Engineered two-dimensional nanomaterials based diagnostics integrated with internet of medical things (IoMT) for COVID-19.

More than four years have passed since an inimitable coronavirus disease (COVID-19) pandemic hit the globe in 2019 after an uncontrolled transmission of the severe acute respiratory syndrome (SARS-CoV-2) infection. The occurrence of this highly contagious respiratory infectious disease led to chaos and mortality all over the world. The peak paradigm shift of the researchers was inclined towards the accurate and rapid detection of diseases. Since 2019, there has been a boost in the diagnostics of COVID-19 via numerous conventional diagnostic tools like RT-PCR, ELISA, etc., and advanced biosensing kits like LFIA, etc. For the same reason, the use of nanotechnology and two-dimensional nanomaterials (2DNMs) has aided in the fabrication of efficient diagnostic tools to combat COVID-19. This article discusses the engineering techniques utilized for fabricating chemically active E2DNMs that are exceptionally thin and irregular. The techniques encompass the introduction of heteroatoms, intercalation of ions, and the design of strain and defects. E2DNMs possess unique characteristics, including a substantial surface area and controllable electrical, optical, and bioactive properties. These characteristics enable the development of sophisticated diagnostic platforms for real-time biosensors with exceptional sensitivity in detecting SARS-CoV-2. Integrating the Internet of Medical Things (IoMT) with these E2DNMs-based advanced diagnostics has led to the development of portable, real-time, scalable, more accurate, and cost-effective SARS-CoV-2 diagnostic platforms. These diagnostic platforms have the potential to revolutionize SARS-CoV-2 diagnosis by making it faster, easier, and more accessible to people worldwide, thus making them ideal for resource-limited settings. These advanced IoMT diagnostic platforms may help with combating SARS-CoV-2 as well as tracking and predicting the spread of future pandemics, ultimately saving lives and mitigating their impact on global health systems.

Electrochemical Nanobiosensor of Ionic Liquid Functionalized MoO3-rGO for Sensitive Detection of Carcinoembryonic Antigen.

Early diagnosis of cancer can be achieved by detecting associated biomarkers before the appearance of symptoms. Herein, we have developed an electrochemical immunosensor of ionic liquid tailored to molybdenum trioxide-reduced graphene oxide (MoO3-rGO-IL) nanocomposite to detect carcinoembryonic antigen (CEA), a cancer biomarker. The MoO3-rGO-IL nanocomposite has been synthesized in situ via the hydrothermal method. The functionalization of 1-butyl-3-methylimidazolium tetrafluoroborate IL with MoO3-rGO synergistically improves the electrochemical and surface properties of the nanocomposite. The characterization studies revealed that the MoO3-rGO-IL nanocomposite is a highly appropriate material for the construction of immunosensors. The material exhibits exceptional electrical conductivity, surface properties, stability, and a large electrochemical effective surface area (13.77×10-2 cm2) making it ideal for fabricating immunosensors. The quantitative outcome showed that the developed immunosensor (BSA/anti-CEA/MoO3-rGO-IL/GCE) possesses excellent sensitivity, broad linearity from 25 fg mL-1 to 100 ng mL-1, and a low detection limit of 1.19 fg mL-1. Moreover, the remarkable selectivity, repeatability, and efficiency of detecting CEA in serum specimens demonstrated the feasibility of the immunosensor. Thus, the projected electrochemical immunosensor can potentially be utilized for the quantification of CEA in clinical specimens.

Synergistically functionalized molybdenum disulfide-reduced graphene oxide nanohybrid based ultrasensitive electrochemical immunosensor for real sample analysis of COVID-19.

