In Vitro Biofouling Performance of Boron-Doped Diamond Microelectrodes for Serotonin Detection Using Fast-Scan Cyclic Voltammetry.

Neurotransmitter release is important to study in order to better understand neurological diseases and treatment approaches. Serotonin is a neurotransmitter known to play key roles in the etiology of neuropsychiatric disorders. Fast-scan cyclic voltammetry (FSCV) has enabled the detection of neurochemicals, including serotonin, on a sub-second timescale via the well-established carbon fiber microelectrode (CFME). However, poor chronic stability and biofouling, i.e., the adsorption of interferent proteins to the electrode surface upon implantation, pose challenges in the natural physiological environment. We have recently developed a uniquely designed, freestanding, all-diamond boron-doped diamond microelectrode (BDDME) for electrochemical measurements. Key potential advantages of the device include customizable electrode site layouts, a wider working potential window, improved stability, and resistance to biofouling. Here, we present a first report on the electrochemical behavior of the BDDME in comparison with CFME by investigating in vitro serotonin (5-HT) responses with varying FSCV waveform parameters and biofouling conditions. While the CFME delivered lower limits of detection, we also found that BDDMEs showed more sustained 5-HT responses to increasing or changing FSCV waveform-switching potential and frequency, as well as to higher analyte concentrations. Biofouling-induced current reductions were significantly less pronounced at the BDDME when using a "Jackson" waveform compared to CFMEs. These findings are important steps towards the development and optimization of the BDDME as a chronically implanted biosensor for in vivo neurotransmitter detection.

Next-Generation Diamond Electrodes for Neurochemical Sensing: Challenges and Opportunities.

Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good biocompatibility. Additionally, methods for processing and patterning diamond allow for high-throughput batch fabrication and customization of electrode arrays with unique architectures. While tradeoffs in sensitivity can undermine the advantages of BDD as a neurochemical sensor, there are numerous untapped opportunities to further improve performance, including anodic pretreatment, or optimization of the FSCV waveform, instrumentation, sp2/sp3 character, doping, surface characteristics, and signal processing. Here, we review the state-of-the-art in diamond electrodes for neurochemical sensing and discuss potential opportunities for future advancements of the technology. We highlight our team's progress with the development of an all-diamond fiber ultramicroelectrode as a novel approach to advance the performance and applications of diamond-based neurochemical sensors.

A quantitative criterion for predicting solid-state disordering during high strain rate deformation.

A quantitative criterion for predicting the onset of disordering during high strain rate deformation is defined that is based on the potential energy (PE) per atom (PE/atom). The criterion is a necessary, but not sufficient condition to predict disorder. The stress state and loading direction of the crystal must allow deviatoric displacements that can induce disordering and the strain rate must be sufficiently high. The criterion is tested using molecular dynamics (MD) simulations for Ag over a range of a stress states and loading directions relative to the crystal axis. It is found that, above a minimum PE per atom of -2.70 ± 0.01 eV/atom, the crystal becomes unstable and disorders at temperatures well below the equilibrium melting temperature. This criterion is found to be independent of stress state and loading direction, and results suggest that it can be applied broadly to other material systems and to scenarios where deformation is non-uniform and time dependent. An example is given for its application to Au in shear. We show that the minimum critical PE for disordering under high strain rate loading is estimated by finding the equilibrium PE per atom at melting, which can be obtained from a single MD simulation for each material. An example is provided that illustrates how PE/atom can be used to predict where a simulated system is with respect to the disordering threshold without conducting multiple simulations.

Flexible, diamond-based microelectrodes fabricated using the diamond growth side for neural sensing.

