Recent Advances in Biosensors for Diagnosis of Autoimmune Diseases.

Over the last decade, autoimmune diseases (ADs) have undergone a significant increase because of genetic and/or environmental factors; therefore, their simple and fast diagnosis is of high importance. The conventional diagnostic techniques for ADs require tedious sample preparation, sophisticated instruments, a dedicated laboratory, and qualified personnel. For these reasons, biosensors could represent a useful alternative to these methods. Biosensors are considered to be promising tools that can be used in clinical analysis for an early diagnosis due to their high sensitivity, simplicity, low cost, possible miniaturization (POCT), and potential ability for real-time analysis. In this review, recently developed biosensors for the detection of autoimmune disease biomarkers are discussed. In the first part, we focus on the main AD biomarkers and the current methods of their detection. Then, we discuss the principles and different types of biosensors. Finally, we overview the characteristics of biosensors based on different bioreceptors reported in the literature.

Integration of Hollow Microneedle Arrays with Jellyfish-Shaped Electrochemical Sensor for the Detection of Biomarkers in Interstitial Fluid.

This study integrates hollow microneedle arrays (HMNA) with a novel jellyfish-shaped electrochemical sensor for the detection of key biomarkers, including uric acid (UA), glucose, and pH, in artificial interstitial fluid. The jellyfish-shaped sensor displayed linear responses in detecting UA and glucose via differential pulse voltammetry (DPV) and chronoamperometry, respectively. Notably, the open circuit potential (OCP) of the system showed a linear variation with pH changes, validating its pH-sensing capability. The sensor system demonstrates exceptional electrochemical responsiveness within the physiological concentration ranges of these biomarkers in simulated epidermis sensing applications. The detection linear ranges of UA, glucose, and pH were 0~0.8 mM, 0~7 mM, and 4.0~8.0, respectively. These findings highlight the potential of the HMNA-integrated jellyfish-shaped sensors in real-world epidermal applications for comprehensive disease diagnosis and health monitoring.

Design of a label-free aptasensor for electrochemical determination of hemoglobin: investigation of the peroxidase-like activity of hemoglobin for the sensing of different substrates.

The unbalanced hemoglobin level in biological fluids can cause several diseases; hence it can be used as a biomarker for diagnosis. We aim, in the present study, to construct a label-free electrochemical aptasensor for the quantification of hemoglobin. For that, a conjugate of L-cysteine and gold nanoparticles was used for the aptamer immobilization on screen printed carbon electrodes. Using square wave voltammetry, the calibration plot was obtained and it was linear in the range of 50 ng ml-1 to 36 000 ng ml-1 while the detection limit was 1.2 ng ml-1. After the binding of Hb on the modified screen-printed carbon electrode surface, the peroxidase-like activity of the bound hemoglobin was explored in the quantification of different substrates. Hydrogen peroxide and nitrite were chosen as model analytes. Amperometric measurements showed wide linear ranges: 0.2 µM-7.7 mM and 3.6 nM-1.3 mM for H2O2 and nitrite, respectively, with detection limits of 0.044 µM and 0.55 nM. In the proposed strategy, the aptamer provides excellent orientation and a biocompatible environment for hemoglobin whose catalytic activity plays a key role in H2O2 and nitrite analysis.

Fabrication of polydopamine decorated carbon cloth as support material to anchor CeO2 nanoparticles for electrochemical detection of ethanol.

A flexible CeO2 nanostructured polydopamine-modified carbon cloth (CeO2/PDA/CC) interface was fabricated via electrodeposition for ethanol detection. The fabrication method involved two consecutive electrochemical steps in which dopamine was firstly electrodeposited on carbon fibers, followed by the electrochemical growth of CeO2 nanoparticles. The CeO2/PDA-based electroactive interface exerts an impressive electrochemical performance on the flexible sensor due to strong synergistic effect of the PDA functionalization with more active sites. Moreover, catalytic activity of CeO2 nanostructures anchored on highly conductive CC incorporate superior electrocatalytic performance of the fabricated interface. The designed electrochemical sensor showed a wide response to ethanol in the linear range 1 to 25 mM with a detection limit of 0.22 mM. The CeO2/PDA/CC flexible sensor showed good anti-interference ability and excellent repeatability and reproducibility (RSD = 1.67%). The fabricated interface performed well in saliva samples with satisfactory recoveries, corroborating the viability of CeO2/PDA/CC integrated interface for practical implementation.

