Automotive 2.1 µm Full-Depth Deep Trench Isolation CMOS Image Sensor with a 120 dB Single-Exposure Dynamic Range.

An automotive 2.1 µm CMOS image sensor has been developed with a full-depth deep trench isolation and an advanced readout circuit technology. To achieve a high dynamic range, we employ a sub-pixel structure featuring a high conversion gain of a large photodiode and a lateral overflow of a small photodiode connected to an in-pixel storage capacitor. With the sensitivity ratio of 10, the expanded dynamic range could reach 120 dB at 85 °C by realizing a low random noise of 0.83 e- and a high overflow capacity of 210 ke-. An over 25 dB signal-to-noise ratio is achieved during HDR image synthesis by increasing the full-well capacity of the small photodiode up to 10,000 e- and suppressing the floating diffusion leakage current at 105 °C.

Temporally Resolved Electrochemical Interrogation for Stochastic Collision Dynamics of Electrogenerated Single Polybromide Droplets.

In this article, we present electrochemical interrogation for collision dynamics of electrogenerated individual polybromide ionic liquid (PBIL) droplets through chronoamperometry combined with fast scan cyclic voltammetry (CA-FSCV). In the CA mode of CA-FSCV, a Pt ultramicroelectrode (UME) acts as the electrochemical generator for PBIL droplets by holding the oxidation potential for Br- in a given time, while FSCV is repetitively performed at a certain frequency. In the FSCV mode of CA-FSCV, a Pt UME serves as the probe to electrochemically monitor Br3- reduction for an adsorbed PBIL droplet during collision with a high temporal resolution. Based on the newly introduced CA-FSCV, we can estimate the dynamic changes in the following parameters for a short collision time: the contact radius of a PBIL droplet on a Pt UME, the concentration of Br- in the droplet, and the apparent charge transfer rate constant for electro-reduction of Br3- to Br- in the droplet, koapp. Moreover, a computational calculation using molecular dynamics is presented that can explain the change in koapp as a function of time for Br- electrolysis in a PBIL droplet. Based on the quantitative estimation of the above parameters, we suggest a more advanced mechanism for the stochastic electrochemical collision process of a PBIL droplet. These findings are important for understanding QBr2n+1/QBr half redox reactions in aqueous energy storage systems, such as Zn-Br redox flow batteries and Br-related redox enhanced electrochemical capacitors.

Feasibility of Applying Fourier Transform Electrochemical Impedance Spectroscopy in Fast Cyclic Square Wave Voltammetry for the In Vivo Measurement of Neurotransmitters.

We previously reported on the use of fast cyclic square wave voltammetry (FCSWV) as a new voltammetric technique. Fourier transform electrochemical impedance spectroscopy (FTEIS) has recently been utilized to provide information that enables a detailed analytical description of an electrified interface. In this study, we report on attempts to combine FTEIS with FCSWV (FTEIS-FCSWV) and demonstrate the feasibility of FTEIS-FCSWV in the in vivo detection of neurotransmitters, thus giving a new type of electrochemical impedance information such as biofouling on the electrode surface. From FTEIS-FCSWV, three new equivalent circuit element voltammograms, consisting of charge-transfer resistance (Rct), solution-resistance (Rs), and double-layer capacitance (Cdl) voltammograms were constructed and investigated in the phasic changes in dopamine (DA) concentrations. As a result, all Rct, Rs, and Cdl voltammograms showed different DA redox patterns and linear trends for the DA concentration (R2 > 0.99). Furthermore, the Rct voltammogram in FTEIS-FCSWV showed lower limit of detection (21.6 ± 15.8 nM) than FSCV (35.8 ± 17.4 nM). FTEIS-FCSWV also showed significantly lower prediction errors than FSCV in selectivity evaluations of unknown mixtures of catecholamines. Finally, Cdl from FTEIS-FCSWV showed a significant relationship with fouling effect on the electrode surface by showing decreased DA sensitivity in both flow injection analysis experiment (r = 0.986) and in vivo experiments. Overall, this study demonstrates the feasibility of FTEIS-FCSWV, which could offer a new type of neurochemical spectroscopic information concerning electrochemical monitoring of neurotransmitters in the brain, and the ability to estimate the degree of sensitivity loss caused by biofouling on the electrode surface.

