An ambient proof and wide tuning range LC VCO with automatic amplitude control for tuner applications

This paper represents a LC VCO with AAC (Auto Amplitude Control), in which PMOS FETs are used as active components, and the varactors are directly connected to ground to widen Kvco linear range. The AAC circuitry adds little noise to the VCO and provides it with robust performance over a wide temperature and carrier frequency range. The VCO is fabricated in 50-GHz 0.35-mu m SiGe BiCMOS process. The measurement results show that it has -127.27-dBc/Hz phase noise at 1-MHz offset and a linear gain of 32.4-MHz/V between 990-MHz and 1.14-GHz. The whole circuit draws 6.6-mA current from 5.0-V supply.

A Low Power Wide Dynamic Range Envelope Detector

We report a 75dB, 2.8mW, 100Hz-10kHz envelope detector in a 1.5mm 2.8V CMOS technology. The envelope detector performs input-dc-insensitive voltage-to-currentconverting rectification followed by novel nanopower current-mode peak detection. The use of a subthreshold wide- linear-range transconductor (WLR OTA) allows greater than 1.7Vpp input voltage swings. We show theoretically that this optimal performance is technology-independent for the given topology and may be improved only by spending more power. A novel circuit topology is used to perform 140nW peak detection with controllable attack and release time constants. The lower limits of envelope detection are determined by the more dominant of two effects: The first effect is caused by the inability of amplified high-frequency signals to exceed the deadzone created by exponential nonlinearities in the rectifier. The second effect is due to an output current caused by thermal noise rectification. We demonstrate good agreement of experimentally measured results with theory. The envelope detector is useful in low power bionic implants for the deaf, hearing aids, and speech-recognition front ends. Extension of the envelope detector to higher- frequency applications is straightforward if power consumption is inc

A Chloro-Bridged Linear Chain Imine-Copper(II) Complex and Its Application as an Enzyme-Free Amperometric Biosensor for Hydrogen Peroxide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Osteryoung square wave voltammetric determination of lactose in food samples by a derivative procedure

A method for determination of lactose in food samples by Osteryoung square wave voltammetry (OSWV) was developed. It was based on the nucleophilic addition reaction between lactose and aqua ammonia. The carbonyl group of lactose can be changed into imido group, and this increases the electrochemical activity in reduction and the sensitivity. The optimal condition for the nucleophilic addition reaction was investigated and it was found that in NH4Cl–NH3 buffer of pH 10.1, the linear range between the peak current and the concentration of lactose was 0.6–8.4 mg L−1, and the detection limits was 0.44 mg L−1. The proposed method was applied to the determination of lactose in food samples and satisfactory results were obtained.

Investigations of an electrochemical platform based on the layered MoS2-graphene and horseradish peroxidase nanocomposite for direct electrochemistry and electrocatalysis

The self-assembly of layered molybdenum disulfide–graphene (MoS2–Gr) and horseradish peroxidase (HRP) by electrostatic attraction into a novel hybrid nanomaterial (HRP–MoS2–Gr) is reported. The properties of the MoS2–Gr were characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (TEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). UV–vis and Fourier transform infrared spectroscopy (FT-IR) indicate that the native structure of the HRP is maintained after the assembly, implying good biocompatibility of MoS2–Gr nanocomposite. Furthermore, the HRP–MoS2–Gr composite is utilized as a biosensor, which displays electrocatalytic activity to hydrogen peroxide (H2O2) with high sensitivity (679.7 μA mM−1 cm−2), wide linear range (0.2 μM–1.103 mM), low detection limit (0.049 μM), and fast amperometric response. In addition, the biosensor also exhibits strong anti-interference ability, satisfactory stability and reproducibility. These desirable electrochemical properties are attributed to the good biocompatibility and electron transport efficiency of the MoS2–Gr composite, as well as the high loading of HRP. Therefore, this biosensor is potentially suitable for H2O2 analysis in environmental, pharmaceutical, food or industrial applications.

Liquid Chromatography-Mass Spectrometry in Studies of Drug Metabolism and Permeability