Development of a label-free electrochemical aptasensor based on diazonium electrodeposition: Application to cadmium detection in water.

In this study we have developed a new aptasensor for cadmium (Cd2+) detection in water. Gold electrode surface has been chemically modified by electrochemical reduction of diazonium salt (CMA) with carboxylic acid outward from the surface. This was used for amino-modified cadmium aptamer immobilization through carbodiimide reaction. Chemical surface modification was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). This latter was also used for Cd2+ detection. The aptasensor has exhibited a good linear relationship between the logarithm of the Cd2+ concentration and the impedance changes in the range from 10-3 to 10-9 M with a correlation R2 of 0.9954. A high sensitivity was obtained with a low limit of detection (LOD) of 2.75*10-10 M. Moreover, the developed aptasensor showed a high selectivity towards Cd2+ when compared to other interferences such as Hg2+, Pb2+ and Zn2+. The developed aptasensor presents a simple and sensitive approach for Cd2+detection in aqueous solutions with application for trace Cd2+ detection in spring water samples.

An Overview of Optical and Electrochemical Sensors and Biosensors for Analysis of Antioxidants in Food during the Last 5 Years.

Antioxidants are a group of healthy substances which are useful to human health because of their antihistaminic, anticancer, anti-inflammatory activity and inhibitory effect on the formation and the actions of reactive oxygen species. Generally, they are phenolic complexes present in plant-derived foods. Due to the valuable nutritional role of these mixtures, analysis and determining their amount in food is of particular importance. In recent years, many attempts have been made to supply uncomplicated, rapid, economical and user-friendly analytical approaches for the on-site detection and antioxidant capacity (AOC) determination of food antioxidants. In this regards, sensors and biosensors are regarded as favorable tools for antioxidant analysis because of their special features like high sensitivity, rapid detection time, ease of use, and ease of miniaturization. In this review, current five-year progresses in different types of optical and electrochemical sensors/biosensors for the analysis of antioxidants in foods are discussed and evaluated well. Moreover, advantages, limitations, and the potential for practical applications of each type of sensors/biosensors have been discussed. This review aims to prove how sensors/biosensors represent reliable alternatives to conventional methods for antioxidant analysis.

Analysis of Recent Bio-/Nanotechnologies for Coronavirus Diagnosis and Therapy.

Despite barrier measures and physical distancing tailored by the populations worldwide, coronavirus continues to spread causing severe health and social-economic problems. Therefore, researchers are focusing on developing efficient detection and therapeutic platforms for SARS-CoV2. In this context, various biotechnologies, based on novel molecules targeting the virus with high specificity and affinity, have been described. In parallel, new approaches exploring nanotechnology have been proposed for enhancing treatments and diagnosis. We discuss in the first part of this review paper, the different biosensing and rapid tests based on antibodies, nucleic acids and peptide probes described since the beginning of the pandemic. Furthermore, given their numerous advantages, the contribution of nanotechnologies is also highlighted.

Fabrication of AuNPs/MWCNTS/Chitosan Nanocomposite for the Electrochemical Aptasensing of Cadmium in Water.

