key: cord-0716598-pqye1ebh
authors: Sharifi, Majid; Hasan, Anwarul; Taghizadeh, Akbar; Haghighat, Setareh; Attar, Farnoosh; Bloukh, Samir Haj; Edis, Zehra; Xue, Mengzhou; Khan, Suliman; Falahati, Mojtaba
title: Rapid diagnostics of coronavirus disease 2019 in early stages using nanobiosensors: challenges and opportunities
date: 2020-09-28
journal: Talanta
DOI: 10.1016/j.talanta.2020.121704
sha: 7b0c358dbcef7e15e5ef69ef01aa0d7db6d2f084
doc_id: 716598
cord_uid: pqye1ebh

The rapid outbreak of coronavirus disease 2019 (COVID-19) around the world is a tragic and shocking event that demonstrates the unpreparedness of humans to develop quick diagnostic platforms for novel infectious diseases. In fact, statistical reports of diagnostic tools show that their accuracy, specificity and sensitivity in the detection of COVID-face challenges that can be eliminated by using nanoparticles (NPs). In this study, we aimed to present an overview on the most important way to diagnose different kinds of viruses followed by the introduction of nanobiosensors. Afterward, some methods of coronavirus detection such as imaging, laboratory and kit-based diagnostic tests are surveyed. Furthermore, nucleic acids/protein- and-immunoglobulin (Ig)-based nanobiosensors for the COVID-19 detection infection are reviewed. Finally, current challenges and future perspective for the development of diagnostic or monitoring technologies in the control of COVID-19 are discussed to persuade the scientists in advancing their technologies beyond imagination. In conclusion, it can be deduced that as rapid COVID-19 detection infection can play a vital role in disease control and treatment, this review may be of great help for controlling the COVID-19 outbreak by providing some necessary information for the development of portable, accurate, selectable and simple nanobiosensors.

Hepatitis HAV ssDNA/ AuNPs 0.65 pM 10 fg/μL-10 pg/μL [14] HBV Silver nanocluster-MoS2 nanosheet 10.7 nM 5-30 nM [15] HBV Indium Tin oxide nanowires 1fM 1fM-10 µM [16] HCV Carbon nanotube-Cobalt NPs 8.82×10 −10 M 1.0 nM-12 μM [17] Human immunodeficiency

Antibody-graphene 100 fg/mL 1 fg/mL-1 μg/mL [18] AuNPs 0.1 pg/mL 1000-0.1 pg/mL [19] copper sulfide nanoplate 25 pM 0.05 to 1 nM [20] Ebola ssDNA-AuNPs 4.7 nM - [21] graphene oxide-AuNPs 1 ng/ml 1-400 ng/ml [22] Influenza H1N1 peptidefunctionalized polydiacetylene 10 KSHV AuNPs ~1 nM 1 Mm-10 pM [27] HHV-5 Zink-silver nanoblooms 97 copies/mL 113-10 3 copies/mL [28] Human papilloma Carbon nano-onions 0.5 nM 0.5-20 nM [29] Au nanosheets 0.15 pM 1 pM-1 µM [30] Au nanotubes 1 fM 0.01 pM-1 µM [31] 137

Briefly, a biosensor can be defined as a bio-receptor for measurement, and a signal transducer 139

for the production of physical signals such as optical, electrical, thermal, and mechanical from 140 biological changes [32, 33] . In this regard, the biosensor needs to be independent of physical 141 parameters such as temperature and pH. Overall, the biosensor investigation method includes 142 J o u r n a l P r e -p r o o f two methods of direct communication with analyte or indirect investigation through generated 143 factors of analyte activity [34] . In both cases, the most common method of activity of 144 biosensors is in medical activities based on antigen-antibody interaction, nucleic acid 145 interaction (two complementary strands), enzymatic interaction (enzyme-substrate), cellular 146 interaction (microorganisms, proteins), and the interaction of biomimetic materials [35, 36] . 147

However, all of the methods have very important challenges including reducing LOD, 148

increasing signal-to-noise ratio and very low concentrations of the compounds under 149 evaluation. Therefore, not only downsizing the device is very important for having a portable 150

system, but also the improvement of the device performance by increasing the contact surface 151

with the reaction agent via nanomaterials has been highly considered. Therefore, the use of 152 nanomaterials to reduce these challenges in the construction of CoV diagnostic biosensors is 153 also recommended. In this regard, the arrangement or composition of nanomaterials used in 154 nanobiosensors as well as the measurement method will be of great importance [37] . In recent 155 years, various nanobiosensors especially electrochemical and optical nanobiosensors have 156 been designed for developing a multi-platform approach for the detection of microorganisms 157 [38] . In addition to these two methods, the use of thermal and mechanical nanobiosensors has 158 also been effective in detecting immunogenic agents resulting in microbial activity [39] . In 159 general, the advantages of nanobiosensors-based diagnostic methods over conventional 160 shows a bilateral pulmonary opacity and infiltrates based on the stage of the disease ( Figure  197 1A, B), while at the beginning of the disease the lung condition can be observed normally. For 198 instance, the results of Ai, et al. [49] showed that the sensitivity and accuracy of COVID- 19 199 diagnosis through radiology technique are 97% and 68% compared to PCR reference method. 200