Herein, we have proposed a straightforward and label-free electrochemical immunosensing strategy supported on a glassy carbon electrode (GCE) modified with a biocompatible and conducting biopolymer functionalized molybdenum disulfide-reduced graphene oxide (CS-MoS2/rGO) nanohybrid to investigate the SARS-CoV-2 virus. CS-MoS2/rGO nanohybrid-based immunosensor employs recombinant SARS-CoV-2 Spike RBD protein (rSP) that specifically identifies antibodies against the SARS-CoV-2 virus via differential pulse voltammetry (DPV). The antigen-antibody interaction diminishes the current responses of the immunosensor. The obtained results indicate that the fabricated immunosensor is extraordinarily capable of highly sensitive and specific detection of the corresponding SARS-CoV-2 antibodies with a LOD of 2.38 zg mL-1 in phosphate buffer saline (PBS) samples over a broad linear range between 10 zg mL-1-100 ng mL-1. In addition, the proposed immunosensor can detect attomolar concentrations in spiked human serum samples. The performance of this immunosensor is assessed using actual serum samples from COVID-19-infected patients. The proposed immunosensor can accurately and substantially differentiate between (+) positive and (-) negative samples. As a result, the nanohybrid can provide insight into the conception of Point-of-Care Testing (POCT) platforms for cutting-edge infectious disease diagnostic methods.

Internet-of-medical-things integrated point-of-care biosensing devices for infectious diseases: Toward better preparedness for futuristic pandemics.

Microbial pathogens have threatened the world due to their pathogenicity and ability to spread in communities. The conventional laboratory-based diagnostics of microbes such as bacteria and viruses need bulky expensive experimental instruments and skilled personnel which limits their usage in resource-limited settings. The biosensors-based point-of-care (POC) diagnostics have shown huge potential to detect microbial pathogens in a faster, cost-effective, and user-friendly manner. The use of various transducers such as electrochemical and optical along with microfluidic integrated biosensors further enhances the sensitivity and selectivity of detection. Additionally, microfluidic-based biosensors offer the advantages of multiplexed detection of analyte and the ability to deal with nanoliters volume of fluid in an integrated portable platform. In the present review, we discussed the design and fabrication of POCT devices for the detection of microbial pathogens which include bacteria, viruses, fungi, and parasites. The electrochemical techniques and current advances in this field in terms of integrated electrochemical platforms that include mainly microfluidic- based approaches and smartphone and Internet-of-things (IoT) and Internet-of-Medical-Things (IoMT) integrated systems have been highlighted. Further, the availability of commercial biosensors for the detection of microbial pathogens will be briefed. In the end, the challenges while fabrication of POC biosensors and expected future advances in the field of biosensing have been discussed. The integrated biosensor-based platforms with the IoT/IoMT usually collect the data to track the community spread of infectious diseases which would be beneficial in terms of better preparedness for current and futuristic pandemics and is expected to prevent social and economic losses.

Electrochemically Exfoliated Graphene Quantum Dots Based Biosensor for CD44 Breast Cancer Biomarker.

An innovative electrochemical biosensor based on graphene quantum dots (GQDs) is developed for a simple, rapid, and highly sensitive primary diagnosis of the breast cancer biomarker cluster of differentiation-44 (CD44) antigen. Herein, electrochemical exfoliation of waste dry batteries provides facile, eco-friendly, and cost-effective synthesis of GQDs. Transmission electron microscopy (TEM) analysis reveals that GQDs exhibit spherical shapes with an average diameter of 4.75 nm. Further, electrochemical analysis through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) reveals that the electrochemical properties of GQDs are suitable for biosensing applications. Subsequently, GQDs have a large electroactive surface area that has been utilized for the immobilization of CD44 antibodies to fabricate the electrochemical biosensor. The electroanalytical performance of GQDs for CD44 biosensing capabilities is studied by differential pulse voltammetry (DPV). The developed electrochemical biosensor has high sensitivity with the lowest detection limit (LOD) of 2.11 fg/mL in the linear range of 0.1 pg/mL to 100.0 ng/mL in phosphate buffer saline (PBS). Further, the linear response of the electrochemical biosensor for CD44 antigen concentration is in the range of 1.0 pg/mL to 100.0 ng/mL with a LOD of 2.71 fg/mL in spiked serum samples. The outcomes suggest that the synthesized GQDs demonstrate promising attributes to be utilized as a viable nanomaterial in biosensing applications.

Functionalized Titanium Dioxide Nanoparticle-Based Electrochemical Immunosensor for Detection of SARS-CoV-2 Antibody.

