@article{de alwis_denison_shah_mccarty_sombers_2023, title={Exploiting Microelectrode Geometry for Comprehensive Detection of Individual Exocytosis Events at Single Cells}, volume={8}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.3c00884}, abstractNote={Carbon fiber microelectrodes are commonly used for real-time monitoring of individual exocytosis events at single cells. Since the nature of an electrochemical signal is fundamentally governed by mass transport to the electrode surface, microelectrode geometry can be exploited to achieve precise and accurate measurements. Researchers traditionally pair amperometric measurements of exocytosis with a ∼10-μm diameter, disk microelectrode in an "artificial synapse" configuration to directly monitor individual release events from single cells. Exocytosis is triggered, and released molecules diffuse to the "post-synaptic" electrode for oxidation. This results in a series of distinct current spikes corresponding to individual exocytosis events. However, it remains unclear how much of the material escapes detection. In this work, the performance of 10- and 34-μm diameter carbon fiber disk microelectrodes was directly compared in monitoring exocytosis at single chromaffin cells. The 34-μm diameter electrode was more sensitive to catecholamines and enkephalins than its traditional, 10-μm diameter counterpart, and it more effectively covered the entire cell. As such, the larger sensor detected more exocytosis events overall, as well as a larger quantal size, suggesting that the traditional tools underestimate the above measurements. Both sensors reliably measured l-DOPA-evoked changes in quantal size, and both exhibited diffusional loss upon adjustment of cell-electrode spacing. Finite element simulations using COMSOL support the improved collection efficiency observed using the larger sensor. Overall, this work demonstrates how electrode geometry can be exploited for improved detection of exocytosis events by addressing diffusional loss─an often-overlooked source of inaccuracy in single-cell measurements.}, journal={ACS SENSORS}, author={De Alwis, A. Chathuri and Denison, J. Dylan and Shah, Ruby and McCarty, Gregory S. and Sombers, Leslie A.}, year={2023}, month={Aug} }
 @article{todorov_mccarty_sombers_2023, title={Exploring Electrochemistry: A Hydrogen Peroxide Sensor Based on a Screen-Printed Carbon Electrode Modified with Prussian Blue}, volume={100}, ISSN={["1938-1328"]}, DOI={10.1021/acs.jchemed.3c00844}, abstractNote={There is an increasing need for fundamental electrochemistry concepts to be taught in the undergraduate curriculum, given the broad applicability of electrochemical technologies in addressing a wide range of global issues from critical energy shortages to real-time medical diagnostics. However, many electrochemical concepts are often taught in disparate laboratory experiments, spread out through the curriculum, which can be intimidating to students (and instructors). This experiment, which has been tested and optimized in the undergraduate classroom over multiple semesters, covers a wide range of electrochemistry topics in realizing the construction of a hydrogen peroxide (H2O2) sensor that is based on Prussian blue electrochemistry. The experiment introduces the fundamentals of cyclic voltammetry by prompting students to distinguish faradaic and capacitive components of voltammograms and to investigate their relationship with scan rate as per electrochemical theory. Students also evaluate electrocatalysis through electrodeposition of a thin film of Prussian blue on the sensor surface and the effects of this modification on electron transfer and sensor performance. Finally, students combine amperometric measurements with the method of standard additions to determine H2O2 concentrations in an unknown sample. Overall, this experiment offers an integrated and cohesive experience that connects many important electroanalytical concepts that are often taught individually into one 3 h, hands-on laboratory experiment that requires minimal resources.}, number={12}, journal={JOURNAL OF CHEMICAL EDUCATION}, author={Todorov, Jovica and McCarty, Gregory S. and Sombers, Leslie A.}, year={2023}, month={Nov}, pages={4853–4859} }
 @article{kimble_twiddy_berger_forderhase_mccarty_meitzen_sombers_2023, title={Simultaneous, Real-Time Detection of Glutamate and Dopamine in Rat Striatum Using Fast-Scan Cyclic Voltammetry}, volume={8}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.3c01267}, abstractNote={Glutamate and dopamine (DA) represent two key contributors to striatal functioning, a region of the brain that is essential to motor coordination and motivated behavior. While electroanalytical techniques can be utilized for rapid, spatially resolved detection of DA in the interferent-rich brain environment, glutamate, a nonelectroactive analyte, cannot be directly detected using electroanalytical techniques. However, it can be probed using enzyme-based sensors, which generate an electroactive reporter in the presence of glutamate. The vast majority of glutamate biosensors have relied on amperometric sensing, which is an inherently nonselective detection technique. This approach necessitates the use of complex and performance-limiting modifications to ensure the desired single-analyte specificity. Here, we present a novel glutamate microbiosensor fabricated on a carbon-fiber microelectrode substrate and coupled with fast-scan cyclic voltammetry (FSCV) to enable the simultaneous quantification of glutamate and DA at single recording sites in the brain, which is impossible when using typical amperometric approaches. The glutamate microbiosensors were characterized for sensitivity, stability, and selectivity by using a voltammetric waveform optimized for the simultaneous detection of both species. The applicability of these sensors for the investigation of neural circuits was validated in the rat ventral striatum. Electrically evoked glutamate and DA release were recorded at single-micrometer-scale locations before and after pharmacological manipulation of glutamatergic signaling. Our novel glutamate microbiosensor advances the state of the art by providing a powerful tool for probing coordination between these two species in a way that has previously not been possible.}, number={11}, journal={ACS SENSORS}, author={Kimble, Laney C. and Twiddy, Jack S. and Berger, Jenna M. and Forderhase, Alexandra G. and Mccarty, Gregory S. and Meitzen, John and Sombers, Leslie A.}, year={2023}, month={Nov}, pages={4091–4100} }
 @article{denison_de alwis_shah_mccarty_sombers_2023, title={Untapped Potential: Real-Time Measurements of Opioid Exocytosis at Single Cells}, volume={145}, ISSN={["1520-5126"]}, DOI={10.1021/jacs.3c07487}, abstractNote={The endogenous opioid system is commonly targeted in pain treatment, but the fundamental nature of neuropeptide release remains poorly understood due to a lack of methods for direct detection of specific opioid neuropeptides in situ. These peptides are concentrated in, and released from, large dense-core vesicles in chromaffin cells. Although catecholamine release from these neuroendocrine cells is well characterized, the direct quantification of opioid peptide exocytosis events has not previously been achieved. In this work, a planar carbon-fiber microelectrode served as a "postsynaptic" sensor for probing catecholamine and neuropeptide release dynamics via amperometric monitoring. A constant potential of 500 mV was employed for quantification of catecholamine release, and a higher potential of 1000 mV was used to drive oxidation of tyrosine, the N-terminal amino acid in the opioid neuropeptides released from chromaffin cells. By discriminating the results collected at the two potentials, the data reveal unique kinetics for these two neurochemical classes at the single-vesicle level. The amplitude of the peptidergic signals decreased with repeat stimulation, as the halfwidth of these signals simultaneously increased. By contrast, the amplitude of catecholamine release events increased with repeat stimulation, but the halfwidth of each event did not vary. The chromogranin dense core was identified as an important mechanistic handle by which separate classes of transmitter can be kinetically modulated when released from the same population of vesicles. Overall, the data provide unprecedented insight into key differences between catecholamine and opioid neuropeptide release from isolated chromaffin cells.}, number={44}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Denison, J. Dylan and De Alwis, A. Chathuri and Shah, Ruby and Mccarty, Gregory S. and Sombers, Leslie A.}, year={2023}, month={Oct}, pages={24071–24080} }