Tonic Serotonin Measurements In Vivo Using N-Shaped Multiple Cyclic Square Wave Voltammetry.

Here, we present the development of a novel voltammetric technique, N-shaped multiple cyclic square wave voltammetry (N-MCSWV) and its application in vivo. It allows quantitative measurements of tonic extracellular levels of serotonin in vivo with mitigated fouling effects. N-MCSWV enriches the electrochemical information by generating high dimensional voltammograms, which enables high sensitivity and selectivity against 5-hydroindoleacetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), histamine, ascorbic acid, norepinephrine, adenosine, and pH. Using N-MCSWV, in combination with PEDOT:Nafion-coated carbon fiber microelectrodes, a tonic serotonin concentration of 52 ± 5.8 nM (n = 20 rats, ±SEM) was determined in the substantia nigra pars reticulata of urethane-anesthetized rats. Pharmacological challenges with dopaminergic, noradrenergic, and serotonergic synaptic reuptake inhibitors supported the ability of N-MCSWV to selectively detect tonic serotonin levels in vivo. Overall, N-MCSWV is a novel voltammetric technique for analytical quantification of serotonin. It offers continuous monitoring of changes in tonic serotonin concentrations in the brain to further our understanding of the role of serotonin in normal behaviors and psychiatric disorders.

Sensitive and Selective Measurement of Serotonin in Vivo Using Fast Cyclic Square-Wave Voltammetry.

Although N-shaped fast scan cyclic voltammetry (N-FSCV) is well-established as an electroanalytical method to measure extracellular serotonin concentrations in vivo, it is in need of improvement in both sensitivity and selectivity. Based on our previous studies using fast cyclic square-wave voltammetry (FCSWV) for in vivo dopamine measurements, we have modified this technique to optimize the detection of serotonin in vivo. A series of large amplitude square-shaped potentials was superimposed onto an N-shaped waveform to provide cycling through multiple redox reactions within the N-shaped waveform to enhance the sensitivity and selectivity to serotonin measurement when combined with a two-dimensional voltammogram. N-Shaped fast cyclic square-wave voltammetry (N-FCSWV) showed significantly higher sensitivity to serotonin compared to conventional N-FSCV. In addition, N-FCSWV showed better performance than conventional N-shaped FSCV in differentiating serotonin from its major interferents, dopamine and 5-hydroxyindoleascetic acid (5-HIAA). It was also confirmed that the large amplitude of the square waveform did not influence local neuronal activity, and it could monitor electrical stimulation evoked phasic release of serotonin in the rat substantia nigra pars reticulata (SNr) before and after systemic injection of escitalopram (ESCIT, 10 mg/kg i.p.), a serotonin selective reuptake inhibitor.

Fast Cyclic Square-Wave Voltammetry To Enhance Neurotransmitter Selectivity and Sensitivity.

Although fast-scan cyclic voltammetry (FSCV) has been widely used for in vivo neurochemical detection, the sensitivity and selectivity of the technique can be further improved. In this study, we develop fast cyclic square-wave voltammetry (FCSWV) as a novel voltammetric technique that combines large-amplitude cyclic square-wave voltammetry (CSWV) with background subtraction. A large-amplitude, square-shaped potential was applied to induce cycling through multiple redox reactions within a square pulse to increase sensitivity and selectivity when combined with a two-dimensional voltammogram. As a result, FCSWV was significantly more sensitive than FSCV ( n = 5 electrodes, two-way ANOVA, p = 0.0002). In addition, FCSWV could differentiate dopamine from other catecholamines (e.g., epinephrine and norepinephrine) and serotonin better than conventional FSCV. With the confirmation that FCSWV did not influence local neuronal activity, despite the large amplitude of the square waveform, it could monitor electrically induced phasic changes in dopamine release in rat striatum before and after injecting nomifensine, a dopamine reuptake inhibitor.

