapid antibacterial susceptibility testing at the point-of-need, which is currently a major challenge in healthcare.

Chip-scale high Q-factor glassblown microspherical shells for magnetic sensing.

A whispering gallery mode resonator based magnetometer using chip-scale glass microspherical shells is described. A neodynium micro-magnet is elastically coupled and integrated on top of the microspherical shell structure that enables transduction of the magnetic force experienced by the magnet in external magnetic fields into an optical resonance frequency shift. High quality factor optical microspherical shell resonators with ultra-smooth surfaces have been successfully fabricated and integrated with magnets to achieve Q-factors of greater than 1.1 × 107 and have shown a resonance shift of 1.43 GHz/mT (or 4.0 pm/mT) at 760 nm wavelength. The main mode of action is mechanical deformation of the microbubble with a minor contribution from the photoelastic effect. An experimental limit of detection of 60 nT Hz-1/2 at 100 Hz is demonstrated. A theoretical thermorefractive limited detection limit of 52 pT Hz-1/2 at 100 Hz is calculated from the experimentally derived sensitivity. The paper describes the mode of action, sensitivity and limit of detection is evaluated for the chip-scale whispering gallery mode magnetometer.

Design of a sustainable prepolarizing magnetic resonance imaging system for infant hydrocephalus.

OBJECTIVES: The need for affordable and appropriate medical technologies for developing countries continues to rise as challenges such as inadequate energy supply, limited technical expertise, and poor infrastructure persist. Low-field magnetic resonance imaging (LF MRI) is a technology that can be tailored to meet specific imaging needs within such countries. Its low power requirements and the possibility of operating in minimally shielded or unshielded environments make it especially attractive. Although the technology has been widely demonstrated over several decades, it is yet to be shown that it can be diagnostic and improve patient outcomes in clinical applications. We here demonstrate the robustness of prepolarizing MRI (PMRI) technology for assembly and deployment in developing countries for the specific application to infant hydrocephalus. Hydrocephalus treatment planning and management requires only modest spatial resolution, such that the brain can be distinguished from fluid-tissue contrast detail within the brain parenchyma is not essential. MATERIALS AND METHODS: We constructed an internally shielded PMRI system based on the Lee-Whiting coil system with a 22-cm diameter of spherical volume. RESULTS: In an unshielded room, projection phantom images were acquired at 113 kHz with in-plane resolution of 3 mm × 3 mm, by introducing gradient fields of sufficient magnitude to dominate the 5000 ppm inhomogeneity of the readout field. DISCUSSION: The low cost, straightforward assembly, deployment potential, and maintenance requirements demonstrate the suitability of our PMRI system for developing countries. Further improvement in image spatial resolution and contrast of LF MRI will broaden its potential clinical utility beyond hydrocephalus.

On-Chip Glass Microspherical Shell Whispering Gallery Mode Resonators.

Arrays of on-chip spherical glass shells of hundreds of micrometers in diameter with ultra-smooth surfaces and sub-micrometer wall thicknesses have been fabricated and have been shown to sustain optical resonance modes with high Q-factors of greater than 50 million. The resonators exhibit temperature sensitivity of -1.8 GHz K-1 and can be configured as ultra-high sensitivity thermal sensors for a broad range of applications. By virtue of the geometry's strong light-matter interaction, the inner surface provides an excellent on-chip sensing platform that truly opens up the possibility for reproducible, chip scale, ultra-high sensitivity microfluidic sensor arrays. As a proof of concept we demonstrate the sensitivity of the resonance frequency as water is filled inside the microspherical shell and is allowed to evaporate. By COMSOL modeling, the dependence of this interaction on glass shell thickness is elucidated and the experimentally measured sensitivities for two different shell thicknesses are explained.

Calorimetric Biosensing System for Quantification of Urinary Creatinine.

