key: cord-0702403-xvazfyiq
authors: Aljabali, Alaa A.A.; Pal, Kaushik; Serrano-Aroca, Angel; Takayama, Kazuo; Dua, Kamal; Tambuwala, Murtaza M.
title: Clinical utility of novel biosensing platform: Diagnosis of coronavirus SARS-CoV-2 at point of care
date: 2021-08-06
journal: Mater Lett
DOI: 10.1016/j.matlet.2021.130612
sha: 7e9c513f20f8d48f7ef43d7ca78ac1943d105438
doc_id: 702403
cord_uid: xvazfyiq

Early detection is the first step in the fight against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, an efficient, rapid, selective, specific, and inexpensive SARS-CoV-2 diagnostic method is the need of the hour. The reverse transcription-polymerase chain reaction (RT-PCR) technology is massively utilized to detect infection with SARS-CoV-2. However, scientists continue to strive to create enhanced technology while continually developing nanomaterial-enabled biosensing methods that can provide new methodologies, potentially fulfilling the present demand for rapid and early identification of coronavirus disease 2019 (COVID-19) patients. Our review presents a summary of the recent diagnosis of SARS-CoV-2 of COVID-19 pandemic and nanomaterial-available biosensing methods. Although limited research on nanomaterials-based nanosensors has been published, allowing for biosensing approaches for diagnosing SARS-CoV-2, this study highlights nanomaterials that provide an enhanced biosensing strategy and potential processes that lead to COVID-19 diagnosis.

pandemic and nanomaterial-available biosensing methods. Although limited research on nanomaterials-based nanosensors has been published, allowing for biosensing approaches for diagnosing SARS-CoV-2, this study highlights nanomaterials that provide an enhanced biosensing strategy and potential processes that lead to COVID-19 diagnosis.

Diagnostics developed using, for example, conventional immunological tests such as radioimmune assay and enzyme-linked immunoassay detect levels of special viral immunoglobulins in serum patients [1] . At the same time, other methods are based on the detection of nucleic acids (DNA or RNA) in aa quantitative and qualitative manner [2] and are amplified using polymerase chain reaction technology (PCR) [3] , the critical development of a point-of-care diagnostic assay for disease detection, monitoring, and management. Such point-of-care includes tests that analyze samples in field hospitals, outside clinical laboratory settings, and are often performed by clinical staff without laboratory training for quick results, and such systems are based on lateral flow immunoassays [4] [5] [6] . Viral isolation is the gold standard procedure and the most sensitive approach, even though it takes 3-7 days and is tedious [7] . Anyway, the serological examinations of viral antibodies against viral antigens are less sensitive and non-specific [8] . Nanosensors are quantitative procedures employed to identify numerous infectious illnesses in straightforward, real-time, and effective methods [9] .

The design of glucose oxidase biosensors reported by Clark and Lyon was one of the earliest biosensor reports at the beginning of the sixties [10] . Biosensors consist of bioreceptor, transducers, and signal processing systems as three primary parts [11] .

Bioreceptor in biosensors may selectively interact with the biomarker utilizing monoclonal antibodies, glycan, nucleic acid, lectin, enzyme, tissue, or entire cells, as depicted in Figure 1 [12] . The transducer converts these interactions to a quantifiable and measurable signal and then analyses and reports qualitative and quantitative pathogen identification using obtained signals [13, 14] . The target analyte comprises antigenic viruses, which might be the entire virion, virus capsid proteins, virus-specific antibodies, and viral nucleic acids. Biosensors have been prepared and functionalized using nanoparticles to improve the specificity and selectivity of the detection of target molecules. The available sensing platforms have been developed over the past few decades. The immobilization of the solid phase transducers (carbon, gold, silicone, or hydrogels) onto a conducting polymer surface (polyaniline or polypyrrole) alternatively covalent conjugation through linkers to form self-assembled monolayers with a terminal functional group (thiol, carboxyl, amine, and maleimide) that binds to the transducer surface. The selective binding between the analyte with the sensing platforms leads to biochemical signals, including pH, electron flow, mass, and heat changes. These generated changes can be converted and amplified to generate a measurable signal (optical and electrochemical biosensors). A general biosensor relies on optical exposure of analytes such as surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) [15, 16] .

Such optical sensing platforms depend on direct and indirect detection techniques.

