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.

Recent Progresses in Optical Biosensors for Interleukin 6 Detection.

Interleukin 6 (IL-6) is pleiotropic cytokine with pathological pro-inflammatory effects in various acute, chronic and infectious diseases. It is involved in a variety of biological processes including immune regulation, hematopoiesis, tissue repair, inflammation, oncogenesis, metabolic control, and sleep. Due to its important role as a biomarker of many types of diseases, its detection in small amounts and with high selectivity is of particular importance in medical and biological fields. Laboratory methods including enzyme-linked immunoassays (ELISAs) and chemiluminescent immunoassays (CLIAs) are the most common conventional methods for IL-6 detection. However, these techniques suffer from the complexity of the method, the expensiveness, and the time-consuming process of obtaining the results. In recent years, too many attempts have been conducted to provide simple, rapid, economical, and user-friendly analytical approaches to monitor IL-6. In this regard, biosensors are considered desirable tools for IL-6 detection because of their special features such as high sensitivity, rapid detection time, ease of use, and ease of miniaturization. In this review, current progresses in different types of optical biosensors as the most favorable types of biosensors for the detection of IL-6 are discussed, evaluated, and compared.

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.

Recent Trends in Biosensing and Diagnostic Methods for Novel Cancer Biomarkers.

Cancer is one of the major public health issues in the world. It has become the second leading cause of death, with approximately 75% of cancer deaths transpiring in low- or middle-income countries. It causes a heavy global economic cost estimated at more than a trillion dollars per year. The most common cancers are breast, colon, rectum, prostate, and lung cancers. Many of these cancers can be treated effectively and cured if detected at the primary stage. Nowadays, around 50% of cancers are detected at late stages, leading to serious health complications and death. Early diagnosis of cancer diseases substantially increases the efficient treatment and high chances of survival. Biosensors are one of the potential screening methodologies useful in the early screening of cancer biomarkers. This review summarizes the recent findings about novel cancer biomarkers and their advantages over traditional biomarkers, and novel biosensing and diagnostic methods for them; thus, this review may be helpful in the early recognition and monitoring of treatment response of various human cancers.

A Review on Aptamers Selection and Application in Heart Diseases Diagnosis.

Biomarkers detection and quantification in biological fluids play a key role in the screening, diagnosing and treating several diseases. Recently, a large number of aptamers have been selected and applied for the sensing of different biomarkers. Combined with different transducers, aptamers provide simple and rapid tools that allow highly sensitive and selective detection. Cardiology requires an accurate assessment of cardiac biomarkers for a complete diagnosis of cardiovascular diseases. The analysis is generally performed by immunoassays using antibodies as biorecognition elements. This review paper focuses on using aptamers as a promising alternative for antibodies in cardiac biomarkers biosensing. First, the different aptamers specific to the most important cardiac biomarkers are Troponin I, the peptide of B-type natriuretic peptide and myoglobin. Then, in the second part, we overview the electrochemical aptasensors principle and characteristics reported in the literature in the last five years.

Recent Advances in Electrochemical Aptasensors for Detection of Biomarkers.

The early diagnosis of diseases is of great importance for the effective treatment of patients. Biomarkers are one of the most promising medical approaches in the diagnosis of diseases and their progress and facilitate reaching this goal. Among the many methods developed in the detection of biomarkers, aptamer-based biosensors (aptasensors) have shown great promise. Aptamers are promising diagnostic molecules with high sensitivity and selectivity, low-cost synthesis, easy modification, low toxicity, and high stability. Electrochemical aptasensors with high sensitivity and accuracy have attracted considerable attention in the field of biomarker detection. In this review, we will summarize recent advances in biomarker detection using electrochemical aptasensors. The principles of detection, sensitivity, selectivity, and other important factors in aptasensor performance are investigated. Finally, advantages and challenges of the developed aptasensors are discussed.

Screen-printed electrochemical immunosensor based on a novel nanobody for analyzing aflatoxin M1 in milk.

This study aimed to devise a nontoxic electrochemical immunosensor to quantitatively determine aflatoxin M1 by chronoamperometry with novel anti-idiotypic nanobody-functionalized screen-printed carbon electrodes (SPCEs). Anti-idiotype nanobodies (AIdnb) were developed to replace the high toxic chemically synthesized antigen. AIdnb was immobilized on the surface of SPCE via covalent coupling as capture reagent. The functionalized SPCEs were followed by characterization using electrochemical impedance spectroscopy, fourier-transform infrared spectroscopy, transmission electron microscopy mapping, and atomic force microscopy. After optimizing experimental parameters, the assembled immunosensor exhibited a good linearity range of 0.25-5.0 ng/mL, with the limit of detection of 0.09 ng/mL. The immunosensor showed a satisfactory selectivity to AFM1, without interference from analogs, including zearalenone, ochratoxin, and fumonisin B1. For practical application, the developed immunosensor was validated using real spiked samples with the recovery range 82.0%-108.0% and relative standard deviation (RSD) 10.1%-13.0%, indicating that it could be used in milk samples.