Diamond possesses many favorable properties for biochemical sensors, including biocompatibility, chemical inertness, resistance to biofouling, an extremely wide potential window, and low double-layer capacitance. The hardness of diamond, however, has hindered its applications in neural implants due to the mechanical property mismatch between diamond and soft nervous tissues. Here, we present a flexible, diamond-based microelectrode probe consisting of multichannel boron-doped polycrystalline diamond (BDD) microelectrodes on a soft Parylene C substrate. We developed and optimized a wafer-scale fabrication approach that allows the use of the growth side of the BDD thin film as the sensing surface. Compared to the nucleation surface, the BDD growth side exhibited a rougher morphology, a higher sp 3 content, a wider water potential window, and a lower background current. The dopamine (DA) sensing capability of the BDD growth surface electrodes was validated in a 1.0 mM DA solution, which shows better sensitivity and stability than the BDD nucleation surface electrodes. The results of these comparative studies suggest that using the BDD growth surface for making implantable microelectrodes has significant advantages in terms of the sensitivity, selectivity, and stability of a neural implant. Furthermore, we validated the functionality of the BDD growth side electrodes for neural recordings both in vitro and in vivo. The biocompatibility of the microcrystalline diamond film was also assessed in vitro using rat cortical neuron cultures.

Indium Tin Oxide Film Characteristics for Cathodic Stripping Voltammetry.

The combination of conductivity, optical transparency, and wide anodic potential window has driven significant interest in indium tin oxide (ITO) as an electrode material for electrochemical measurements. More recently, ITO has been applied to the detection of trace metals using cathodic stripping voltammetry (CSV), specifically manganese (Mn). However, the optimization of ITO fabrication for a voltammetric method such as CSV is yet to be reported, nor have the microstructural properties of ITO been investigated for CSV. Furthermore, CSV does not require optical transparency, thereby allowing nontransparent substrates to be used for deposition. This enables microfabrication procedures to be expanded and simplified compared to glass or quartz. Combining this with the profound importance of sensitive, selective detection of toxic metal ions in environmentally and biologically relevant samples makes ITO especially attractive. In this work, we report a thorough investigation of ITO deposition and processing on silicon (Si) substrates for CSV analysis using Mn as the model analyte. Several ITO process parameters were examined such as heated deposition and post-process annealing. Each ITO film was characterized using a variety of surface, bulk (X-ray diffraction), and electrochemical measurements. Although each ITO film type showed electrochemical activity, the heated and annealed (HA) ITO fabrication process yielded superior results for Mn CSV; a limit of detection (LOD) of 0.1 ppb (1.8 nM) was obtained. This work exemplifies new applications of ITO as an electrode material while providing a baseline for trace detection of toxic metals and other contaminants amenable to detection by CSV.

Isatin Detection Using a Boron-Doped Diamond 3-in-1 Sensing Platform.

Boron-doped diamond (BDD) is a promising electrochemical tool that exhibits excellent chemical sensitivity and stability. These intrinsic advantages coupled with the material's vast microfabrication flexibility make BDD an attractive sensing device. In this study, two different 3-in-1 BDD electrode sensors were fabricated, characterized, and investigated for their capability to detect isatin, an anxiogenic indole that possesses anticonvulsant activity. Each device was comprised of a working, reference, and auxiliary electrode, all made of BDD. Two different working electrode geometries were studied, a 2 mm diameter macroelectrode (MAC) and a microelectrode array (MEA). The BDD quasi-reference electrode was studied by measuring its potential against a traditional Ag/AgCl reference electrode. While the potential shifted as a function of solution pH, a miniscule potential drift was observed when holding the solution pH constant. Specifically, the BDD quasi-reference electrode had a potential of -0.2 V (vs Ag/AgCl) in a pH 7 solution, and this remained stable for a 30-h time period. For the detection of isatin, solutions were analyzed using both sensors in pH 7.4 phosphate buffered saline (PBS). Using the MEA sensor, the limit of detection (LOD, (3σ)/m) for isatin was found to be 0.04 µM; an increase to 0.22 µM was observed with the MAC sensor. These results were compared to those obtained from UV-vis spectrophotometry, where a 0.57 µM LOD was observed. The feasibility for use in a complex sample matrix was also examined by completing measurements in urine simulant. The results presented herein indicate that both 3-in-1 BDD sensors are applicable at low limits of detection with potential application as an electrochemical detector for chromatographic methods.

Large-scale, all polycrystalline diamond structures transferred onto flexible Parylene-C films for neurotransmitter sensing.

