key: cord-0701826-tcdlbuw1
authors: Aziz, Ayesha; Asif, Muhammad; Ashraf, Ghazala; Farooq, Umer; Yang, Qiaoli; Wang, Shenqi
title: Trends in biosensing platforms for SARS-CoV-2 detection: A critical appraisal against standard detection tools
date: 2021-01-20
journal: Curr Opin Colloid Interface Sci
DOI: 10.1016/j.cocis.2021.101418
sha: a1ab92f95d1a1e8425b439ead624ab80fbfd8603
doc_id: 701826
cord_uid: tcdlbuw1

In this ongoing theme of COVID-19 pandemic, highly sensitive analytical testing platforms are extremely necessary to detect SARS-CoV-2 RNA and antiviral antibodies. To limit the viral spread, prompt and precise diagnosis is crucial to facilitate treatment and ensure effective isolation. Accurate detection of antibodies (IgG and IgM) is imperative to understand the prevalence of SARS-CoV-2 in public and to inspect the proportion of immune individuals. In this review, we demonstrate and evaluate some tests which have been used commonly to detect SARS-CoV-2. These include nucleic acid tests and serological tests for the detection of SARS-CoV-2 RNA and specific antibodies in infected people. Moreover, the vitality of biosensing technologies emphasizing on optical and electrochemical biosensors towards the detection of SARS-CoV-2 has also been discussed here. The early diagnosis of COVID-19 based on detection of reactive oxygen species (ROS) overproduction owing to virus induced dysfunctioning of lung cells has also been highlighted.

Recently, COVID-19 has caused a world health disaster and socioeconomic adversity by infecting millions and killing thousands of people. This pandemic is reported to have appeared as a result of a novel mutation of coronavirus as the seventh member of corona family outbreaking J o u r n a l P r e -p r o o f in December 2019 in Wuhan, China [1] . Subsequently, it was noticed that this novel coronavirus possessed 96% genome sequence similarity with SARSr-CoV-RaTG13 (bat SARS) and 79.5% with SARS-CoV [2] . The single stranded RNA β-coronavirus [3] with Nidovirales order belongs to the Coronaviridae family [4] and comprises of nucleocapsid, spike (S), membrane (M) and envelope (E) proteins as shown in Figure 1A . The receptor-binding domain (RBD) in spikeprotein shares the angiotensin-converting enzyme 2 (ACE2) of human cells as a receptor [5] . The spike proteins are strongly attracted towards ACE2 which defines the virus-host array to receptor binding domain and ensures the viral fusion with host cell membrane [6] .

As of today, in the absence of any recommended vaccine so far, swift and reliable diagnostic methods are of great significance for the diagnosis of symptomatic as well as asymptomatic COVID-19 cases [7] . The quick and reliable treatment decisions and quarantine strategies to slow down the spread of this infectious disease are all based on the diagnostics [8] . Some conventional testing methodologies like thoracic imaging, portable chest X-ray, flexible bronchoscopy and computed tomography (CT) scan have been used for the preliminary diagnosis of infection. The quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) based testing [9] is regarded as the most popular test these days. Although these testing techniques are of great value but time consumption, tedious sample preparation and the need of expertise put them at the back. The infection rate and contagiousness of SARS-CoV-2 is much higher compared with other SARS infections. Therefore, rapid and point of care diagnostic methods are highly desirable to overcome the limitations of conventional techniques.

For rapid and point of care detection, lateral flow assay (LFA), loop-mediated isothermal amplification (LAMP) method, reverse transcription-LAMP (RT-LAMP) approach , clustered regularly interspaced short palindromic repeats (CRISPR) technology [10] and SHERLOCK [11] detection methods are generally implemented these days. Moreover, enzyme-linked immunosorbent assay (ELISA), lateral flow assays and microfluidic devices are the point of care testing methods under consideration. The technology behind testing is based upon biosensing; either in the form of undeviating detection of biochemical and biotic molecules from the living sources or it is biomarker detection from bionics. The direct binding of analyte with target molecules and biochemical reactions are two benchmark spectacles of biosensing approaches.

However easy handling, small sample size, real time analyte tracing, and flexibility to detect the target analyte of interest within seconds are the other major advantages of biosensing platforms J o u r n a l P r e -p r o o f which can circumvent the bottlenecks of other techniques [12] . It is also worth mentioning that electrochemical biosensors are reliable analytical techniques with the potential of being modest to sample absorbance or turbidity for the detection of contagious disease.

