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.

Electrochemical Immunosensor for Early Detection of ß-Amyloid Alzheimer's Disease Biomarker Based on Aligned Carbon Nanotubes Gold Nanocomposites.

Beta-amyloid (ßA) peptides accompanying the physiological change in brain induce Alzheimer's disease. In this work, a highly sensitive electrochemical (EC) immunosensor platform has been developed for the quantitative detection of ßA peptides, using the gold nanoparticle functionalized chitosan-aligned carbon nanotube (CS-aCNT-Au) nanocomposites on glassy carbon electrodes (GCE). The immunosensor has been fabricated by immobilization of the anti-ßA antibody upon CS-aCNT-Au/GCE. In the CS-aCNT nanocomposite, CS has high biocompatibility. Hydroxy and amine functionalities favor the antibody immobilization and prevent the leaching of nanocomposites of the modified electrode due to the adhesive environment. Moreover, aCNT offers high conductivity, stability, and a large surface area (the calculated effective surface area of the CS-aCNT/GCE is 8.594 × 10-2 cm2). However, the incorporation of AuNPs further enhances the conductivity of the CS-aCNT-Au nanocomposite based on differential pulse voltammetry (DPV) results, and also improves the effective surface area (9.735 × 10-2 cm2). The surface morphology and electrochemical studies of the nanocomposite, as well as its modifications by the anti-ßA antibody and BSA, were carried out through field emission scanning electron microscope (FESEM), cyclic voltammetry (CV), and DPV. The quantitative immunosensing of the ßA in phosphate-buffered saline (PBS) solution is accomplished via DPV, which reveals that the immunosensor has a high sensitivity of 157.60 µA pg-1 mL cm-2 and a broad detection range of 10.0 pg mL-1-100.0 µg mL-1, with a limit of detection (LOD) of 0.87 pg mL-1. Subsequently, we detected the spiked ßA in diluted serum with a linear detection range of 10.0 pg mL-1-1.0 ng mL-1 and LOD of 0.95 pg mL-1. Moreover, a selectivity study exhibited a high affinity of immunosensors towards ßA. Thus, we propose that this highly efficient immunosensor can potentially be applied for the point-of-care (POC) sensing of ßA in clinical samples.

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.

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.

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.

Biosensor-based diagnostic approaches for various cellular biomarkers of breast cancer: A comprehensive review.

Breast cancer is the most commonly occurring cancer among women which leads to thousands of deaths worldwide. The chances of survival are more if the breast cancer is diagnosed at early stage. At present, mammography, magnetic resonance imaging, ultrasound and tissue biopsies are the main diagnostic techniques available for the detection of breast cancer. However, despite of offering promising results, requirement of expensive setup, skilled supervision, expert analysis, invasive procedure (biopsy) and low capacity of multiplexing are the main limitations of these diagnostic techniques. Due to high cost, these screening tests are out of reach of people belonging to low socioeconomic groups and this poses serious health burden to the society. Recently, biosensor-based diagnostic technology for early detection of various types of cancers and other non-oncological disorders have gained considerable attention because of their several advantageous features over existing diagnostic technologies such as high throughput, noninvasive nature, cost effectiveness, easy interpretable results and capacity for multiplexing. Further, biosensors can be designed for biomarkers which are confined to particular type of cancer. In this review, we have discussed about various genomic, transcriptomic, proteomic and metabolomic biomarkers associated with breast cancer, various biosensors-based diagnostic approaches designed for detection of specific biomarkers associated with breast cancer are also described. Further, this review throws insight on various biomarkers linked with breast cancer which can be effectively exploited to develop new diagnostic technology. The assessment of these biomarkers associated with BC using biosensors in large population are cost-effective, non-invasive and high throughput. They help in risk assessment of disease at very initial stage even in backward areas and also help to lower the disease burden of society and economic cost of treatment for a common man. This review would provide new avenues for the development of biosensor based diagnostic technology for the detection of biomarkers associated with breast cancer.

Point-of-Care Biosensor-Based Diagnosis of COVID-19 Holds Promise to Combat Current and Future Pandemics.

Efficient and rapid detection of viruses plays an extremely important role in disease prevention, diagnosis, and environmental monitoring. Early screening of viral infection among the population has the potential to combat the spread of infection. However, the traditional methods of virus detection being used currently, such as plate culturing and quantitative RT-PCR, give promising results, but they are time-consuming and require expert analysis and costly equipment and reagents; therefore, they are not affordable by people in low socio-economic groups in developing countries. Further, mass or bulk testing chosen by many governments to tackle the pandemic situation has led to severe shortages of testing kits and reagents and hence are affecting the demand and supply chain drastically. We tried to include all the reported current scenario-based biosensors such as electrochemical, optical, and microfluidics, which have the potential to replace mainstream diagnostic methods and therefore could pave the way to combat COVID-19. Apart from this, we have also provided information on commercially available biosensors for detection of SARS-CoV-2 along with the challenges in development of better diagnostic approaches. It is therefore expected that the content of this review will help researchers to design and develop more sensitive advanced commercial biosensor devices for early diagnosis of viral infection, which can open up avenues for better and more specific therapeutic outcomes.