 @article{mccarty_dunaway_denison_sombers_2022, title={Neurotransmitter Readily Escapes Detection at the Opposing Microelectrode Surface in Typical Amperometric Measurements of Exocytosis at Single Cells}, volume={6}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.2c00060}, abstractNote={For decades, carbon-fiber microelectrodes have been used in amperometric measurements of neurotransmitter release at a wide variety of cell types, providing a tremendous amount of valuable information on the mechanisms involved in dense-core vesicle fusion. The electroactive molecules that are released can be detected at the opposing microelectrode surface, allowing for precise quantification as well as detailed kinetic information on the stages of neurotransmitter release. However, it remains unclear how much of the catecholamine that is released into the artificial synapse escapes detection. This work examines two separate mechanisms by which released neurotransmitter goes undetected in a typical amperometric measurement. First, diffusional loss is assessed by monitoring exocytosis at single bovine chromaffin cells using carbon-fiber microelectrodes fabricated in a recessed (cavity) geometry. This creates a microsampling vial that minimizes diffusional loss of analyte prior to detection. More molecules were detected per exocytotic release event when using a recessed cavity sensor as compared to the conventional configuration. In addition, pharmacological inhibition of the norepinephrine transporter (NET), which serves to remove catecholamine from the extracellular space, increased both the size and the time course of individual amperometric events. Overall, this study characterizes distinct physical and biological mechanisms by which released neurotransmitter escapes detection at the opposing microelectrode surface, while also revealing an important role for the NET in “presynaptic” modulation of neurotransmitter release.}, journal={ANALYTICAL CHEMISTRY}, author={McCarty, Gregory S. and Dunaway, Lars E. and Denison, J. Dylan and Sombers, Leslie A.}, year={2022}, month={Jun} }
 @article{meunier_denison_mccarty_sombers_2020, title={Interpreting Dynamic Interfacial Changes at Carbon Fiber Microelectrodes Using Electrochemical Impedance Spectroscopy}, volume={36}, ISSN={0743-7463 1520-5827}, url={http://dx.doi.org/10.1021/acs.langmuir.9b03941}, DOI={10.1021/acs.langmuir.9b03941}, abstractNote={Carbon-fiber microelectrodes are an instrumental tool in neuroscience, used for electroanalysis of neurochemical dynamics and recordings of neural activity. However, performance is variable and dependent on fabrication strategies, the biological response to implantation, and the physical and chemical composition of the recording environment. This presents an analytical challenge, as electrode performance is difficult to quantitatively assess in situ, especially when electrodes are permanently implanted or cemented in place. We previously reported that electrode impedance directly impacts electrochemical performance for molecular sensing. In this work, we investigate the impact of individual components of the electrochemical system on impedance. Equivalent circuit models for glass- and silica-insulated carbon-fiber microelectrodes were determined using electrochemical impedance spectroscopy (EIS). The models were validated based on the ability to assign individual circuit elements to physical properties of the electrochemical system. Investigations were performed to evaluate the utility of the models in providing feedback on how changes in ionic strength and carbon fiber material alter impedance properties. Finally, EIS measurements were used to investigate the electrode/solution interface prior to, during, and following implantation in live brain tissue. A significant increase in impedance and decrease in capacitance occur during tissue exposure and persist following implantation. Electrochemical conditioning, which occurs continually during fast-scan cyclic voltammetry recordings, etches and renews the carbon surface, mitigating these effects. Overall, the results establish EIS as a powerful method for characterization of carbon-fiber microelectrodes, providing unprecedented insight into how real-world factors affect the electrode/solution interface.}, number={15}, journal={Langmuir}, publisher={American Chemical Society (ACS)}, author={Meunier, Carl J. and Denison, J. Dylan and McCarty, Gregory S. and Sombers, Leslie A.}, year={2020}, month={Mar}, pages={4214–4223} }
 @article{meunier_mccarty_sombers_2019, title={Drift Subtraction for Fast-Scan Cyclic Voltammetry Using Double-Waveform Partial-Least-Squares Regression}, volume={91}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/acs.analchem.9b01083}, DOI={10.1021/acs.analchem.9b01083}, abstractNote={Background-subtracted fast-scan cyclic voltammetry (FSCV) provides a method for detecting molecular fluctuations with high spatiotemporal resolution in the brain of awake and behaving animals. The rapid scan rates generate large background currents that are subtracted to reveal changes in analyte concentration. Although these background currents are relatively stable, small changes do occur over time. These changes, referred to as electrochemical drift, result in background-subtraction artifacts that constrain the utility of FSCV, particularly when quantifying chemical changes that gradually occur over long measurement times (minutes). The voltammetric features of electrochemical drift are varied and can span the entire potential window, potentially obscuring the signal from any targeted analyte. We present a straightforward method for extending the duration of a single FSCV recording window. First, we have implemented voltammetric waveforms in pairs that consist of a smaller triangular sweep followed by a conventional voltammetric scan. The initial, abbreviated waveform is used to capture drift information that can serve as a predictor for the contribution of electrochemical drift to the subsequent full voltammetric scan using partial-least-squares regression (PLSR). This double-waveform partial-least-squares regression (DW-PLSR) paradigm permits reliable subtraction of the drift component to the voltammetric data. Here, DW-PLSR is used to improve quantification of adenosine, dopamine, and hydrogen peroxide fluctuations occurring >10 min from the initial background position, both in vitro and in vivo. The results demonstrate that DW-PLSR is a powerful tool for evaluating and interpreting both rapid (seconds) and gradual (minutes) chemical changes captured in FSCV recordings over extended durations.}, number={11}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Meunier, Carl J. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2019}, month={May}, pages={7319–7327} }
 @article{smith_gosrani_lee_mccarty_sombers_2018, title={Carbon-Fiber Microbiosensor for Monitoring Rapid Lactate Fluctuations in Brain Tissue Using Fast-Scan Cyclic Voltammetry}, volume={90}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/acs.analchem.8b03694}, DOI={10.1021/acs.analchem.8b03694}, abstractNote={Recent studies have described a role for lactate in brain energy metabolism and energy formation, challenging the conventional view that glucose is the principle energy source for brain function. To date, lactate dynamics in the brain are largely unknown, limiting insight into function. We addressed this by developing and characterizing a lactate oxidase-modified carbon-fiber microelectrode coupled with fast-scan cyclic voltammetry. This new tool boasts a sensitivity for lactate of 22 ± 1 nA·mM-1 and LOD of 7.0 ± 0.7 μM. The approach has enabled detection of rapid lactate fluctuations with unprecedented spatiotemporal resolution as well as excellent stability, selectivity, and sensitivity. The technology was characterized both in vitro and in vivo at discrete recording sites in rat striatum. We provide evidence that striatal lactate availability increases biphasically in response to electrical stimulation of the dopaminergic midbrain in the anesthetized rat. This new tool for real-time detection of lactate dynamics promises to improve understanding of how lactate availability underscores neuronal function and dysfunction.}, number={21}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Smith, Samantha K. and Gosrani, Saahj P. and Lee, Christie A. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2018}, month={Oct}, pages={12994–12999} }