Herein, we outline the SARS-CoV-2 detection techniques with their pros and cons. We also present recent advances in standard testing tools and emerging biosensing platforms as portable devices for the timely detection of SARS-CoV-2 in order to prevent the spread of the infection.

We also aim to offer a new perspective on the biosensor-based technologies for the rapid and reliable detection of SARS-CoV-2 to carry out the early diagnosis of COVID-19. This review concludes with a short discussion regarding current challenges and future perspectives.

The most commonly used techniques for COVID-19 diagnostics are nucleic acid test and CT scan. The procedure of identification and targeting the virus is considered more suitable when molecular approaches are used in comparison to syndromic or CT scan methods. These molecular approaches are developed after analyzing the proteomic and genomic structure of the microbes. The first genomic research on SARS-CoV-2 was done using metagenomic RNA sequence which is an efficient way of sequencing different genomes [13] .

The RT-qPCR is a version qPCR technique which is unequivocally developed for RNA detection.

So, it is being used for SARS-CoV-2 detection because it directly tests for the existence of virus RNA. RT-qPCR is regarded as the standard approach for COVID-19 identification. This approach is sufficiently reliable and can complete the results in few hours [14] . The commercially available kits use RT-qPCR techniques which detect more than two target regions and consequently the detection sensitivity is enhanced. This technique amplifies even a small viral genetic material in the testing samples. It works on two consecutive reactions; firstly, it converts the virus RNA to small complementary DNA sequence (cDNA) for special identification of paired sequencing on viral RNA. Secondly, cDNA is amplified through PCR utilizing gene-specified primers and fluorescent labeled hydrolysis probes. The DNA produced in first step is used in second step where it is multiplied though repeated thermal cycling and finally the virus is detected by using quantitative qPCR machine. To date, numerous RT-qPCR J o u r n a l P r e -p r o o f kits has been established for the SARS-CoV-2 detection by targeting the structural proteins and accessory genes (nucleocapsid (N), spike (S) protein, (RdRP), envelope (E) or ORF1b, ORF8 genes) as biomarkers for SARS-CoV-2 detection. The reverse transcription of SARS-CoV-2 RNA into complementary DNA (cDNA) takes place in RT-qPCR test case where the specific cDNA zone is further amplified to complete the process [15, 16] . Zambon's research group conducted a research on alignment and investigation of several SARS-associated genome sequencing to develop the primers and probes [17] . The E, N proteins and RNAP (RNA polymerase) gene are amid three of discovered genes at present. First two of the three genes are found to have high analytical sensitivity while the third one offers feeble sensitivity for detection. The RT-qPCR tests are carried out both in single-step and double-step procedure. The single-step assay exhibits rapid response and good reproducibility, and the whole process of reverse transcription and PCR amplification takes place in one step. However, this procedure finds it difficult to optimize reverse transcription and amplification based on the simultaneous occurrence of both steps. In comparison, double-step assay shows high sensitivity but requires more time as the reactions are completed in separate tubes. Although the two steps assay is highly sensitive and flexible but one step assay is favored for the detection of SARS-CoV-2 owing to its speed, simplicity, limited sample requirement, minimum counter time as well as less cross contamination during the RT and real time polymerase reaction periods [18, 19] . Xiang's research group presented DNA nanoscaffold-based SARS-CoV-2 detection to diagnose COVID-19 [20] . Recently, Lubke's research group designed RNA extraction free protocol based on RT-qPCR for the detection of SARS-CoV-2 where the E-gene was targeted as novel primer [21] . Without dilution and heat inactivated 5 µl respiratory samples were used. The assay was validated using 91 respiratory samples where 81.3% samples were detected positive. It is concluded that direct RT-qPCR is a well-acknowledged alternative to conventional RNA RT-qPCR for analyzing fresh samples. Li et al. has studied 610 patients who were diagnosed with COVID-19 according to CT scan diagnosis, and reported the higher rate of false negative RT-PCR results for SARS-CoV-2 detection [22] .