Poor pharmacokinetics is one of the reasons for the withdrawal of drug candidates from clinical trials. There is an urgent need for investigating in vitro ADME (absorption, distribution, metabolism and excretion) properties and recognising unsuitable drug candidates as early as possible in the drug development process. Current throughput of in vitro ADME profiling is insufficient because effective new synthesis techniques, such as drug design in silico and combinatorial synthesis, have vastly increased the number of drug candidates. Assay technologies for larger sets of compounds than are currently feasible are critically needed. The first part of this work focused on the evaluation of cocktail strategy in studies of drug permeability and metabolic stability. N-in-one liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the multiple component analysis of samples in cocktail experiments. Together, cocktail dosing and LC/MS/MS were found to form an effective tool for increasing throughput. First, cocktail dosing, i.e. the use of a mixture of many test compounds, was applied in permeability experiments with Caco-2 cell culture, which is a widely used in vitro model for small intestinal absorption. A cocktail of 7-10 reference compounds was successfully evaluated for standardization and routine testing of the performance of Caco-2 cell cultures. Secondly, cocktail strategy was used in metabolic stability studies of drugs with UGT isoenzymes, which are one of the most important phase II drug metabolizing enzymes. The study confirmed that the determination of intrinsic clearance (Clint) as a cocktail of seven substrates is possible. The LC/MS/MS methods that were developed were fast and reliable for the quantitative analysis of a heterogenous set of drugs from Caco-2 permeability experiments and the set of glucuronides from in vitro stability experiments. The performance of a new ionization technique, atmospheric pressure photoionization (APPI), was evaluated through comparison with electrospray ionization (ESI), where both techniques were used for the analysis of Caco-2 samples. Like ESI, also APPI proved to be a reliable technique for the analysis of Caco-2 samples and even more flexible than ESI because of the wider dynamic linear range. The second part of the experimental study focused on metabolite profiling. Different mass spectrometric instruments and commercially available software tools were investigated for profiling metabolites in urine and hepatocyte samples. All the instruments tested (triple quadrupole, quadrupole time-of-flight, ion trap) exhibited some good and some bad features in searching for and identifying of expected and non-expected metabolites. Although, current profiling software is helpful, it is still insufficient. Thus a time-consuming largely manual approach is still required for metabolite profiling from complex biological matrices.

Accurate mass-based analysis in human sport doping control : Application of liquid chromatography - time-of-flight mass spectrometry

Human sport doping control analysis is a complex and challenging task for anti-doping laboratories. The List of Prohibited Substances and Methods, updated annually by World Anti-Doping Agency (WADA), consists of hundreds of chemically and pharmacologically different low and high molecular weight compounds. This poses a considerable challenge for laboratories to analyze for them all in a limited amount of time from a limited sample aliquot. The continuous expansion of the Prohibited List obliges laboratories to keep their analytical methods updated and to research new available methodologies. In this thesis, an accurate mass-based analysis employing liquid chromatography - time-of-flight mass spectrometry (LC-TOFMS) was developed and validated to improve the power of doping control analysis. New analytical methods were developed utilizing the high mass accuracy and high information content obtained by TOFMS to generate comprehensive and generic screening procedures. The suitability of LC-TOFMS for comprehensive screening was demonstrated for the first time in the field with mass accuracies better than 1 mDa. Further attention was given to generic sample preparation, an essential part of screening analysis, to rationalize the whole work flow and minimize the need for several separate sample preparation methods. Utilizing both positive and negative ionization allowed the detection of almost 200 prohibited substances. Automatic data processing produced a Microsoft Excel based report highlighting the entries fulfilling the criteria of the reverse data base search (retention time (RT), mass accuracy, isotope match). The quantitative performance of LC-TOFMS was demonstrated with morphine, codeine and their intact glucuronide conjugates. After a straightforward sample preparation the compounds were analyzed directly without the need for hydrolysis, solvent transfer, evaporation or reconstitution. The hydrophilic interaction technique (HILIC) provided good chromatographic separation, which was critical for the morphine glucuronide isomers. A wide linear range (50-5000 ng/ml) with good precision (RSD<10%) and accuracy (±10%) was obtained, showing comparable or better performance to other methods used. In-source collision-induced dissociation (ISCID) allowed confirmation analysis with three diagnostic ions with a median mass accuracy of 1.08 mDa and repeatable ion ratios fulfilling WADA s identification criteria. The suitability of LC-TOFMS for screening of high molecular weight doping agents was demonstrated with plasma volume expanders (PVE), namely dextran and hydroxyethylstarch (HES). Specificity of the assay was improved, since interfering matrix compounds were removed by size exclusion chromatography (SEC). ISCID produced three characteristic ions with an excellent mean mass accuracy of 0.82 mDa at physiological concentration levels. In summary, by combining TOFMS with a proper sample preparation and chromatographic separation, the technique can be utilized extensively in doping control laboratories for comprehensive screening of chemically different low and high molecular weight compounds, for quantification of threshold substances and even for confirmation. LC-TOFMS rationalized the work flow in doping control laboratories by simplifying the screening scheme, expediting reporting and minimizing the analysis costs. Therefore LC-TOFMS can be exploited widely in doping control, and the need for several separate analysis techniques is reduced.

