Design Of Electrochemical Biosensors Research Articles

Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol.

The monitoring of stress levels in humans has become increasingly relevant, given the recent incline of stress-related mental health disorders, lifestyle impacts, and chronic physiological diseases. Long-term exposure to stress can induce anxiety and depression, heart disease, and risky behaviors, such as drug and alcohol abuse. Biomarker molecules can be quantified in biological fluids to study human stress. Cortisol, specifically, is a hormone biomarker produced in the adrenal glands with biofluid concentrations that directly correlate to stress levels in humans. The rapid, real-time detection of cortisol is necessary for stress management and predicting the onset of psychological and physical ailments. Current methods, including mass spectrometry and immunoassays, are effective for sensitive cortisol quantification. However, these techniques provide only single measurements which pose challenges in the continuous monitoring of stress levels. Additionally, these analytical methods often require trained personnel to operate expensive instrumentation. Alternatively, low-cost electrochemical biosensors enable the real-time detection and continuous monitoring of cortisol levels while also providing adequate analytical figures of merit (e.g., sensitivity, selectivity, sensor response times, detection limits, and reproducibility) in a simple design platform. This review discusses the recent developments in electrochemical biosensor design for the detection of cortisol in human biofluids. Special emphasis is given to biosensor recognition elements, including antibodies, molecularly imprinted polymers (MIPs), and aptamers, as critical components of electrochemical biosensors for cortisol detection. Furthermore, the advantages and limiting factors of various electrochemical techniques and sensing in complex biofluid matrices are overviewed. Remarks on the current challenges and future perspectives regarding electrochemical biosensors for stress monitoring are provided, including matrix effects (pH dependence and biological interferences), wearability, and large-scale production.

Application and progress of electrochemical biosensors for the detection of pathogenic viruses

Viruses, with high fatality rates, have posed significant threat to global public health recent decades, necessitating rapid and accurate diagnostic methods to cut off their transmission effectively. To meet with this ongoing demand, electrochemical biosensors have emerged as powerful tools for virus detection due to their high sensitivity, good selectivity, cost-effectiveness, and rapid response. In this review, the fundamental components in the design of electrochemical biosensors, including biological recognition elements, nanomaterials, and signal outputs are introduced and their respective advantages and limitations are discussed. Furthermore, the employment of emerging innovative techniques, such as electrochemical collision technique and artificial intelligence technology and their combination with electrochemical biosensors for virus detection are discussed, which will provide valuable insights into the future prospects of electrochemical biosensors in virus detection.

The Impact of Microelectrode Pattern on the Sensitivity of Tracing Environmental CO2 Deficiency in Cellular Metabolism by a New Design of Electrochemical Biosensor.

Here, two different electrode patterns are described as cyclic voltammetry (CV) biosensors to detect the effect of a hypo CO2 condition (for 6 h) in ambient on cellular secretion. The cells were selected from breast cancer and endothelial standard lines. Changes in CV peaks of the secretions were recorded by the modified pattern whereby increasing the interactive surface with homogenous electric paths was considered by simulation before fabrication. The results of the simulation and experimental procedures showed a meaningful correlation between hypo CO2 samples and the occurrence of CV oxidative peaks at about 0.07 V and reductive peaks at approximately -0.22 V in the modified biosensor in all cell lines, while no apoptosis was found in any of the control and hypo CO2 samples. This observation could not be related to the lack of H+ (alkaline pH induction) in the media solution as such peaks were not observed in the pure cell culture medium but had been maintained in the hypo CO2 ambient. This approach could be used as a cell-free sensor to monitor ambient shocks. This may not induce apoptosis but may be vital in the proliferation and protein expression of the cells, such as the hypo CO2 ambient. The sensor is not disposable in use and showed repeatable responses after rinsing.