The variations in the results by RT-PCR detection might be possible due to the low viral load in the test samples at early stages of infection, prolonged RNA conversion and transmutations in the probes target regions [23] . PCR assays are not sensitive enough to differentiate between symptomatic and asymptomatic patients [24] and susceptible to few generalizations which limit their applications such as, J o u r n a l P r e -p r o o f i. The small countryside hospitals are not well equipped to carry out PCR tests. Lack of expertise and infrastructure limit this facility.

ii. There is a possibility of false negative results because the appropriate sampling time for nasopharyngeal swab is still vague for the patients on ventilators [25] .

iii. A tedious procedure for sample preparation is required which includes cell lysis and nucleic acid purification. Also the extractions kits are less than the ramping up demand of tests [26] .

iv. During transportation, the denaturation of sample may occur which leads to false negative results [27] .

v. In case of fully recovered patients, PCR testing can even result false positive outcome detecting genetic material of inactive SARS-CoV-2 which is actually not reinfection. The genetic material never dies and can persist in the body for several days to months so it can be detected after months of recovery [28] .

vi. The nucleic acid amplification is employed in PCR testing where distinct primers and probes for every target are needed that consequently limit PCR's flexibility of scaling up for other nucleic acids in an easy and prompt way.

vii. If mutations of SARS-CoV-2 (which are likely to be) are undergoing then it may be a problem for same target. Thus, continuous monitoring of viral genetic material is mandatory to warrant the accuracy of test [29] .

No doubt qPCR and RT-qPCR are evolving day by day with the number of advantages but these few considerations are needed to be improved in RT-qPCR to make quick, more sensitive and especially cost effective detection method.

In case of inadequate availability of these kits and false negative results of RT-qPCR, a noninvasive CT scan technique has also been used in clinical diagnostics of COVID-19 [30] . The characteristics of these images are closely related to stage of infection when the symptoms are shown. At the early stage infection, transparent, localized lesions were confined to the subpleural area of one or both lungs of patients after the appearance of symptoms [31] . When bilateral and peripheral ground-glass denseness and amalgamation of the lungs are appeared then these are the characteristic symbols of COVID-19. With the progression of COVID-19 infection, the lungs consolidation increases in addition to crazy paving pattern. The aforementioned outcomes have J o u r n a l P r e -p r o o f revealed that CT scan method showing better false negative rates is more sensitive in comparison with RT-qPCR but the initial level screening with CT scan is restricted. The major drawback of CT scan method in COVID-19 diagnosis is the lack of specificity due to the overlap of lungs images with other pneumonia. Moreover, the CT scan diagnoses the patients at advanced stage of infection [32] .

The reliable diagnosis of COVID-19 is carried out using protein tests such as antigens and antibodies [33] . The saliva test may vary with passage of time after the symptoms appear but in comparison, antibodies persist for a long time which enable large span for indirect SARS-CoV-2 detection [34] . The commonly used methods for antibody detection are lateral flow assays and enzyme-linked immunosorbent assay (ELISA). In lateral flow assay, the sample is deposited onto sample pad of cassette like device and moved through strip by capillary action. The antibodies labeled with Au NPs bind with target molecules present in sample at the first line. IgM type antibodies or both, there should be one, two or three stripes in display window [35] .

The average test time of 10 to 30 minutes places it in the rapid diagnostic methods. It provides only qualitative analysis but has the advantages of easy handling and cost effectiveness and allows direct assessment of ongoing infection as anti-CoV antibodies are used instead of immobilized viral antigen [36] . Recently, Kong's group has developed highly sensitive, fast, easy to use and on-site immunoassay which can complete the assay in 15 min to detect SARS-CoV-2 antibodies and antigens at the same time. The antibodies from human serum samples and SARS-CoV-2 antigens from nasal swab were detected successfully from 26 COVID-19 infected and 28 healthy individuals by using this integrated method [37] . Moreover, Feng's research group has constructed a simple operated point of care lateral flow immunoassay to simultaneously detect antibodies (IgG, IgM) developed against SARS-CoV-2 in blood samples of affected people at various phases of infection. The achieved sensitivity and selectivity of this testing method were 86.6% and 90.6% respectively [38] . The assay for simultaneous detection of detect anti-SARS-CoV-2 S1 IgG from human serum using just 8 µl sample [39] . The practicability of this method has been verified in detecting anti-SARS-CoV-2 S1 IgG in 16 convalescent SARS-CoV-2 infected persons.

The immunoglobulin IgG and IgM have been detected from serum sample of infected individuals by employing ELISA where nucleocapsid protein of SARS-CoV-2 is used. The typical result time of ELISA is 60 min to 5 hours either the test is quantitative or qualitative.

