Electrochemical Sensor System Research Articles

A 3-D-Printed Integrated PCB-Based Electrochemical Sensor System

In this paper, we report a fully 3-D-printed, flexible, amperometric lactate sensor system with a 3-D-printed, integrated electrochemical circuit platform, a so-called potentiostat, realized via a novel 3-D printing method. First, a lactate sensor was designed in a three-electrode configuration with a layer of deposited enzyme on the conductive silver electrodes. The thin silver electrodes were printed on a flexible substrate. Second, a highly integrated potentiostat circuit prototype was designed and printed on a rigid epoxy board. Both sensor electrodes and printed circuit board (PCB) were fabricated using a novel direct ink writing (DIW) technology with highly viscous silver nanoparticle ink. The fully 3-D-printed potentiostat system along with the sensor demonstrated reliable lactate detection for concentrations in the range of 0–20 mM. The purely additive manufacturing strategy of DIW demonstrated the capability of 3-D printing double-sided circuits with high-density chip-on-board designs as well as the ability to significantly reduce the lead time of PCB prototyping. The 3-D-printed electrochemical sensor system is suitable for wearable devices for continuous monitoring of human metabolisms.

A human whole blood chemically modified electrode for the hydrogen peroxide reduction and sensing: Real-time interaction studies of hemoglobin in the red blood cell with hydrogen peroxide

A human whole blood-chemically modified electrode prepared using graphitized mesoporous carbon and Nafion, as an in-vitro model system, has been studied for the specific interaction of hydrogen peroxide at biased potentials by cyclic volumetric technique. A blood-chemically modified electrode prepared by modifying a few drops of human whole blood with the carbon nanomaterial and Nafion had showed a well-defined redox peak at an apparent standard electrode potentials, E°′~− 0.38 V vs Ag/AgCl in N2 purged pH 7 phosphate buffer solution, similar to an isolated hemoglobin protein redox feature. When the blood modified electrode is exposed with dilute solution of hydrogen peroxide, selective electrochemical reduction behaviour where the heme site redox potential exists was noticed. The electrochemical reduction reaction is found to follow diffusion controlled mechanism. The H2O2 reduction peak current was linear with the concentration in a range of 100 to 800 μM with a current sensitivity of 0.048 μA μM−1. Qualitative cyclic voltammetric patterns of the blood modified electrode in the entire concentration window of H2O2 are same indicating intact biomolecular arrangement of the heme site. Kinetic parameters of the electron-transfer reaction of H2O2 were estimated using rotating disc technique and Michaelis-Menten reaction approaches. The electron-transfer function of the heme in the RBC is not influenced by any other electroactive biochemicals such as glucose, nitrate, ascorbic acid, uric acid and dopamine, except nitrite. As an independent study, the blood-chemically modified electrode has been used as an electrochemical sensor system for the flow injection analysis of H2O2.

A Printed Organic Amplification System for Wearable Potentiometric Electrochemical Sensors

Electrochemical sensor systems with integrated amplifier circuits play an important role in measuring physiological signals via in situ human perspiration analysis. Signal processing circuitry based on organic thin-film transistors (OTFTs) have significant potential in realizing wearable sensor devices due to their superior mechanical flexibility and biocompatibility. Here, we demonstrate a novel potentiometric electrochemical sensing system comprised of a potassium ion (K+) sensor and amplifier circuits employing OTFT-based pseudo-CMOS inverters, which have a highly controllable switching voltage and closed-loop gain. The ion concentration sensitivity of the fabricated K+ sensor was 34 mV/dec, which was amplified to 160 mV/dec (by a factor of 4.6) with high linearity. The developed system is expected to help further the realization of ultra-thin and flexible wearable sensor devices for healthcare applications.