A baseline drift detrending technique for fast scan cyclic voltammetry.

Fast scan cyclic voltammetry (FSCV) has been commonly used to measure extracellular neurotransmitter concentrations in the brain. Due to the unstable nature of the background currents inherent in FSCV measurements, analysis of FSCV data is limited to very short amounts of time using traditional background subtraction. In this paper, we propose the use of a zero-phase high pass filter (HPF) as the means to remove the background drift. Instead of the traditional method of low pass filtering across voltammograms to increase the signal to noise ratio, a HPF with a low cutoff frequency was applied to the temporal dataset at each voltage point to remove the background drift. As a result, the HPF utilizing cutoff frequencies between 0.001 Hz and 0.01 Hz could be effectively used to a set of FSCV data for removing the drifting patterns while preserving the temporal kinetics of the phasic dopamine response recorded in vivo. In addition, compared to a drift removal method using principal component analysis, this was found to be significantly more effective in reducing the drift (unpaired t-test p < 0.0001, t = 10.88) when applied to data collected from Tris buffer over 24 hours although a drift removal method using principal component analysis also showed the effective background drift reduction. The HPF was also applied to 5 hours of FSCV in vivo data. Electrically evoked dopamine peaks, observed in the nucleus accumbens, were clearly visible even without background subtraction. This technique provides a new, simple, and yet robust, approach to analyse FSCV data with an unstable background.

Monitoring In Vivo Changes in Tonic Extracellular Dopamine Level by Charge-Balancing Multiple Waveform Fast-Scan Cyclic Voltammetry.

Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods. To measure tonic changes in DA concentrations over several hours, we applied a novel charge-balancing multiple waveform FSCV (CBM-FSCV), combined with a dual background subtraction technique, to minimize temporal variations in background capacitive currents. Using this method, in vitro, charge variations from a reference time point were nearly zero for 48 h, whereas with conventional background subtraction, charge variations progressively increased. CBM-FSCV also demonstrated a high selectivity against 3,4-dihydroxyphenylacetic acid and ascorbic acid, two major chemical interferents in the brain, yielding a sensitivity of 85.40 ± 14.30 nA/µM and limit of detection of 5.8 ± 0.9 nM for DA while maintaining selectivity. Recorded in vivo by CBM-FSCV, pharmacological inhibition of DA reuptake (nomifensine) resulted in a 235 ± 60 nM increase in tonic extracellular DA concentrations, while inhibition of DA synthesis (α-methyl-dl-tyrosine) resulted in a 72.5 ± 4.8 nM decrease in DA concentrations over a 2 h period. This study showed that CBM-FSCV may serve as a unique voltammetric technique to monitor relatively slow changes in tonic extracellular DA concentrations in vivo over a prolonged time period.

Enhanced Dopamine Sensitivity Using Steered Fast-Scan Cyclic Voltammetry.

Fast-scan cyclic voltammetry (FSCV) is a technique for measuring phasic release of neurotransmitters with millisecond temporal resolution. The current data are captured by carbon fiber microelectrodes, and non-Faradaic current is subtracted from the background current to extract the Faradaic redox current through a background subtraction algorithm. FSCV is able to measure neurotransmitter concentrations in vivo down to the nanomolar scale, making it a very robust and useful technique for probing neurotransmitter release dynamics and communication across neural networks. In this study, we describe a technique that can further lower the limit of detection of FSCV. By taking advantage of a "waveform steering" technique and by amplifying only the oxidation peak of dopamine to reduce noise fluctuations, we demonstrate the ability to measure dopamine concentrations down to 0.17 nM. Waveform steering is a technique to dynamically alter the input waveform to ensure that the background current remains stable over time. Specifically, the region of the input waveform in the vicinity of the dopamine oxidation potential (∼0.6 V) is kept flat. Thus, amplification of the input waveform will amplify only the Faradaic current, lowering the existing limit of detection for dopamine from 5.48 to 0.17 nM, a 32-fold reduction, and for serotonin, it lowers the limit of detection from 57.3 to 1.46 nM, a 39-fold reduction compared to conventional FSCV. Finally, the applicability of steered FSCV to in vivo dopamine detection was also demonstrated in this study. In conclusion, steered FSCV might be used as a neurochemical monitoring tool for enhancing detection sensitivity.

