Optical biosensors for diagnosis of COVID-19: nanomaterial-enabled particle strategies for post pandemic era.

The COVID-19 pandemic underlines the need for effective strategies for controlling virus spread and ensuring sensitive detection of SARS-CoV-2. This review presents the potential of nanomaterial-enabled optical biosensors for rapid and low-cost detection of SARS-CoV-2 biomarkers, demonstrating a comprehensive analysis including colorimetric, fluorescence, surface-enhanced Raman scattering, and surface plasmon resonance detection methods. Nanomaterials including metal-based nanomaterials, metal-organic frame-based nanoparticles, nanorods, nanoporous materials, nanoshell materials, and magnetic nanoparticles employed in the production of optical biosensors are presented in detail. This review also discusses the detection principles, fabrication methods, nanomaterial synthesis, and their applications for the detection of SARS-CoV-2 in four categories: antibody-based, antigen-based, nucleic acid-based, and aptamer-based biosensors. This critical review includes reports published in the literature between the years 2021 and 2024. In addition, the review offers critical insights into optical nanobiosensors for the diagnosis of COVID-19. The integration of artificial intelligence and machine learning technologies with optical nanomaterial-enabled biosensors is proposed to improve the efficiency of optical diagnostic systems for future pandemic scenarios.

Water monitoring with an automated smart sensor supported with solar power for real-time and long range detection of ferrous iron.

Low-power and smart sensing systems for iron detection are necessary for in situ monitoring of water quality. Here, a potentiometric Fe2+-selective electrode (ISE) was fabricated based on cyanomethyl N-methyl-N-phenyl dithiocarbamate for the first time as an ionophore. Under optimal conditions, the ISE showed a Nernstian slope of 29.76 ± 0.6 mV per decade for Fe2+ ions over a wide concentration range from 1.0 × 10-1 to 1.0 × 10-5 M with a lower detection limit (LOD) of 1.0 × 10-6 M. The ISE interference of various cations on the potentiometric response was also investigated. The ISE had a response time less than 3 s and the lifetime was two months. Also, an automated, long-range (LoRa), wireless enabled sampling microfluidic device powered with a solar panel as an autonomous power source was developed for a continuous sampling and sensing process. The sensing platform was employed in the determination of Fe2+ in acid mine drainage and spiked water samples with an average recovery of 100.7%. This simple, inexpensive (below $350), portable sensing platform will allow for rapid real-time monitoring of ground-, drinking-, and industrial waters contaminated with iron.

Recent Trends in Nanomaterial Based Electrochemical Sensors for Drug Detection: Considering Green Assessment.

An individual's therapeutic drug exposure level is directly linked to corresponding clinical effects. Rapid, sensitive, inexpensive, portable and reliable devices are needed for diagnosis related to drug exposure, treatment, and prognosis of diseases. Electrochemical sensors are useful for drug monitoring due to their high sensitivity and fast response time. Also, they can be combined with portable signal read-out devices for point-of-care applications. In recent years, nanomaterials such as carbon-based, carbon-metal nanocomposites, noble nanomaterials have been widely used to modify electrode surfaces due to their outstanding features including catalytic abilities, conductivity, chemical stability, biocompatibility for development of electrochemical sensors. This review paper presents the most recent advances about nanomaterials-based electrochemical sensors including the use of green assessment approach for detection of drugs including anticancer, antiviral, anti-inflammatory, and antibiotics covering the period from 2019 to 2023. The sensor characteristics such as analyte interactions, fabrication, sensitivity, and selectivity are also discussed. In addition, the current challenges and potential future directions of the field are highlighted.

Recent Advances of Optical Biosensors in Veterinary Medicine: Moving Towards the Point of Care Applications.

While food safety issues are attracting public concern due to their detrimental effects on human health, monitoring livestock health is urgently needed to diagnose animal diseases at an early stage by applying proper treatments, controlling, and preventing outbreaks, particularly in resource- limited countries. In addition, unhealthy farms are not only a threat to livestock but also to human lives. The available diagnostic techniques for the detection of key health threats within both the food and livestock sectors require labor-intensive and time-consuming experimental procedures and sophisticated and expensive instruments. To tackle this issue, optical biosensing strategies have been incorporated into point-of-care (POC) systems, offering real-time monitoring, field-deployable, and low-cost devices, which help make on-the-spot decisions. This review aims to discuss the recent cutting-edge research on POC optical biosensing platforms for on-farm diagnosis of animal diseases and on-site detection of animal-derived food-borne contaminants, including pathogens, antibiotics, and mycotoxins. Moreover, this review briefly presents the basic knowledge of various types of optical biosensors and their development using various recent strategies, including nanomaterial combinations, to enhance their performance in POC tests. This review is expected to help scientists to understand the evolution and challenges in the development of point-of-care biosensors for the food and livestock industry, benefiting global healthcare.