In this work, we demonstrate the quantification of creatinine in human urine samples using a microcalorimetric sensing system. The calorimetric sensor is based on an array of microfabricated Y-cut quartz resonators. The piezoelectric quartz is etched down to a thickness of 10 µm and exhibits a bulk acoustic resonance of 166 MHz. The temperature sensitivity of this high-frequency quartz resonator is 14 600 Hz/K due to the high phenomenological sensitivity of quartz. Most importantly, the quartz sensors and the analyte fluidics are decoupled providing a significantly more robust calorimetric sensing system than directly contacted chip calorimeters. A reference resonator, consisting of a suspended structure held by four arms, was realized to thermal isolation from the bulk quartz by using focused ion beam etching. We employ alginate entrapped creatinine deiminase to transduce urinary creatinine into temperature signatures, permitting the quantification of creatinine. Fairly good agreement with the measured creatinine values in the 5 urine samples using calorimetric and HPLC methods is obtained.

Modified Random Sequential Adsorption Model for Understanding Kinetics of Proteins Adsorption at a Liquid-Solid Interface.

In this Article, we experimentally measure the adsorption kinetics of human serum albumin (HSA) on a hydrophobic hexadecanethiolated gold surface. We use micromachined quartz crystal resonators with fundamental frequency of 83 MHz to accomplish these measurements in real time. In this work, we focus on two key results: (i) asymptotic behavior of the sensor responses upon HSA adsorption and (ii) the jamming limit of adsorbed layer formed by both single-injection and multi-injection experiments with the same value of final concentration. We develop a new interface-depletion modified random sequential adsorption (RSA) model to elucidate the adsorption kinetics and the transport properties of the protein molecules. Analysis of the experimentally measured data shows that the results can be explained on the basis of the exponentially depleting interfacial layer RSA model. To better understand the origin of the formation of the interfacial depletion region where the supply of protein molecules is dramatically reduced, we performed a series of molecular dynamics (MD) simulations using the ReaxFF method. These simulations predict that the resulting adsorption of the protein molecules on the thiolated surface results in a specific orientation at the interface and the diffusion constant of the protein molecules in this layer is significantly reduced. This interplay between the surface adsorption rate and the reduced diffusion coefficient leads to the depletion of the protein molecules in the interfacial layer where the concentration of the protein molecules is much less than the bulk concentration and explains the observed slowdown of the HSA adsorption characteristics on a hydrophobic surface.

Self-Healing Textile: Enzyme Encapsulated Layer-by-Layer Structural Proteins.

Self-healing materials, which enable an autonomous repair response to damage, are highly desirable for the long-term reliability of woven or nonwoven textiles. Polyelectrolyte layer-by-layer (LbL) films are of considerable interest as self-healing coatings due to the mobility of the components comprising the film. In this work mechanically stable self-healing films were fabricated through construction of a polyelectrolyte LbL film containing squid ring teeth (SRT) proteins. SRTs are structural proteins with unique self-healing properties and high elastic modulus in both dry and wet conditions (>2 GPa) due to their semicrystalline architecture. We demonstrate LbL construction of multilayers containing native and recombinant SRT proteins capable of self-healing defects. Additionally, we show these films are capable of utilizing functional biomolecules by incorporating an enzyme into the SRT multilayer. Urease was chosen as a model enzyme of interest to test its activity via fluorescence assay. Successful construction of the SRT films demonstrates the use of mechanically stable self-healing coatings, which can incorporate biomolecules for more complex protective functionalities for advanced functional fabrics.

Cellulose Microfibril Formation by Surface-Tethered Cellulose Synthase Enzymes.