Therefore, the use of imaging methods in the early diagnosis of COVID-19 seems desirable 201 due to lower cost, rapid processing, lack of aggressive activities and lack of sampling error. 202

However, this strategy is associated with difficulties in examining the COVID-9, which has 203 reduced its apparent efficiency in diagnostic platforms such as the need for the expertise in 204 whereas the amount of lymphocytes decreases significantly [52, 53, 55] . In addition, despite 244 rising erythrocyte sedimentation rates, reports indicate a decrease in red blood cells and 245 hemoglobin levels [51, 54, 55] . Despite the reported changes in blood parameters, due to the 246 influence of health statues or different diseases on these parameters, it is not possible to prove 247 that some specific changes in biochemical parameters induced by COVID-19 infection. samples, and sensitivity [58] . Therefore, using RT-PCR technique in real time compared to 271 real time PCR, in addition to simplicity of work, lead to a rapid and early diagnosis of 272 Fluorescent RT-PCR kit.

In vitro RT-PCR combining fluorescent probing.

Altona-Diagnostics. [67] Commercial Kit. RT-PCR Kit.

--Germany

The Loop mediated isothermal amplification (LAMP) method is a much simpler, faster (2.5-298

3.0 folds), more sensitive (10-100 times) and even more efficient method of detecting viruses 299 than PCR methods, which can be performed without complex and expensive experimental 300 equipment [68] [69] [70] . The results obtained in this technique can be easily repeated and due to 301 the use of a single-stage test tube in less than fifty minutes, it has a high speed and efficiency 302 in diagnosis [68] . However, the high sensitivity of LAMP method can show many false 303 positive outcomes resulting from Trans and Cis priming between the oligonucleotide primer 304

and non-specific detection of the amplicon. Therefore, to reduce this error, a special primer 305

can be used to detect the COVID-19, which increases the test time ( Because serological reactions are a common occurrence when viruses are present ( Figure 1D (E), and (N) nucleocapsid, which are important sites for serological measurements [83, 84] . 346

Among the above structures, CoV S protein is of great importance due to its binding and 347

fusion to the host [83, 85] . The human serine protease TMPRSS2 is accountable for priming 348 the S protein, and the angiotensin-converting enzyme 2 is employed as a receptor for the entry 349

of COVID-19 [84] . Also, N protein has received a lot of attention due to its important role in 350 viral pathogenesis, RNA replication and packaging [86] . Among antibodies, rapid 351 measurement of IgM and IgG undoubtedly play an important role in COVID-19 identification 352 [87, 88] . In this regard, the results of Hu, et al. [89] 

With the advent of nanotechnology in the 1960s, this technology has received a great deal of 367 attention in various fields of biomedicine, with the improvement of biological and chemical 368 analysis based on unique optical, electrochemical, magnetical, and mechanical properties [33, 369 92] . However, as mentioned earlier, the first use of nanomaterials in the detection of viruses in 370 the late 1990s was used to detect human papillomavirus [93] . Today, various types of organic 371 and inorganic nanomaterials, especially AuNPs, magnetic NPs, and carbon-based NPs with 372 biomolecular compounds loaded on them (for instance, nucleic acid, antibodies, antigens, or 373 capsid peptides) for diagnosis viruses have been used [94, 95] . One of the most important 374 J o u r n a l P r e -p r o o f advantages of using nanomaterials compared to the methods mentioned above is the 375 possibility of using several probes simultaneously with biological and non-biological labels in 376 detecting viruses [96] . The results of nanotechnology studies based on Table 1 the diagnosis compared to conventional methods (Table 6 ). On the other hand, to isolate 402 patients, the use of nucleic acids or special proteins will be much more effective than 403

antibodies that increase generally after 14 to 28 days of illness. 404 405 [10] 407

In this line, in order to achieve the early diagnosis of COVID-19, Seo, et al. 