ELISA being fast, flexible, robotics, high throughput with variable sensitive range and ability to test multiple samples is specifically suitable as point of care purpose [40, 41] . In ELISA test, human serum sample is added to the well where the recombinant viral antigen is already coated.

The bindings occur between antibodies and target antigen present in sample and then washing is done several times to make sure the complete removal of unbound substrate. Another solution comprising of labeled antibodies is mixed and binding will occur if the antibodies of interest are present in the sample. After washing again to remove unbound substrate, horseradish peroxidase is used as color changing reaction to confirm the binding of target antibodies. Using a spectrometer, color change is read and concentration of antibodies is measured [42] . It has been noticed that the antibodies are developed in SARS-CoV-2 infected people after around 14 days of onset of symptoms. However, some studies depict the development of IgG and IgM antibodies after five days of SARS-CoV-2 infection [43] . The level of antibodies in patients may go on increasing after five days of symptoms appear. The antibodies were also found in respiratory fluids, blood and fecal specimens.

Lateral flow assays are preferred over ELISA tests because these tests can be performed at home without the need of any expert. ELISA is the analytical technique which can only be carried out in laboratories with the help of skilled personnel and high protocol as well as it requires different steps, long turnaround time and special instruments. Owing to these limitations, the recent studies are more focusing to enhance the sensitivity and selectivity of lateral flow assays. Therefore, signal amplification and multiplexed detection methods are under development in order to achieve increased sensitivity, selectivity and detection throughput. The development in serological tests for SARS-CoV-2 antibody faces the issues of being cross-reactive with other J o u r n a l P r e -p r o o f family members of coronavirus. Okba observed the cross-reactivity among S proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. But there was no cross-reactivity for S1 subunit of MERS-CoV spike protein. The most conserved subunit among all coronaviruses is S2 which can increase the suitability of S1 subunit for serological tests [44] .

Antigen tests can be considered more reliable compared with antibodies tests because antigens are target specific and introduce antibodies [45] . Both the lateral flow assays and ELISA methods can be used for the detection of antigens. Kim's research group developed a novel detection method where they used ACE2 receptor to detect SARS-CoV-2 spike 1 (S1) protein [46] . The receptor is further paired with commercially available antibodies and this pair was captured and detected using lateral flow immunoassay. There was no cross-reactivity with other coronaviruses showing a detection limit of 1. and SARS-CoV that mean the kit is unable to make differentiation between these two viruses. The kit showed clinical sensitivity of 80% and selectivity of 100% for 47 positive and 96 negative individuals [47] . Following the failures of kits, WHO discouraged the medical staff to use rapid commercial assays to detect SARS-CoV-2. There are two companies "QUIDEL and, Avacta and Cytiva" which are working for the development of trustworthy antigen test kits. The targets for these two kits are N protein, and SARS-CoV-2 viral antigens or S glycoproteins [48] Point of care testing J o u r n a l P r e -p r o o f Point of care testing is also much imperative to diagnose SARS-CoV-2 infected persons without sending them to hospitals. In pandemic, the most important is the mass testing to identify the persons with viral exposure for quarantine and treatment strategies. When the viral infection continues to spread at exponential rate then RT-PCR and immunoassays become limited due to 

The imperative need of time is, to develop nucleic acid and protein based testing for diagnosing COVID-19 to compensate the RT-qPCR drawbacks. Fascinatingly, an international company has used the combination of PCR with lateral flow assay technique as an alternate method to detect SARS-CoV-2 within the exhaled breath condensate. Moreover, isothermal amplification of genetic material is an alternative approach to PCR for developing point of care devices in order to carry out the quick detection of nucleic acid.

Several organizations are striving to implement the isothermal nucleic acid amplification techniques in the detection of SARS-CoV-2. The isothermal amplification approaches are the best options that can be operated at a single temperature without particular laboratory apparatus providing sensitive results [52] . The helicase-dependent amplification, loop-mediated isothermal amplification (LAMP) and reverse transcription (RT-LAMP) approaches turned out to be established to detect SARS-CoV-2 and are more specific, sensitive and reaction efficient [53] .