Cellulose microfibrils are pseudocrystalline arrays of cellulose chains that are synthesized by cellulose synthases. The enzymes are organized into large membrane-embedded complexes in which each enzyme likely synthesizes and secretes a ß-(1→4) glucan. The relationship between the organization of the enzymes in these complexes and cellulose crystallization has not been explored. To better understand this relationship, we used atomic force microscopy to visualize cellulose microfibril formation from nickel-film-immobilized bacterial cellulose synthase enzymes (BcsA-Bs), which in standard solution only form amorphous cellulose from monomeric BcsA-B complexes. Fourier transform infrared spectroscopy and X-ray diffraction techniques show that surface-tethered BcsA-Bs synthesize highly crystalline cellulose II in the presence of UDP-Glc, the allosteric activator cyclic-di-GMP, as well as magnesium. The cellulose II cross section/diameter and the crystal size and crystallinity depend on the surface density of tethered enzymes as well as the overall concentration of substrates. Our results provide the correlation between cellulose microfibril formation and the spatial organization of cellulose synthases.

Optimization of Metglas 2605SA1 and PZT-5A Magnetoelectric Laminates for Magnetic Sensing Applications.

Via optimization of the mechanical coupling, alignment of Metglas® magnetic domains, relief of residual stress, and operation of the PZT-5A under a DC electric field of 2 kV/cm an unprecedented magnetoelectric voltage coefficient of 9.52 V/cm-Oe is achieved; resulting to a magnetic field sensitivity of 150 pT at 20 Hz for a d31 Metglas®/PZT-5A laminate. Mechanical coupling is improved by reducing the thickness and porosity of the epoxy. The Metglas® residual stress reduction and easy axis alignment is accomplished by a 30 minute 400 °C anneal under a 1600 Oe magnetic field in vacuum. Finally, a DC electric field bias is applied to increase the d 31 coefficient of the PZT-5A piezoelectric.

Remote calorimetric detection of urea via flow injection analysis.

The design and development of a calorimetric biosensing system enabling relatively high throughput sample analysis are reported. The calorimetric biosensor system consists of a thin (∼20 µm) micromachined Y-cut quartz crystal resonator (QCR) as a temperature sensor placed in close proximity to a fluidic chamber packed with an immobilized enzyme. Layer by layer enzyme immobilization of urease is demonstrated and its activity as a function of the number of layers, pH, and time has been evaluated. This configuration enables a sensing system where a transducer element is physically separated from the analyte solution of interest and is thereby free from fouling effects typically associated with biochemical reactions occuring on the sensor surface. The performance of this biosensing system is demonstrated by detection of 1-200 mM urea in phosphate buffer via a flow injection analysis (FIA) technique. Miniaturized fluidic systems were used to provide continuous flow through a reaction column. Under this configuration the biosensor has an ultimate resolution of less than 1 mM urea and showed a linear response between 0-50 mM. This work demonstrates a sensing modality in which the sensor itself is not fouled or contaminated by the solution of interest and the enzyme immobilized Kapton® fluidic reaction column can be used as a disposable cartridge. Such a system enables reuse and reliability for long term sampling measurements. Based on this concept a biosensing system is envisioned which can perform rapid measurements to detect biomarkers such as glucose, creatinine, cholesterol, urea and lactate in urine and blood continuously over extended periods of time.

Design, fabrication and analysis of stagnation flow microreactors used to study hypergolic reactions.

A novel method to study the condensed phase reactions that occur during the ignition of hypergolic propellants (very fast liquid reactions) using microreactors is presented. Planar counterflow microreactors are used to isolate liquid-phase reactions and diffusion from secondary gas-phase chemical and transport processes that often occur concurrently during the overall ignition process. The counterflow microreactor has made it possible to achieve valuable insight into the preignition mechanisms of hypergolic propellants hitherto not possible using conventional drop or impinging jet tests. In the present paper, the microreactor fabrication, flow field characterization, and reactivity of 2-dimethylaminoethylazide and nitric acid as hypergols are presented. Particle image velocimetry and numerical simulations were conducted to characterize the laminar velocity flow-field from which stagnation point strain rates and contact residence times along the centerline of the microreactor were evaluated. Temperature measurements at the exit of the reactor (as well as at the stagnation point) were used as a measure for the extent of the reaction or the heat released from the reaction. For the hypergols, an increase in reactant flow (or equivalently strain rate at the stagnation point) was found to initially increase reactivity, but eventually resulted in a decrease in temperature, revealing a maxima in temperature and reactivity. The trends indicated a reaction that was initially diffusion or heat loss controlled, which transitioned towards kinetic control at higher strain (flow) rates. This paper details the first comprehensive measurements and analysis of the effects of diffusion based mixing on the interfacial reactions occurring between hypergols.