Large-scale fabrication of ion-selective electrodes for simultaneous detection of Na+, K+, and Ca2+ in biofluids using a smartphone-based potentiometric sensing platform.

A significant bottleneck exists for mass-production of ion-selective electrodes despite recent developments in manufacturing technologies. Here, we present a fully-automated system for large-scale production of ISEs. Three materials, including polyvinyl chloride, polyethylene terephthalate and polyimide, were used as substrates for fabricating ion-selective electrodes (ISEs) using stencil printing, screen-printing and laser engraving, respectively. We compared sensitivities of the ISEs to determine the best material for the fabrication process of the ISEs. The electrode surfaces were modified with various carbon nanomaterials including multi-walled carbon nanotubes, graphene, carbon black, and their mixed suspensions as the intermediate layer to enhance sensitivities of the electrodes. An automated 3D-printed robot was used for the drop-cast procedure during ISE fabrication to eliminate manual steps. The sensor array was optimized, and the detection limits were 10-5 M, 10-5 M and 10-4 M for detection of K+, Na+ and Ca2+ ions, respectively. The sensor array integrated with a portable wireless potentiometer was used to detect K+, Na+ and Ca2+ in real urine and simulated sweat samples and results obtained were in agreement with ICP-OES with good recoveries. The developed sensing platform offers low-cost detection of electrolytes for point-of-care applications.

Label free electrochemical DNA biosensor for COVID-19 diagnosis.

The COVID-19 pandemic has significantly increased the development of the development of point-of-care (POC) diagnostic tools because they can serve as useful tools for detecting and controlling spread of the disease. Most current methods require sophisticated laboratory instruments and specialists to provide reliable, cost-effective, specific, and sensitive POC testing for COVID-19 diagnosis. Here, a smartphone-assisted Sensit Smart potentiostat (PalmSens) was integrated with a paper-based electrochemical sensor to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A disposable paper-based device was fabricated, and the working electrode directly modified with a pyrrolidinyl peptide nucleic acid (acpcPNA) as the biological recognition element to capture the target complementary DNA (cDNA). In the presence of the target cDNA, hybridization with acpcPNA probe blocks the redox conversion of a redox reporter, leading to a decrease in electrochemical response correlating to SARS-CoV-2 concentration. Under optimal conditions, a linear range from 0.1 to 200 nM and a detection limit of 1.0 pM were obtained. The PNA-based electrochemical paper-based analytical device (PNA-based ePAD) offers high specificity toward SARS-CoV-2 N gene because of the highly selective PNA-DNA binding. The developed sensor was used for amplification-free SARS-CoV-2 detection in 10 nasopharyngeal swab samples (7 SARS-CoV-2 positive and 3 SARS-CoV-2 negative), giving a 100% agreement result with RT-PCR.

A smartphone-assisted hybrid sensor for simultaneous potentiometric and distance-based detection of electrolytes.

At home electrolyte analysis is of growing interest due to the importance for early diagnosis for various diseases. This work presents the first device that integrates a potentiometric ion-selective electrode (ISE) with distance-based colorimetric detection for the simultaneous analysis of K+ and Cl- ions at the point of care (POC). This hybrid sensing device was designed in a two-dimensional configuration using a plastic transparency sheet containing a stencil printed K+-ISE and a paper substrate for distance-based colorimetric detection of Cl-. K+ quantification was performed using a low-cost (<$25) lab-made Wi-Fi supported potentiometer with a custom smartphone application while Cl- ions were quantified with an instrument-free distance-based paper analytical device (dPAD). The total analysis time is 5 min once the sample is added. The K+-ISE showed a sensitivity of 55.89 ± 2.52 mV/decade from 0.1 to 100 mM with a limit of detection (LOD) of 0.01 mM. The linear working range for Cl- detection was 0.5-50 mM whereas the LOD was 0.16 ± 0.05 mM. The proof-of-concept application of the sensing hybrid device was demonstrated in human urine and artificial sweat samples containing K+ and Cl- ions at physiologically relevant ranges. The recoveries were found to be 88-108% for K+ and 90-104% for Cl-, showing the potential use of the proposed device for low-cost routine analysis of biological samples at POC.

Dual-mode ion-selective electrodes and distance-based microfluidic device for detection of multiple urinary electrolytes.