Ethanol sensing using CuO/MWNT thin film

Copper (II) oxide (CuO)/multiwall carbon nanotube (MWNT) thin film based ethanol-sensors were fabricated by dispersing CVD-prepared MWNTs in varying concentration over DC magnetron sputtered-CuO films. The responses of these sensors as a function of MWNT concentrations and temperatures were measured, and compared. The sensing response was the maximum at an operating temperature near 400 degrees C for all the samples irrespective of the MWNTs dispersed over them. At optimum operating temperature (T(opt)) of 407 +/- 1 degrees C, the response is linear for 100-700 ppm range and tends to saturate at higher concentrations. In comparison with bare CuO sample, the response of CuO/MWNT sensing films increased up to 50% in the linear range. The response improvement for 2500 ppm of ethanol was up to 90% compared to bare CuO sample. In addition, the sensing response time also reduced to around 23% for lowest ethanol concentration at T(opt). However, a decrease in the sensor response was observed on films with very high concentrations of MWNTs. (C) 2011 Elsevier B.V. All rights reserved.

Platinum surface additive based nanostructured CuO films for ethanol sensing

In the present work, Platinum (Pt)/Copper (II) oxide (CuO) thin film based ethanol sensors were fabricated by sputtering of Pt in varying concentrations over pre-sputtered nanostructured CuO films. The responses of these sensors as a function of Pt concentrations were studied using operating temperature modulation (200-450 °C) and ethanol concentration modulation (100-2500 ppm). During these modulations, it was found that the sensing response was maximum at operating temperature near 400 °C for all the samples irrespective of the Pt concentration dispersed over them. Moreover, the sensing behavior improves for lower Pt concentration (Pt/CuO-60s) and deteriorates for higher Pt concentration (Pt/CuO-120s). In comparison with bare CuO sample, the sensitivity of Pt/CuO-60s increased up to 22% in the linear range and 33% for maximum ethanol concentration. Hence, the well dispersed optimum Pt additive concentration improves the overall sensing behavior including sensitivity, linear working range and response as well as recovery time.

Sensitive detection of C-reactive protein using optical fiber Bragg gratings

An accurate and highly sensitive sensor platform has been demonstrated for the detection of C-reactive protein (CRP) using optical fiber Bragg gratings (FBGs). The CRP detection has been carried out by monitoring the shift in Bragg wavelength (Delta lambda(B)) of an etched FBG (eFBG) coated with an anti-CRP antibody (aCRP)-graphene oxide (GO) complex. The complex is characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy. A limit of detection of 0.01 mg/L has been achieved with a linear range of detection from 0.01 mg/L to 100 mg/L which includes clinical range of CRP. The eFBG sensor coated with only aCRP (without GO) show much less sensitivity than that of aCRP-GO complex coated eFBG. The eFBG sensors show high specificity to CRP even in the presence of other interfering factors such as urea, creatinine and glucose. The affinity constant of similar to 1.1 x 10(10) M-1 has been extracted from the data of normalized shift (Delta lambda(B)/lambda(B)) as a function of CRP concentration. (C) 2014 Elsevier B.V. All rights reserved.

Highly sensitive and rapid detection of acetylcholine using an ITO plate modified with platinum-graphene nanoparticles

Determining the concentrations of acetylcholine (ACh) and choline (Ch) is clinically important. ACh is a neurotransmitter that acts as a key link in the communication between neurons in the spinal cord and in nerve skeletal junctions in vertebrates, and plays an important role in transmitting signals in the brain. A bienzymatic sensor for the detection of ACh was prepared by co-immobilizing choline oxidase (ChO) and acetylcholinesterase (AChE) on graphene matrix/platinum nanoparticles, and then electrodepositing them on an ITO-coated glass plate. Graphene nanoparticles were decorated with platinum nanoparticles and were electrodeposited on a modified ITO-coated glass plate to form a modified electrode. The modified electrode was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies. The optimum response of the enzyme electrode was obtained at pH 7.0 and 35 degrees C. The response time of this ACh-sensing system was shown to be 4 s. The linear range of responses to ACh was 0.005-700 mu M. This biosensor exhibits excellent anti-interferential abilities and good stability, retaining 50% of its original current even after 4 months. It has been applied for the detection of ACh levels in human serum samples.

Superior Performance of a MoS2-RGO Composite and a Borocarbonitride in the Electrochemical Detection of Dopamine, Uric Acid and Adenine

A MoS2-RGO composite and borocarbonitride (BC5N) have been used as electrodes to selectively detect dopamine and uric acid in the presence of ascorbic acid. Both the electrodes show excellent eletrocatalytic activity towards the detection of dopamine, the detection limits being 0.55 mu M and 2.1 mu M in the case of MoS2-RGO and BCN respectively. MoS2-RGO shows a linear range of current over the 1-110 mu M concentrations of dopamine, while BCN shows over the 2.3-20 mu M range. BCN also exhibits satisfactory performance in the oxidation of uric acid with a detection limit of 3.8 mu M and the linear range from 4 to 40 mu M. The MoS2-RGO has also been used to detect adenine as well.