Cadmium (Cd2+) is one of the most toxic heavy metals causing serious health problems; thus, designing accurate analytical methods for monitoring such pollutants is highly urgent. Herein, we report a label-free electrochemical aptasensor for cadmium detection in water. For this, a nanocomposite combining the advantages of gold nanoparticles (AuNPs), carbon nanotubes (CNTs) and chitosan (Cs) was constructed and used as immobilization support for the cadmium aptamer. First, the surface of a glassy carbon electrode (GCE) was modified with CNTs-CS. Then, AuNPs were deposited on CNTs-CS/GCE using chrono-amperometry. Finally, the immobilization of the amino-modified Cd-aptamer was achieved via glutaraldehyde cross-linking. The different synthesis steps of the AuNPs/CNTs/CS nano assembly were characterized by cyclic voltammetry (CV). Electrochemical impedance spectroscopy (EIS) was employed for cadmium determination. The proposed biosensor exhibited excellent performances for cadmium detection at a low applied potential (-0.5 V) with a high sensitivity (1.2 KΩ·M-1), a detection limit of 0.02 pM and a wide linear range (10-13-10-4 M). Moreover, the aptasensor showed a good selectivity against the interfering ions: Pb2+; Hg2+ and Zn2+. Our electrochemical biosensor provides a simple and sensitive approach for Cd2+ detection in aqueous solutions, with promising applications in the monitoring of trace amounts of heavy metals in real samples.

Wearable Biosensors: An Alternative and Practical Approach in Healthcare and Disease Monitoring.

With the increasing prevalence of growing population, aging and chronic diseases continuously rising healthcare costs, the healthcare system is undergoing a vital transformation from the traditional hospital-centered system to an individual-centered system. Since the 20th century, wearable sensors are becoming widespread in healthcare and biomedical monitoring systems, empowering continuous measurement of critical biomarkers for monitoring of the diseased condition and health, medical diagnostics and evaluation in biological fluids like saliva, blood, and sweat. Over the past few decades, the developments have been focused on electrochemical and optical biosensors, along with advances with the non-invasive monitoring of biomarkers, bacteria and hormones, etc. Wearable devices have evolved gradually with a mix of multiplexed biosensing, microfluidic sampling and transport systems integrated with flexible materials and body attachments for improved wearability and simplicity. These wearables hold promise and are capable of a higher understanding of the correlations between analyte concentrations within the blood or non-invasive biofluids and feedback to the patient, which is significantly important in timely diagnosis, treatment, and control of medical conditions. However, cohort validation studies and performance evaluation of wearable biosensors are needed to underpin their clinical acceptance. In the present review, we discuss the importance, features, types of wearables, challenges and applications of wearable devices for biological fluids for the prevention of diseased conditions and real-time monitoring of human health. Herein, we summarize the various wearable devices that are developed for healthcare monitoring and their future potential has been discussed in detail.

Highly sensitive label-free in vitro detection of aflatoxin B1 in an aptamer assay using optical planar waveguide operating as a polarization interferometer.

This work reports on further development of an optical biosensor for the in vitro detection of mycotoxins (in particular, aflatoxin B1) using a highly sensitive planar waveguide transducer in combination with a highly specific aptamer bioreceptor. This sensor is built on a SiO2-Si3N4-SiO2 optical planar waveguide (OPW) operating as a polarization interferometer (PI), which detects a phase shift between p- and s-components of polarized light propagating through the waveguide caused by the molecular adsorption. The refractive index sensitivity (RIS) of the recently upgraded PI experimental setup has been improved and reached values of around 9600 rad per refractive index unity (RIU), the highest RIS values reported, which enables the detection of low molecular weight analytes such as mycotoxins in very low concentrations. The biosensing tests yielded remarkable results for the detection of aflatoxin B1 in a wide range of concentrations from 1 pg/mL to 1 µg/mL in direct assay with specific DNA-based aptamers. Graphical abstract Optical planar waveguide polarization interferometry biosensor for detection of aflatoxin B1 using specific aptamer.

Ultrasensitive ciprofloxacin assay based on the use of a fluorescently labeled aptamer and a nanocomposite prepared from carbon nanotubes and MoSe2.