Gold Nanoparticles-Thiol-Functionalized Reduced Graphene Oxide Coated Electrochemical Sensor System for Selective Detection of Mercury Ion

Reduced graphene oxide (rGO) dispersion was obtained by ultrasonication of rGO powder using dodecanethiol (-SH) as an exfoliating agent. Using thiol chemistry, the gold nanoparticles (Au-NPs) were assembled onto the rGO-SH modified glassy carbon electrode (GCE) which showed a strong binding with the surface of the coated electrode. Furthermore, the GCE/rGO-SH/Au-NPs electrode was used to detect mercury (Hg2+) ions in the aqueous solution. When employed as a working electrode, Hg2+ ions get adsorbed on the electrode surface which was later electrochemically oxidized by differential pulse voltammetry (DPV) with the enhanced oxidation current at +0.172 V. Moreover, this sensor platform showed linear response for Hg detection from 1–10 μM in phosphate buffer saline (PBS) solution and the detection limit was found to be 0.2 μM (S/N = 3). The characterization of the Au-NPs and rGO-SH films were studied by Fourier-transform infrared spectroscopy (FT-IR), UV-Visible spectroscopy, transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM). The application of the prepared sensor was also demonstrated in detecting mercury ions in tap water samples with satisfactory recovery analysis.

A Metal‐Free, Non‐Enzymatic Electrochemical Glucose Sensor with a de‐Bundled Single‐Walled Carbon Nanotube‐Modified Electrode

A new metal‐free, non‐enzymatic electrochemical sensor system for the detection of glucose was developed in this study. The developed sensor uses a de‐bundled single‐walled carbon nanotube (SWCNT)‐modified glassy carbon electrode (GCE). SWCNTs were de‐bundled in aqueous solution by adding a synthesized polymer dispersant, sulfonated poly(ether sulfone). The de‐bundled SWCNTs showed two significant characteristics: (1) improvement of the aspect ratio and dispersibility in aqueous solution and (2) suitability for use as a selective and sensitive sensing element in non‐enzymatic glucose sensors. The experimental results clearly demonstrated that the SWCNTs/GCE possesses high electro‐catalytic activity and efficient sensitivity with a stable and faster amperometric response production. Furthermore, interference by ascorbic acid, acetaminophen, uric acid, and dopamine is effectively avoided. Therefore, the proposed approach is favorable for the design and development of non‐enzymatic glucose sensors.

Single Microfluidic Electrochemical Sensor System for Simultaneous Multi-Pulmonary Hypertension Biomarker Analyses

Miniaturized microfluidic biosensors have recently been advanced for portable point-of-care diagnostics by integrating lab-on-a-chip technology and electrochemical analysis. However, the design of a small, integrated, and reliable biosensor for multiple and simultaneous electrochemical analyses in a single device remains a challenge. Here, we present a simultaneous microfluidic electrochemical biosensing system to detect multiple biomarkers of pulmonary hypertension diseases in a single device. The miniaturized biosensor, which is composed of five chambers, is precisely and individually controlled using in-house-built pneumatic microvalves to manipulate the flow pathway. Each chamber is connected to an electrochemical sensor designed to detect four different biomarkers plus a reference control. Our design allows for loading of multiple reagents for simultaneous analyses. On the basis of the developed microfluidic electrochemical sensor system, we successfully detected four well-defined pulmonary hypertension-associated biomarkers, namely, fibrinogen, adiponectin, low-density lipoprotein, and 8-isoprostane. This novel approach offers a new platform for a rapid, miniaturized, and sensitive diagnostic sensor in a single device for various human diseases.

Flexible Hybrid Mouth-Guard-Based Electrochemical Biosensing

PARC and UCSD are developing a flexible hybrid biosensor platform to enable continuous remote monitoring of bioanalyte concentrations in saliva. The electrochemical sensor system will be fabricated on a small, flexible plastic foil for mounting on a mouth guard, and enable continuous sensing of lactate, glucose, or other analytes. Chronoamperometry based on enzymatic oxidation of target species has been demonstrated to have high sensitivity and capability for quantification of analyte concentrations. Saliva is favorable for biosensing because of its accessibility and the correlation with blood concentrations of important analytes. The goal of the current work is to demonstrate a manufacturable, reliable sensor system. To this end, the electronics will be fully encapsulated and include wireless charging and readout, with easily removable and replaceable printed electrodes. Here, we will present an overview of the system and discuss current progress.