The advancement in biosensors can overcome the challenges faced by conventional diagnostic techniques for the detection of the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, the development of an accurate, rapid, sensitive, and selective diagnostic technique can mitigate adverse health conditions caused by SARS-CoV-2. This work proposes the development of an electrochemical immunosensor based on bio-nanocomposites for the sensitive detection of SARS-CoV-2 antibodies through the differential pulse voltammetry (DPV) electroanalytical method. The facile synthesis of chitosan-functionalized titanium dioxide nanoparticles (TiO2-CS bio-nanocomposites) is performed using the sol-gel method. Characterization of the TiO2-CS bio-nanocomposite is accomplished using UV-vis spectroscopy, Raman spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). The electrochemical performance is studied using cyclic voltammetry (CV), DPV, and electrochemical impedance spectroscopy (EIS) for its electroanalytical and biosensing capabilities. The developed immunosensing platform has a high sensitivity with a wide range of detection from 50 ag mL-1 to 1 ng mL-1. The detection limit of the SARS-CoV-2 antibody in buffer media is obtained to be 3.42 ag mL-1 and the limit of quantitation (LOQ) to be 10.38 ag mL-1. The electrochemical immunosensor has high selectivity in different interfering analytes and is stable for 10 days. The results suggest that the developed electrochemical immunosensor can be applicable for real sample analysis and further high-throughput testing.

Polydopamine decorated MoS2 nanosheet based electrochemical immunosensor for sensitive detection of SARS-CoV-2 nucleocapsid protein in clinical samples.

The outbreak of the highly contagious disease COVID-19, which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demands a rapid, low-cost, and highly sensitive immunosensor that can detect and identify the virus efficiently. Here, an electrochemical immunosensor based on a nanocomposite consisting of molybdenum disulfide nanosheets decorated with polydopamine (MoS2-PDA) is developed for highly sensitive detection of SARS-CoV-2 nucleocapsid protein (N protein). The MoS2-PDA nanocomposite possesses various hydroxyl and amine groups that have excellent chemistry with crosslinkers and act as adhesive agents to bind with the working electrode surface. Furthermore, the optical, functional, structural, vibrational, and morphological properties of the MoS2-PDA nanocomposite are studied using various characterization techniques such as UV-vis, FTIR, and Raman spectroscopies, XRD, and TEM. The electrochemical immunosensor is fabricated by functionalizing the MoS2-PDA nanocomposite with anti-SARS-CoV-2 nucleocapsid IgG antibody (Ab) and has a very high sensitivity against the N protein with a linear range between 10 ag mL-1 and 100 ng mL-1. The electrochemical immunosensor exhibits a lowest limit of detection (LOD) of 2.80 ag mL-1 and a limit of quantification (LOQ) of 8.48 ag mL-1via electrochemical impedance spectroscopy (EIS). Furthermore, the electrochemical immunosensor is successfully employed to detect the N protein in nasopharyngeal swab specimens and displays good consistency with the conventional RT-PCR test results. The results show that the MoS2-PDA nanocomposite-based electrochemical platform can serve as a highly sensitive and selective detector of N protein and will pave the way for the development of a point-of-care (POC) electrochemical immunosensor for rapid detection of other infectious viruses.

MXene-modified molecularly imprinted polymers as an artificial bio-recognition platform for efficient electrochemical sensing: progress and perspectives.

The development of efficient electrochemical sensors of exceptional features, molecularly imprinted polymers (MIPs), has been extensively utilized due to their great vitality as an alternative to bio-recognition elements. MIPs as an artificial bio-recognition element are getting significant attention due to their affordability, easy processability, and scaling-up capabilities. However, the challenge of longer stability and higher sensitivity associated with MIP-based sensing technology is still a remaining challenge. This can be addressed by modifying MIPs with electro-active nano-systems. Correspondingly, MXene is an emerging material of choice to make MIP-based sensing platforms more efficient and develop a bio-active-free sensing system. This review highlights state-of-the-art MXene-modified MIP electrochemical sensing platforms to overcome the associated limitations of pristine MIPs. As a proof-of-concept, the sensitive and selective detection of markers for health monitoring can be efficiently fulfilled by the high-performance MXene-MIP nanocomposite-based electrochemical sensor. Moreover, the challenges associated with this research area along with the potential solutions are also discussed. An attempt has been made to explore MXene-MIP nanocomposites as a next-generation sensing platform suitable for point-of-care testing (POCT) applications.