A nanocomposite was prepared from carbon nanotubes and MoSe2 (CNT-MoSe2). This nanomaterial quenches the fluorescence of fluorescein-labeled aptamers. When ciprofloxacin (CIP) binds to the aptamer, an aptamer/G-quadruplex complex will be formed and the interaction between labeled aptamer and CNT-MoSe2 nanostructures is weakened. This leads to significant fluorescence recovery. Under optimized experimental conditions, the limit of detection is 0.63 ng mL-1 with a good linearity in the range from 0.63 to 80 ng mL-1. The assay was applied to the determination of CIP in spiked milk, and the recoveries range between 94.3 and 97.0% (n = 3). Conceivably, the method is a generic approach that can be extended to the determination of other analyte for which adequate aptamers are available. Graphical abstract Schematic presentation of CNT-MoSe2 quenching based aptamer assay for the detection of ciprofloxacin. The assay exhibits good selectivity, stability and reproducibility, and low limit of detection.

Polymer scaffold layers of screen-printed electrodes for homogeneous deposition of silver nanoparticles: application to the amperometric detection of hydrogen peroxide.

A method is described for electrochemical oxidation of polymers on the surface of screen-printed electrodes (SPCE). These act as scaffold layers for homogeneous deposition of silver nanoparticles (AgNPs). Hexamethylenediamine (HMDA) and poly(ethylene glycol) were immobilized on the SPCE surface via electrochemical oxidation. AgNPs were then electrodeposited on the scaffolds on the SPCE. This type of different carbon chain containing materials like PEG and HMDA act as big tunnels for electron mobility and are useful for the homogenous deposition of AgNPs on the SPCE surface without agglomeration. The resulting sensor was applied to the determination of hydrogen peroxide (H2O2) as a model analyte. It is found to display favorable catalytic and conductive properties towards the reduction of H2O2. Cyclic voltammetry and amperometry revealed that the modified electrode performs better than other modified SPCEs. Best operated at a potential of around -0.61 V (vs Ag|AgCl), the amperometric response is linear in the 10-180 µM H2O2 concentration range and the detection limit is 1.5 µM. The sensor is stable and reproducible. The resultant sensor was appplied to toothpaste analysis, and good recovery values were gained. Graphical abstractSchematic representation of electropolymerization of poly(ethylene glycol) and hexamethylenediamine scaffold layers on screen-printed electrodes for homogeneous electrodeposition of silver nanoparticles. This electrode was applied for the amperometric determination of hydrogen peroxide.

Development of an Impedimetric Aptasensor for Label Free Detection of Patulin in Apple Juice.

In the present work, an aptasensing platform was developed for the detection of a carcinogenic mycotoxin termed patulin (PAT) using a label-free approach. The detection was mainly based on a specific interaction of an aptamer immobilized on carbon-based electrode. A long linear spacer of carboxy-amine polyethylene glycol chain (PEG) was chemically grafted on screen-printed carbon electrodes (SPCEs) via diazonium salt in the aptasensor design. The NH2-modified aptamer was then attached covalently to carboxylic acid groups of previously immobilized bifunctional PEG to build a diblock macromolecule. The immobilized diblocked molecules resulted in the formation of long tunnels on a carbon interface, while the aptamer was assumed as the gate of these tunnels. Upon target analyte binding, the gates were assumed to be closed due to conformational changes in the structure of the aptamer, increasing the resistance to the charge transfer. This increase in resistance was measured by electrochemical impedance spectroscopy, the main analytical technique for the quantitative detection of PAT. Encouragingly, a good linear range between 1 and 25 ng was obtained. The limit of detection and limit of quantification was 2.8 ng L-1 and 4.0 ng L-1, respectively. Selectivity of the aptasensor was confirmed with mycotoxins commonly occurring in food. The developed apta-assay was also applied to a real sample, i.e., fresh apple juice spiked with PAT, and toxin recovery up to 99% was observed. The results obtained validated the suitability and selectivity of the developed apta-assay for the identification and quantification of PAT in real food samples.

Carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection.