Novel electrochemical biosensor for Escherichia coli using gold-coated tungsten wires and antibody functionalized short multiwalled carbon nanotubes

Rapid and easy detection of pathogens, especially bacteria, plays an important role in daily life in the face of increasing environmental pollution. Nanosensors focus on carbon nanotubes, which can bind various molecules to large surfaces and have high electron conductivity. They are widely used in the development of electrochemical biosensors. In this study, a new design of electrochemical biosensors is presented by integrating gold-coated tungsten wires (GC-TW) and acid-functionalized multi-walled carbon nanotubes (MWCNTs) in a two-step coating process. GC-TWs are coated with acid-functionalized short MWCNTs. Fourier transforms infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) results show efficient immobilization of the electrodes. The performance for Escherichia coli (E. coli) K-12 is evaluated based upon the change in current following antibody-antigen interactions. Bioimpedance measurements are performed from 50 Hz to 10 MHz to achieve optimal coverage of impedance changes. The measurements show that the electrode has a detection limit of 0.8 CFU/mL. The response of the electrode saturates when the bacterial concentration is increased to 1.70 x 102 CFU/mL. The biosensor is capable of detecting E. coli between 0.8 and 1.70 × 102 CFU/mL. The data show that this MWCNT-based biosensor can be developed into a highly sensitive device for E. coli.

Effect of symmetry and substituents of cobalt based phthalocyanines in aptasensor design for the electrochemical impedimetric detection of the human epidermal growth factor receptor 2

Surface functionalization in biosensor design remains the major contributor to biosensor efficiency and selectivity. In electrochemical biosensor design, the surface is usually functionalized to achieve immobilization of the biorecognition element as well as electron transfer mediation for signal amplification. An asymmetric cobalt tris-(acetylphenoxy)-mono-phenoxyacrylic acid phthalocyanine (CoMPhAaPc) and a symmetric cobalt tetra-acetylphenoxy phthalocyanine were used for immobilization of HB5 aptamer and signal amplification towards the electrochemical detection of the human epidermal growth factor 2 (HER2). The efficiency of the two phthalocyanines is compared in relation to the substituents and symmetry. The two phthalocyanines were further coupled with sulphur nitrogen graphene quantum dots (SNGQDs) via π-π interactions, for enhanced activity and performance towards HER2 detection. The efficiency of the designed sensors was tested using the detection of HER2 in human serum. The best performance was observed for the SNGQDs(π)CoMPhAaPc/HB5 (amide) with limit of detection value of 0.0027 ng/mL and sensitivity of 72,253 Ωng−1mL. Considering these results, the aptasensors demonstrate great potential for improved monitoring of human epidermal growth factor receptor 2 levels for the management of breast cancer.

Recent Advances in CMOS Electrochemical Biosensor Design for Microbial Monitoring: Review and Design Methodology.

Rapid, high-sensitivity, and real-time characterization of microorganisms plays a significant role in several areas, including clinical diagnosis, human healthcare, early detection of outbreaks, and the protection of living beings. Integrating microbiology and electrical engineering promises the development of low-cost, miniaturized, autonomous, and high-sensitivity sensors to quantify and characterize bacterial strains at various concentrations. Electrochemical-based biosensors are receiving particular attention in microbiological applications among the different biosensing devices. Several approaches have been adopted to design and fabricate cutting-edge, miniaturized, and portable electrochemical biosensors to track and monitor bacterial cultures in real time. These techniques differ in their sensing interface circuits and microelectrode fabrication. The goals of this review are (i) to summarize the current state of CMOS sensing circuit designs in label-free electrochemical biosensors for bacteria monitoring and (ii) to discuss the material and size of the electrodes used in electrochemical biosensors in microbiological applications. In this paper, we reviewed the latest and most advanced CMOS integrated interface circuits that have recently been used in electrochemical biosensors to identify and characterize bacteria species, such as impedance spectroscopy, capacitive, amperometry, and voltammetry, etc. In addition to the interface circuit design, other crucial factors, such as the material and scale of the electrodes, must be considered to increase the sensitivity of electrochemical biosensors. Surveying the literature in this field improves our knowledge about the impact of electrode designs and materials on sensing precision and will help future designers adapt, design, and fabricate appropriate electrode configurations based on their application. Thus, we summarized the conventional microelectrode designs and materials mainly employed in microbial sensors, including interdigitated electrodes (IDEs), microelectrode arrays (MEAs), paper, and carbon-based electrodes, etc.