Boron-doped diamond (BDD) has superior electrochemical properties for bioelectronic systems. However, due to its high synthesis temperature, traditional microfabrication methods have limits to integrating BDD with emerging classes of flexible, polymer-based bioelectronic systems. This paper introduces a novel fabrication solution to this challenge, which features (i) a wafer-scale substrate transfer process with all diamond structures transferred onto a flexible Parylene-C substrate and (ii) Parylene anchors introduced to strengthen the bonding between BDD and Parylene substrates, as demonstrated by a peeling test. The electrochemical properties of the transferred BDD-polymer electrodes are evaluated using (i) an outer sphere redox couple Ru(NH3)62+/3+ to study the electron transfer process and (ii) quantitative and qualitative studies of the neurotransmitter redox couple dopamine/dopamine-o-quinone. A linear response of the BDD sensor to dopamine concentrations of 0.5 µM to 100 µM is observed (R2 = 0.999) with a sensitivity of 0.21 µA cm-2 µM-1. These examples of fabricated diamond-polymer devices suggest a broad application in advanced bioelectronics and optoelectronics.

Light-Directed Reversible Assembly of Plasmonic Nanoparticles Using Plasmon-Enhanced Thermophoresis.

Reversible assembly of plasmonic nanoparticles can be used to modulate their structural, electrical, and optical properties. Common and versatile tools in nanoparticle manipulation and assembly are optical tweezers, but these require tightly focused and high-power (10-100 mW/µm2) laser beams with precise optical alignment, which significantly hinders their applications. Here we present light-directed reversible assembly of plasmonic nanoparticles with a power intensity below 0.1 mW/µm2. Our experiments and simulations reveal that such a low-power assembly is enabled by thermophoretic migration of nanoparticles due to the plasmon-enhanced photothermal effect and the associated enhanced local electric field over a plasmonic substrate. With software-controlled laser beams, we demonstrate parallel and dynamic manipulation of multiple nanoparticle assemblies. Interestingly, the assemblies formed over plasmonic substrates can be subsequently transported to nonplasmonic substrates. As an example application, we selected surface-enhanced Raman scattering spectroscopy, with tunable sensitivity. The advantages provided by plasmonic assembly of nanoparticles are the following: (1) low-power, reversible nanoparticle assembly, (2) applicability to nanoparticles with arbitrary morphology, and (3) use of simple optics. Our plasmon-enhanced thermophoretic technique will facilitate further development and application of dynamic nanoparticle assemblies, including biomolecular analyses in their native environment and smart drug delivery.

Spatial bandwidth analysis of fast backward Fresnel diffraction for precise computer-generated hologram design.

Designing near-field computer-generated holograms (CGHs) for a spatial light modulator (SLM) requires backward diffraction calculations. However, direct implementation of the discrete computational model of the Fresnel diffraction integral often produces inaccurate reconstruction. Finite sizes of the SLM and the target image, as well as aliasing, are major sources of error. Here we present a new design prescription for precise near-field CGHs based on comprehensive analysis of the spatial bandwidth. We demonstrate that, by controlling two free variables related to the target image, the designed hologram is free from aliasing and can have minimum error. To achieve this, we analyze the geometry of the target image, hologram, and Fourier transform plane of the target image to derive conditions for minimizing reconstruction error due to truncation of spatial frequencies lying outside of the hologram. The design prescription is verified by examples showing reconstruction error versus controlled parameters. Finally, it is applied to precise three-dimensional image reconstruction.

Highly sensitive detection of urinary cadmium to assess personal exposure.

A series of Boron-Doped Diamond (BDD) ultramicroelectrode arrays were fabricated and investigated for their performance as electrochemical sensors to detect trace level metals such as cadmium. The steady-state diffusion behavior of these sensors was validated using cyclic voltammetry followed by electrochemical detection of cadmium in water and in human urine to demonstrate high sensitivity (>200 µA ppb(-1) cm(-2)) and low background current (<4 nA). When an array of ultramicroelectrodes was positioned with optimal spacing, these BDD sensors showed a sigmoidal diffusion behavior. They also demonstrated high accuracy with linear dose dependence for quantification of cadmium in a certified reference river water sample from the U.S. National Institute of Standards and Technology (NIST) as well as in a human urine sample spiked with 0.25-1 ppb cadmium.