Here, we developed a microfluidic paper device by combining ion-selective electrodes (ISE) and a distance-based paper device (dPAD) for simultaneous potentiometric and colorimetric detection of urine electrolytes including K+, Na+ and Cl-. The working and reference electrode zones were coated with polystyrene as a non-ionic polymer to improve hydrophobic properties on the paper surface for fabrication of K+-ISE and Na+-ISE. The layer of polymer coating was optimized to enhance the sensitivity of the ISEs. Under optimized conditions, the electrode surfaces were modified with carbon black to improve the electrochemical characteristics of the ISEs. The ISEs showed good performance with sensitivities of 54.14 ± 3.94 mV per decade and 55.08 ± 1.15 mV per decade for K+ and Na+ within the linear concentration range 0.100 mM-100 mM K+ and 5 mM-1 M Na+, respectively. The limits of detection (LOD) were 0.05 mM and 1.36 mM for K+ and Na+, respectively. The linear working range of Cl- was 0.50 to 50 mM and the LOD and limit of quantification (LOQ) were found to be 0.16 ± 0.05 mM (3SD) and 0.53 ± 0.05 mM (10SD), respectively. The dual-mode ISE-dPAD was validated in human urine and recoveries were obtained as 90-108%, 94-105%, and 90-96% for K+, Na+, and Cl-, respectively, showing successful application of the developed device in a complex matrix. The ISE-dPAD has advantages including low-cost ($ 0.33 per test), eco-friendly, portability, simple operation, the need of low sample volume (100 µL), and simultaneous analysis on a single device.

Carbon composite thermoplastic electrodes integrated with mini-printed circuit board for wireless detection of calcium ions.

Here, a smartphone-based portable sensing system is developed for real-time detection of Ca2+ ions in a variety of biofluids. A solid-contact calcium-selective electrode (Ca2+-ISE) consisting of an ion-selective membrane (ISM), carbon black nanomaterial and polystyrene-graphite nanoplatelets as a solid contact was fabricated. The polyvinylchloride (PVC)-based ISM was optimized using different plasticizers and ion-exchangers. Under optimized conditions, the solid contacts were electrochemically characterized by electrochemical impedance spectroscopy (EIS), chronopotentiometric and potentiometric measurements. The Ca2+-ISE showed a Nernst response with a slope of 31.2 ± 0.6 mV/decade in the concentration range from 0.1 M to 10-4 M Ca2+ with a limit of detection (LOD) of 1.0 × 10-5 M. In addition, the ISEs exhibited good selectivity to Ca2+ ions over various interfering electrolytes and metabolites. The Ca2+-ISEs were applied in human urine and, artificial serum and cerebrospinal fluid samples. The ISEs showed good recoveries between 90 and 105%, indicating potential applicability of these electrodes in biological fluids. The portable lab-made potentiometer provides wireless data signaling and transmission to a smartphone and final Ca2+ concentration display due to its customized software. Therefore, the developed smartphone-based sensing platform offers low cost (< $25), rapid, user-friendly detection of Ca2+ especially in resource-limited areas.

Rapid prototyping of ion-selective electrodes using a low-cost 3D printed internet-of-things (IoT) controlled robot.

We report automated fabrication of solid-contact sodium-selective (Na+-ISEs) and potassium-selective electrodes (K+-ISEs) using a 3D printed liquid handling robot controlled with Internet of Things (IoT) technology. The printing system is affordable and can be customized for the use with micropipettes for applications such as drop-casting, biological assays, sample preparation, rinsing, cell culture, and online analyte monitoring using multi-well plates. The robot is more compact (25 × 30 × 35 cm) and user-friendly than commercially available systems and does not require mechatronic experience. For fabrication of ion-selective electrodes, a carbon black intermediate layer and ion-selective membrane were successively drop-cast on the surface of stencil-printed carbon electrode using the dispensing robot. The 3D-printed robot increased ISE robustness while decreasing the modification time by eliminating manual steps. The Na+-ISEs and K+-ISEs were characterized for their potentiometric responses using a custom-made, low-cost (<$25) multi-channel smartphone-based potentiometer capable of signal processing and wireless data transmission. The electrodes showed Nernstian responses of 58.2 ± 2.6 mV decade-1 and 56.1 ± 0.7 mV decade-1 for Na+ and K+, respectively with an LOD of 1.0 × 10-5 M. We successfully applied the ISEs for multiplexed detection of Na+ and K+ in urine and artificial sweat samples at clinically relevant concentration ranges. The 3D-printed pipetting robot cost $100 and will pave the way for more accessible mass production of ISEs for those who cannot afford the expensive commercial robots.