Improved micromachined column design and fluidic interconnects for programmed high-temperature gas chromatography separations.

This work focuses on the development and experimental evaluation of micromachined chromatographic columns for use in a commercial gas chromatography (GC) system. A vespel/graphite ferrule based compression sealing technique is presented using which leak-proof fluidic interconnection between the inlet tubing and the microchannel was achieved. This sealing technique enabled separation at temperatures up to 350°C on a µGC column. This paper reports the first high-temperature separations in microfabricated chromatographic columns at these temperatures. A 2m microfabricated column using a double Archimedean spiral design with a square cross-section of 100µm×100µm has been developed using silicon microfabrication techniques. The microfabricated column was benchmarked against a 2m 100µm diameter commercial column and the performance between the two columns was evaluated in tests performed under identical conditions. High temperature separations of simulated distillation (ASTM2887) and polycyclic aromatic hydrocarbons (EPA8310) were performed using the µGC column in temperature programmed mode. The demonstrated µGC column along with the high temperature fixture offers one more solution toward potentially realizing a portable µGC device for the detection of semi-volatile environmental pollutants and explosives without the thermal limitations reported to date with µGC columns using epoxy based interconnect technology.

Monitoring biochemical reactions using Y-cut quartz thermal sensors.

In this paper, we present a micromachined Y-cut quartz resonator based thermal sensor array which is configured with a reaction chamber that is physically separated but located in close proximity to the resonator for sensitive calorimetric biosensing applications. The coupling of heat from the reaction chamber to the quartz resonator is achieved via radiation and conduction through ambient gas. The sensor was packaged onto a 300 µm thick stainless plate with an opening in the middle. The sensor array was aligned to the opening and mounted from the underside of the plate. A reaction chamber designed for performing (bio)chemical reactions was used in the measurements. This configuration of the sensor allows for a very robust sensing platform with no fouling of the sensor surface or degradation in its performance metrics. Impedance-based tracking of resonance frequency was used for chemical, enzymatic, and cellular activity measurements. The sensor described has an impedance sensitivity of 852 Ω °C(-1) or a frequency sensitivity of 7.32 kHz °C(-1) for the 91 MHz resonator used in this work. Results on exothermic reaction between hydrochloric acid and ammonium hydroxide, the hydrolysis reaction of urea by urease and the catalytic reaction of glucose with glucose dehydrogenase are reported. From the signal to noise ratio analysis of the glucose sensor, <10 µM glucose sensitivity could be obtained improving the detection limit by a factor of 250 in comparison to our previous work using thermopile sensors. Finally, calcium ionophore induced cellular activity was measured in pancreatic cancer cells using the sensor.

Volumetric interpretation of protein adsorption: interfacial packing of protein adsorbed to hydrophobic surfaces from surface-saturating solution concentrations.

