Non-planar diamond electrodes for biomedical neural sensing and stimulating

Abstract Conductive diamond has exceptional chemical stability, making it an appealing candidate material for long-term medical device implants. This work describes the characterization, and fabrication of four diamond-based neural devices. A previously developed 30 µm diamond-disk in vitro needle electrode was characterized. The device could detect 1 nM concentration analytes in a flow cell using fast scan cyclic voltammetry, but the fabrication was not reproducible. A novel in vitro diamond device was developed with diamond selectively grown at the tip of a hollow quartz capillary, resulting in a 2-4 µm tip diameter. The diamond tip shape and size were geometrically reproducible, although an electrical connection to these tips is still needed. Two novel in vivo diamond based devices were also fabricated. The first generation in vivo diamond electrode was assembled by attaching a brittle diamond electrode to a flexible insulated substrate. The device fabrication time was 6 hrs of hands-on activity, but it was successfully implanted in a freely behaving Aplysia californica. Electrical recordings were compared to a stainless steel standard for two surgeries, respectively 8 days post surgery and 12 days post surgery. However, external electrical connections to equipment had sufficiently large noise and signal variability. No definitive conclusions could be reached about differences in recordings by diamond and steel.A second generation in vivo diamond electrode was fabricated on a substrate that remained flexible after diamond growth, also reducing the fabrication time by 4 hrs. Substrates typically become embrittled during diamond growth because of surface carbide formation. Two rhenium alloys, 75% tungsten / 25% rhenium (v/v) and 47.5% molybdenum / 52.5% rhenium (v/v), were investigated as flexible substrates that might not form carbides during diamond growth but adhere strongly to diamond. Three growth times were explored, with the rhenium alloys compared to a traditional tungsten substrate. Diamond grown for 20 hours on 47.5% molybdenum / 52.5% rhenium alloy had the highest diamond quality (crystal size, sp3 content, and good electrochemical activity), with the substrate remaining flexible after the diamond growth. This device has not yet been insulated with a biocompatible material; however, in vitro recordings were obtained with Aplysia

Non-planar diamond electrodes for biomedical neural sensing and stimulating

Abstract Conductive diamond has exceptional chemical stability, making it an appealing candidate material for long-term medical device implants. This work describes the characterization, and fabrication of four diamond-based neural devices. A previously developed 30 µm diamond-disk in vitro needle electrode was characterized. The device could detect 1 nM concentration analytes in a flow cell using fast scan cyclic voltammetry, but the fabrication was not reproducible. A novel in vitro diamond device was developed with diamond selectively grown at the tip of a hollow quartz capillary, resulting in a 2-4 µm tip diameter. The diamond tip shape and size were geometrically reproducible, although an electrical connection to these tips is still needed. Two novel in vivo diamond based devices were also fabricated. The first generation in vivo diamond electrode was assembled by attaching a brittle diamond electrode to a flexible insulated substrate. The device fabrication time was 6 hrs of hands-on activity, but it was successfully implanted in a freely behaving Aplysia californica. Electrical recordings were compared to a stainless steel standard for two surgeries, respectively 8 days post surgery and 12 days post surgery. However, external electrical connections to equipment had sufficiently large noise and signal variability. No definitive conclusions could be reached about differences in recordings by diamond and steel.A second generation in vivo diamond electrode was fabricated on a substrate that remained flexible after diamond growth, also reducing the fabrication time by 4 hrs. Substrates typically become embrittled during diamond growth because of surface carbide formation. Two rhenium alloys, 75% tungsten / 25% rhenium (v/v) and 47.5% molybdenum / 52.5% rhenium (v/v), were investigated as flexible substrates that might not form carbides during diamond growth but adhere strongly to diamond. Three growth times were explored, with the rhenium alloys compared to a traditional tungsten substrate. Diamond grown for 20 hours on 47.5% molybdenum / 52.5% rhenium alloy had the highest diamond quality (crystal size, sp3 content, and good electrochemical activity), with the substrate remaining flexible after the diamond growth. This device has not yet been insulated with a biocompatible material; however, in vitro recordings were obtained with Aplysia