Microfluidic-based ion-selective thermoplastic electrode array for point-of-care detection of potassium and sodium ions.

A microfluidic paper-based thermoplastic electrode (TPE) array has been developed for point-of-care detection of Na+ and K+ ions using a custom-made portable potentiometer. TPEs were fabricated using polystyrene as the binder and two different types of graphite to compare the electrode performance. The newly designed TPE array embedded in a polymethyl methacrylate chip consists of two working electrodes modified with carbon black nanomaterial and an ion-selective membrane, and an all-solid-state reference electrode modified with Ag/AgCl ink and poly(butyl methacrylate-co-methyl methacrylate) membrane via drop-casting. Ion-selective membrane compositions and conditioning steps were optimized. Under optimized conditions, ion-selective TPEs demonstrated fast response time (4 s) and good stability. The TPE array demonstrated a Nernstian behavior for K+ with a sensitivity of 59.2 ± 0.2 mV decade-1 and near-Nernstian response for Na+ with a sensitivity of 54.0 ± 1.1 mV decade-1 in the range 10-1 - 10-4 M and 1 -  10-3 M, respectively. The detection limits were 1 × 10-5 M and 1 × 10-4 M for K+ and Na+, respectively. In addition, a K+ and Na+ selective microfluidic paper-based analytical device (µPAD) was applied to artificial serum analysis and found in good agreement with average recoveries of 101.3% and 99.7%, respectively, suggesting that the developed ISE array is suitable for detection of sodium and potassium in complex matrix.

Monitoring microalgal growth of Chlorella minutissima with a new all solid-state contact nitrate selective sensor.

As third generation feedstock, microalgae are microorganisms that can grow only in the optimum conditions. There are parameters including the concentration of macro and microelements in nutrient solution, pH, temperature and light intensity that have significant impact on microalgal growth. In recent years, various sensing devices have been developed for sensitive measurement of these parameters during microalgal growth. In this study, a new potentiometric nitrate selective sensor was developed to indicate the nitrate uptake of microalgae and the effect of nitrate nutrient on microalgal growth, specifically, and this sensor was successfully applied to determine nitrate concentration in medium during microalgal growth. Moreover, the effects of nitrate, carbonate and phosphate concentration in the growth medium on biomass production of Chlorella minutissima were investigated by using Box-Behnken design method, and optimum conditions were determined for the highest biomass production of microalgae. As a result of the experiments, it was seen that the highest C. minutissima production was achieved using the medium consist of 2.63 g/L NaNO3 , 0.35 g/L Na2 CO3 and 0.4 g/L KH2 PO4. Statistically, it was observed that there was a proportional relationship between the microalgae production and investigated parameters such as carbon, nitrogen and phosphate amounts of culture mediums. The electrode showed a wide linear range between 1.0 × 10-1 and 5.0 × 10-5  M with a detection limit of the 5 × 10-6  M and the response time was found as 10 s. The results showed that developed nitrate selective sensor could be successfully applied for continuous measurement of nitrate in microalgal productions at reduced cost.

Synthesis and grafting of diazonium tosylates for thermoplastic electrode immunosensors.

For electrochemical immunosensors, inexpensive electrodes with fast redox kinetics, and simple stable methods of electrode functionalization are vital. However, many inexpensive and easy to fabricate electrodes suffer from poor redox kinetics, and functionalization can often be difficult and/or unstable. Diazonium tosylates are particularly stable soluble salts that can be useful for electrode functionalization. Recently developed thermoplastic electrodes (TPEs) have been inexpensive, moldable, and highly electroactive carbon composite materials. Herein, the synthesis and grafting of diazonium tosylate salts were optimized for modification of TPEs and used to develop the first TPE immunosensors. With diazonium tosylates, TPEs were amine functionalized either directly through grafting of p-aminophenyl diazonium salt or indirectly through grafting p-nitrophenyl diazonium salt followed by electrochemical reduction to an amine. Diazonium tosylates were synthesized in situ as a paste in 6 min. Once the reaction paste was spread over the electrodes, near monolayer coverage (1.0 ± 0.2 nmol cm-2) was achieved for p-nitrophenyl diazonium salt within 5 min. Amine functionalized electrodes were conjugated to C-reactive protein (CRP) antibodies. Antibody-modified TPEs were applied for the sensitive detection of CRP, a biomarker of cardiovascular disease using electrochemical enzyme-linked immunosorbent assays (ELISA). LODs were determined to be 2 ng mL-1 in buffer, with high selectivity against interfering species for both functionalization methods. The direct p-aminophenyl modification method had the highest sensitivity to CRP and was further tested in spiked serum with an LOD of 10 ng mL-1. This low-cost and robust TPE immunosensor platform can be easily adapted for other analytes and multiplexed detection.