Highly Sensitive Electrochemical Immunosensor Platforms for Dual Detection of SARS-CoV-2 Antigen and Antibody based on Gold Nanoparticle Functionalized Graphene Oxide Nanocomposites.

In this work, we report a facile synthesis of graphene oxide-gold (GO-Au) nanocomposites by electrodeposition. The fabricated electrochemical immunosensors are utilized for the dual detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen and SARS-CoV-2 antibody. The GO-Au nanocomposites has been characterized by UV-vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS) for its biosensing properties. The linear detection range of the SARS-CoV-2 antigen immunosensor is 10.0 ag mL-1 to 50.0 ng mL-1, whereas that for the antibody immunosensor ranges from 1.0 fg mL-1 to 1.0 ng mL-1. The calculated limit of detection (LOD) of the SARS-CoV-2 antigen immunosensor is 3.99 ag mL-1, and that for SARS-CoV-2 antibody immunosensor is 1.0 fg mL-1 with high sensitivity. The validation of the immunosensor has also been carried out on patient serum and patient swab samples from COVID-19 patients. The results suggest successful utilization of the immunosensors with a very low detection limit enabling its use in clinical samples. Further work is needed for the standardization of the results and translation in screen-printed electrodes for use in portable commercial applications.

An Electrochemical Immunosensor Based on Gold-Graphene Oxide Nanocomposites with Ionic Liquid for Detecting the Breast Cancer CD44 Biomarker.

We develop a highly sensitive electrochemical immunosensor for the detection of a cluster of differentiation-44 (CD44) antigen, a breast cancer biomarker. The hybrid nanocomposite consists of graphene oxide, ionic liquid, and gold nanoparticles (GO-IL-AuNPs) immobilized on a glassy carbon electrode. GO favors the immobilization of antibodies because of the availability of oxygen functionalities. However, 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM.BF4) and AuNPs facilitate electron transfer and increase the effective surface area, which enhances the performance of the immunosensor. Furthermore, UV-visible, fourier transform infrared and Raman spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, voltammetry, and electrochemical impedance spectroscopy characterization techniques have been employed to investigate the structural and chemical properties of the nanomaterials. The quantitative detection of CD44 antigen has been accomplished via differential pulse voltammetry and EIS detection techniques. It has been quantified that the proposed immunosensor offers excellent detection ability in both phosphate-buffered saline (PBS) and serum samples. Under optimum conditions, the linear detection range of the immunosensor for CD44 antigen is 5.0 fg mL-1 to 50.0 µg mL-1 and the limit of detection is 2.0 and 1.90 fg mL-1 as observed via DPV and EIS, respectively, in PBS. Additionally, the immunosensor has high sensitivity and specificity and can be successfully applied for the detection of CD44 antigen in clinical samples.

Heavy metal pollution and risks in a highly polluted and populated Indian river-city pair using the systems approach.

A sectorial approach for assessing heavy metal pollution in rivers neglects the inter-relationship between its environmental compartments and thus fails to report realistic pollution status and associated ecological and human health risks. Therefore, a systems approach was adopted to assess heavy metal pollution and associated risks in the Yamuna River (Delhi, India), one of the world's most polluted and populated river-city pairs. Sampling sites selected along the river with distinct land use were uncultivated natural floodplain vegetation, marshy area, invasive community, arable land, and human settlements. The multivariate analysis identified sources of pollutions (Pb, Cd, Cr, and Ni [anthropogenic]; Fe and Zn [geogenic]). Across the land use, a high log Kp value of Zn and Pb in water-soil phase than in water-sediment phase indicates their long-range transfer, whereas low log Kp (water-soil) of Cd suggests river sediments as its reservoirs. Comparison of pollution indices of Cd, Cr, and Pb in water, sediment, and soil across the land use suggested the role of vegetation in reducing pollution in the environment. Ecological risk also gets reduced progressively from water to sediment to the soil in naturally vegetated sites. Similarly, in river water, Cr, Cd, Ni, and Pb pose carcinogenic and non-carcinogenic risks to adults and children, which are also reduced in sediments and soil of different vegetation regimes. This study showed the eco-remediation services rendered by natural vegetation in reducing pollution and associated ecological and human health risks. To conclude, using a systems approach has significance in assessing pollution at the ecosystem level, and focusing on riverbank land use remains significant in developing methods to reduce pollution and ecological and human health risks for sustainable riverbank management.