The LAMP technique is more sensitive and specific but it uses high number of primers. In to detect SARS-CoV-2 through ORF1ab and N gene detection [57] . The SARS-CoV-2 detection is possible in less than 13 minutes but the one sample/run and the optimizations of primers and reaction conditions are the major limitations associated with LAMP techniques [58] . These isothermal amplification systems may also be multiplexed at the amplification and/or readout stages. The process of multiplexing is done by using organic fluorescent molecules as beads for barcoding. Furthermore, visual detection approaches are also being carried out using some dyes which utilize intrinsic by-products of widespread DNA synthesis. Fascinatingly, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12 lateral flow test was utilized to achieve enhanced sensitivity, simplified result read and reduced detection time for RT-LAMP method [59] . Researchers are devoting much efforts in utilizing collateral cleavage activity of 

The biosensors are emerging area of analytical chemistry. The biosensing systems are able to provide quantitative analysis and measurements without demanding extra processing steps or reagents [63, 64] . The biosensor-based technologies offer alternative approach to standard PCR tests which are not only sensitive but also helpful in diagnostics and therapeutic assessments.

Biosensors have the capability to detect pathogens in numerous environments without requiring tedious sample preparing steps [65, 66] . Several biosensors with diverse biorecognition elements (enzyme, antibody, deoxyribonucleic acid, cell, or microorganisms) and transducers (such as mechanical and optical transducers) have been extensively applied in the detection of pathogens [67] . Labels can also be named as reporters which are molecular species including organic dyes or quantum dots which bind to the target, either in a direct way or via a biorecognition element to enable the detection [68, 69] . The biosensors are now trending for SARS-CoV-2 detection, specifically the clustered regularly interspaced short palindromic repeats (CRISPR) technologybased biosensing systems such as CRISPR-Chip to electrically detect genetic mutations [70] and electrochemical CRISPR-biosensing platforms for microRNA analysis [71] . These approaches are easily adapted to any nucleic acid and can be able to report the mutations of SARS-CoV-2 in timely way. Moreover, successful differentiation in similar gene sequences with superb sensitivity has been recently reported by using combination of plasmonic photothermal effect and localized surface plasmon resonance. Here we have summarized the recently used several analytical approaches (see Table 1 ) for the detection of SARS-CoV-2. 

To timely and efficiently diagnose COVID-19 infection, the detection of immunoglobulin A (IgA) specific to SARS-CoV-2 is highly crucial to complement the assays used in the detection of IgM and IgG. Anfossi's research group has designed a dual functioning optical/chemiluminescence immunosensor for the detection of IgA from serum and saliva samples as presented in Figure 2A J o u r n a l P r e -p r o o f

The biosensors are considered most trustworthy diagnosis approaches as an alternate way out to clinical analysis, real-time and nonstop monitoring in order to promote epidemic prevention and control [85, 86] . It is well-documented that huge optical cross sections are shown by plasmonic nanoparticles and abundant heat energy is produced as a result of nonradiative relaxing process of absorbed light [87] . biosensors with microfluidic systems may increase overall sensitivity of device helping in miniaturization process [89] .

In last decades, microfluidic devices have been used for the contagious ailments like HIV, SARS-CoV and others which target the biomarkers in less than 5 min consuming only 6 μL of blood plasma sample [90] . 

Moreover, electrochemical biosensors have attracted immense attention of the researchers because of their capabilities to offer sophisticated ways to interface at molecular level, DNA recognition and signal transduction elements and are economical requiring low volume and power for DNA detection [93, 94] . The electrochemical biosensing podium to detect different viruses including SARS-CoV-2 has been described in Figure 4A The scheme representing the concept of SPCE/NPs/nano-Dendroids/GO/Ab probe fabrication to diagnose COVID-19 has been shown in Figure 4B 

The biomarker based detection of COVID-19 without using viral RNA, antigen, antibodies and whole virus particles for detection, may be an interesting strategy in pandemic. It is welldocumented that the existence of viral RNA is acknowledged to initiate the activation of NLRP3 inflammasome through RNA-modulating proteins and to trigger the generation of reactive oxygen species (ROS) [108] . Moreover, Zika virus has also been found to induce oxidative stress which ultimately lowers antioxidant enzyme activities. During in-vitro and in-vivo studies, it has been confirmed that the infection caused by Zika virus significantly enhances ROS production and lipid peroxidation products while decreases superoxide dismutase and catalase activities [109] . 

The detailed comparison among various detection approaches has been discussed with their distinguish characteristics as given in Table 3 . There are different detection methods such as immunofluorescence approaches, cell culture based methods, molecular assays and electrochemical biosensing based approaches. 