Jeffrey Halpern, Assistant Professor of Chemical Engineering, CEPS travels to Ireland

Prof. Halpern attended a metabolomics conference in Ireland for academic collaborations and cultural exploration. He continued on to the UK, Germany, and Greece to continue those goals

Recent advances in non-enzymatic electrochemical detection of hydrophobic metabolites in biofluids

This review focuses on recent advances in non-enzymatic electrochemical biosensors for detection of hydrophobic metabolites. Electrochemical approaches have been widely applied in many established and emerging technologies and a large range of electrochemical biosensors have been used for detection of various hydrophobic metabolites. Despite the progress made in this field, some problems still exist, specifically, electrochemical detection of hydrophobic biomarkers can be challenging in complex biological fluids. In this review, we have highlighted some of the most representative surface modification technologies that have been employed in electrochemical biosensors to counter the problems of poor sensitivity and selectivity towards hydrophobic metabolites. The hydrophobic metabolites discussed in this review include uric acid, epinephrine, cortisol, cholesterol, tyrosine, adenine, guanine, cytosine, and thymine. This is followed by discussion on future research directions for electrochemical sensing of hydrophobic biomarkers

Measurement of an AGN Central Mass on Centiparsec Scales: Results of Long-Term Optical Monitoring of Arp 102B

The optical spectrum of the broad-line radio galaxy Arp 102B has been monitored for more than thirteen years to investigate the nature of the source of its broad, double-peaked hydrogen Balmer emission lines. The shape of the lines varied subtly; there was an interval during which the variation in the ratio of the fluxes of the two peaks appeared to be sinusoidal, with a period of 2.16 years and an amplitude of about 16% of the average value. The variable part of the broad H-alpha line is well fit by a model in which a region of excess emission (a quiescent ``hot spot'') within an accretion disk (fitted to the non-varying portion of the double-peaked line) completes at least two circular orbits and eventually fades. Fits to spectra from epochs when the hot spot is not present allow determination of the disk inclination, while fits for epochs when it is present provide a measurement of the radius of the hot spot's orbit. From these data and the period of variation, we find that the mass within the hot spot's orbit is 2.2 +0.2/-0.7 times 10^8 solar masses, within the range of previous estimates of masses of active galactic nuclei. Because this mass is determined at a relatively small distance (~1000 AU) from the central body, it is extremely difficult to explain without assuming that a supermassive black hole lies within Arp 102B. The lack of any systematic change in the velocity of the blue peak over time yields a lower limit on the combined mass of the two bodies in a binary black hole model like that of Gaskell (1983) of 10^10 solar masses.Comment: 29 pages, including 6 figures; to appear in the Astrophysical Journal 199

Probably Approximately Knowing

Whereas deterministic protocols are typically guaranteed to obtain particular goals of interest, probabilistic protocols typically provide only probabilistic guarantees. This paper initiates an investigation of the interdependence between actions and subjective beliefs of agents in a probabilistic setting. In particular, we study what probabilistic beliefs an agent should have when performing actions, in a protocol that satisfies a probabilistic constraint of the form: 'Condition C should hold with probability at least p when action a is performed'. Our main result is that the expected degree of an agent's belief in C when it performs a equals the probability that C holds when a is performed. Indeed, if the threshold of the probabilistic constraint should hold with probaility p=1-x^2 for some small value of x then, with probability 1-x, when the agent acts it will assign a probabilistic belief no smaller than 1-x to the possibility that C holds. In other words, viewing strong belief as, intuitively, approximate knowledge, the agent must probably approximately know (PAK-know) that C is true when it acts.Comment: 23 pages, 2 figures, a full version of a paper whose extended abstract appears in the proceeding of PODC 202

Rejection of the Binary Broad-Line Region Interpretation of Double-Peaked Emission Lines in Three Active Galactic Nuclei