Multi-waveform fast-scan cyclic voltammetry mapping of adsorption/desorption kinetics of biogenic amines and their metabolites.

Fast-scan cyclic voltammetry (FSCV) is an effective method for investigating electro-active neurochemical species. In recent years, FSCV has been used to measure electro-active neurotransmitters in a variety of neuroscience studies. We previously reported on the use of paired-pulse voltammetry (PPV) that enables FSCV to differentiate various analytes and minimize confounding factors by taking advantage of the adsorption characteristics of the analyte on carbon fiber microelectrodes. In spite of a number of studies regarding adsorption/desorption characteristics of neurotransmitters, the difference in adsorption/desorption properties among neurotransmitters has yet to be fully explored. To calculate adsorption/desorption constants for neurotransmitters, we propose the use of multi-waveform FSCV (M-FSCV), which consists of decade triangular waveforms in a single scan. Within the multiple waveforms, the voltammetric response of dopamine decayed exponentially because of the decreased adsorption time period. The decay pattern was mathematically described using adsorption/desorption characteristics and two additional initial points: an exponential decay constant (K) and an initial quantity (A), which were extracted from the decay equation. Using this method, we were able to quantify the decay constant (K-map) and an initial quantity (A-map) color plot in addition to a conventional pseudo color plot. M-FSCV was evaluated with two biogenic amine groups (catecholamines and indolamines) to characterize their inherent adsorption/desorption constants. As a result, the A-map showed a high correlation with concentration and the K-map for each group to be significantly differentiated. These results demonstrate that M-FSCV has the potential to be a useful technique for acquiring additional adsorption/desorption information regarding neurotransmitters.

Tracking tonic dopamine levels in vivo using multiple cyclic square wave voltammetry.

For over two decades, fast-scan cyclic voltammetry (FSCV) has served as a reliable analytical method for monitoring dopamine release in near real-time in vivo. However, contemporary FSCV techniques have been limited to measure only rapid (on the order of seconds, i.e. phasic) changes in dopamine release evoked by either electrical stimulation or elicited by presentation of behaviorally salient stimuli, and not slower changes in the tonic extracellular levels of dopamine (i.e. basal concentrations). This is because FSCV is inherently a differential method that requires subtraction of prestimulation tonic levels of dopamine to measure phasic changes relative to a zeroed baseline. Here, we describe the development and application of a novel voltammetric technique, multiple cyclic square wave voltammetry (M-CSWV), for analytical quantification of tonic dopamine concentrations in vivo with relatively high temporal resolution (10 s). M-CSWV enriches the electrochemical information by generating two dimensional voltammograms which enable high sensitivity (limit of detection, 0.17 nM) and selectivity against ascorbic acid, and 3,4-dihydroxyphenylacetic acid (DOPAC), including changes in pH. Using M-CSWV, a tonic dopamine concentration of 120 ±â€¯18 nM (n = 7 rats, ±â€¯SEM) was determined in the striatum of urethane anethetized rats. Pharmacological treatments to elevate dopamine by selectively inhibiting dopamine reuptake and to reduce DOPAC by inhibition of monoamine oxidase supported the selective detection of dopamine in vivo. Overall, M-CSWV offers a novel voltammetric technique to quantify levels and monitor changes in tonic dopamine concentrations in the brain to further our understanding of the role of dopamine in normal behavior and neuropsychiatric disorders.