Overview on the Design of Magnetically Assisted Electrochemical Biosensors.

Electrochemical biosensors generally require the immobilization of recognition elements or capture probes on the electrode surface. This may limit their practical applications due to the complex operation procedure and low repeatability and stability. Magnetically assisted biosensors show remarkable advantages in separation and pre-concentration of targets from complex biological samples. More importantly, magnetically assisted sensing systems show high throughput since the magnetic materials can be produced and preserved on a large scale. In this work, we summarized the design of electrochemical biosensors involving magnetic materials as the platforms for recognition reaction and target conversion. The recognition reactions usually include antigen-antibody, DNA hybridization, and aptamer-target interactions. By conjugating an electroactive probe to biomolecules attached to magnetic materials, the complexes can be accumulated near to an electrode surface with the aid of external magnet field, producing an easily measurable redox current. The redox current can be further enhanced by enzymes, nanomaterials, DNA assemblies, and thermal-cycle or isothermal amplification. In magnetically assisted assays, the magnetic substrates are removed by a magnet after the target conversion, and the signal can be monitored through stimuli-response release of signal reporters, enzymatic production of electroactive species, or target-induced generation of messenger DNA.

Mobile device integrated graphene oxide quantum dots based electrochemical biosensor design for detection of miR-141 as a pancreatic cancer biomarker

Among all cancer forms, pancreatic cancer has one of the highest mortality rates. Early pancreatic cancer detection is crucial at this time. For this purpose, in this study, a simple and sensitive electrochemical sensor was developed for the detection of microRNA (miRNAs-(miR-141)), which is a pancreatic cancer biomarker. Graphene oxide quantum dots (GoQdot) modified and thiolated single-stranded DNA detection probes (thiol-ss-DNA) on Screen Printed Electrode (SPE) interacted with miR-141 and gave significant results on electron transfer. Differential Pulse Voltammetry (DPV) and Cyclic Voltammetry (CV) measurements showed that the binding of ss-DNA to SPE and the concentration-dependent increase of miR-141 decreased electron transfer. The current values obtained for 2.3 and 6.1 nM miR-141 concentrations were calculated, and the detection limit (LOD) was found to be 0.091 pM and the limit of quantitation (LOQ) was calculated as 0.27 pM. Significant results were obtained by connecting to mobile devices with SPE. The resulting sensor system had label-free, fast, and easy application possibilities. This sensor system, obtained with GoQdot, has achieved innovative outputs for the early detection of this type of cancer diseases.

Free-standing vertically aligned tin disulfide nanosheets for ultrasensitive aptasensor design toward Alzheimer’s diagnosis applications

Despite a single drug, Aducanumab, recently approved by the U.S. Food and Drug Administration for Alzheimer’s disease (AD)-modifying treatments, the development of non-invasive, highly sensitive, and early screening devices to halt the disease remains a critical challenge. In this study, an electrochemical biosensor for amyloid-β (42) oligomers (AβOs) detection based on immobilized DNA aptamer onto vertical aligned tin disulfide nanosheets (SnS2 NSs) is developed for the first time. Highly crystalline, uniform, and vertical aligned SnS2 NSs were synthesized via a facile chemical vapor deposition (CVD) process. The sensing platform, comprising of Aβ (42)-specific capture aptamer covalently immobilized onto self-assembled-3-mercaptopropyl-trimethoxysilane (MPTMS)-SnS2 binds specifically toward AβOs. The biosensor can detect the AβOs at wide linear concentration range from 10-4 to 103 ng/mL with a low limit of detection (LOD) of 238.9 fg/mL and 56.9 fg/mL in physiological buffer and human serum (HS), respectively. The developed biosensor was successfully used to detect AβOs in the mice blood serum samples indicating its potential for clinical application in Alzheimer’s biomarker detection. Moreover, the SnS2-aptasensor shows good stability, selectivity, and interference-resistance. The predominant edge-plane active site and energetically preference for vertical SnS2 over its planar structure were unveiled by density-functional theory calculations which emphasize the advantages of applying nanomaterial with vertical orientated configuration into electrocatalytic reaction. The as-designed SnS2-aptasensor could shed light not only on multifunctional electrochemical biosensor design, but also for advancements on future Alzheimer’s diagnosis.