It has been suggested that the peculiar double-peaked Balmer lines of certain broad-line radio galaxies come from individual broad-line regions associated with the black holes of a supermassive binary. We continue to search for evidence of the radial velocity variations characteristic of a double-lined spectroscopic binary that are required in such a model. After spectroscopic monitoring of three suitable candidates (Arp 102B, 3C 390.3, and 3C 332) spanning two decades, we find no such long-term systematic changes in radial velocity. A trend noticed by Gaskell in one of the Balmer-line peaks of 3C 390.3 before 1988 did not continue after that year, invalidating his inferred orbital period and mass. Instead, we find lower limits on the plausible orbital periods that would require the assumed supermassive binaries in all three objects to have total masses in excess of 10^10 solar masses. In the case of 3C 390.3 the total binary mass must exceed 10^11 solar masses to satisfy additional observational constraints on the inclination angle. Such large binary black hole masses are difficult to reconcile with other observations and with theory. In addition, there are peculiar properties of the line profiles and flux ratios in these objects that are not explained by ordinary broad-line region cloud models. We therefore doubt that the double-peaked line profiles of the three objects arise in a pair of broad-line regions. Rather, they are much more likely to be intimately associated with a single black hole.Comment: To appear in the Astrophysical Journal. 17 pages, TeX, with postscript figures includede

Sensor technologies for quality control in engineered tissue manufacturing

The use of engineered cells, tissues, and organs has the opportunity to change the way injuries and diseases are treated. Commercialization of these groundbreaking technologies has been limited in part by the complex and costly nature of their manufacture. Process-related variability and even small changes in the manufacturing process of a living product will impact its quality. Without real-time integrated detection, the magnitude and mechanism of that impact are largely unknown. Real-time and non-destructive sensor technologies are key for in-process insight and ensuring a consistent product throughout commercial scale-up and/or scale-out. The application of a measurement technology into a manufacturing process requires cell and tissue developers to understand the best way to apply a sensor to their process, and for sensor manufacturers to understand the design requirements and end-user needs. Furthermore, sensors to monitor component cells’ health and phenotype need to be compatible with novel integrated and automated manufacturing equipment. This review summarizes commercially relevant sensor technologies that can detect meaningful quality attributes during the manufacturing of regenerative medicine products, the gaps within each technology, and sensor considerations for manufacturing

Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER

We describe 280 GHz bolometric detector arrays that instrument the balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to measure the large-scale B-mode polarization of the cosmic microwave background in search of the cosmic-inflation, gravitational-wave signature. 280 GHz channels aid this science goal by constraining the level of B-mode contamination from galactic dust emission. We present the focal plane unit design, which consists of a 16$\times$16 array of conical, corrugated feedhorns coupled to a monolithic detector array fabricated on a 150 mm diameter silicon wafer. Detector arrays are capable of polarimetric sensing via waveguide probe-coupling to a multiplexed array of transition-edge-sensor (TES) bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which in total contains 765 spatial pixels and 1,530 polarization sensitive bolometers. By fabrication and measurement of single feedhorns, we demonstrate 14.7$^{\circ}$ FHWM Gaussian-shaped beams with $<$1% ellipticity in a 30% fractional bandwidth centered at 280 GHz. We present electromagnetic simulations of the detection circuit, which show 94% band-averaged, single-polarization coupling efficiency, 3% reflection and 3% radiative loss. Lastly, we demonstrate a low thermal conductance bolometer, which is well-described by a simple TES model and exhibits an electrical noise equivalent power (NEP) = 2.6 $\times$ 10$^{-17}$ W/$\sqrt{\mathrm{Hz}}$, consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201

Genotype, Childhood Maltreatment, and Their Interaction in the Etiology of Adult Antisocial Behaviors

BACKGROUND: Maltreatment by an adult or caregiver during childhood is a prevalent and important predictor of antisocial behaviors in adulthood. A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated as a moderating factor in the relationship between childhood maltreatment and antisocial behaviors. Although there have been numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this gene-environment interaction hypothesis in a sample of 3356 white and 960 black men (aged 24-34) participating in the National Longitudinal Study of Adolescent Health. RESULTS: Primary analysis indicated that childhood maltreatment was a significant risk factor for later behaviors that violate rules and the rights of others (p .05). Power analyses indicated that these results were not due to insufficient statistical power. CONCLUSIONS: We could not confirm the hypothesis that MAOA genotype moderates the relationship between childhood maltreatment and adult antisocial behaviors