Borophene as an emerging 2D flatland for biomedical applications: current challenges and future prospects.

Recently, two-dimensional (2D)-borophene has emerged as a remarkable translational nanomaterial substituting its predecessors in the field of biomedical sensors, diagnostic tools, high-performance healthcare devices, super-capacitors, and energy storage devices. Borophene justifies its demand due to high-performance and controlled optical, electrical, mechanical, thermal, and magnetic properties as compared with other 2D-nanomaterials. However, continuous efforts are being made to translate theoretical and experimental knowledge into pragmatic platforms. To cover the associated knowledge gap, this review explores the computational and experimental chemistry needed to optimize borophene with desired properties. High electrical conductivity due to destabilization of the highest occupied molecular orbital (HOMO), nano-engineering at the monolayer level, chemistry-oriented biocompatibility, and photo-induced features project borophene for biosensing, bioimaging, cancer treatment, and theragnostic applications. Besides, the polymorphs of borophene have been useful to develop specific bonding for DNA sequencing and high-performance medical equipment. In this review, an overall critical and careful discussion of systematic advancements in borophene-based futuristic biomedical applications including artificial intelligence (AI), Internet-of-Things (IoT), and Internet-of-Medical Things (IoMT) assisted smart devices in healthcare to develop high-performance biomedical systems along with challenges and prospects is extensively addressed. Consequently, this review will serve as a key supportive platform as it explores borophene for next-generation biomedical applications. Finally, we have proposed the potential use of borophene in healthcare management strategies.

Functional Ionic Liquids Decorated Carbon Hybrid Nanomaterials for the Electrochemical Biosensors.

Ionic liquids are gaining high attention due to their extremely unique physiochemical properties and are being utilized in numerous applications in the field of electrochemistry and bio-nanotechnology. The excellent ionic conductivity and the wide electrochemical window open a new avenue in the construction of electrochemical devices. On the other hand, carbon nanomaterials, such as graphene (GR), graphene oxide (GO), carbon dots (CDs), and carbon nanotubes (CNTs), are highly utilized in electrochemical applications. Since they have a large surface area, high conductivity, stability, and functionality, they are promising in biosensor applications. Nevertheless, the combination of ionic liquids (ILs) and carbon nanomaterials (CNMs) results in the functional ILs-CNMs hybrid nanocomposites with considerably improved surface chemistry and electrochemical properties. Moreover, the high functionality and biocompatibility of ILs favor the high loading of biomolecules on the electrode surface. They extremely enhance the sensitivity of the biosensor that reaches the ability of ultra-low detection limit. This review aims to provide the studies of the synthesis, properties, and bonding of functional ILs-CNMs. Further, their electrochemical sensors and biosensor applications for the detection of numerous analytes are also discussed.

High-performance antiviral nano-systems as a shield to inhibit viral infections: SARS-CoV-2 as a model case study.