Graphite nanocrystals coated paper-based electrode for detection of SARS-Cov-2 gene using DNA-functionalized Au@carbon dot core–shell nanoparticles

Currently, the development of biosensors is an urgent need due to the rapid spread of SARS-CoV-2 and the limitations of current standard methods for the diagnosis of COVID-19. Hence, many researchers have focused on the design of high-performance biosensors for measuring coronavirus genes. In this study, a voltammetric genosensor was developed for the determination of SARS-CoV-2 RdRP gene based on the format of cDNA probe/Au@CD core–shell NPs/graphite nanocrystals (GNCs)/paper electrode. For the first time, graphite nanocrystals were used in the electrochemical biosensor design. This genosensor was exposed to different concentrations of virus gene and then the hybridization between cDNA probe and RdRP gene was monitored by redox-active toluidine blue (TB). With increasing the RdRP concentration, the reduction peak current of TB enhanced in a linear range of 0.50 pM-12.00 nM according to the regression equation of I (μA) = 7.60 log CRdRP (pM) + 25.78. The repeatability with a RSD of 2.2% clearly exhibited that the response of modified electrode is stable because of the high adhesion of GNC layer on the paper substrate and the high stability of cDNA-Au@CD bioconjugates. The spike-and-recovery studies showed the acceptable recoveries for the sputum samples (>95%).

Nonlinear Analytics for Electrochemical Biosensor Design Using Enzyme Aggregates and Delayed Mass Action

The paper is devoted to the extension of Brown’s model of enzyme kinetics to the case with distributed delays. Firstly, we construct a multi-substrate multi-inhibitor model using discrete and distributed delays. Furthermore, we consider simplified models including one substrate and one inhibitor, for which an experimental study has been performed. The algorithm of parameter identifications was developed which was tested on the experimental data of solution conductivity. Both the model and Kohlrausch’s law parameters are obtained as a result of the optimization procedure. Comparison of plots constructed with the help of the estimated parameters has shown that in such case the model with distributed delays is more chemically adequate in comparison with the discrete one. The methods of generalization of the results to the multi-substrate multi-inhibitor cases are discussed.

The latest trends in the design of electrochemical biosensors for the diagnosis and monitoring of diabetes mellitus.

The overworld health problem, the incurable disease, the global burden on health insurers and society, and above all one of the leading causes of death - all characterize diabetes mellitus, a lifelong chronic disease that affects hundreds of millions of people around the world. The new types of biosensors bring new opportunities in the care of diabetic patients and improve current methods. The practical relevance of the recent findings is expected in medicine in next years. The authors summarized the modern possibilities of biosensing, their pros and cons, and their perspectives for the future. The discussion outcome from the current literature (Tab. 4, Fig. 1, Ref. 63).

In Situ Assembly of Nanomaterials and Molecules for the Signal Enhancement of Electrochemical Biosensors.

The physiochemical properties of nanomaterials have a close relationship with their status in solution. As a result of its better simplicity than that of pre-assembled aggregates, the in situ assembly of nanomaterials has been integrated into the design of electrochemical biosensors for the signal output and amplification. In this review, we highlight the significant progress in the in situ assembly of nanomaterials as the nanolabels for enhancing the performances of electrochemical biosensors. The works are discussed based on the difference in the interactions for the assembly of nanomaterials, including DNA hybridization, metal ion–ligand coordination, metal–thiol and boronate ester interactions, aptamer–target binding, electrostatic attraction, and streptavidin (SA)–biotin conjugate. We further expand the range of the assembly units from nanomaterials to small organic molecules and biomolecules, which endow the signal-amplified strategies with more potential applications.

Nanostructured Titanium Dioxide Surfaces for Electrochemical Biosensing.