 @article{calhoun_meunier_lee_mccarty_sombers_2018, title={Characterization of a Multiple-Scan-Rate Voltammetric Waveform for Real-Time Detection of Met-Enkephalin}, volume={10}, ISSN={1948-7193 1948-7193}, url={http://dx.doi.org/10.1021/acschemneuro.8b00351}, DOI={10.1021/acschemneuro.8b00351}, abstractNote={Opioid peptides are critically involved in a variety of physiological functions necessary for adaptation and survival, and as such, understanding the precise actions of endogenous opioid peptides will aid in identification of potential therapeutic strategies to treat a variety of disorders. However, few analytical tools are currently available that offer both the sensitivity and spatial resolution required to monitor peptidergic concentration fluctuations in situ on a time scale commensurate with that of neuronal communication. Our group has developed a multiple-scan-rate waveform to enable real-time voltammetric detection of tyrosine containing neuropeptides. Herein, we have evaluated the waveform parameters to increase sensitivity to methionine-enkephalin (M-ENK), an endogenous opioid neuropeptide implicated in pain, stress, and reward circuits. M-ENK dynamics were monitored in adrenal gland tissue, as well as in the dorsal striatum of anesthetized and freely behaving animals. The data reveal cofluctuations of catecholamine and M-ENK in both locations and provide measurements of M-ENK dynamics in the brain with subsecond temporal resolution. Importantly, this work also demonstrates how voltammetric waveforms can be customized to enhance detection of specific target analytes, broadly speaking.}, number={4}, journal={ACS Chemical Neuroscience}, publisher={American Chemical Society (ACS)}, author={Calhoun, S. E. and Meunier, C. J. and Lee, C. A. and McCarty, G. S. and Sombers, L. A.}, year={2018}, month={Dec}, pages={2022–2032} }
 @article{meunier_mitchell_roberts_toups_mccarty_sombers_2018, title={Electrochemical Selectivity Achieved Using a Double Voltammetric Waveform and Partial Least Squares Regression: Differentiating Endogenous Hydrogen Peroxide Fluctuations from Shifts in pH}, volume={90}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ACS.ANALCHEM.7B03717}, DOI={10.1021/ACS.ANALCHEM.7B03717}, abstractNote={Hydrogen peroxide (H2O2) is a reactive oxygen species that serves as an important signaling molecule in normal brain function. At the same time, excessive H2O2 concentrations contribute to myriad pathological consequences resulting from oxidative stress. Studies to elucidate the diverse roles that H2O2 plays in complex biological environments have been hindered by the lack of robust methods for probing dynamic H2O2 fluctuations in living systems with molecular specificity. Background-subtracted fast-scan cyclic voltammetry at carbon-fiber microelectrodes provides a method of detecting rapid H2O2 fluctuations with high temporal and spatial resolution in brain tissue. However, H2O2 fluctuations can be masked by local changes in pH (ΔpH), because the voltammograms for these species can have significant peak overlap, hindering quantification. We present a method for removing ΔpH-related contributions from complex voltammetric data. By employing two distinct potential waveforms per scan, one in which H2O2 is electrochemically silent and a second in which both ΔpH and H2O2 are redox active, a clear distinction between H2O2 and ΔpH signals is established. A partial least-squares regression (PLSR) model is used to predict the ΔpH signal and subtract it from the voltammetric data. The model has been validated both in vitro and in vivo using k-fold cross-validation. The data demonstrate that the double waveform PLSR model is a powerful tool that can be used to disambiguate and evaluate naturally occurring H2O2 fluctuations in vivo.}, number={3}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Meunier, Carl J. and Mitchell, Edwin C. and Roberts, James G. and Toups, Jonathan V. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2018}, month={Jan}, pages={1767–1776} }
 @article{smith_lugo-morales_tang_gosrani_lee_roberts_morton_mccarty_khan_sombers_2018, title={Quantitative Comparison of Enzyme Immobilization Strategies for Glucose Biosensing in Real-Time Using Fast-Scan Cyclic Voltammetry Coupled with Carbon-Fiber Microelectrodes}, volume={19}, ISSN={1439-4235}, url={http://dx.doi.org/10.1002/CPHC.201701235}, DOI={10.1002/CPHC.201701235}, abstractNote={Abstract}, number={10}, journal={ChemPhysChem}, publisher={Wiley}, author={Smith, Samantha K. and Lugo-Morales, Leyda Z. and Tang, C. and Gosrani, Saahj P. and Lee, Christie A. and Roberts, James G. and Morton, Stephen W. and McCarty, Gregory S. and Khan, Saad A. and Sombers, Leslie A.}, year={2018}, month={Feb}, pages={1197–1204} }
 @article{meunier_roberts_mccarty_sombers_2017, title={Background Signal as an in Situ Predictor of Dopamine Oxidation Potential: Improving Interpretation of Fast-Scan Cyclic Voltammetry Data}, volume={8}, ISSN={["1948-7193"]}, DOI={10.1021/acschemneuro.6b00325}, abstractNote={Background-subtracted fast-scan cyclic voltammetry (FSCV) has emerged as a powerful analytical technique for monitoring subsecond molecular fluctuations in live brain tissue. Despite increasing utilization of FSCV, efforts to improve the accuracy of quantification have been limited due to the complexity of the technique and the dynamic recording environment. It is clear that variable electrode performance renders calibration necessary for accurate quantification; however, the nature of in vivo measurements can make conventional postcalibration difficult, or even impossible. Analyte-specific voltammograms and scaling factors that are critical for quantification can shift or fluctuate in vivo. This is largely due to impedance changes, and the effects of impedance on these measurements have not been characterized. We have previously reported that the background current can be used to predict electrode-specific scaling factors in situ. In this work, we employ model circuits to investigate the impact of impedance on FSCV measurements. Additionally, we take another step toward in situ electrode calibration by using the oxidation potential of quinones on the electrode surface to accurately predict the oxidation potential for dopamine at any point in an electrochemical experiment, as both are dependent on impedance. The model, validated both in adrenal slice and live brain tissue, enables information encoded in the shape of the background voltammogram to determine electrochemical parameters that are critical for accurate quantification. This improves data interpretation and provides a significant next step toward more automated methods for in vivo data analysis.}, number={2}, journal={ACS CHEMICAL NEUROSCIENCE}, author={Meunier, Carl J. and Roberts, James G. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2017}, month={Feb}, pages={411–419} }
 @article{smith_lee_dausch_horman_patisaul_mccarty_sombers_2017, title={Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum}, volume={8}, ISSN={1948-7193 1948-7193}, url={http://dx.doi.org/10.1021/acschemneuro.6b00363}, DOI={10.1021/acschemneuro.6b00363}, abstractNote={Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.}, number={2}, journal={ACS Chemical Neuroscience}, publisher={American Chemical Society (ACS)}, author={Smith, Samantha K. and Lee, Christie A. and Dausch, Matthew E. and Horman, Brian M. and Patisaul, Heather B. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2017}, month={Jan}, pages={272–280} }