Despite significant accomplishments in developing efficient rapid sensing systems and nano-therapeutics of higher efficacy, the recent coronavirus disease (COVID-19) pandemic is not under control successfully because the severe acute respiratory syndrome virus (SARS-CoV-2, original and mutated) transmits easily from human to -human and causes life-threatening respiratory disorders. Thus, it has become crucial to avoid this transmission through precautions and keep premises hygienic using high-performance anti-viral nanomaterials to trap and eradicate SARS-CoV-2. Such an antiviral nano-system has successfully demonstrated useful significant contribution in COVID-19 pandemic/endemic management effectively. However, their projection with potential sustainable prospects still requires considerable attention and efforts. With this aim, the presented review highlights various severe life-threatening viral infections and the role of multi-functional anti-viral nanostructures with manipulative properties investigated as an efficient precative shielding agent against viral infection progression. The salient features of such various nanostructures, antiviral mechanisms, and high impact multi-dimensional roles are systematically discussed in this review. Additionally, the challenges associated with the projection of alternative approaches also support the demand and significance of this selected scientific topic. The outcomes of this review will certainly be useful to motivate scholars of various expertise who are planning future research in the field of investigating sustainable and affordable high-performance nano-systems of desired antiviral performance to manage not only COVID-19 infection but other targeted viral infections as well.

Rapid diagnosis of SARS-CoV-2 using potential point-of-care electrochemical immunosensor: Toward the future prospects.

Coronavirus disease (COVID-19) is an emerging and highly infectious disease making global public health concern and socio-economic burden. It is caused due to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). It has the tendency to spread rapidly through person-to-person. Currently, several molecular diagnostic platforms such as PCR, qRT-PCR, reverse transcription loop-mediated isothermal amplification (RT-LAMP), CRISPR are utilized for the diagnosis of SARS-CoV-2. These conventional techniques are costly, time consuming and require sophisticated instrumentation facility with well trained personnel for testing. Hence, it is tough to provide testing en-masse to the people in developing countries. On the other hand, several serological biosensors such as lateral flow immunosensor, optical, electrochemical, microfluidics integrated electrochemical/fluorescence is currently utilized for the diagnosis of SARS-CoV-2. In current pandemic situation, there is an urgent need of rapid and efficient diagnosis on mass scale of SARS-CoV-2 for early stage detection. Early monitoring of viral infections can help to control and prevent the spreading of infections in large chunk of population. In this review, the SARS-CoV-2 and their biomarkers in biological samples, collection of samples and recently reported potential electrochemical immunosensors for the rapid diagnosis of SARS-CoV-2 are discussed.

SERS Based Lateral Flow Immunoassay for Point-of-Care Detection of SARS-CoV-2 in Clinical Samples.

The current scenario, an ongoing pandemic of COVID-19, places a dreadful burden on the healthcare system worldwide. Subsequently, there is a need for a rapid, user-friendly, and inexpensive on-site monitoring system for diagnosis. The early and rapid diagnosis of SARS-CoV-2 plays an important role in combating the outbreak. Although conventional methods such as PCR, RT-PCR, and ELISA, etc., offer a gold-standard solution to manage the pandemic, they cannot be implemented as a point-of-care (POC) testing arrangement. Moreover, surface-enhanced Raman spectroscopy (SERS) having a high enhancement factor provides quantitative results with high specificity, sensitivity, and multiplex detection ability but lacks in POC setup. In contrast, POC devices such as lateral flow immunoassay (LFIA) offer rapid, simple-to-use, cost-effective, reliable platform. However, LFIA has limitations in quantitative and sensitive analyses of SARS-CoV-2 detection. To resolve these concerns, herein we discuss a unique modality that is an integration of SERS with LFIA for quantitative analyses of SARS-CoV-2. The miniaturization ability of SERS-based devices makes them promising in biosensor application and has the potential to make a better alternative of conventional diagnostic methods. This review also demonstrates the commercially available and FDA/ICMR approved LFIA kits for on-site diagnosis of SARS-CoV-2.

Rapid detection of SARS-CoV-2 using graphene-based IoT integrated advanced electrochemical biosensor.

Unique characteristics like large surface area, excellent conductivity, functionality, ease of fabrication, etc., of graphene and its derivatives, have been extensively studied as potential candidates in healthcare applications. They have been utilized as a potential nanomaterial in biosensor fabrication for commercialized point-of-care (POC) devices. This review concisely provided innovative graphene and its derivative-based-IoT (Internet-of-Things) integrated electrochemical biosensor for accurate and advanced high-throughput testing of SARS-CoV-2 in POC setting.