TiO2 electrochemical biosensors represent an option for biomolecules recognition associated with diseases, food or environmental contaminants, drug interactions and related topics. The relevance of TiO2 biosensors is due to the high selectivity and sensitivity that can be achieved. The development of electrochemical biosensors based on nanostructured TiO2 surfaces requires knowing the signal extracted from them and its relationship with the properties of the transducer, such as the crystalline phase, the roughness and the morphology of the TiO2 nanostructures. Using relevant literature published in the last decade, an overview of TiO2 based biosensors is here provided. First, the principal fabrication methods of nanostructured TiO2 surfaces are presented and their properties are briefly described. Secondly, the different detection techniques and representative examples of their applications are provided. Finally, the functionalization strategies with biomolecules are discussed. This work could contribute as a reference for the design of electrochemical biosensors based on nanostructured TiO2 surfaces, considering the detection technique and the experimental electrochemical conditions needed for a specific analyte.

Novel Trends in Electrochemical Biosensors for Early Diagnosis of Alzheimer's Disease.

Background Alzheimer's disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder affecting mainly the population over 65 years of age. It is becoming a global health and socioeconomic problem, and the current number of patients reaching 30–50 million people will be three times higher over the next thirty years. Objective Late diagnosis caused by decades of the asymptomatic phase and invasive and cost-demanding diagnosis are problems that make the whole situation worse. Electrochemical biosensors could be the right tool for less invasive and inexpensive early diagnosis helping to reduce spend sources— both money and time. Method This review is a survey of the latest advances in the design of electrochemical biosensors for the early diagnosis of Alzheimer's disease. Biosensors are divided according to target biomarkers. Conclusion Standard laboratory methodology could be improved by analyzing a combination of currently estimated markers along with neurotransmitters and genetic markers from blood samples, which make the test for AD diagnosis available to the wide public.

The Role of Peptides in the Design of Electrochemical Biosensors for Clinical Diagnostics.

Peptides represent a promising class of biorecognition elements that can be coupled to electrochemical transducers. The benefits lie mainly in their stability and selectivity toward a target analyte. Furthermore, they can be synthesized rather easily and modified with specific functional groups, thus making them suitable for the development of novel architectures for biosensing platforms, as well as alternative labelling tools. Peptides have also been proposed as antibiofouling agents. Indeed, biofouling caused by the accumulation of biomolecules on electrode surfaces is one of the major issues and challenges to be addressed in the practical application of electrochemical biosensors. In this review, we summarise trends from the last three years in the design and development of electrochemical biosensors using synthetic peptides. The different roles of peptides in the design of electrochemical biosensors are described. The main procedures of selection and synthesis are discussed. Selected applications in clinical diagnostics are also described.

Conducting Polymers in the Design of Biosensors and Biofuel Cells.

Fast and sensitive determination of biologically active compounds is very important in biomedical diagnostics, the food and beverage industry, and environmental analysis. In this review, the most promising directions in analytical application of conducting polymers (CPs) are outlined. Up to now polyaniline, polypyrrole, polythiophene, and poly(3,4-ethylenedioxythiophene) are the most frequently used CPs in the design of sensors and biosensors; therefore, in this review, main attention is paid to these conducting polymers. The most popular polymerization methods applied for the formation of conducting polymer layers are discussed. The applicability of polypyrrole-based functional layers in the design of electrochemical biosensors and biofuel cells is highlighted. Some signal transduction mechanisms in CP-based sensors and biosensors are discussed. Biocompatibility-related aspects of some conducting polymers are overviewed and some insights into the application of CP-based coatings for the design of implantable sensors and biofuel cells are addressed. New trends and perspectives in the development of sensors based on CPs and their composites with other materials are discussed.

The Abtamer: A Novel Antibody-Aptamer Conjugate for Electrochemical Biosensing Applications