In this work, we have developed for the first time a carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection using methylene blue (MB). The developed immunosensor is highly sensitive for detection of biomarker Mucin1 (MUC1) in human serum samples. Development of this disposable electrochemical immunosensor was premeditated by applying specific monoclonal antibodies against MUC1. In this method, we explored highly conductive surface of carboxylic group (-COOH-) rich graphene oxide (GO) on screen-printed carbon electrodes (SPCE). This modified GO-COOH-SPCE was employed for the detection of MUC1 protein based on the reaction with methylene blue (MB) redox probe using differential pulse voltammetry (DPV) technique. Developed immunosensor exhibited good detection range for MUC1 with excellent linearity (0.1 U/mL- 2 U/mL), with a limit of detection of 0.04 U/mL. Upon potential application of developed biosensor, good recoveries were recorded in the range of 96-96.67% with % R.S.D 4.2. Analytical performance of the developed immunosensor assures the applicability in clinical diagnostic applications.

Detection of Antibiotics and Evaluation of Antibacterial Activity with Screen-Printed Electrodes.

This review provides a brief overview of the fabrication and properties of screen-printed electrodes and details the different opportunities to apply them for the detection of antibiotics, detection of bacteria and antibiotic susceptibility. Among the alternative approaches to costly chromatographic or ELISA methods for antibiotics detection and to lengthy culture methods for bacteria detection, electrochemical biosensors based on screen-printed electrodes present some distinctive advantages. Chemical and (bio)sensors for the detection of antibiotics and assays coupling detection with screen-printed electrodes with immunomagnetic separation are described. With regards to detection of bacteria, the emphasis is placed on applications targeting viable bacterial cells. While the electrochemical sensors and biosensors face many challenges before replacing standard analysis methods, the potential of screen-printed electrodes is increasingly exploited and more applications are anticipated to advance towards commercial analytical tools.

Photoinduced discharge of electrons stored in a TiO2-MWCNT composite to an analyte: application to the fluorometric determination of hydrogen peroxide, glucose and aflatoxin B1.

The authors describe an analytical detection scheme based on the use of multiwalled carbon nanotubes (MWCNTs) that accept and store electrons upon contact with photo-irradiated TiO2 nanoparticles (TiO2-NPs). The Fermi level equilibration with photo-irradiated TiO2-NPs has a storage value of 0.35 mM of electrons per 120 mg·L-1 of MWCNTs. The stored electrons can be discharged on demand upon addition of electron acceptors to the TiO2-NP/MWCNT composite. These findings are applied to detect the quencher hydrogen peroxide. H2O2 also is produced on enzymatic action of glucose oxidase on glucose, and this enables glucose also to be quantified by using the TiO2-NP/MWCNT fluorescent nanoprobe. The wide scope of the method also is demonstrated by an assay for aflatoxin B1 that is making use of an FAM-labeled aptamer where the FAM fluorophore on the aptamer quenches the emission of the nanoprobe. The following analytical linear ranges and limits of detection are found: H2O2: 0.1-100 µM and 15 nM; glucose: 5-200 µM and 0.5 µM; aflatoxin: 0.1-40 ng·mL-1 and 0.02 ng·mL-1. The method was applied to the determination of glucose in human serum. Graphical abstract The assays demonstrated in (b) and (c) are based on the fluorescence quenching ability of MWCNTs-TiO2. In the presence of the target (analyte), the fluorescence is restored and the target concentration is determined from the percentage of fluorescence recovery.

An Overview on Recent Progress in Electrochemical Biosensors for Antimicrobial Drug Residues in Animal-Derived Food.

Anti-microbial drugs are widely employed for the treatment and cure of diseases in animals, promotion of animal growth, and feed efficiency. However, the scientific literature has indicated the possible presence of antimicrobial drug residues in animal-derived food, making it one of the key public concerns for food safety. Therefore, it is highly desirable to design fast and accurate methodologies to monitor antimicrobial drug residues in animal-derived food. Legislation is in place in many countries to ensure antimicrobial drug residue quantities are less than the maximum residue limits (MRL) defined on the basis of food safety. In this context, the recent years have witnessed a special interest in the field of electrochemical biosensors for food safety, based on their unique analytical features. This review article is focused on the recent progress in the domain of electrochemical biosensors to monitor antimicrobial drug residues in animal-derived food.