The maximum capacity of a hydrophobic adsorbent is interpreted in terms of square or hexagonal (cubic and face-centered-cubic, FCC) interfacial packing models of adsorbed blood proteins in a way that accommodates experimental measurements by the solution-depletion method and quartz-crystal-microbalance (QCM) for the human proteins serum albumin (HSA, 66 kDa), immunoglobulin G (IgG, 160 kDa), fibrinogen (Fib, 341 kDa), and immunoglobulin M (IgM, 1000 kDa). A simple analysis shows that adsorbent capacity is capped by a fixed mass/volume (e.g. mg/mL) surface-region (interphase) concentration and not molar concentration. Nearly analytical agreement between the packing models and experiment suggests that, at surface saturation, above-mentioned proteins assemble within the interphase in a manner that approximates a well-ordered array. HSA saturates a hydrophobic adsorbent with the equivalent of a single square or hexagonally-packed layer of hydrated molecules whereas the larger proteins occupy two-or-more layers, depending on the specific protein under consideration and analytical method used to measure adsorbate mass (solution depletion or QCM). Square or hexagonal (cubic and FCC) packing models cannot be clearly distinguished by comparison to experimental data. QCM measurement of adsorbent capacity is shown to be significantly different than that measured by solution depletion for similar hydrophobic adsorbents. The underlying reason is traced to the fact that QCM measures contribution of both core protein, water of hydration, and interphase water whereas solution depletion measures only the contribution of core protein. It is further shown that thickness of the interphase directly measured by QCM systematically exceeds that inferred from solution-depletion measurements, presumably because the static model used to interpret solution depletion does not accurately capture the complexities of the viscoelastic interfacial environment probed by QCM.

Adsorption of ammonia on graphene.

We report on experimental studies of NH3 adsorption/desorption on graphene surfaces. The study employs bottom-gated graphene field effect transistors supported on Si/SiO2 substrates. Detection of NH3 occurs through the shift of the source-drain resistance maximum ('Dirac peak') with the gate voltage. The observed shift of the Dirac peak toward negative gate voltages in response to NH3 exposure is consistent with a small charge transfer (f approximately 0.068 +/- 0.004 electrons per molecule at pristine sites) from NH3 to graphene. The desorption kinetics involves a very rapid loss of NH3 from the top surface and a much slower removal from the bottom surface at the interface with the SiO2 that we identify with a Fickian diffusion process.

Thermopower enhancement in nanowires via junction effects.

We present thermopower measurements on free-standing, straight and "junctioned" gold nanowires using a micromachined thermoelectric workbench. Measurements on straight 70 nm diameter gold nanowires show a thermopower similar to that of bulk gold; however for "junctioned" gold nanowires we observed a hitherto unreported peak in the thermopower near room temperature. The observed enhancement can be explained by approximating the "junctioned" nanowires as tunnel junctions in combination with Coulombic effect of the electrons crossing the junction. The electron transfer across the barrier can be expected to be stochastic in nature. Under thermal equilibrium conditions and in the absence of temperature gradient across the tunnel junction, the time averaged random fluctuation of the electrons across the tunnel junction results in a net zero voltage. However, in the presence of a temperature gradient across the junction, the time averaged fluctuation of the electrons across the junction is now offset by the tunnel junction thermoelectric effect and is measured by the lock-in amplifier. A hundredfold enhancement in the ZT of "junctioned" nanowires has been observed for the gold nanowires measured over several samples.

Human serum albumin adsorption study on 62-MHz miniaturized quartz gravimetric sensors.

We have designed and fabricated 25-microm-thick quartz resonators operating at a fundamental resonance frequency of approximately 62 MHz. The results show a substantial increase in the mass sensitivity compared to single monolithic commercial resonators operating at lower frequencies in the approximately 5-10-MHz range. The overall performance of the micromachined resonators is demonstrated for the example of human serum albumin protein adsorption from aqueous buffer solutions onto gold electrodes functionalized with self-assembled monolayers. The results show a saturation adsorption frequency change of 6.8 kHz as opposed to 40 Hz for a commercial approximately 5-MHz sensor under identical loading conditions. From the analysis of the adsorption isotherm, the equilibrium adsorption constant of the adsorption of the protein layer was found to be K = 8.03 x 10(6) M(-1), which is in agreement with the values reported in the literature. The high sensitivity of the miniaturized QCM devices can be a significant advantage in both vapor and solution adsorption analyses.