Because the body's immune system is able to produce Ig in the face of the COVID-19, using 504

nanobiosensor-based serological tests to determine specific antibodies can be helpful. In this 505 case, the response of IgG is revealed after almost two weeks of the disease, while the response 506 of IgM can be observed four to ten days after the virus enters [110, 111] . In this regard, 507

Zhang, et al. [112] illustrated that one day after the onset of COVID-19, the IgM and IgG 508 increased by 81 and 50 %, respectively. While five days after the disease, the rate of increase 509 is 100 and 81%, respectively. Therefore, to identify the fast, simple, and inexpensive of 510 

Due to the rapid outbreak of the COVID-19 around the world and its hidden movement 586 among carriers (for ten to fourteen days), the use of quick, easy, inexpensive diagnostic 587 methods and available to all is very important. Despite the use of common methods in the 588 diagnosis of COVID-19, such as imaging, blood tests, PCR, etc. due to high costs, low 589 sensitivity in some cases, low specificity and selectivity, and lack of sufficient expertise due 590 to limited personnel and advanced equipment generally show some limitations. To this end, 591 this review attempts to explain the advantages and disadvantages of current methods and the 592 possibility of their improvement by using new technologies, especially nanotechnology. 593

Expression of nanotechnology features in the improvement of COVID-19 diagnostic methods 594

Glycan shield and epitope masking of a coronavirus spike protein observed by 629 cryo-electron microscopy

Molecular mechanism for antibody-dependent enhancement of coronavirus entry

Piezoelectric immunosensor for SARS-634 associated coronavirus in sputum

Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid 637 protein in human serum using a localized surface plasmon coupled fluorescence fiber-optic 638

An isothermal, label-free, and rapid one-step RNA amplification/detection assay for 641 diagnosis of respiratory viral infections

An electrochemical immunosensor for the corona virus associated 643 with the Middle East respiratory syndrome using an array of gold nanoparticle-modified 644 carbon electrodes

Clinical and diagnostic virology, Cambridge university 646 press2009

Molecular diagnosis of influenza

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electrochemical DNA biosensor for detecting hepatitis A virus

A versatile DNA detection scheme based on the 657 quenching of fluorescent silver nanoclusters by MoS 2 nanosheets: application to aptamer-658 based determination of hepatitis B virus and of dopamine

The field effect transistor DNA biosensor based on ITO nanowires in label-661 free hepatitis B virus detecting compatible with CMOS technology

chitosan and MWCNT for the determination of daclatasvir: a hepatitis C 665 antiviral drug

A smart nanosensor for the detection of human immunodeficiency virus and associated 668 cardiovascular and arthritis diseases using functionalized graphene-based transistors

Two types of nanoparticle-based bio-barcode amplification assays to detect HIV-1 p24 672 antigen

Copper sulfide nanoplates as nanosensors for fast, 674 sensitive and selective detection of DNA

A novel electrochemical DNA biosensor for Ebola virus detection

Field-678 effect transistor biosensor for rapid detection of Ebola antigen

Colorimetric detection of influenza A (H1N1) virus by a peptide-functionalized 681 polydiacetylene (PEP-PDA) nanosensor

Electrophoresis-enhanced detection of 683 deoxyribonucleic acids on a membrane-based lateral flow strip using avian influenza H5 684 genetic sequence as the model

Novel magnetic 686 relaxation nanosensors: an unparalleled "spin" on influenza diagnosis

Direct acoustic profiling of 689 DNA hybridisation using HSV type 1 viral sequences

Multiplexed colorimetric detection of 691

Kaposi's sarcoma associated herpesvirus and Bartonella DNA using gold and silver 692 nanoparticles

Portable bioactive 694 paper based genosensor incorporated with Zn-Ag nanoblooms for herpes detection at the 695 point-of-care

Reactive carbon nano-onion modified glassy 697 carbon surfaces as DNA sensors for human papillomavirus oncogene detection with enhanced 698 sensitivity

Impedimetic biosensor for the DNA of the human papilloma virus based on the use of gold 701 nanosheets

An ultrasensitive label free 703 human papilloma virus DNA biosensor using gold nanotubes based on nanoporous 704

polycarbonate in electrical alignment

Plasmonic and chiroplasmonic nanobiosensors based on gold 708 nanoparticles

Cancer diagnosis using nanomaterials based electrochemical 711 nanobiosensors

Chapter 4 -Nanobiosensors for virus detection in the environment

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Nanosensors for Smart Cities

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Seattle Region-Case Series

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Isothermal Amplification Technology to Reduce Community Transmission of SARS-CoV-2

Evaluation of COVID-19 RT-qPCR test in 784 multi-sample pools

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RNA as a control for multiplex real-time reverse transcription-PCR detection of influenza 790 virus and severe acute respiratory syndrome coronavirus

Detection of 2019 novel coronavirus (2019-nCoV) by 794 real-time RT-PCR

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Improved molecular diagnosis of COVID-19 800 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse 801 transcription-PCR assay validated in vitro and with clinical specimens

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Co-diagnostics Inc designs test for new coronavirus using coprimer 806 platform

Bgi develops real-time fluorescent rt-pcr kit for detecting the 2019 novel 809 coronavirus

Altona diagnostics is developing a rt-pcr kit for detection of novel 812

novel coronavirus disease (COVID-19): 815 paving the road for rapid detection and point-of-care diagnostics