Highly specific and sensitive. Sensitivity is less as compared to cell culture based methods, as well as, being highly specific cannot be used for all types of viruses, exhibit poor sensitivity against some viral particles. Moreover, need expertise. [112] Cell culture based methods Sensitivity is higher as compared to most antigen testing methods. Specific viral particles can be isolated even from the mixed culture medium. Facilitate the Antiviral, serotype as well as epidemiological studies.

Long incubation period and need of expertise are major disadvantages related to cell culturing methods.

[113]

Sensitivity and specificity is good enough, turnout time is less in real time analysis, even appropriately can detect the viral particles which cannot be cultured by cell culture methods. [ 115, 116] The issues need to be addressed 

The ultrasensitive and specific diagnostic methods are necessary for the early detection of SARS-CoV-2 in order to expedite the treatment and isolation of infected individuals. In addition, diagnostic techniques are highly mandatory to empower medical staff with direct resources and to better combat with COVID-19. These days, CT scan, RT-PCR and lateral flow immunoassays have been developed for the diagnosis of COVID-19. The nucleic acid testing methods and RT-PCR kits being sensitive and specific offer the best way to detect SARS-CoV-2 but, the reduction in false negative results is needed to increase the applicability of RT-PCR test. To overcome the bottleneck of standard diagnostic tools, emerging diagnostic approaches with low cost, wide availability, rapid response and superb reliability are very essential to identify and handle the viral spread. Here of, we have critically discussed the state of the art biosensing strategies for SARS-CoV-2 detection. Biomarker based diagnosis potential of biosensors will be the captivating approach in combination with clinical observations and risk factors to treat the patients according to the severity of their disease. Recently, biosensors have successfully detected SARS-CoV-2 from biological samples; therefore the use of biosensing technologies is the best way to diagnose the disease at its earliest stage.

With the innovation of nanotechnology, the sensing performance of biosensor devices should be further improved in terms of low detection limits, specificity and reproducibility, making them more trustworthy for in-vitro and in-vivo diagnostics. In order to improve the accuracy, combined detection of various biomarkers with multiplex biosensors can be the alternative sensitive approach. To guarantee the fast measurements at the point of care, sensing devices should be inexpensive and easy to handle. More work is required to connect sensing devices through databases with medical staff to realize a decentralized healthcare which would be an important tool for the diagnosis of emerging infectious disease and to determine the herdimmunity regions. Furthermore, colorimetric strips and smartphone based biosensors that can target antibody or antigen possess great potential as home-used point of care testing. Moreover, rapid translation of laboratory research on biosensors into commercially practicable prototype by industry is the main challenge to bridge the gap between laboratory work and industrial needs.

The wastewater-based epidemiology should be further explored to develop proficient analytical devices for accurate and fast detection of trace level of SARS-CoV-2 in order to determine the virus carrier regions. The society needs the massive defense to contain the enormous SARS-CoV-2 like viral attacks and we believe the best way to deal with such situations is, the development of the highly sensitive, swift, easily accessible point of care testing kits which can be employed even by the common man.

There is no competing interest among authors.

COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses.: The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

Epidemiology, genetic recombination, and pathogenesis of coronaviruses

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses

Another decade, another coronavirus

Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease

Clinical characteristics of coronavirus disease 2019 in China

Diagnosing COVID-19: the disease and tools for detection

Positive RT-PCR test results in patients recovered from COVID-19

All-in-One dual CRISPR-cas12a (AIOD-CRISPR) assay: a case for rapid, ultrasensitive and visual detection of novel coronavirus SARS-CoV-2 and HIV virus

A protocol for detection of COVID-19 using CRISPR diagnostics

Ultrasensitive Monolayer MoS2 Field-Effect Transistor Based DNA Sensors for Screening of Down Syndrome

Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries

What tests could potentially be used for the screening , diagnosis and monitoring of COVID-19 and what are their advantages

Quantitative RT-PCR: pitfalls and potential

Broadly reactive and highly sensitive assay for Norwalk-like viruses based on real-time quantitative reverse transcription-PCR

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

Real-time PCR for mRNA quantitation

AZ of Quantitative PCR

DNA nanoscaffold-based SARS-CoV-2 detection for COVID-19 diagnosis

Extraction-free SARS-CoV-2 detection by rapid RT-qPCR universal for all primary respiratory materials

Stability issues of RT PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

Prolonged nucleic acid conversion and false-negative RT-PCR results in patients with COVID-19: A case series

False negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence

Inappropriate Nasopharyngeal Sampling for SARS-CoV-2 Detection Is a Relevant Cause of False-Negative Reports

Microfluidic sample preparation: cell lysis and nucleic acid purification

Fighting COVID-19: Integrated Micro-and Nanosystems for Viral Infection Diagnostics

This article describes the micro and nanosystems against viral infections diagnostics

Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test

Comparing the analytical performance of three SARS-CoV-2 molecular diagnostic assays

COVID-19 pneumonia: what has CT taught us?