 @article{mitchell_dunaway_mccarty_sombers_2017, title={Spectroelectrochemical Characterization of the Dynamic Carbon-Fiber Surface in Response to Electrochemical Conditioning}, volume={33}, ISSN={0743-7463 1520-5827}, url={http://dx.doi.org/10.1021/acs.langmuir.7b01443}, DOI={10.1021/acs.langmuir.7b01443}, abstractNote={The effects of electrochemical preconditioning of P-55 pitch-based carbon-fiber microelectrodes were quantitatively examined in this study. Microstructural characterization of the electrode surface was done using Raman spectroscopy and scanning electron microscopy. Electrochemical performance was evaluated using cyclic voltammetry. The data show that application of positive potentials provides beneficial structural modifications to the electrode surface. Electrodes that were preconditioned using a static potential of +1.0 V exhibited enhanced sensitivity and electron transfer properties when compared to electrodes conditioned for the same amount of time with dynamic (triangular) waveforms reaching +1.0 V. Conditioning elicited microstructural changes to the electrode surface that were dependent on the amount of time spent at potentials greater than ∼1.0 V. Importantly, the data demonstrate that the carbon-fiber microstructure is dynamic. It is able to quickly and continuously undergo rapid structural reorganization as potential is applied, repeatedly alternating between a relatively ordered state and one that exhibits greater disorder in response to applied electrochemical potentials that span the range commonly used in voltammetric experiments.}, number={32}, journal={Langmuir}, publisher={American Chemical Society (ACS)}, author={Mitchell, Edwin C. and Dunaway, Lars E. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2017}, month={Aug}, pages={7838–7846} }
 @article{walton_edwards_mccarty_wightman_2016, title={Design and characterization of a microfabricated hydrogen clearance blood flow sensor}, volume={267}, ISSN={["1872-678X"]}, DOI={10.1016/j.jneumeth.2016.04.014}, abstractNote={Modern cerebral blood flow (CBF) detection favors the use of either optical technologies that are limited to cortical brain regions, or expensive magnetic resonance. Decades ago, inhalation gas clearance was the choice method of quantifying CBF, but this suffered from poor temporal resolution. Electrolytic H2 clearance (EHC) generates and collects gas in situ at an electrode pair, which improves temporal resolution, but the probe size has prohibited meaningful subcortical use. We microfabricated EHC electrodes to an order of magnitude smaller than those existing, on the scale of 100 μm, to permit use deep within the brain. Novel EHC probes were fabricated. The devices offered exceptional signal-to-noise, achieved high collection efficiencies (40–50%) in vitro, and agreed with theoretical modeling. An in vitro chemical reaction model was used to confirm that our devices detected flow rates higher than those expected physiologically. Computational modeling that incorporated realistic noise levels demonstrated devices would be sensitive to physiological CBF rates. The reduced size of our arrays makes them suitable for subcortical EHC measurements, as opposed to the larger, existing EHC electrodes that would cause substantial tissue damage. Our array can collect multiple CBF measurements per minute, and can thus resolve physiological changes occurring on a shorter timescale than existing gas clearance measurements. We present and characterize microfabricated EHC electrodes and an accompanying theoretical model to interpret acquired data. Microfabrication allows for the high-throughput production of reproducible devices that are capable of monitoring deep brain CBF with sub-minute resolution.}, journal={JOURNAL OF NEUROSCIENCE METHODS}, author={Walton, Lindsay R. and Edwards, Martin A. and McCarty, Gregory S. and Wightman, R. Mark}, year={2016}, month={Jul}, pages={132–140} }
 @article{johnson_macpherson_smith_block_keyton_2016, title={Facilitating Teamwork in Adolescent and Young Adult Oncology}, volume={12}, ISSN={["1935-469X"]}, DOI={10.1200/jop.2016.013870}, abstractNote={ A case of a young adult patient in the days immediately after a cancer diagnosis illustrates the critical importance of three interrelated core coordinating mechanisms—closed-loop communication, shared mental models, and mutual trust—of teamwork in an adolescent and young adult multidisciplinary oncology team. The case illustrates both the opportunities to increase team member coordination and the problems that can occur when coordination breaks down. A model for teamwork is presented, which highlights the relationships among these coordinating mechanisms and demonstrates how balance among them works to optimize team function and patient care. Implications for clinical practice and research suggested by the case are presented. }, number={11}, journal={JOURNAL OF ONCOLOGY PRACTICE}, author={Johnson, Rebecca H. and Macpherson, Catherine Fiona and Smith, Ashley W. and Block, Rebecca G. and Keyton, Joann}, year={2016}, month={Nov}, pages={1067-+} }
 @article{dengler_wightman_mccarty_2015, title={Microfabricated Collector-Generator Electrode Sensor for Measuring Absolute pH and Oxygen Concentrations}, volume={87}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.5b02866}, abstractNote={Fast-scan cyclic voltammetry (FSCV) has attracted attention for studying in vivo neurotransmission due to its subsecond temporal resolution, selectivity, and sensitivity. Traditional FSCV measurements use background subtraction to isolate changes in the local electrochemical environment, providing detailed information on fluctuations in the concentration of electroactive species. This background subtraction removes information about constant or slowly changing concentrations. However, determination of background concentrations is still important for understanding functioning brain tissue. For example, neural activity is known to consume oxygen and produce carbon dioxide which affects local levels of oxygen and pH. Here, we present a microfabricated microelectrode array which uses FSCV to detect the absolute levels of oxygen and pH in vitro. The sensor is a collector-generator electrode array with carbon microelectrodes spaced 5 μm apart. In this work, a periodic potential step is applied at the generator producing transient local changes in the electrochemical environment. The collector electrode continuously performs FSCV enabling these induced changes in concentration to be recorded with the sensitivity and selectivity of FSCV. A negative potential step applied at the generator produces a transient local pH shift at the collector. The generator-induced pH signal is detected using FSCV at the collector and correlated to absolute solution pH by postcalibration of the anodic peak position. In addition, in oxygenated solutions a negative potential step at the generator produces hydrogen peroxide by reducing oxygen. Hydrogen peroxide is detected with FSCV at the collector electrode, and the magnitude of the oxidative peak is proportional to absolute oxygen concentrations. Oxygen interference on the pH signal is minimal and can be accounted for with a postcalibration.}, number={20}, journal={ANALYTICAL CHEMISTRY}, author={Dengler, Adam K. and Wightman, R. Mark and McCarty, Gregory S.}, year={2015}, month={Oct}, pages={10556–10564} }