A Sensitive Aptasensor Using Biotin-Streptavidin System for Patulin Detection in Apple Juice.

Patulin contamination in fruits, vegetables, and their products is considered a serious health risk factor for food safety and human health. Thus, a rapid, simple detection method for patulin is becoming important, which could provide a tool for routine screening and food surveys. The objective of this study was to develop a sensitive aptamer-based lateral flow assay (FLA) using Streptavidin functionalized gold nanoparticles for sensitive patulin detection. An excellent dynamic range for patulin detection was obtained (2.7~139.8 ng/mL in the buffer and 7.07~359.5 ng/mL in the sample) with no affinity for other mycotoxins such as zearalenone (ZEN), ochratoxin A (OTA), aflatoxin B1 (AFB1), citrinin or tenuazonic acid (TEA). The limit of detection was 0.19 ng/mL in the buffer and 0.36 ng/mL in the real sample. The recoveries were 83.3% to 107.1%, with a satisfactory RSD value from 6.5% to 7.5%. Hence the established LFA could be used as a rapid, simple, on-site screening tool for PAT determination in apple juice.

Aptamer-Based Lateral Flow Assays: Current Trends in Clinical Diagnostic Rapid Tests.

The lateral flow assay (LFA) is an extensively used paper-based platform for the rapid and on-site detection of different analytes. The method is user-friendly with no need for sophisticated operation and only includes adding sample. Generally, antibodies are employed as the biorecognition elements in the LFA. However, antibodies possess several disadvantages including poor stability, high batch-to-batch variation, long development time, high price and need for ethical approval and cold chain. Because of these limitations, aptamers screened by an in vitro process can be a good alternative to antibodies as biorecognition molecules in the LFA. In recent years, aptamer-based LFAs have been investigated for the detection of different analytes in point-of-care diagnostics. In this review, we summarize the applications of aptamer technology in LFAs in clinical diagnostic rapid tests for the detection of biomarkers, microbial analytes, hormones and antibiotics. Performance, advantages and drawbacks of the developed assays are also discussed.

Optical Biosensors for Diagnostics of Infectious Viral Disease: A Recent Update.

The design and development of biosensors, analytical devices used to detect various analytes in different matrices, has emerged. Biosensors indicate a biorecognition element with a physicochemical analyzer or detector, i.e., a transducer. In the present scenario, various types of biosensors have been deployed in healthcare and clinical research, for instance, biosensors for blood glucose monitoring. Pathogenic microbes are contributing mediators of numerous infectious diseases that are becoming extremely serious worldwide. The recent outbreak of COVID-19 is one of the most recent examples of such communal and deadly diseases. In efforts to work towards the efficacious treatment of pathogenic viral contagions, a fast and precise detection method is of the utmost importance in biomedical and healthcare sectors for early diagnostics and timely countermeasures. Among various available sensor systems, optical biosensors offer easy-to-use, fast, portable, handy, multiplexed, direct, real-time, and inexpensive diagnosis with the added advantages of specificity and sensitivity. Many progressive concepts and extremely multidisciplinary approaches, including microelectronics, microelectromechanical systems (MEMSs), nanotechnologies, molecular biology, and biotechnology with chemistry, are used to operate optical biosensors. A portable and handheld optical biosensing device would provide fast and reliable results for the identification and quantitation of pathogenic virus particles in each sample. In the modern day, the integration of intelligent nanomaterials in the developed devices provides much more sensitive and highly advanced sensors that may produce the results in no time and eventually help clinicians and doctors enormously. This review accentuates the existing challenges engaged in converting laboratory research to real-world device applications and optical diagnostics methods for virus infections. The review's background and progress are expected to be insightful to the researchers in the sensor field and facilitate the design and fabrication of optical sensors for life-threatening viruses with broader applicability to any desired pathogens.

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.

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.

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.

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.

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.

Advances in Colorimetric Strategies for Mycotoxins Detection: Toward Rapid Industrial Monitoring.