Metal oxide intercalated layered double hydroxide nanosphere: With enhanced electrocatalyic activity towards H2O2 for biological applications

Structurally integrated metal oxide intercalated layered double hydroxide (LDH) nanospheres (NSs) hybrid material has been of considerable current interest because of their unique structure and synergistic combination of multi- functional properties of nanocomposites. In this work, we report a new type of MnAl LDH wrapped CuO (CuO@MnAl LDHs) NSs by anchoring CuO nanoparticles (NPs) with MnAl LDHs via a facile co-precipitation and hydrothermal approach, and explore its practical application as high-efficient electrocatalyst towards H2O2 reduction for biological application. Our findings demonstrate that the integration of n-type spinel of CuO and p-type semiconductive channels of MnAl LDHs can accelerate electron transfer at breakdown voltage of p-n junction. Owing to the synergistic effect of the high surface area of CuO NPs, superb intercalation features of semiconductive MnAl LDHs for encapsulating NSs, and their intrinsic p-n junction characteristics, CuO@MnAl NSs have exhibited excellent electrocatalytic activity towards the reduction of H2O2. When implemented in electrochemical sensor system, the CuO@MnAl NSs modified electrode displays high nonenzymatic sensing performances towards H2O2 including a broad linear range 6μM–22mM, a low detection limit of 0.126μM, good selectivity and long term stability, which can be exploited for in vitro detection of H2O2 in human serum and urine samples, as well as real-time tracking H2O2 secreted from different human live cells.

Tannic acid assisted copper oxide nanoglobules for sensitive electrochemical detection of bisphenol A

ABSTRACTThis study describes the development of an electrochemical sensor system for the determination of bisphenol A using tannic acid functionalized CuO nanoglobules. The utilized tannic acid acted simultaneously as both bio-compatible template and functionalizing agent for the as-synthesised CuO nanostructures. The excellent synergy of high surface area and favorable interactions between the moieties of tannic acid and bisphenol A molecules enabled sensitive electrochemical oxidation of bisphenol A within wide detection window (0.1–5.5 µM) and limit of detection estimated to be 0.01 µM. Moreover, the sensor exhibited satisfactory stability and strong anti-interference capability when evaluated against common interferents molecules such as phenol, hydroquinone, and 4-nitrophenol.

Glutaric Acid Assisted Fabrication of CuO Nanostructures and their Application in Development of Highly Sensitive Electrochemical Sensor System for Carbamates

AbstractThis work describes the fabrication of unique arrow head shaped CuO nanostructures using simple hydrothermal treatment method. The highly attractive features were obtained by the application of glutaric acid utilised simultaneous as template and functionalising agent. The functionalised nanostructures were known to possess excellent potential towards the electro‐catalytic oxidation of carbofuran pesticide. The generated intense electrochemical signal with lower potential value enabled sensitive and selective determination of carbofuran up to 1×10−3 µM with wide sensing window in range of 0.01 to 0.16 µM. The feasibility of the developed sensor system for the practical application was also studied by testing its potential in real sample extracts of various vegetables. The excellent recoveries demonstrated the analytical robustness of the developed sensor system. The sensor system utilises a new and simple approach towards sensitive determination of toxic pesticides reflecting its wide spectrum application in various fields.

Microfabricated, amperometric, enzyme-based biosensors for in vivo applications.

Miniaturized electrochemical in vivo biosensors allow the measurement of fast extracellular dynamics of neurotransmitter and energy metabolism directly in the tissue. Enzyme-based amperometric biosensing is characterized by high specificity and precision as well as high spatial and temporal resolution. Aside from glucose monitoring, many systems have been introduced mainly for application in the central nervous system in animal models. We compare the microsensor principle with other methods applied in biomedical research to show advantages and drawbacks. Electrochemical sensor systems are easily miniaturized and fabricated by microtechnology processes. We review different microfabrication approaches for in vivo sensor platforms, ranging from simple modified wires and fibres to fully microfabricated systems on silicon, ceramic or polymer substrates. The various immobilization methods for the enzyme such as chemical cross-linking and entrapment in polymer membranes are discussed. The resulting sensor performance is compared in detail. We also examine different concepts to reject interfering substances by additional membranes, aspects of instrumentation and biocompatibility. Practical considerations are elaborated, and conclusions for future developments are presented.Graphical ᅟ