 @article{schmidt_dunaway_roberts_mccarty_sombers_2014, title={Multiple Scan Rate Voltammetry for Selective Quantification of Real-Time Enkephalin Dynamics}, volume={86}, ISSN={["1520-6882"]}, DOI={10.1021/ac501725u}, abstractNote={Methionine-enkephalin (M-ENK) and leucine-enkephalin (L-ENK) are small endogenous opioid peptides that have been implicated in a wide variety of complex physiological functions, including nociception, reward processing, and motivation. However, our understanding of the role that these molecules play in modulating specific brain circuits remains limited, largely due to challenges in determining where, when, and how specific neuropeptides are released in tissue. Background-subtracted fast-scan cyclic voltammetry coupled with carbon-fiber microelectrodes has proven to be sensitive and selective for detecting rapidly fluctuating neurochemicals in vivo; however, many challenges exist for applying this approach to the detection of neuropeptides. We have developed and characterized a novel voltammetric waveform for the selective quantification of small tyrosine-containing peptides, such as the ENKs, with rapid temporal (subsecond) and precise spatial (10s of micrometers) resolution. We have established that the main contributor to the electrochemical signal inherent to M-ENK is tyrosine and that conventional waveforms provide poor peak resolution and lead to fouling of the electrode surface. By employing two distinct scan rates in each anodic sweep of this analyte-specific waveform, we have selectively distinguished M-ENK from common endogenous interfering agents, such as ascorbic acid, pH shifts, and even L-ENK. Finally, we have used this approach to simultaneously quantify catecholamine and M-ENK fluctuations in live tissue. This work provides a foundation for real-time measurements of endogenous ENK fluctuations in biological locations, and the underlying concept of using multiple scan rates is adaptable to the voltammetric detection of other tyrosine-containing neuropeptides.}, number={15}, journal={ANALYTICAL CHEMISTRY}, author={Schmidt, Andreas C. and Dunaway, Lars E. and Roberts, James G. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2014}, month={Aug}, pages={7806–7812} }
 @article{amos_roberts_qi_sombers_mccarty_2014, title={Reducing the Sampling Rate of Biochemical Measurements Using Fast-Scan Cyclic Voltammetry for In Vivo Applications}, volume={14}, ISSN={["1558-1748"]}, DOI={10.1109/jsen.2014.2321479}, abstractNote={Recent advances in science and technology have permitted the development of wireless systems that can make biochemical measurements within functioning tissue in behaving animals. However, data transfer requirements and power limitations have significantly limited the applicability of these systems. In an effort to create protocols that will reduce the density of the data to be transferred and the power consumption of wireless systems, this paper evaluates reducing the sampling rate of a proven in vivo measurement technology, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes. Existing FSCV protocols to measure biochemical signaling in the brain were created without consideration for data density or power consumption. In this paper, the sampling rate of the FSCV protocol for detecting the neurotransmitter dopamine in functioning brain tissue was reduced from 10 to 1 Hz. In vitro experiments showed that the 1-Hz protocol did not negatively affect sensor responsivity or selectivity. The reduced sampling rate was verified in vivo by directly monitoring dopamine fluctuations in intact brain tissue. The 1-Hz sampling rate reduces the quantity of data generated by an order of magnitude compared with the existing protocol, and with duty cycling is expected to decrease power consumption by a similar value in wireless systems.}, number={9}, journal={IEEE SENSORS JOURNAL}, author={Amos, Alison N. and Roberts, James G. and Qi, Lingjiao and Sombers, Leslie A. and McCarty, Gregory S.}, year={2014}, month={Sep}, pages={2975–2980} }
 @article{roberts_toups_eyualem_mccarty_sombers_2013, title={In Situ Electrode Calibration Strategy for Voltammetric Measurements In Vivo}, volume={85}, ISSN={["1520-6882"]}, DOI={10.1021/ac402884n}, abstractNote={Technological advances have allowed background-subtracted fast-scan cyclic voltammetry to emerge as a powerful tool for monitoring molecular fluctuations in living brain tissue; however, there has been little progress to date in advancing electrode calibration procedures. Variability in the performance of these handmade electrodes renders calibration necessary for accurate quantification; however, experimental protocol makes standard postcalibration difficult or in some cases impossible. We have developed a model that utilizes information contained in the background charging current to predict electrode sensitivity to dopamine, ascorbic acid, hydrogen peroxide, and pH shifts at any point in an electrochemical experiment. Analysis determined a high correlation between predicted sensitivity and values obtained using the traditional postcalibration method, across all analytes. To validate this approach in vivo, calibration factors obtained with this model at electrodes in brain tissue were compared to values obtained at these electrodes using a traditional ex vivo calibration. Both demonstrated equal power of predictability for dopamine concentrations. This advance enables in situ electrode calibration, allowing researchers to track changes in electrode sensitivity over time and eliminating the need to generalize calibration factors between electrodes or across multiple days in an experiment.}, number={23}, journal={ANALYTICAL CHEMISTRY}, author={Roberts, James G. and Toups, J. Vincent and Eyualem, Eyob and McCarty, Gregory S. and Sombers, Leslie A.}, year={2013}, month={Dec}, pages={11568–11575} }
 @article{dengler_mccarty_2013, title={Microfabricated microelectrode sensor for measuring background and slowly changing dopamine concentrations}, volume={693}, ISSN={["1572-6657"]}, DOI={10.1016/j.jelechem.2013.01.022}, abstractNote={The electrochemical detection of neurotransmitters in vivo has centered on fast scan cyclic voltammetry (FSCV) due to its temporal resolution, sensitivity and chemical selectivity. FSCV is a differential technique that records phasic (second-to-second) changes in the concentration of electroactive neurotransmitters such as dopamine (DA). To isolate the currents due to fluctuations in analyte concentration, in other words to make these phasic measurements, requires the subtraction of a large background current. The subtraction of this background and its volatility renders FSCV unable to determine background or slowly varying concentrations of electroactive analytes. However, there is still a need to readily determine the background and slowly changing concentrations of electroactive analytes in tissue. For example, the background concentrations of DA vary throughout the brain and can affect the dynamics of dopaminergic systems. So, this report presents a microfabricated electrochemical sensor for measuring background and slowly changing concentrations of DA in vitro with the selectivity and sensitivity of FSCV. The sensor is comprised of two microfabricated microelectrodes which are spaced 8 μm apart. Varying the applied potential of the outer electrode manipulates the local concentration of electroactive species including concentration at the inner electrode. These changes are measured at the inner electrode using FSCV. The resulting signal with calibration can determine the background and slowly changing concentration of DA with the selectivity and sensitivity of FSCV. In this study the background of DA is determined in vitro using this sensor. The DA signal is shown to be the result of adsorption/desorption at the outer electrode. Interference from ascorbate on the DA signal is shown to be minimal for this approach.}, journal={JOURNAL OF ELECTROANALYTICAL CHEMISTRY}, author={Dengler, Adam K. and McCarty, Gregory S.}, year={2013}, month={Mar}, pages={28–33} }
 @article{takmakov_zachek_keithley_walsh_donley_mccarty_wightman_2010, title={Carbon Microelectrodes with a Renewable Surface}, volume={82}, ISSN={["1520-6882"]}, DOI={10.1021/ac902753x}, abstractNote={Electrode fouling decreases sensitivity and can be a substantial limitation in electrochemical experiments. In this work we describe an electrochemical procedure that constantly renews the surface of a carbon microelectrode using periodic triangle voltage excursions to an extended anodic potential at a scan rate of 400 V s(-1). This methodology allows for the regeneration of an electrochemically active surface and restores electrode sensitivity degraded by irreversible adsorption of chemical species. We show that repeated voltammetric sweeps to moderate potentials in aqueous solution causes oxidative etching of carbon thereby constantly renewing the electrochemically active surface. Oxidative etching was established by tracking surface-localized fluorine atoms with XPS, by monitoring changes in carbon surface morphology with AFM on pyrolyzed photoresist films, and also by optical and electron microscopy. The use of waveforms with extended anodic potentials showed substantial increases in sensitivity toward the detection of catechols. This enhancement arose from the adsorption of the catechol moiety that could be maintained with a constant regeneration of the electrode surface. We also demonstrate that application of the extended waveform could restore the sensitivity of carbon microelectrodes diminished by irreversible adsorption (electrode fouling) of byproducts resulting from the electrooxidation and polymerization of tyramine. Overall, this work brings new insight into the factors that affect electrochemical processes at carbon electrodes and provides a simple method to remove or reduce fouling problems associated with many electrochemical experiments.}, number={5}, journal={ANALYTICAL CHEMISTRY}, author={Takmakov, Pavel and Zachek, Matthew K. and Keithley, Richard B. and Walsh, Paul L. and Donley, Carrie and McCarty, Gregory S. and Wightman, R. Mark}, year={2010}, month={Mar}, pages={2020–2028} }
 @article{takmakov_zachek_keithley_bucher_mccarty_wightman_2010, title={Characterization of Local pH Changes in Brain Using Fast-Scan Cyclic Voltammetry with Carbon Microelectrodes}, volume={82}, ISSN={["1520-6882"]}, DOI={10.1021/ac102399n}, abstractNote={Transient local pH changes in the brain are important markers of neural activity that can be used to follow metabolic processes that underlie the biological basis of behavior, learning and memory. There are few methods that can measure pH fluctuations with sufficient time resolution in freely moving animals. Previously, fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used for the measurement of such pH transients. However, the origin of the potential dependent current in the cyclic voltammograms for pH changes recorded in vivo was unclear. The current work explored the nature of these peaks and established the origin for some of them. A peak relating to the capacitive nature of the pH CV was identified. Adsorption of electrochemically inert species, such as aromatic amines and calcium could suppress this peak, and is the origin for inconsistencies regarding in vivo and in vitro data. Also, we identified an extra peak in the in vivo pH CV relating to the presence of 3,4-dihydroxyacetic acid (DOPAC) in the brain extracellular fluid. To evaluate the in vivo performance of the carbon-fiber sensor, carbon dioxide inhalation by an anesthetized rat was used to induce brain acidosis induced by hypercapnia. Hypercapnia is demonstrated to be a useful tool to induce robust in vivo pH changes, allowing confirmation of the pH signal observed with FSCV.}, number={23}, journal={ANALYTICAL CHEMISTRY}, author={Takmakov, Pavel and Zachek, Matthew K. and Keithley, Richard B. and Bucher, Elizabeth S. and McCarty, Gregory S. and Wightman, R. Mark}, year={2010}, month={Dec}, pages={9892–9900} }
 @article{mccarty_moody_zachek_2010, title={Enhancing electrochemical detection by scaling solid state nanogaps}, volume={643}, ISSN={["1873-2569"]}, DOI={10.1016/j.jelechem.2010.03.018}, abstractNote={The ability to quickly and inexpensively fabricate planar solid state nanogaps has enabled research to be effectively performed on devices down to just a few nanometers. Here, nanofabricated electrode pairs with electrode-to-electrode spacings of <4, 6 and 20 nm are utilized for monitoring an electroactive molecule, dopamine, in ionic solution. The results show a several order of magnitude enhancement of the electrochemical signal, collected current, for the solid state nanogaps with 6 nm electrode–electrode spacings as compared to traditional microelectrodes. The data from the <4 nm and 20 nm solid state nanogaps verify that this enhancement is due to cycling of the redox molecules in the confined geometry of the nanogap. In addition the data collected for the <4 nm nanogap emphasizes and reinforces that scaling does have limits and that as device sizes move to the few nanometer scale, the influence of a molecule’s size and other physical properties becomes increasingly important and can eventually dominate the generated signals.}, number={1-2}, journal={JOURNAL OF ELECTROANALYTICAL CHEMISTRY}, author={McCarty, Gregory S. and Moody, Benjamin and Zachek, Matthew K.}, year={2010}, month={May}, pages={9–14} }
 @article{moody_haslauer_kirk_kannan_loboa_mccarty_2010, title={In Situ Monitoring of Adipogenesis with Human-Adipose-Derived Stem Cells Using Surface-Enhanced Raman Spectroscopy}, volume={64}, ISSN={["1943-3530"]}, DOI={10.1366/000370210793335106}, abstractNote={ Methods capable of nondestructively collecting high-quality, real-time chemical information from living human stem cells are of increasing importance given the escalating relevance of stem cells in therapeutic and regenerative medicines. Raman spectroscopy is one such technique that can nondestructively collect real-time chemical information. Living cells uptake gold nanoparticles and transport these particles through an endosomal pathway. Once inside the endosome, nanoparticles aggregate into clusters that give rise to large spectroscopic enhancements that can be used to elucidate local chemical environments through the use of surface-enhanced Raman spectroscopy. This report uses 40-nm colloidal gold nanoparticles to create volumes of surface-enhanced Raman scattering (SERS) within living human-adipose-derived adult stem cells enabling molecular information to be monitored. We exploit this method to spectroscopically observe chemical changes that occur during the adipogenic differentiation of human-adipose-derived stem cells over a period of 22 days. It is shown that intracellular SERS is able to detect the production of lipids as little as one day after the onset of adipogenesis and that a complex interplay between lipids, proteins, and chemical messengers can be observed shortly thereafter. After 22 days of differentiation, the cells show visible and spectroscopic indications of completed adipogenesis yet still share spectral features common to the progenitor stem cells. }, number={11}, journal={APPLIED SPECTROSCOPY}, author={Moody, Benjamin and Haslauer, Carla M. and Kirk, Elizabeth and Kannan, Arthi and Loboa, Elizabeth G. and McCarty, Gregory S.}, year={2010}, month={Nov}, pages={1227–1233} }
 @article{zachek_park_takmakov_wightman_mccarty_2010, title={Microfabricated FSCV-compatible microelectrode array for real-time monitoring of heterogeneous dopamine release}, volume={135}, ISSN={0003-2654 1364-5528}, url={http://dx.doi.org/10.1039/c0an00114g}, DOI={10.1039/c0an00114g}, abstractNote={Fast scan cyclic voltammetry (FSCV) has been used previously to detect neurotransmitter release and reuptake in vivo. An advantage that FSCV has over other electrochemical techniques is its ability to distinguish neurotransmitters of interest (i.e. monoamines) from their metabolites using their respective characteristic cyclic voltammograms. While much has been learned with this technique, it has generally only been used in a single working electrode arrangement. Additionally, traditional electrode fabrication techniques tend to be difficult and somewhat irreproducible. Described in this report is a fabrication method for a FSCV compatible microelectrode array (FSCV-MEA) that is capable of functioning in vivo. The microfabrication techniques employed here allow for better reproducibility than traditional fabrication methods of carbon fiber microelectrodes, and enable batch fabrication of electrode arrays. The reproducibility and electrochemical qualities of the probes were assessed along with crosstalk in vitro. Heterogeneous release of electrically evoked dopamine was observed in real-time in the striatum of an anesthetized rat using the FSCV-MEA. The heterogeneous effects of pharmacology on the striatum were also observed and shown to be consistent across multiple animals.}, number={7}, journal={The Analyst}, publisher={Royal Society of Chemistry (RSC)}, author={Zachek, Matthew K. and Park, Jinwoo and Takmakov, Pavel and Wightman, R. Mark and McCarty, Gregory S.}, year={2010}, pages={1556} }