Relationship to Duration of Infection. Radiol

Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

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

Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

Strategies for developing sensitive and specific nanoparticle-based lateral flow assays as point-of-care diagnostic device

Diagnosis of acute respiratory syndrome coronavirus 2 infection by detection of nucleocapsid protein

Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min

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

Rapid and quantitative detection of SARS-CoV-2 specific IgG for convalescent serum evaluation

Cellex qSARS-CoV-2 IgG/IgM Rapid Test

Approval of Cellex, Inc. qSARS-CoV-2 IgG/IgM Rapid Test

Evaluations of the serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak

COVID-19 pandemic-A focused review for clinicians

SARS-CoV-2 specific antibody responses in COVID-19

SARS-CoV-2 coronavirus laboratory and point-of-care diagnostics. Diagnostic

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2)

Rapid SARS-CoV-2 antigen detection by immunofluorescence -a new tool to detect infectivity

Sofia 2 SARS Antigen FIA. FDA U 2020

Evaluation of Enzyme-Linked Immunoassay and Colloidal Gold-Immunochromatographic Assay Kit for Detection of Novel Coronavirus (SARS-Cov-2) Causing an Outbreak of Pneumonia (COVID-19). MedRxiv, 2020

Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution

This article highlighted the point of care testing platform for SARS-CoV-2

Isothermal nucleic acid amplification technologies for point-of-care diagnostics: a critical review

Rapid Molecular Detection of SARS-CoV-2 (COVID-19) Virus RNA Using Colorimetric LAMP. medRxiv

Development of reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays targeting SARS-CoV-2

Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2

Contamination-free visual detection of SARS-CoV-2 with CRISPR/Cas12a: A promising method in the point-of-care detection

The CRISPR based technology for contamination free visual detection of SAR-CoV-2 has been presented in this article

Multiplex reverse transcription loopmediated isothermal amplification combined with nanoparticle-based lateral flow biosensor for the diagnosis of COVID-19

In vitro diagnostic assays for COVID-19: recent advances and emerging trends

CRISPR-Cas12-based detection of SARS-CoV-2

Development and evaluation of a CRISPRbased diagnostic for 2019-novel coronavirus

The paper proposed an ultrasensitive visual SARS-CoV-2 detection method integrated RT-LAMP and CRISPR/Cas cleavage in one

SHERLOCK: nucleic acid detection with CRISPR nucleases

Real-time tracking of hydrogen peroxide secreted by live cells using MnO 2 nanoparticles intercalated layered doubled hydroxide nanohybrids

Facet-energy inspired metal oxide extended hexapods decorated with graphene quantum dots: sensitive detection of bisphenol A in live cells

Core-shell iron oxide-layered double hydroxide: High electrochemical sensing performance of H 2 O 2 biomarker in live cancer cells with plasma therapeutics

Hierarchical CNTs@CuMn Layered Double Hydroxide Nanohybrid with Enhanced Electrochemical Performance in H 2 S Detection from Live Cells

The role of biosensors in coronavirus disease-2019 outbreak

Self-stacking of exfoliated charged nanosheets of LDHs and graphene as biosensor with real-time tracking of dopamine from live cells

Advancements in electrochemical sensing of hydrogen peroxide, glucose and dopamine by using 2D nanoarchitectures of layered double hydroxides or metal dichalcogenides. A review

Detection of unamplified target genes via CRISPR-Cas9 immobilized on a graphene field-effect transistor

Unamplified gene sensing via Cas9 on graphene

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia. Radiol

A single and two-stage, closed-tube, molecular test for the 2019 Novel Coronavirus (COVID-19) at home, clinic, and points of entry

Point-of-care RNA-based diagnostic device for COVID-19

eCovSens-Ultrasensitive Novel In-House Built Printed Circuit Board Based Electrochemical Device for Rapid Detection of nCovid-19 antigen, a spike protein domain 1 of SARS-CoV-2. BioRxiv, 2020. This manuscript sheds light on the ultrasensitive eCovSens EC devices for fast detection of SARS-CoV-2 via spike protein