Indirect binding through the fluorophores as tagging and labeling methods, the direct methods depend on the refraction of the analyte with optical properties and measure the changes in the refractive index at the interface as measured by SPR based sensors allow for real-time monitoring. Nanomaterials such as silver NPs (AgNPs), gold (AuNPs), carbon-based are commonly used with optical sensing [17] . The photon strikes the metallic surface of the NPs at a precise angle. This is followed by light energy pairs with the electrons of the metallic surface, leading to excitation due to electrons movement as in the SPR example [18, 19] .

One of the significant challenges for the development of biosensor platforms is to design appropriate biological sensors for screening or diagnostics, and it is necessary to determine the clinical infectious dosage of SARS-CoV-2. Most viral RNA samples in higher respiratory tract concentrations are between 10 2 -10 8 copies per swab, and the highest is 7.11 copies per dab at the first week of the start of the symptoms and, in most cases, more than 10 2 per dab at the first week in sputum and stool dose [20] . As indicated by a recently completed virological laboratory analysis of 9 patients, most viruses in the RNA samples are more than 10 2 copies per dab [20] .

For example, the use of ultrasensitive graphene field-effect transistor immunosensor has been described in recent times as an effort to easily and rapidly screening for SARS-CoV-2 [21] . The SARS-CoV-2-spike S1 subunit antibody protein (ACE2) or the angiotensin-converting (2) receptor has been conjugated to a graphene surface. The hybridization of the S1 protein receptor-binding domain (RBD) with the immobilized spike S1 subunit protein antibody/ACE2 receptors, which could be read electrically in a mild form, changes its conducting/resistance via the field effect [22] . This immunebased biosensor can instantly recognize the SARS-CoV-2 spike S1 at 0.2 pM, instantaneously and without being labeled, and accurately bind to it. The graphenecoated surface with SARS-CoV-2 antibodies generated measurable electrical changes that can be directly correlated with the viral presence from samples obtained via saliva swabs or serum. This approach was reported from 19 patient's data and reported to be sensitive with a load of detection that reached 2.42 × 10 2 copies/mL [23] . Such an approach holds great potential in minimizing false positive detections, giving the complexity of biological samples used to detect the virus. One possible approach to developing a SARS-CoV-2 biosensor is using non-structural surface glycoproteins ORF8 and E2 that may bind and release the heme porphyrin inside the 1-beta hemoglobin chain. SARS-CoV-2 proteins attach to hemoglobin molecules of the transducer that releases a hemoglobin portion that generates an electric signal when considered for heme concentration measurement before and after the examination.

Alternatively, the anti-spike RBD monoclonal antibodies of Human-IgG1 bind directly with the analyte spike RBD [12] . A lateral flow test for detecting immunoglobulins that can distinguish between COVID-19 patients within 15 minutes and identify the infection stage by detecting IgG or IgM for precise and rapid viral detection.

Another approach following the metagenomic RNA sequencing method was utilized to distinguish the SARS-CoV-2 genome shortly after the preliminary occurrence was reported based on next-generation sequencing. However, this technique is sensitive and is limited by performance, turn-around time, expenditure, and high technological capability needs. During pulmonary dysfunctions caused by SARS-CoV-2 infections, traces of mitochondrial reactive oxygen species (ROS) have been overproduced. Therefore, a reliable and straightforward ROS sensor has been developed using this phenomenon for a sample isolated from 500 µl patients' sputum samples [24] . The electrochemical immunosensor comprises carbon nanotubes coated on a steel needle's tip with three electrodes resembling electrochemical cells (work, counter, and reference). The observations have been obtained under sweeping potential from -0.8 to 0.8 V with a scan rate of 100 mV/s. The reported result showed that over 97% of the actual positive patient test were detected using this ROS system in 30 seconds [25] .