High-brightness X-ray free-electron laser with an optical undulator by pulse shaping.

A normal-incident flattop laser with a tapered end is proposed as an optical undulator to achieve a high-gain and high-brightness X-ray free electron laser (FEL). The synchronic interaction of an electron bunch with the normal incident laser is realized by tilting the laser pulse front. The intensity of the flattop laser is kept constant during the interaction time of the electron bunch and the laser along the focal plane of a cylindrical lens. Optical shaping to generate the desired flattop pulse with a tapered end from an original Gaussian pulse distribution is designed and simulated. The flattop laser with a tapered end can enhance the X-ray FEL beyond the exponential growth saturation power by one order to reach 1 Gigawatt as compared to that without a tapered end. The peak brightness can reach 1030 photons/mm2/mrad2/s/0.1% bandwidth, more than 10 orders brighter than the conventional incoherent Thompson Scattering X-ray source.

Suppression of the zero-order diffracted beam from a pixelated spatial light modulator by phase compression.

Phase compression is used to suppress the on-axis zero-order diffracted (ZOD) beam from a pixelated phase-only spatial light modulator (SLM) by a simple modification to the computer generated hologram (CGH) loaded onto the SLM. After CGH design, the phase of each SLM element is identically compressed by multiplying by a constant scale factor and rotated on the complex unit-circle to produce a cancellation beam that destructively interferes with the ZOD beam. Experiments achieved a factor of 3 reduction of the ZOD beam using two different liquid-crystal SLMs. Numerical simulation analyzed the reconstructed image quality and diffraction efficiency versus degree of phase compression and showed that phase compression resulted in little image degradation or power loss.

High-precision laser beam shaping using a binary-amplitude spatial light modulator.

We have achieved high-precision laser beam shaping by using a binary-amplitude spatial light modulator, a digital micromirror device (DMD), followed by an imaging telescope that contains a pinhole low-pass filter (LPF). An error diffusion algorithm was used to design the initial DMD pixel pattern based on the measured input beam profile. This pattern was iteratively refined by simulating the optically low-pass filtered DMD image and changing DMD pixels to lift valleys and suppress peaks. We noted the gap between the experimental result of 1.4% root-mean-square (RMS) error and the simulated result for the same DMD pattern of 0.3% RMS error. Therefore, we deemed it necessary to introduce iterative refinement based on actual measurements of the output image to further improve the uniformity of the beam. Using this method, we have demonstrated the ability to shape raw, non-spatially filtered laser beams (quasi-Gaussian beams) into beams with precisely controlled profiles that have an unprecedented level of RMS error with respect to the target profile. We have shown that our iterative refinement process is able to improve the light intensity uniformity to around 1% RMS error in a raw camera image for both 633 and 1064 nm laser beams. The use of a digital LPF on the camera image is justified in that it matches the performance of the pinhole filter in the experimental setup. The digital low-pass filtered results reveal that the actual optical beam profiles have RMS error down to 0.23%. Our approach has also demonstrated the ability to produce a range of target profiles as long as they have similar spatial-frequency content (i.e., a slowly varying beam profile). Circular and square cross-section flat-top beams and beams with a linear intensity variation within a circular and square cross section were produced with similarly low RMS errors. The measured errors were about twice the ultimate limit of 0.1% RMS error based on the number of binary DMD pixels that participate in the beam-formation process.

1.5% root-mean-square flat-intensity laser beam formed using a binary-amplitude spatial light modulator.