An Electrochemical Sensor System with Renewable Copper Nano-clusters Modified Electrode for Continuous Nitrate Determination

An automatic electrochemical sensor system based on a sequential injection analysis technique for continuous nitrate determination is demonstrated. A three-electrode-system (Pt–Pt–Ag/AgCl), in which the Pt working-electrode was modified with renewable copper nano-clusters, was designed and fabricated to implement sensitive and reproducible nitrate detection under a programmed operation protocol. Based on an optimal potential protocol, the continuous renewal of copper sensing material was achieved on the working-electrode surface to ensure each measurement could be performed on a fresh and highly active copper surface, which guaranteed that automotive and continuous nitrate determination could be performed in a long period of time. The experiment results revealed that the response of the sensor system toward standard nitrate samples was linear and reproducible with an average sensitivity of 1.093 $\mu \text{A}/\text {mg}~\cdot ~\text {L}^{-1}$ over the concentration range from 0 to 12.1 mg/L in a continuous long-term operation. The standard deviation for the fluctuation of the sensitivity was only 0.036 during the continuous repeated measurements. The developed system was used to detect nitrate in real freshwater samples. The results were in good agreement with the data obtained by the standard ultraviolet spectrophotometric method for nitrate detection with the maximal difference of 16.64%.

Building Selectivity for NO Sensing in a NOx Mixture with Sonochemically Prepared CuO Structures

Several technologies are available for decreasing nitrogen oxide (NOx) emissions from combustion sources, including selective catalytic reduction methods. In this process, ammonia reacts with nitric oxide (NO) and nitrogen dioxide (NO2). As the stoichiometry of the two reactions is different, electrochemical sensor systems that can distinguish between NO and NO2 in a mixture of these two gases are of interest. Since NO and NO2 can be brought to equilibrium, depending on the temperature and the surfaces that they are in contact with, the detection of NO and NO2 independently is a difficult problem and has not been solved to date. In this study, we explore a high surface area sonochemically prepared CuO as the resistive sensing medium. CuO is a poor catalyst for NOx equilibration, and requires temperatures of 500 C to bring about equilibration. Thus, at 300 C, NO and NO2 retain their levels after interaction with CuO surface. In addition, NO adsorbs more strongly on the CuO over NO2. Using these two concepts, we can detect NO with minimal interference from NO2, if the latter gas concentration does not exceed 20% in a NOx mixture over a range of 100–800 ppm. Since this range constitutes most of the range of total NOx concentrations in diesel and other lean burn engines, this sensor should find application in selective detection of NO in this combustion application. A limitation of this sensor is the interference with CO, but with combustion in excess air, this problem should be alleviated.

Simultaneous voltammetric determination of dopamine and uric acid based on Langmuir–Blodgett film of calixarene modified glassy carbon electrode

Langmuir–Blodgett (LB) film of C-Undecylcalix[4]resorcinarene (CUCR) as molecular receptor and pretreated glassy carbon electrode (GCE) as enhancer of electron transfer are integrated in the electrochemical sensor system. The new electrochemical sensor possesses the properties of calixarene (high supramolecular recognition and enrichment capability) and pretreated GCE (large surface area and high active sites). At the resulting electrode, the peak current of dopamine (DA) and uric acid (UA) increased dramatically compared with that on the bare GCE and pretreated GCE which due to the synergetic effects of LB film of CUCR and pretreated GCE. Using differential pulse voltammetry, the resulting electrode was applied to develop a high sensitive electrochemical sensor for the simultaneous determination of DA and UA in the presence of ascorbic acid (AA) for the first time. Under the selected conditions, the linear response ranges for DA and UA are 8.0×10−8 to 6.0×10−6molL−1 and 4.0×10−7 to 4.0×10−5molL−1, with the detection limits of 2.0×10−8molL−1 and 8.0×10−8molL−1, respectively. Besides, the resulting electrode also showed an excellent selectivity, stability and reproducibility.