Rapid Detection of SARS-CoV-2 Using Reverse transcription RT-LAMP method

Overcoming the 821 bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for

COVID-19 detection

Detection of Middle East respiratory syndrome coronavirus using reverse 825 loop-mediated isothermal amplification (RT-LAMP)

Development and evaluation of a novel loop-mediated isothermal amplification 829 method for rapid detection of severe acute respiratory syndrome coronavirus

Development of Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) 833

Assays Targeting SARS-CoV-2

Coronavirus (COVID19) by Reverse Transcription-Loop-Mediated Isothermal Amplification

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Coronavirus Disease 2019

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Detection of 2019 novel coronavirus (2019-nCoV) in 851 suspected human cases by RT-PCR

Detection of second case of 854 2019-ncov infection in japan

Serology of 856 severe acute respiratory syndrome: implications for surveillance and outcome

Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA 860 and neutralization assay against viral spike pseudotyped virus

A review on the cleavage priming of the spike protein 864 on coronavirus by angiotensin-converting enzyme-2 and furin

The expression level of angiotensin-converting enzyme 2 determine the severity of 868

COVID-19: lung and heart tissue as targets

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Secondary attack rate and superspreading events for 873

Breadth of concomitant immune responses prior to patient 876 recovery: a case report of non-severe COVID-19

Connecting clusters of COVID-19: an epidemiological and 879 serological investigation

Heat 881 inactivation of serum interferes with the immunoanalysis of antibodies to SARS-CoV-2, 882 medRxiv

Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-885 reactivity with SARS-CoV

Antibody responses to SARS-CoV-2 in patients with COVID-19

Gold nanomaterials as key suppliers in biological and 891 chemical sensing, catalysis, and medicine

Detection of human 894 papillomavirus in laryngeal papillomas, Recent advances in bronchoesophagology

Plasmonic and chiroplasmonic nanobiosensors based 898 on gold nanoparticles

Biosensing and therapeutic activities

Plasmonic gold nanoparticles: Optical manipulation, imaging, drug delivery and 904 therapy

plasmonic photothermal biosensors for highly accurate severe acute respiratory syndrome 907 coronavirus 2 detection

Trends and innovations in biosensors for COVID-19 mass testing

Colorimetric detection of DNA sequences based on electrostatic 911 interactions with unmodified gold nanoparticles

Electrical Detection 915 of the SARS Virus N-Protein with Nanowire Biosensors Utilizing Antibody Mimics as

Genosensor for detection 918 of four pneumoniae bacteria using gold nanostructured screen-printed carbon electrodes as 919 transducers

Detection of severe acute respiratory syndrome (SARS) coronavirus 922

nucleocapsid protein using AlGaN/GaN high electron mobility transistors

Multiplex Paper-Based Colorimetric DNA Sensor Using Pyrrolidinyl Peptide Nucleic Acid-926

Induced AgNPs Aggregation for Detecting MERS-CoV, MTB, and HPV Oligonucleotides

Development 929 of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles

Rapid COVID-19 detection causative virus (SARS-CoV-2) in human 933 nasopharyngeal swab specimens using field-effect transistor-based biosensor

Electrical probing of COVID-19 spike protein receptor binding domain via a graphene field-937 effect transistor

eCovSens-Ultrasensitive Novel In-939

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Selective Naked-Eye Detection of 942

SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic 943

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Performance of VivaDiag COVID-19 IgM/IgG Rapid Test is inadequate 948 for diagnosis of COVID-19 in acute patients referring to emergency room department

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Rapid 957 and sensitive detection of anti-SARS-CoV-2 IgG using lanthanide-doped nanoparticles-based 958 lateral flow immunoassay

Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-961

CoV-2 infection diagnosis

In this review article, the methods of detecting COVID-19 and their advantages and disadvantages were discussed

Recent challenges and advances in the diagnosis of COVID-19 and the possible place of nanomaterials in them have been described

The challenges and prospects of using nanobiosensors in the detection of COVID-19 were explained

based on pre-designed patterns can increase the hopes of diagnosing and controlling COVID-595 19 infection. On the other hand, the use of nanotechnology in diagnosis can enable point-by-596 point and low-cost control of patients during treatment with high sensitivity and selectivity. 597As well, the results of this study show that the simultaneous use of several diagnostic factors 598in COVID-19 can increase the sensitivity and selectivity of diagnostic tools that can be easily 599 implemented in nanobiosensors. Finally, due to the lack of vaccine, the control and prevention 600 of the COVID-19 is a priority for healthcare institutions. Therefore, the use of nanobiosensors 601can hold a great promise in providing a cost-effective strategy for the the rapid and sensitive 602

Acknowledgment 604The 

☒ 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:J o u r n a l P r e -p r o o f