We demonstrate a digital micromirror device (DMD)-based optical system that converts a spatially noisy quasi-Gaussian to an eighth-order super-Lorentzian flat-top beam. We use an error-diffusion algorithm to design the binary pattern for the Texas Instruments DLP device. Following the DMD, a telescope with a pinhole low-pass filters the beam and scales it to the desired sized image. Experimental measurements show a 1% root-mean-square (RMS) flatness over a diameter of 0.28 mm in the center of the flat-top beam and better than 1.5% RMS flatness over its entire 1.43 mm diameter. The power conversion efficiency is 37%. We develop an alignment technique to ensure that the DMD pattern is correctly positioned on the incident beam. An interferometric measurement of the DMD surface flatness shows that phase uniformity is maintained in the output beam. Our approach is highly flexible and is able to produce not only flat-top beams with different parameters, but also any slowly varying target beam shape. It can be used to generate the homogeneous optical lattice required for Bose-Einstein condensate cold atom experiments.

Alternative concept of ventilation during cardiopulmonary resuscitation (CPR) in dental chairs.

Infrequent training of artificial ventilation in dental facilities implies poor performance of this procedure under CPR. Gastric inflation is a significant issue when ventilation is performed on an unprotected airway. An Easy Grip (EG) Bag-Valve-Mask Resuscitator, a Laryngeal Tube (LT), size #5, and a SMART BAG (SB) resuscitator, a pressure-limiting device, were tested to assess the respiratory effects especially focussing on prevention of gastric inflation during simulated CPR. Twenty academic dental staff members performed ten ventilations on a manikin during CPR by use of EG, LT and SB in a randomized order. In twelve experiments the oesophageal sphincter pressure was adjusted to 15 mbar (best case), in eight experiments to 0 mbar (worst case scenario). Best case scenario median tidal volume distributions achieved by EG (median 144 ml) and LT (75 ml) did not differ, whereas differences were found between EG and SB (31 ml; p = 0.055) as well as between SB and LT (p = 0.042). None of the values met recommended ranges. Almost no gastric inflation occurred. Worst case scenario ventilation by use of the LT resulted in profoundly lower median gastric inflation volumes (median 13 ml) compared to SB (median 288 ml; p=0.008) and EG (800 ml; p = 0.008). Median tidal volume distributions also differed between LT (225 ml) vs EG (100 ml) (p=0.016) and LT vs SB (19 ml) (p =0.008). Chest compression was delayed in ten experiments by LT insertion for 28 s (median). In a later stage of CPR or in case of mask ventilation difficulties, the LT may serve as a helpful tool in dental facilities. CPR training must focus on the importance of chest compression which must not be discontinued if an LT is inserted. The SB might gain value if higher tidal volumes are achieved, exerting a higher risk of gastric inflation.

Determination of properties of wedged, nonuniformly thick, and absorbing thin films by using a new numerical method.

Nonuniformity in the thickness of thin films can severely distort their transmission spectra as compared with those of flat, smooth films. Methods that extract properties such as refractive index, thickness, and extinction coefficient of such films can suffer inaccuracies when they are applied to wedged or nonuniformly thick films. To accurately extract optical properties of nonuniform films, we have developed a novel numerical method and efficient constitutive relations that can determine film properties from just the transmission spectrum for films that are locally smooth with negligible scattering loss. This optimum parameter extraction (OPE) method can accommodate films with two-dimensional thickness variation that would result in significant errors in the values of refractive index and film thickness if not considered. We show that for carefully chosen test cases and for actual pulsed-laser-deposition AlN thin films, properties such as refractive index, extinction coefficient, and film thickness were very accurately determined by using our OPE method. These results are compared with previous techniques to determine the properties of thin films, and the accuracy of and applicable conditions for all these methods are discussed.

Optical correlation of spatial-frequency-shifted images in a photorefractive BSO correlator.

The optical cross correlation of an image with another image that was spatial-frequency shifted in one dimension was demonstrated in a photorefractive VanderLugt correlator. The first image was stored as a Fourier-transform hologram in a photorefractive Bi12SiO20 crystal (BSO) and was successively correlated with different spatial-frequency-shifted versions of a second image. We implemented the spatial-frequency shift by rotating a galvanometer mirror in an image plane, causing the Fourier transform to be shifted laterally in the BSO. We verified that the resulting operation in the BSO was an accurate complex multiplication of the shifted and the stored Fourier transforms. As many as 20 successive readouts were conducted without measurable erasure of the stored hologram. The dynamic range, saturation behavior, and other performance parameters were measured and are discussed.