Paper-based analytical devices for virus detection: Recent strategies for current and future pandemics.

The importance of user-friendly, inexpensive, sensitive, and selective detection of viruses has been highlighted again due to the recent Coronavirus disease 2019 (COVID-19) pandemic. Among the analytical tools, paper-based devices (PADs) have become a leading alternative for point-of-care (POC) testing. In this review, we discuss the recent development strategies and applications in nucleic acid-based, antibody/antigen-based and other affinity-based PADs using optical and electrochemical detection methods for sensing viruses. In addition, advantages and drawbacks of presented PADs are identified. Current state and insights towards future perspectives are presented regarding developing POC diagnosis platform for COVID-19. This review considers state-of-the-art technologies for further development and improvement in PADs performance for virus detection.

Microfluidic Paper-Based Analytical Devices: From Design to Applications.

Microfluidic paper-based analytical devices (µPADs) have garnered significant interest as a promising analytical platform in the past decade. Compared with traditional microfluidics, µPADs present unique advantages, such as easy fabrication using established patterning methods, economical cost, ability to drive and manipulate flow without equipment, and capability of storing reagents for various applications. This Review aims to provide a comprehensive review of the field, highlighting fabrication methods available to date with their respective advantages and drawbacks, device designs and modifications to accommodate different assay needs, detection strategies, and the growing applications of µPADs. Finally, we discuss how the field needs to continue moving forward to realize its full potential.

Emerging point-of-care biosensors for rapid diagnosis of COVID-19: current progress, challenges, and future prospects.

Coronavirus disease 2019 (COVID-19) pandemic is currently a serious global health threat. While conventional laboratory tests such as quantitative real-time polymerase chain reaction (qPCR), serology tests, and chest computerized tomography (CT) scan allow diagnosis of COVID-19, these tests are time-consuming and laborious, and are limited in resource-limited settings or developing countries. Point-of-care (POC) biosensors such as chip-based and paper-based biosensors are typically rapid, portable, cost-effective, and user-friendly, which can be used for COVID-19 in remote settings. The escalating demand for rapid diagnosis of COVID-19 presents a strong need for a timely and comprehensive review on the POC biosensors for COVID-19 that meet ASSURED criteria: Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable to end users. In the present review, we discuss the importance of rapid and early diagnosis of COVID-19 and pathogenesis of COVID-19 along with the key diagnostic biomarkers. We critically review the most recent advances in POC biosensors which show great promise for the detection of COVID-19 based on three main categories: chip-based biosensors, paper-based biosensors, and other biosensors. We subsequently discuss the key benefits of these biosensors and their use for the detection of antigen, antibody, and viral nucleic acids. The commercial POC biosensors for COVID-19 are critically compared. Finally, we discuss the key challenges and future perspectives of developing emerging POC biosensors for COVID-19. This review would be very useful for guiding strategies for developing and commercializing rapid POC tests to manage the spread of infections.Graphical abstract.

Review-Chemical and Biological Sensors for Viral Detection.

Infectious diseases commonly occur in contaminated water, food, and bodily fluids and spread rapidly, resulting in death of humans and animals worldwide. Among infectious agents, viruses pose a serious threat to public health and global economy because they are often difficult to detect and their infections are hard to treat. Since it is crucial to develop rapid, accurate, cost-effective, and in-situ methods for early detection viruses, a variety of sensors have been reported so far. This review provides an overview of the recent developments in electrochemical sensors and biosensors for detecting viruses and use of these sensors on environmental, clinical and food monitoring. Electrochemical biosensors for determining viruses are divided into four main groups including nucleic acid-based, antibody-based, aptamer-based and antigen-based electrochemical biosensors. Finally, the drawbacks and advantages of each type of sensors are identified and discussed.

A Very Rare Congenital Dyserythropoietic Anemia Variant-Type IV in a Patient With a Novel Mutation in the KLF1 Gene: A Case Report and Review of the Literature.

Congenital dyserythropoietic anemias comprise a group of very rare hereditary disorders characterized by ineffective erythropoiesis and distinct morphologic abnormalities of the erythroblasts in the bone marrow. The wide variety of phenotypes observed in these patients makes the diagnosis difficult; identification of the genetic variants is crucial in differential diagnosis and clinical management. We report the nineth case with congenital dyserythropoietic anemia type IV, with a novel mutation that has not been reported before.