Dual lateral flow optical/chemiluminescence immunosensors for the rapid detection of salivary and serum IgA in patients with COVID-19 disease

Development of a SERS-based lateral flow immunoassay for rapid and ultra-sensitive detection of anti-SARS-CoV-2 IgM/IgG in clinical samples

One-step rapid quantification of SARS-CoV-2 virus particles via low-cost nanoplasmonic sensors in generic microplate reader and point-of-care device

A Rapid and Quantitative Serum Test for SARS-CoV-2 Antibodies with Portable Surface Plasmon Resonance Sensing

Pig Sera-derived Anti-SARS-CoV-2 Antibodies in Surface Plasmon Resonance Biosensors

Detection of antibodies against SARS-CoV-2 spike protein by gold nanospikes in an opto-microfluidic chip

Homogeneous circle-to-circle amplification for real-time optomagnetic detection of SARS-CoV-2 RdRp coding sequence

Metal oxide intercalated layered double hydroxide nanosphere: With enhanced electrocatalyic activity towards H2O2 for biological applications

Superlattice stacking by hybridizing layered double hydroxide nanosheets with layers of reduced graphene oxide for electrochemical simultaneous determination of dopamine, uric acid and ascorbic acid

Plasmonic heating of nanostructures

Dual-functional plasmonic photothermal biosensors for highly accurate severe acute respiratory syndrome coronavirus 2 detection

A localized surface plasmon resonance-based portable instrument for quick on-site biomolecular detection

Ultra-rapid, sensitive and specific digital diagnosis of HIV with a dual-channel SAW biosensor in a pilot clinical study

Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles

Development of RNA-based assay for rapid detection of SARS-CoV-2 in clinical samples

Facet-Inspired Core-Shell Gold Nanoislands on Metal Oxide Octadecahedral Heterostructures: High Sensing Performance toward Sulfide in Biotic Fluids

A review on electrochemical biosensing platform based on layered double hydroxides for small molecule biomarkers determination

Ultrasensitive detection of pathogenic viruses with electrochemical biosensor: State of the art

Genosensor on gold films with enzymatic electrochemical detection of a SARS virus sequence

Genosensor for SARS Virus Detection Based on Gold Nanostructured Screen-Printed Carbon Electrodes

Piezoelectric quartz crystal aptamer biosensor for detection and quantification of SARS CoV helicase protein

Rapid, Ultrasensitive, and Quantitative Detection of SARS-CoV-2 Using Antisense Oligonucleotides Directed Electrochemical Biosensor Chip

Miniaturized label-free smartphone assisted electrochemical sensing approach for personalized COVID-19 diagnosis

Rapid detection of SARS-CoV-2 antibodies using electrochemical impedance-based detector

Excellent explaination about the rapid, label free detection of SARS-CoV-2 using commercially available equipment

Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor

Magnetic beads combined with carbon black-based screen-printed electrodes for COVID-19: A reliable and miniaturized electrochemical immunosensor for SARS-CoV-2 detection in saliva

Ultrasensitive supersandwich-type electrochemical sensor for SARS-CoV-2 from the infected COVID-19 patients using a smartphone

Ultrasensitive smartphone based EC sensors for the detection SARS-CoV-2

Development of a Portable, Ultra-Rapid and Ultra-Sensitive Cell-Based Biosensor for the Direct Detection of the SARS-CoV-2 S1 Spike Protein Antigen

This paper reported the SPR resonance, as a promising substitute of traditional lab-based techniques for the detection and quantification of miRNAs

Ultrasensitive and Selective Detection of SARS-CoV-2 using Thermotropic Liquid Crystals and Image-based Machine Learning

Detection of viruses by inflammasomes

Zika virus induces oxidative stress and decreases antioxidant enzyme activities in vitro and in vivo

Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis

Realtime 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

Methods for rapid virus identification and quantification

Growth of carbon nanotubes on electrospun cellulose fibers for high performance supercapacitors

Advanced pathology techniques for detecting emerging infectious disease pathogens

Poly (Amino Hydroxy Naphthalene Sulphonic Acid) Modified Glassy Carbon Electrode; An Effective Sensing Platform for the Simultaneous Determination of Xanthine and Hypoxanthine

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive

Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling

Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China