Electrochemical methods in biomedical studies

Own experimental studies on the development of highly sensitive methods of electrochemical analysis applicable for biochemical research in the postgenomic era as well as electrochemical sensor systems for analysis of various biological objects have been summarized. Electroanalysis of catalytic activity of cytochrome P450 resulted in the development of a system for screening potential substrates and/or inhibitors of this class hemoproteins, as well as biologically active compounds modulating the catalytic function of this protein. The study of kinetics of bioaffinity troponin I/anti-troponin I (antibody to TnI) interactions in human plasma resulted in the development of a highly sensitive piezoelectric immunosensor, performing direct registration of biochemical interactions based on the difference of the kinetic parameters of specific and nonspecific bioaffinity interactions without additional administration of labels and without chemical modifications. The developed methods of direct registration of the electrochemical activity of bacterial cells Escherichia coli JM109 are applicable for real time evaluation of antibacterial activity of drug substances; this requires minimal volumes of cells (106 CFU/electrode). Special attention is paid to experimental data on preparation of polymers with molecular imprints (molecularly imprinted polymers, MIP) as analogues of antibodies and biorecognizing elements, carrying selective complementary analytes binding based on the “lock and key” principle.

Electrochemical sensor system for breath analysis of aldehydes, CO and NO

Bulky and hyphenated laboratory-based analytical instrumentation such as gas chromatography/mass spectrometry is still required to trace breath biomarkers in the low ppbV level. Innovative sensor-based technologies could provide on-site and point-of-care (POC) detection of volatile biomarkers such as breath aldehydes related to oxidative stress and cancer.An electrochemical sensor system was developed for direct detection of the total abundance of aldehydes in exhaled breath in the ppbV level and for simultaneous determination of the airway inflammation markers carbon monoxide (CO) and nitric oxide (NO). The sensor system was tested in vitro with gaseous standard mixtures and in vivo in spontaneously breathing patients and under mechanical ventilation in an animal model.The sensor system provided in vitro and in vivo detection of trace levels of aldehydes, CO and NO. Inertness of the tubing system was important for reliable results. Sensitivity of the aldehyde sensor increased with humidity. Response time for analysis of breath samples was about 22 s and relative standard deviations of sensor amplitudes were <5%. Detection limits in the low ppbV range and a linear range of more than two orders of magnitude could be achieved for volatile aldehydes. Cross sensitivities were moderate for alcohols such as ethanol or isopropanol and negligible for other typical breath volatile organic compounds such as acetone, isoprene or propofol. In proof of concept analyses in patients suffering from lung cancer and diabetes, aldehyde and CO sensor signals differed between the groups. Elevated CO levels indicated previous smoking. In a mechanically ventilated pig, continuous monitoring of breath aldehyde concentrations in the low ppbV was realized.Cumulative aldehyde measurements may add interesting and complementary information to the conventional parameters used in clinical breath research. POC applicability, easy handling and low cost of sensors facilitate measurements in large patient cohorts.

Fully printed flexible and disposable wireless cyclic voltammetry tag.

A disposable cyclic voltammetry (CV) tag is printed on a plastic film by integrating wireless power transmitter, polarized triangle wave generator, electrochemical cell and signage through a scalable gravure printing method. By proximity of 13.56 MHz RF reader, the printed CV tag generates 320 mHz of triangular sweep wave from +500 mV to −500 mV which enable to scan a printed electrochemical cell in the CV tag. By simply dropping any specimen solution on the electrochemical cell in the CV tag, the presence of solutes in the solution can be detected and shown on the signage of the CV tag in five sec. 10 mM of N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) was used as a standard solute to prove the working concept of fully printed disposable wireless CV tag. Within five seconds, we can wirelessly diagnose the presence of TMPD in the solution using the CV tag in the proximity of the 13.56 MHz RF reader. This fully printed and wirelessly operated flexible CV tag is the first of its kind and marks the path for the utilization of inexpensive and disposable wireless electrochemical sensor systems for initial diagnose hazardous chemicals and biological molecules to improve public hygiene and health.