 @article{zachek_takmakov_park_wightman_mccarty_2010, title={Simultaneous monitoring of dopamine concentration at spatially different brain locations in vivo}, volume={25}, ISSN={0956-5663}, url={http://dx.doi.org/10.1016/j.bios.2009.10.008}, DOI={10.1016/j.bios.2009.10.008}, abstractNote={When coupled with a microelectrode, background-subtracted fast scan cyclic voltammetry (FSCV) allows fast, sensitive and selective determination of analytes within a small spatial location. For the past 30 years experiments using this technique have been largely confined to recordings at a single microelectrode. Arrays with closely separated microelectrodes would allow researchers to gain more informative data as well as probe regions in close spatial proximity. This work presents one of the first FSCV microelectrode arrays (MEA) implemented in vivo with the ability to sample from different regions in close spatial proximity (equidistant within 1 mm). The array is manufactured from fused silica capillaries and a microfabricated electrode spacer. The functionality of the array is assessed by simultaneously monitoring electrically stimulated dopamine (DA) release in the striatum of anesthetized rat. As expected, heterogeneous dopamine release was simultaneously observed. Additionally, the pharmacological effect of raclopride (D2 receptor antagonist) and cocaine (monoamine uptake blocker) on the heterogeneity of DA release, in spatially different brain regions was shown to alter neurotransmitter release at all four electrode sites.}, number={5}, journal={Biosensors and Bioelectronics}, publisher={Elsevier BV}, author={Zachek, Matthew K. and Takmakov, Pavel and Park, Jinwoo and Wightman, R. Mark and McCarty, Gregory S.}, year={2010}, month={Jan}, pages={1179–1185} }
 @article{roberts_moody_mccarty_sombers_2010, title={Specific Oxygen-Containing Functional Groups on the Carbon Surface Underlie an Enhanced Sensitivity to Dopamine at Electrochemically Pretreated Carbon Fiber Microelectrodes}, volume={26}, ISSN={["0743-7463"]}, DOI={10.1021/la9048924}, abstractNote={The in vivo use of carbon-fiber microelectrodes for neurochemical investigation has proven to be selective and sensitive when coupled with background-subtracted fast-scan cyclic voltammetry (FSCV). Various electrochemical pretreatments have been established to enhance the sensitivity of these sensors; however, the fundamental chemical mechanisms underlying these enhancement strategies remain poorly understood. We have investigated an electrochemical pretreatment in which an extended triangular waveform from -0.5 to 1.8 V is applied to the electrode prior to the voltammetric detection of dopamine using a more standard waveform ranging from -0.4 to 1.3 V. This pretreatment enhances the electron-transfer kinetics and significantly improves sensitivity. To gain insight into the chemical mechanism, the electrodes were studied using common analytical techniques. Contact atomic force microscopy (AFM) was used to demonstrate that the surface roughness was not altered on the nanoscale by electrochemical pretreatment. Raman spectroscopy was utilized to investigate oxide functionalities on the carbon surface and confirmed that carbonyl and hydroxyl functional groups were increased by electrochemical conditioning. Spectra collected after the selective chemical modification of these groups implicate the hydroxyl functionality, rather than the carbonyl, as the major contributor to the enhanced electrochemical signal. Finally, we have demonstrated that this electrochemical pretreatment can be used to create carbon microdisc electrodes with sensitivities comparable to those associated with larger, conventionally treated cylindrical carbon fiber microelectrodes.}, number={11}, journal={LANGMUIR}, author={Roberts, James G. and Moody, Benjamin P. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2010}, month={Jun}, pages={9116–9122} }
 @article{zachek_takmakov_moody_wightman_mccarty_2009, title={Simultaneous Decoupled Detection of Dopamine and Oxygen Using Pyrolyzed Carbon Microarrays and Fast-Scan Cyclic Voltammetry}, volume={81}, ISSN={["1520-6882"]}, DOI={10.1021/ac900790m}, abstractNote={Microfabricated structures utilizing pyrolyzed photoresist have been shown to be useful for monitoring electrochemical processes. These previous studies, however, were limited to constant-potential measurements and slow-scan voltammetry. The work described in this paper utilizes microfabrication processes to produce devices that enable multiple fast-scan cyclic voltammetry (FSCV) waveforms to be applied to different electrodes on a single substrate. This enabled the simultaneous, decoupled detection of dopamine and oxygen. In this paper we describe the fabrication process of these arrays and show that pyrolyzed photoresist electrodes possess surface chemistry and electrochemical properties comparable to PAN-type, T-650, carbon fiber microelectrodes using background-subtracted FSCV. The functionality of the array is discussed in terms of the degree of cross talk in response to flow injections of physiologically relevant concentrations of dopamine and oxygen. Finally, other applications of pyrolyzed photoresist microelectrode arrays are shown, including spatially resolved detection of analytes and combining FSCV with amperometry for the detection of dopamine.}, number={15}, journal={ANALYTICAL CHEMISTRY}, author={Zachek, Matthew K. and Takmakov, Pavel and Moody, Benjamin and Wightman, R. Mark and McCarty, Gregory S.}, year={2009}, month={Aug}, pages={6258–6265} }
 @article{moody_mccarty_2009, title={Solid state nanogaps for differential measurements of molecular properties}, volume={94}, ISSN={0003-6951 1077-3118}, url={http://dx.doi.org/10.1063/1.3103616}, DOI={10.1063/1.3103616}, abstractNote={This paper demonstrates the production and probing of solid state nanogaps. These nanogaps can be inexpensively and controllably produced using a combination of molecular and standard photolithography. These nanogaps are implemented for chemical monitoring by using surface enhanced Raman spectroscopy to collect molecular information at the nanogap and current-voltage traces to probe the charge transport of the nanogap. These data show that the oligonucleotides used as the molecular resist are degraded, that some of the degraded oligonucleotides are removed, and then new oligonucleotides are adsorbed.}, number={12}, journal={Applied Physics Letters}, publisher={AIP Publishing}, author={Moody, Benjamin and McCarty, Gregory S.}, year={2009}, month={Mar}, pages={122104} }
 @article{moody_mccarty_2009, title={Statistically Significant Raman Detection of Midsequence Single Nucleotide Polymorphisms}, volume={81}, ISSN={["1520-6882"]}, DOI={10.1021/ac802247y}, abstractNote={This report highlights methodologies that enable statistically significant data to be collected for single nucleotide polymorphisms using surface enhanced Raman spectroscopy. Single-stranded oligonucleotides functionalized with 40 nm gold nanoparticles are hybridized with oligonucleotides adsorbed to a photolithographically defined gold surface thus creating a surface enhanced Raman environment around the DNA duplex. With this design characteristic Raman spectra have been collected and explored for differences between DNA duplexes formed from complementary oligonucleotides, completely mismatched oligonucleotides, and those formed from oligonucleotides that have a midsequence single nucleotide mismatch. The results show that statistically significant differences in Raman intensity for characteristic peaks can be collected for the three cases.}, number={5}, journal={ANALYTICAL CHEMISTRY}, author={Moody, Benjamin and McCarty, Gregory}, year={2009}, month={Mar}, pages={2013–2016} }