Tetramethyl-6-carboxyrhodamine quenching-based aptasensing platform for aflatoxin B1: Analytical performance comparison of two aptamers.

In this study, a simple TAMRA (tetramethyl-6-carboxyrhodamine) quenching-based aptasensing platform was designed for the detection of aflatoxin B1 (AFB1). Here, we compared the analytical performance of two aptamer sequences: seqA and seqB. The AFB1 detection was based on the interactions of FAM (carboxyfluorescein)-labeled aptamer with TAMRA-labeled DNA complementary strand in the presence and absence of target analyte. Under optimized experimental conditions, TAMRA-labeled strand quenched the fluorescence response of FAM-labeled aptamer due to the noncovalent interaction between the two DNA strands. The binding of AFB1 induced the complex formation and weakened the interaction between FAM-labeled aptamer and TAMRA-labeled complementary strand, resulting in the fluorescence recovery. By using this principle concept, an assay was constructed for the detection of AFB1. The method exhibited good sensitivity, good selectivity with a limit of detection of 0.2 ng ml(-1), and a wide linear range from 0.25 to 32 ng ml(-1). For real sample application, the aptasensors were tested in beer and wine samples, with good recovery rates obtained for AFB1 detection.

Ligand Assisted Stabilization of Fluorescence Nanoparticles; an Insight on the Fluorescence Characteristics, Dispersion Stability and DNA Loading Efficiency of Nanoparticles.

This work reports on the ligand assisted stabilization of Fluospheres® carboxylate modified nanoparticles (FCMNPs), and subsequently investigation on the DNA loading capacity and fluorescence response of the modified particles. The designed fluorescence bioconjugate was characterized with enhanced fluorescence characteristics, good stability and large surface area with high DNA loading efficiency. For comparison purpose, bovine serum albumin (BSA) and polyethylene glycol (PEG) with three different length strands were used as cross linkers to modify the particles, and their DNA loading capacity and fluorescence characteristics were investigated. By comparing the performance of the particles, we found that the most improved fluorescence characteristics, enhanced DNA loading and high dispersion stability were obtained, when employing PEG of long spacer arm length. The designed fluorescence bioconjugate was observed to maintain all its characteristics under varying pH over an extended period of time. These types of bioconjugates are in great demand for fluorescence imaging and in vivo fluorescence biomedical application, especially when most of the as synthesized fluorescence particles cannot withstand to varying in vivo physiological conditions with decreases in fluorescence response and DNA loading efficiency.

Electrochemical Affinity Biosensors Based on Disposable Screen-Printed Electrodes for Detection of Food Allergens.

Food allergens are proteins from nuts and tree nuts, fish, shellfish, wheat, soy, eggs or milk which trigger severe adverse reactions in the human body, involving IgE-type antibodies. Sensitive detection of allergens in a large variety of food matrices has become increasingly important considering the emergence of functional foods and new food manufacturing technologies. For example, proteins such as casein from milk or lysozyme and ovalbumin from eggs are sometimes used as fining agents in the wine industry. Nonetheless, allergen detection in processed foods is a challenging endeavor, as allergen proteins are degraded during food processing steps involving heating or fermentation. Detection of food allergens was primarily achieved via Enzyme-Linked Immuno Assay (ELISA) or by chromatographic methods. With the advent of biosensors, electrochemical affinity-based biosensors such as those incorporating antibodies and aptamers as biorecognition elements were also reported in the literature. In this review paper, we highlight the success achieved in the design of electrochemical affinity biosensors based on disposable screen-printed electrodes towards detection of protein allergens. We will discuss the analytical figures of merit for various disposable screen-printed affinity sensors in relation to methodologies employed for immobilization of bioreceptors on transducer surface.