Molecularly imprinted polymers in electro analysis of proteins

In the review the main approaches to creation of recognition materials capable of competing with biological specific receptors, (polymeric analogs of antibodies or molecularly imprinted polymers, MIP) for the electro analysis of functionally significant proteins such as a myoglobin, troponin T, albumin, human ferritin, calmodulin are considered. The main types of monomers for MIP fabrication, and methods for MIP/protein interactions, such as a surface plasmon resonance (SPR), nanogravimetry with use of the quartz crystal resonator (QCM), spectral and electrochemical methods are discussed. Experimental data on electrochemical registration of a myoglobin using MIP/electrode are presented. For a development of electrochemical sensor systems based on MIPs, o-phenylenediamine (1,2-diaminobenzene was used as a monomer. It was shown that the imprinting factor Imax(MIP)/Imax(NIP), calculated as a myoglobin signal ratio when embedding in MIP to a myoglobin signal when embedding in the polymer received without molecular template (NIP) corresponds 2-4.

An electrochemical sensor for fast detection of wound infection based on myeloperoxidase activity

Infection can lead to severe complications during wound healing. We have developed an electrochemical sensor for fast and simple detection of wound infection based on the quantification of myeloperoxidase activity as a marker for infection.Applicability of the enzyme was confirmed with a correlation study with silver standard wound diagnostics. Significant higher enzyme activities comparing non infected and infected wound fluids were determined (P=0.01). To eliminate supplemental substrate addition, the chlorination activity of the enzyme – the formation of hypochlorous acid (HOCl) from chloride and hydrogen peroxide – was investigated in different wound fluids and correlated with the peroxidation activity measurements. Significant activity differences were likewise obtained (P=0.01). Based on this we constructed an electrochemical hydrogen peroxide sensor system for the quantification of chlorination activity in wound fluids. Furthermore, immobilized glucose oxidase was integrated into the system to provide hydrogen peroxide required by myeloperoxidase.Infected wound fluids were indeed identified by using the sensor system quantifying the consumption of hydrogen peroxide consumed by myeloperoxidase. Thereby, immobilized glucose oxidase was shown to produce enough hydrogen peroxide for the myeloperoxidase reaction from glucose present in wound fluids. There is a strong need for a simple but effective sensor system to determine infections in wounds. This sensor measuring hydrogen peroxide consumption could effectively identify infected wound fluids based on the myeloperoxidase activity.

Superoxide microsensor integrated into a Sensing Cell Culture Flask microsystem using direct oxidation for cell culture application

A new electrochemical sensor system for reliable and continuous detection of superoxide radical release from cell culture was developed utilizing direct oxidation of superoxide on polymer covered gold microelectrodes. Direct superoxide oxidation was demonstrated to provide robust measurement principle for sensitive and selective reactive oxygen species (ROS) quantification without the need for biocomponent supported conversion. Sensor performance was investigated by using artificial enzymatic superoxide production revealing a sensitivity of 2235AM−1m−2. An electrode protection layer with molecular weight cut-off property from adsorbed linear branched polyethylenimine was successfully introduced for long term and selectivity improvement. Thin-film based sensor chip fabrication with implemented three-electrode setup and full integration into the technological platform Sensing Cell Culture Flask was described. Cell culturing directly on-chip and free radical release by phorbol-12-myristate-13-acetate (PMA) stimulation was demonstrated using T-47D human breast cancer carcinoma cell model. Transient extracellular superoxide production upon stimulation was successfully observed from amperometric monitoring. Signal inhibition from scavenging of extracellular superoxide by specific superoxide dismutase (SOD) showed the applicability for selective in vitro ROS determination. The results confirm the possibility of direct superoxide oxidation, with exclusion of the main interfering substances uric acid and hydrogen peroxide. This offers new insights into the development of reliable and robust ROS sensors.