 @article{zachek_hermans_wightman_mccarty_2008, title={Electrochemical dopamine detection: Comparing gold and carbon fiber microelectrodes using background subtracted fast scan cyclic voltammetry}, volume={614}, ISSN={["1572-6657"]}, DOI={10.1016/j.jelechem.2007.11.007}, abstractNote={Electrochemical detection is becoming increasingly important for the detection of biological species. Most current biological research with electrochemical detection is done with carbon fiber electrodes due to their many beneficial properties. The ability to build electrochemical sensor from noble metals instead of carbon fibers may be beneficial in developing inexpensive multiplexed electrochemical detection schemes. To advance understanding and to test the feasibility of using noble metal electrochemical sensors the detection of dopamine, a biologically important small molecule was studied here. Specifically, dopamine detection on gold microelectrodes was characterized and compared to P-55 carbon fiber microelectrodes of the same geometry, using background subtracted fast scan cyclic voltammetry. While not as sensitive to dopamine as carbon fibers, it was observed that gold microelectrodes have six times the saturation coverage per area and 40 times the linear working range. Selectivity to dopamine, in comparison to several other neurotransmitters and their derivatives, is also quantitatively described.}, number={1-2}, journal={JOURNAL OF ELECTROANALYTICAL CHEMISTRY}, author={Zachek, Matthew K. and Hermans, Andre and Wightman, R. Mark and McCarty, Gregory S.}, year={2008}, month={Mar}, pages={113–120} }
 @article{daniel_uppili_mccarty_allara_2007, title={Effects of Molecular Structure and Interfacial Ligation on the Precision of Cu-Bound α,ω-Mercaptoalkanoic Acid “Molecular Ruler” Stacks}, volume={23}, ISSN={0743-7463 1520-5827}, url={http://dx.doi.org/10.1021/la0621719}, DOI={10.1021/la0621719}, abstractNote={Nanolithography processes based on designed, precision thickness multilayer thin films (molecular rulers) have been reported that enable patterning of features on surfaces from a few to the hundred nanometer range. These strategies are unique in their potential ability to enable wafer scale patterning of features of just a few nanometers. If these techniques could be developed to be sufficiently precise and generally applicable, they would fill a long-standing need in nanoscience. In this study a systematic and detailed analysis of the growth mechanisms and molecular layer structures has been carried out for the mercaptoalkanoic acid−copper ion multilayer thin film system currently used as the standard nanolithography resist. Our results show these films form via a redox reaction of thiol groups with surface-ligated Cu(II) ions to form adlayers at only ∼50% coverage with islanding of the alkyl chains, thereby leading to rough topographies and less than theoretical thicknesses based on a 1:1 ideal adlayer....}, number={2}, journal={Langmuir}, publisher={American Chemical Society (ACS)}, author={Daniel, Thomas A. and Uppili, Sundarajan and McCarty, Gregory and Allara, David L.}, year={2007}, month={Jan}, pages={638–648} }
 @article{anderson_mihok_tanaka_tan_horn_mccarty_weiss_2006, title={Hybrid Approaches to Nanolithography: Photolithographic Structures with Precise, Controllable Nanometer-Scale Spacings Created by Molecular Rulers}, volume={18}, ISSN={0935-9648 1521-4095}, url={http://dx.doi.org/10.1002/adma.200600108}, DOI={10.1002/adma.200600108}, abstractNote={In the field of nanofabrication, the combination of conventional lithographic techniques with chemical processes has potential for patterning surfaces with nanometer-scale resolution. The fusion of these technologies also addresses another important aspect of this field—the parallel creation of hierarchical structures that interface components on the 1–100 nm range with micrometer-scale structures. Key to the application and adoption of these hybrid strategies is showing their compatibility with, and advantages over, commercially used methods (i.e., photolithography). As reported here, aligned microstructures with precisely defined nanometer-scale spacing and edge resolution were produced by combining photolithography with molecular rulers—selectively placed, self-assembled multilayers. Photolithography was used to define the structures, and self-assembled molecular-ruler resists precisely tailored the structures’ spacings. This work demonstrates the compatibility and robustness of hybrid strategies employing molecular rulers with conventional photo-lithographic fabrication schemes and processes. Other methods, such as soft lithography, [1,2] scanning probe nanolithography, [3–5] nanosphere lithography, [6,7] and self-assembled monolayer etch resists, [}, number={8}, journal={Advanced Materials}, publisher={Wiley}, author={Anderson, M. E. and Mihok, M. and Tanaka, H. and Tan, L.-P. and Horn, M. W. and McCarty, G. S. and Weiss, P. S.}, year={2006}, month={Apr}, pages={1020–1022} }
 @article{mccarty_2006, title={Monitoring the addition of molecular species to electrodes utilizing inherent electronic properties}, volume={99}, ISSN={0021-8979 1089-7550}, url={http://dx.doi.org/10.1063/1.2177427}, DOI={10.1063/1.2177427}, abstractNote={The ability to accurately, efficiently, and inexpensively detect biological species is critical to the diagnosis and treatment of disease. In this work, electrode pairs featuring nanometer scale junctions are utilized to detect the addition of an amino acid to nanogap sensors through variations in their electronic properties. A series of nanogap sensors was monitored as succinimide groups and then the amino acid phenylalanine was added to functionalized nanogap sensors. The addition of these species caused a statistically significant increase in charge transfer through the nanogap sensors. This flexible detection scheme has the potential of offering a powerful, nonoptical alternative for biological monitoring in extremely small volumes and of extremely low concentrations.}, number={6}, journal={Journal of Applied Physics}, publisher={AIP Publishing}, author={McCarty, Gregory S.}, year={2006}, month={Mar}, pages={064701} }
 @article{mccarty_weiss_2004, title={Formation and Manipulation of Protopolymer Chains}, volume={126}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja038930g}, DOI={10.1021/ja038930g}, abstractNote={We define "protopolymer" to mean that the monomer units of a polymer are together and aligned, but are not yet reacted to their final form, the polymer. We have created, observed, and manipulated this new chemical state in linear chains of phenylene on Cu[111] at low temperature. We demonstrate that protopolyphenylene forms by manipulating individual monomer units out of the chains using a scanning tunneling microscope. Both the bare and the phenylene-covered Cu[111] surface can serve as an extended catalytic active site to bring together and to align the monomer phenylene units formed from the dissociative chemisorption of p-diiodobenzene. When short segments of protopolymer chains are moved on the phenylene-covered surface, the intermolecular interactions are sufficiently strong to realign the chains in new locations. The alignment due to these interactions may be used in the controlled growth and assembly, as well as for the simplified manipulation of complex, hierarchical structures.}, number={51}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={McCarty, Gregory S. and Weiss, Paul S.}, year={2004}, month={Dec}, pages={16772–16776} }
 @article{mccarty_2004, title={Molecular Lithography for Wafer-Scale Fabrication of Molecular Junctions}, volume={4}, ISSN={1530-6984 1530-6992}, url={http://dx.doi.org/10.1021/nl049375z}, DOI={10.1021/nl049375z}, abstractNote={High-resolution patterning is critical for the development of functional devices and sensors with nanometer dimensions. To date, no patterning methodology exists with the capability to produce molecular-scale features reliably over an entire wafer. In this paper, a lithographic process is presented to fabricate pairs of electrodes reproducibly with nanometer-scale resolution quickly, efficiently, and economically. Additionally, this work demonstrates that molecules of interest can be added to, or removed from, patterned molecular junctions. This novel technology provides a relatively simple and economical means to produce devices capable of monitoring the addition of molecules to a structure.}, number={8}, journal={Nano Letters}, publisher={American Chemical Society (ACS)}, author={McCarty, Gregory S.}, year={2004}, month={Aug}, pages={1391–1394} }