Introduction: We propose an innovated semisynthetic biosensing molecule, the Abtamer, an antibody-aptamer one-to-one complex. An important consideration in the design of electrochemical biosensors is the molecular recognition element (MRE) from which the signal to be transduced is generated. Among MREs utilized for affinity principle based electrochemical biosensors, antibodies are commonly used due to their high sensitivity and selectivity towards specific targets. However, antibodies’ structural rigidity proves limiting in biosensing applications.In contrast, DNA/RNA aptamers are easily-synthesized, versatile biomolecules, which are able to exhibit a high affinity and sensitivity towards their selected target [1]. Owing to their structure, aptamers are inherently flexible which allows for pronounced conformational changes upon binding. Furthermore, their small size allows for the immobilization of a larger density of molecules on the sensor surface, aiding in their sensitivity [2]. However, these same characteristics put aptamers at a disadvantage in terms of their selectivity towards targets. Without various post-synthesis modifications, DNA/RNA oligonucleotides can exhibit nonspecific electrostatic interactions with other analytes in solution.To this end, we propose a new biosensing molecule for biomedical sensor applications based on antibody-aptamer conjugates, designated as “Abtamers,” which includes advantages of both antibodies and aptamers; e.g. high sensitivity, selectivity with molecular dynamics upon target binding, facilitating signals for sensing. We propose to use insulin as a model target for an electrochemical sensor employing this novel biorecognition element. The electrochemical detection of insulin levels in persons with diabetes would provide another useful metric in diabetes technology, as insulin measurements are typically done via ELISA. Methods: The antibody-aptamer conjugate constructed utilized an insulin single chain variable fragment (scFv) and an insulin aptamer. To circumvent the non-optimal binding of polypeptides to oligonucleotides, we utilized the SpyCatcher/SpyTag complex as the bioconjugation system to couple the scFv to the aptamer in a one-to-one manner [3-4]. We created a recombinant fusion molecule of the insulin scFv and SpyCatcher, and created a SpyTag-insulin aptamer fusion molecule. The combination of these two fusion molecules results in an insulin antibody-insulin aptamer conjugate. We aim to employ this new MRE to detect insulin via square wave voltammetry. Results and Discussion: Through the binding of the two fusion molecules, we have created an irreversibly bound conjugate, conserving the structures of both the antibody and aptamer. The modification of a redox probe to the insulin aptamer domain in the Abtamer conjugate allows for a simple and facile method to create an electroactive biomolecule which can be immobilized to an electrode surface. We expect the binding affinity of this molecule to be higher towards specified targets due to both an antibody and aptamer binding event. Furthermore, the flexibility of the aptamer allows for conformational changes upon binding which can be exploited in electrochemical sensing applications. The developed insulin antibody-insulin aptamer conjugate can be applied as a biorecognition element for an electrochemical sensing platform, thereby realizing a unique biosensing principle, the “Abta-sensor”

MXenes-Based Bioanalytical Sensors: Design, Characterization, and Applications.

MXenes are recently developed 2D layered nanomaterials that provide unique capabilities for bioanalytical applications. These include high metallic conductivity, large surface area, hydrophilicity, high ion transport properties, low diffusion barrier, biocompatibility, and ease of surface functionalization. MXenes are composed of transition metal carbides, nitrides, or carbonitrides and have a general formula Mn+1Xn, where M is an early transition metal while X is carbon and/or nitrogen. Due to their unique features, MXenes have attracted significant attention in fields such as clean energy production, electronics, fuel cells, supercapacitors, and catalysis. Their composition and layered structure make MXenes attractive for biosensing applications. The high conductivity allows these materials to be used in the design of electrochemical biosensors and the multilayered configuration makes them an efficient immobilization matrix for the retention of activity of the immobilized biomolecules. These properties are applicable to many biosensing systems and applications. This review describes the progress made on the use and application of MXenes in the development of electrochemical and optical biosensors and highlights future needs and opportunities in this field. In particular, opportunities for developing wearable sensors and systems with integrated biomolecule recognition are highlighted.

Optimization Design of Electrochemical Biosensors Based on Gold Nanomaterials

At present, chemical biosensors still have poor reproducibility and stability due to that the density of nanomaterials particles is not ideal. Therefore, an optimal design method of electrochemical biosensor based on gold nanomaterials is proposed. Two types of sensors, namely DNA biosensor and immune biosensor, were designed in this work. A DNA biosensor with gold nanorod nanocomposite modified electrode was prepared, and its electrical activity was measured by Methylene blue. In contrast, an electrochemical immune sensor with gold nanorod-modified electrode was prepared and used for detection of alpha fetoprotein. The experimental results show that the designed DNA biosensor and electrochemical immune sensor have the advantages of simple preparation, high sensitivity, good selectivity and good stability.