Voltammetric determination of paracetamol, tramadol and caffeine using poly(Nile blue) modified glassy carbon electrode

A poly(Nile blue) modified glassy carbon electrode (PNBMGCE) was fabricated by electropolymerisation of Nile blue (NB) monomer using cyclic voltammetry (CV) and was used for the determination of paracetamol (ACOP), tramadol (TRA) and caffeine (CAF). The electrochemical investigations showed that PNB - film formed on the surface of glassy carbon electrode (GCE) improved the electroactive surface area and displayed a remarkable increase in the peak current and a substantial decrease in over potential of ACOP, TRA and CAF when compared to bare GCE. The dependence of peak current and potential on pH, sweep rate and concentration were also investigated at the surface of PNBMGCE. It showed good sensitivity and selectivity in a wide linear range from 2.0 x 10(-7) to 1.62 x 10(-5) M, 1.0 x 10(-6) to 3.1 x 10(-4) M and 8.0 x 10(-7) to 2.0 x 10(-5) M, with detection limits of 0.08, 0.5 and 0.1 mu M, for ACOP, TRA and CAF, respectively. The PNBMGCE was also successfully applied for the determination of ACOP, TRA and CAF in pharmaceutical dosage forms. (C) 2016 Elsevier B.V. All rights reserved.

Enzyme-free glucose biosensor based on low density CNT forest grown directly on a Si/SiO2 substrate

A highly sensitive nonenzymatic amperometric glucose sensor was fabricated by using Ni nanoparticles homogeneously dispersed within and on the top of a vertically aligned CNT forest (CNT/Ni nanocomposite sensor), which was directly grown on a Si/SiO2 substrate. The surface morphology and elemental analysis were characterized using scanning electron microscopy and energy dispersive spectroscopy, respectively. Cyclic voltammetry and chronoamperometry were used to evaluate the catalytic activities of CNT/Ni electrode. The CNT/Ni nanocomposite sensor exhibited a great enhancement of anodic peak current after adding 5 mM glucose in alkaline solution. The sensor can also be applied to the quantification of glucose content with a linear range covering from 5 μM to 7 mM, a high sensitivity of 1433 μA mM-1 cm-2, and a low detection limit of 2 μM. The CNT/Ni nanocomposite sensor exhibits good reproducibility and long-term stability, moreover, it was also relatively insensitive to commonly interfering species, such as uric acid, ascorbic acid, acetaminophen, sucrose and d-fructose. © 2013 Elsevier B.V.

A solid-phase microextraction fiber coated with diglycidyloxycalix[4]arene yields very high extraction selectivity and sensitivity during the analysis of chlorobenzenes in soil

A novel fiber coated with novel sol-gel (5,11,17,23-tetra-tert-butyl-25,27-dihydroxy-26,28-diglycidyloxycalix[4]arene/hydroxy-terminated silicone oil; diglycidyloxy-C[4]/OH-TSO) was prepared for use with headspace solid-phase microextraction (HS-SPME) combined with gas chromatography (GC) and electron capture detection (ECD), which was applied in order to determine nine chlorobenzenes in soil matrices. Due to the improved fiber preparation, which increases the percentage of calixarene in the coating, the new calixarene fiber exhibits very high extraction selectivity and sensitivity to chlorine-substituted compounds. Various parameters affecting the extraction efficiency were optimized in order to maximize the sensitivity during the chlorobenzene analysis. Interferences from different soil matrices with different characteristics were investigated, and the amount extracted was strongly influenced by the matrix. Therefore, a standard addition protocol was performed on the real soil samples. The linear ranges of detection for the chlorobenzenes tested covered three orders of magnitude, and correlation coefficients > 0.9976 and relative standard deviations (RSD) < 8% were observed. The detection limits were found at sub-ng/g of soil levels, which were about an order of magnitude lower than those given by the commercial poly(dimethylsiloxane) (PDMS) coating for most of the compounds. The recoveries ranged from 64 to 109.6% for each analyte in the real kaleyard soil matrix when different concentration levels were determined over the linear range, which confirmed the reliability and feasibility of the HS-SPME/GC-ECD approach using the fiber coated with diglycidyloxy-C[4]/OH-TSO for the ultratrace analysis of chlorobenzenes in complex matrices.