Mycotoxins contamination is a global public health concern. Therefore, highly sensitive and selective techniques are needed for their on-site monitoring. Several approaches are conceivable for mycotoxins analysis, among which colorimetric methods are the most attractive for commercialization purposes thanks to their visual read-out, easy operation, cost-effectiveness, and rapid response. This review covers the latest achievements in the last five years for the development of colorimetric methods specific to mycotoxins analysis, with a particular emphasis on their potential for large-scale applications in food industries. Gathering all types of (bio)receptors, main colorimetric methods are critically discussed, including enzyme-linked assays, lateral flow-assays, microfluidic devices, and homogenous in-solution strategies. This special focus on colorimetry as a versatile transduction method for mycotoxins analysis is comprehensively reviewed for the first time.

Investigation of a Truncated Aptamer for Ofloxacin Detection Using a Rapid FRET-Based Apta-Assay.

In this work, we describe the use of a new truncated aptamer for the determination of ofloxacin (OFL), being a principal quinolone commonly used in both human and animal healthcare. Since the affinity of a 72-mer ssDNA sequence has been previously described without further investigations, this paper demonstrates the first computational prediction of the binding motif between this aptamer and OFL through in silico molecular docking studies. Besides, we suggest the application of the characterized recognition mechanism in a simple FRET (Förster Resonance Energy Transfer) pattern for the rapid aptasensing of the quinolone of interest. Accordingly, our approach harnesses the fluorescence quenching of the fluorescein-tagged aptamer (FAM-APT) induced by its partial hybridization to a tetramethyl rhodamine-labelled complementary ssDNA (TAMRA-cDNA). In such a structure, dye labels brought into close proximity act as a FRET pair. Upon ofloxacin addition, an affinity competition occurs to form a more stable FAM-APT/OFL complex, thus unquenching the FAM-APT signal. Interestingly, the recovered fluorescence intensity was found to correlate well with the antibiotic's concentrations in the range of 0.2-200 µM in HEPES buffer, with a linear response that ranged between 0.2 and 20 µM. The rapid apta-assay achieved limits of detection and quantification of 0.12 and 0.40 µM, respectively. The truncated aptamer has also shown an improved specificity toward OFL than other quinolones, compared to the original full-length aptamer described in previous works. Finally, the practical application of the developed apta-assay was successfully confirmed to detect OFL quinolone in spiked milk samples, with satisfactory recoveries ranging between 97.4% and 111.4%.

Urea Biosensor Based on a CO2 Microsensor.

Urea sensors based on electrodes in direct contact with the medium have limited long-term stability when exposed to complex media. Here, we present a urea biosensor based on urease immobilized in an alginate polymer, buffered at pH 6, and placed in front of a newly developed fast and sensitive CO2 microsensor, where the electrodes are shielded by a gas-permeable membrane. The CO2 produced by the urease in the presence of urea diffuses into the microsensor and is reduced at a Ag cathode. Oxygen interference is prevented by a Cr2+ trap. The 95% response time to changes in urea concentration was 120 s with a linear calibration curve in the range 0-1000 µM and a detection limit of 1 µM. The Ni2+ cofactor to improve sensor performance was continuously supplied from a reservoir behind the sensor tip. The stability of the urea sensor was optimized by the addition of bovine serum albumin as a stabilizer to the urease/alginate mixture that was cross-linked with glutaraldehyde and Ca2+ ions. This immobilization strategy resulted in about 70% of the initial urea sensor sensitivity after two weeks of continuous operation. The sensor was successfully tested in blood serum.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies.

The emergence and rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a potentially fatal disease, is swiftly leading to public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to a seafood market in Wuhan City, China in December 2019. It has been suggested that the infection is likely to be of zoonotic origin and transmitted to humans through a not-yet-known intermediary. As of 22 May 2020, the World Health Organization reported that there were approximately 4,995,996 confirmed cases and 327,821 deaths. SARS-CoV-2 is transmitted via inhalation or direct contact with droplets from infected people. It has an incubation period ranging from 2 to ≥14 days. The rate of spread of SARS-CoV-2 is greater than that for severe acute respiratory syndrome coronavirus and Middle East respiratory coronavirus. The symptoms are similar to influenza (i.e. breathlessness, sore throat and fatigue) and infected cases are isolated and treated. Infection is mild in most cases, but in elderly (>50 years) patients and those with cardiac and respiratory disorders, it may progress to pneumonia, acute respiratory distress syndrome and multi-organ failure. People with strong immunity or those who have developed herd immunity are asymptomatic. The fatality rate ranges from 3% to 4%. Recommended methods for diagnosis of COVID-19 are molecular tests (e.g. polymerase chain reaction) on respiratory secretions, chest scan and common laboratory diagnosis. Currently, treatment is essentially supportive, and the role of antiviral agents is yet to be established as a vaccine is not yet available. This review will focus on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.