During this pandemic, the need to develop reliable and fast detection methods was in high demand. Hence the development of paper-based biosensors as a cheaper alternative, biodegradable, and the ease to fabricate makes them one of the suitable alternative detection methods [26] . Lateral flow test strips, for example, were used to identify SARS-CoV-2. It is intended to detect IgG and IgM in patient serum, blood, or plasma samples [27] . Thus every test strip typically comprises of (i) sample pad for the test samples; (ii) a SARS-CoV-2 antigen, conjugated to gold-SARS-CoV-2; and the gold-rabbit IgG;(iii) IgG-coated control line with an IgG test line with an anti-human IgG-coating and IgM test line with an anti-human IgM [28] . Once IgM and/or IgG are present in-patient samples, antibodies react to form a complex containing gold-SARS-CoV-2 antigen migrating over the nitrocellulose membrane, interacting on their respective test lines with anti-IgMs and/or IgGs. In turn, the gold-rabbit IgG reacts to the visible red color utilizing the anti-rabbit IgG coated at the control line. A positive IgM or negative IgG or positive suggests a primary or acute infection in both directions, but a positive IgG denotes a secondary or later stage of infection with negative IgM [29] . The glass fiber for viral nucleic acid detection, loop-mediated isothermal amplification is another rapid technology analytic strip an alternative (LAMP), and integrated lateral flow test strip to generate a detectable colorimetric signal [30] .

Nevertheless, compared to the primary detecting method, such an essential instrument requires a heat block for amplification. Each functional layer is separated by hydrophobic polyvinylchloride substrates, which control the fluid flow between layers.

To substantially simplify processes, a simple, automated, feasible, and integrated paperbased biosensor has been built [17] Conclusions:

Following the shocking numbers of casualties and the catastrophic economic crisis globally, rapid advances have been made to fight against coronavirus disease 2019 (COVID-19). Improved and accurate methods are essential in this context to avoid and control any potential future viral or microbial outbreaks. Thus, laboratory-independent, high-throughput and reliable, inexpensive, and portable screening is the most crucial technology to be developed. Along with considerations of extraordinary responsiveness, minimal size, and low costs, new sensors based on well-designed nanomaterials, nanotechnology, and innovative sensing processes have the potential to develop next-generation biosensors. Advances in molecular and synthetic biotechnology, the finding and bioengineering of new coupling materials such as nanobodies and aptamers could make it easier to identify new pathogens in the future.

New intelligent sensing techniques combine biosensors' incredible sensitivity with improvements in artificial intelligence and various technologies that can improve control over the spread of pathogens. In summary, developing nano-based biosensors with such appealing features can provide the opportunity for rapidly screening for viral infection within a population and contribute toward confining viral spread.

Rapid and Non-Radiolabeled Immune Assay to Detect Anti-AChR Antibodies in Myasthenia Gravis

Advanced Evanescent-Wave Optical Biosensors for the Detection of Nucleic Acids: An Analytic Perspective

A review on microscale polymerase chain reaction based methods in molecular diagnosis, and future prospects for the fabrication of fully integrated portable biomedical devices

Tailored Biofunctionalized Biosensor for the Label-Free Sensing of Prostate-Specific Antigen

Kaushik, 1 -Nanotechnology and its application: a review

Laboratory Testing Methods for Novel Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)

Chapter 30 -Virus detection using nanosensors

What is a Biosensor?

Short-term BOD (BODst) as a parameter for on-line monitoring of biological treatment process: Part I. A novel design of BOD biosensor for easy renewal of bio-receptor

Biosensors as a future diagnostic approach for COVID-19

Advances in nanowire transistors for biological analysis and cellular investigation

Advanced biosensors for detection of pathogens related to livestock and poultry

Clinical infectious diseases : an official publication of the Infectious Diseases Society of

Nanoscale virus biosensors: state of the art

Noble metal nanoparticles in biosensors: recent studies and applications

Surface plasmon resonance: a versatile technique for biosensor applications

Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era

Virological assessment of hospitalized patients with COVID-2019

Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes

Electrical probing of COVID-19 spike protein receptor binding domain via a graphene fieldeffect transistor

Facile biosensors for rapid detection of COVID-19

Real-time diagnosis of reactive oxygen species (ROS) in fresh sputum by electrochemical tracing; correlation between COVID-19 and viral-induced ROS in lung/respiratory epithelium during this pandemic

Biomarkers associated with COVID-19 disease progression

Predicting COVID-19-Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management

Development of Point-of-Care Biosensors for COVID-19

Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis

Detection of antibodies against SARS-CoV-2 in patients with COVID-19

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

 For the diagnosis of SARS-CoV-2, several amplification and sensing assays could be used  Summarize research of nanomaterials enabled biosensors for SARS-CoV-2 detection  Biosensing outputs must be quantitatively presented to achieve more accurate and comprehensible outcomes

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: