2D Materials As Diagnostic Platform For Detection and Sensing of SARS-CoV-2 Virus A Bird-Eye View

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2D Materials as diagnostic platform for detection and sensing of

SARS-CoV-19 Virus: A Bird-Eye View
Journal of Materials Chemistry B Accepted Manuscript

Pranay Ranjan1, Vinoy Thomas2* and Prashant Kumar3*
Published on 17 February 2021. Downloaded by Jeonbuk National University on 3/17/2021 9:55:14 AM.
1Department of Physics, UAE University, Al-Ain, Abu Dhabi 15551, United Arab Emirates
2Department of Materials Science and Engineering, University of Albama at Birmingham, USA
3Department of Physics, Indian Institute of Technology Patna, India
Abstract:
Worldwide infection and fatality by SARS-CoV-19 virus and its variants responsible for COVID 19 have impeded
economic growth of developing nations beyond repair, General public in several nations have lost their livelihood, it
has left severely impacted international relations and most importantly health infrastructures across the world have
been tormented. This pandemic has already left footprints on human psychology, traits, and priorities and is
certainly going to lead towards new world order in time to come. As always, science and technology come to rescue
the human race. The prevention of infection by instant and repeated cleaning of surfaces which are most likely to be
touched in daily life and sanitization drives using medically prescribed sanitizers and UV exposure of textiles are the
first steps to break the chain. However, the real challenge is to develop and uplift medical infrastructure such as
diagnostic tools capable of prompt diagnosis, instant and economic medical treatment available to masses. Two
dimensional (2D) materials such as graphene are atomic sheets which have been in news from quite some time due
to unprecedented electronic mobilities, high thermal conductivity, appreciable thermal stability, excellent anchoring
capabilities, their optical transparency, mechanical flexibility and their unique capability to integrate to arbitrary
surfaces. These attributes of 2D materials make them lucrative for their use as active materials platform for authentic
and prompt (within minutes) disease diagnosis via electrical or optical diagnostic tools or via electrochemical
diagnosis. We present the opportunities provided by 2D materials as materials platform for COVID 19 diagnosis.
*Correspondence Prof. Prashant Kumar, Phone: (+91) 0612 302 8141, Mobile: (+91) 9102830953, E-
mail: prashantkumar@iitp.ac.in, magmemory@gmail.com., Prof. Vinoy Thomas, Ph. (205) 975-4098,
Email: vthomas@uab.edu
Journal of Materials Chemistry B Page 2 of 23
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Introduction to COVID 19 infection:

The World Health Organization (WHO) received an alarming call from China Health
Authority (CHA) on 31st December 2019 about an unknown infection spreading at
Wuhan City in central China whose initial symptoms seems to be like pneumonia.
However, little details were known about the virus origination and transmission rate.
Acknowledging the call from CHA, WHO team visited Wuhan and Hubei provinces and
reported an unknown strain of virus (a genetically modified form of Severe Acute
Respiratory Syndrome human coronavirus (SARS-CoV)) on January 7th 2020 and
named it as “2019-nCoV”[1]. Later, on further investigation, it was concluded that
exposure to 2019-nCoV leads to the acute respiratory syndrome. Moreover, the genetic
sequence of the virus matches nearly 70% of the genetic sequence SARS-CoV virus
and, therefore, the virus has been renamed as “SARS-CoV-2 or COVID-19”[2]. All this
investigation process and understanding took nearly a month to realize how deadly this
virus is for humans and within such a small time-span the number of an infected person
raised to millions. The end of January 2020, marks nearly hundred thousand active
cases reports recorded in worldwide, however, this was just the beginning of
widespread of COVID-19, 82 countries reported confirmation cases of COVID-19 strain
and thus WHO declared this outbreak of COVID-19 as a Public Health Emergency of
International Concern (PHEIC) on 30th January 2020 [3-4]. Further, this PHEIC has
been recognized globally as pandemic on 11th March 2020 [3].
COVID-19 was found to be a modified form of Severe Acute Respiratory Syndrome
human coronavirus (SARS-CoV) and thus been marked the entry into the family of
Coronaviridae and other similar Nidovirale viruses [5]. Figure 1 represents the family
and sub-categorized family members of the COVID-19 virus.
Figure 1. Family of Coronaviridae virus

Amongst the family of coronavirus alpha-coronavirus, and beta-coronavirus are the two
types of viruses which are contagious to humans, while Gamma-coronavirus and delta-
coronavirus are contagious to animals like pigs, birds and whales [5-8]. It was found that
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the origination of these viruses is from a bat, however, this was just mere a speculation
as only 79% similarity of the genome has matched with the genome of strain collected
from the bat which has SARS-CoV or MERS-CoV virus[7-8]. Moreover, homology

modelling discloses that although there is a variation in amino acid of COVID-19 virus in
comparison to SARS-CoV the receptor-binding domain structures are the same[9].
However, it is early to say and it’s yet not specified that the origination of this virus is
from a bat or some sea-foods. The question and understanding of origination, mutation,
and transmission of COVID-19 virus warrant urgent investigation.
Fatality and transmission rate
In order, to understand the transmission rate of COVID-19 (SARS-CoV- 2), we have
considered some viruses which belong to the Coronaviridae virus family and some
widely known viruses. At the time of writing this article, we found that the COVID-19
virus has a fatality rate of ~3%, while viruses such as Avian H7N9 (2013), Seasonal Flu,
Hantavirus, Spanish Flu (1918), Ebola Virus, H1N1 (1918), HIV, SARS-CoV, Small Pox,
Pertussis/whooping cough, Chicken Pox, Mumps, Measles Virus have a fatality rate of
40 %, 0%, 35%, 2%, 70%, 80%, 10%, 65%, 3%, 4%, 0%, 1% and 0.3% respectively[10-
18]. While it is clear from Fig.2 that COVID-19 has less fatality rate compared to other
widely known viruses from his and another family, it does not mean that it will die out
very soon and is harmless compared to others. Untreated humans can go to a ventilator
in 7 days, as this virus attack severely to lungs and if not went to ventilator can damage
the lungs and lead to death in 10 to 14 days.
Moreover, with a growing population, the density of people living in an area increases,
therefore it will be misleading to compare the transmission rate of other known virus
existing and COVID-19. As a result, the graph (Fig.2) is meant to develop a perception
to the reader, how viruses’ transmitted rate varies depending on the type of virus.
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Figure 2. Fatality and Transmission rate of viruses.

The mortality/fatality rate of these deadly viruses needs to detect at an early stage (see

Fig. 3). However, presently relies on conventional techniques which although being
reliable need time for getting test result. Therefore, worldwide there is a huge demand
for the development of more realistic and reliable technology for the detection of specific
biospecies/microorganism using very accurate diagnosis for monitoring the health of the
patient. Fluorescence-based polymerase chain reaction (PCR), sequencing and
immuno/affinity reaction biosensing are some of the ways to detect the COVID-19 virus
(see Fig 4.) [19-21].
Figure 3. Sensitivity and time of detection for COVID-19.
Covid 19 detection
Nasopharyngeal swabs sample collection is the initial step for the RT-PCR test.
Contrary to the conventional PCR test, which needs an agarose gel and gives result
after a complete scan, RT-PCR test used to detect and quantify nucleic acid presence
during the succession of the reaction [22]. It can also detect the amount of DNA in the
sample. Detection of SARS-CoV-2 involves a) identification of the envelope gene (E
gene), the nucleocapsid protein gene (N gene) and the S gene [22-27]of the nucleic
acid, b) opting any two identified gene and getting their fluorescent. This improves the
sensitivity and specificity of the testing kit as it has been cross-verified two times in a
single run. Chan et al. [28] further analyzed, designed and modified the RT-PCR assay
by targeting the RdRp/Helicase. In comparison to RdRp-P2 assay, RdRp/Helicase
assay does not get reacted with other member or family of coronaviruses. Thus,
increases the sensitivity. Moreover, when the test sample is connected with PCR for the
analysis, the signals for the virus are just being amplified only in the regions containing
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the virus sites [29]. In addition to this, a PCR test can be performed only by a skilled
individual, thus, one can conclude that the use of PCR equipment for detecting COVID-
19 virus makes it a labour-intensive, sophisticated, time consuming and expensive

methodology, thus limiting their use in general laboratories [29].
Alongside laboratory testing, which often takes longer duration for detection, a prime
detection technique which nowadays is very useful for the identification of COVID-19 is
computed tomography imaging (CT-imaging). As COVID-19, attacks the lower
respiratory tract infection such as pneumonia or bronchitis, it is easy to detect its
presence through X-ray or Chest CT imaging.
Figure 4. CT-imaging of a COVID person recorded over a while.[30]

CT imaging has shown a promising role in the detection of COVID, the CT imaging
report of a COVID infected person shows a deterioration in his lung capacity as well as
an increase in a bilateral multiple lobular over a while (see Fig. 4 (a-d)). This kind of
report is found to be similar in case of diagnosis for pneumonia. However, the cases
from the COVID infected person and pneumonia can be easily segregated if artificial
intelligence (AI) can be implemented. For instance, AI-driven CT images can be used to
understand the signature for COVID based on high resolution coloured image and
signature of lobular obtained. This can be the key initial indicators for differentiating the
results from pneumonia and can help to get control over the outbreak of the pandemic.
These detection techniques are bound to reduce the fatality or the death rate as well as
is expected to reduce hospitalization.
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Figure 5. COVID-19 detection techniques

Out of several existing techniques (see Fig. 5) for detecting COVID rapidly and with
high sensitivity, one of the promising ways is through Loop-mediated isothermal
amplification (LAMP) test. Unlike, PCR test which is quite complex and is not
economical, LAMP use to amplify nucleic acid signature under isothermal condition [31-
32].LAMP is a well-known and established a technique to detect a different kind of
viruses. Le et al. used the LAMP technique for real-time monitoring of patients sample
infected by influenza-like illness. The high sensitivity of > 88.8%, as well as specificity
of ~100%, has been demonstrated by Takayama et. al in 2019 [33]. However, the
techniques used by Takayama et al. involves the purification step of nucleic acid
through the use of commercially available RNA isolation kit as well as preparation of the
reaction mixture at very low temperature. Nakauchi et al. [34] proposed a much-
optimized LAMP technique and is known as rRT-LAMP. It involves the preparation of
reaction mixture in a lyophilized form, which eases the integration into the diagnostic
kits, thereby enhancing transport and storage time during shipment. This technique is
also known as the new direct rRT-LAMP assay is predicted to be a solution for rapid
and simple molecular detection of viruses (such as COVID or influenza) as they have
high sensitivity and specificity.
Lateral flow (LF) immunoassay tests, is yet another technique widely adopted for the
detection of COVID virus detection since introduced in the mid-1980s. It is also known
as immune-chromatographic strip tests. As the name suggests “lateral flow” there is an
involvement of fluid migration through paper or plastics. It is a very complex and more
used technique instead involvement of many manuals as well as instrumental read and
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store test result for the targeted analytes[35]. LF is also been used in clinics, hospitals,
and at home as it offers versatility to the manufacturers to tune its selectivity and
specificity for any situation, which involves rapid detection. It also involves detection of

disease-specific samples from urine, saliva, serum, plasma, blood, tissue or fluids.
Another prominent reason for using more LF test is the cost and time involved in making
the kit. In addition to all these technique SERS based detection technique is predicted
to be most sensitive and accurate for detection of COVID (discussed in the later section
of the draft).
A brief comparison of different detection technique for COVID has been depicted in Fig.
6. It can be seen that RT-PCR and Immunoassays methods have a sensitivity of 95%,
and 20% to 80% respectively, but a minimum of 2 h for detection time is required in both
the cases. Interestingly, LAMP and Computed Tomography are the only two amongst
various test, which has a sensitivity greater than 97% and 95% respectively. In
comparison to RT-PCR and Immunoassays methods, LAMP and Computed
Tomography requires only 30 min and >1 min respectively for detection of the COVID.
Figure 6. Sensitivity and time of detection for COVID-19.

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Ahmadivand et al. [36] have proposed and detected (SARS)-CoV-2 virus protein at low
level using femtomolar (fM) by a very effective and efficient mode of detection using
plasmonic meta sensor technology. They fabricated a miniaturized plasmonic

immunosensor based on toroidal electrodynamics concept, which works in terahertz
(THz) frequencies. It enables SARS-CoV-2 spike proteins to detect at Femto-mole-level
concentrations with high precision and can detect SARS-CoV-2 protein within ~ 80 min.
In yet another seminal work reported by Kaushik et al. [37], Mujawar et al. [38] and
Paliwal et al. [39] detection of SARS-CoV-2 virus using biosensing integrated with AI
and IoT supported platform has been discussed to create a database for early-stage
diagnosis, cognizance of the spread and its effect, type of strain and related disease in
a sequential manner to overcome the problems associated with it. Moreover, the role of
AI and IoT supported SARS-CoV-2 detection selectively at the low level desired for
early-stage COVID-19 diagnostics point-of-care (POC) sensing by suitably opting
nanotechnology-based device and its design, packaging, integration and sense has
been discussed. POC was further used to generate crucial information in understanding
the efficacy of therapy, progression of the disease, etc. Furthermore, Mujawar et al.
have described the use of low-level targeted disease biomarker (pM level), detection
which eventually is useful to correlate and study the progression of the disease and its
therapy. Kaushik et al. have [40] reported an effective way to neutralize SARS-CoV-19
virus through manipulative magnetic nanomedicine (MMN) therapy technique which
offers control over drug delivery and option to choose desired therapeutic medicine. In
another seminal work by Vicky et al. [41] the authors have summarized, analyzed more
than one thousand articles related to SARS-CoV-19 and justified why the Alzheimer and
dementia-related illness person are more prone to risk. They reviewed nearly 28
vaccines, their treatment protocol, clinical trials, along with the diagnostic tools and
therapeutics for SARS-CoV-19, for an effective and efficient way of handling the
disease.
Suitability of 2D Materials in COVID 19 sensing
Two-dimensional (2D) materials such as graphene, borophene, transition metals
dichalcogenides (TMDCs), MXenes, Plumbene, Hematene etc. have unprecedented
physical and chemical properties. They have a high surface area, weak inter-layer
bonding and strong covalent in-plane bonding open up a plethora of application in the
sensitive, selective and specific platform which can rapidly detect and paves the path for
early detection of analyte or molecules or microbes at parts per million/billion level [42].
Amongst the family of 2D materials, graphene, borophene and phosphorene have
shown potential to address global societal challenges including healthcare-related
problems. The role of 2D material (owing to their large surface-to-volume ratio,
anchoring capability, thermal stability) is crucial in the detection of the analyte as they
provide aggrandize electrical, optical, mechanical and chemical property for devices
performance. Owing to their excellent optical and electronic properties, they have been
considered as futuristic materials for imaging in photo-acoustic, photo-thermal and X-ray
computed tomography. Moreover, due to their superior optoelectronic properties, they
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have been used in photodynamic and photothermal therapy. Transition metal

dichalcogenides seem to be an obstacle for various biosensing applications due to their
relatively lower carrier mobility in comparison to MXene (borophene, phosphorene and

their cousins) and graphene. MXene family offers tunable bandgap which has the
potentials to manipulate the interaction between electromagnetic waves and the Xenes,
within the wavelength of NIR to UV region [43]. Surprisingly, these 2D materials and
detection of molecules (such as germs or microbes) integrate many branches of science

which includes nanotechnology, chemistry, physics, material science and collectively
drives bioelectronics and bioengineering.
Sensing via SERS is a more rapid and effective detection technique for COVID virus
and is an integral part of bioelectronics. It saves time and money. Bioelectronics plays a
crucial role in the detection of various biological microorganism. It has opened a vibrant
and vivid research field in the field of electronics, bioengineering and biotechnology.
Detection of functional bioactive molecules such as DNA, RNA, protein, microorganism,
antibodies [48-56] using techniques such as field-effect transistors (FETs), nanowire
array, optical resonators, Surface-enhanced Raman scattering (SERS) and
electrochemical sensing etc. (See Fig.7) have been evolved over the past few
decades[57-69]. Bioelectronic devices generate signals on interaction with bio-species.
Typically, the signal generated is in the form of impulse or current, voltage, resistance,
conductance, or frequency.
Field-effect transistor based sensing

In the 1970s, ion-sensitive field-effect transistors (ISFET) was invented by Bergveld et
al. [70]. It was realized that the ISFET can be used for detection of numerous biosensor
targets. The upcoming time-based evolution of technology has changed the designed
and fabrication of FETs. Typically, a FET consists of a semiconductor path called
sensing channels, which has its two sides connected to the source (S) and drain (D)
electrodes. The backside of the sensing channel is generally connected to the third
electrode and is called a gate (G) (see Fig.8). It is used for biasing and enhancing the
sensitivity as well as selectivity of the device. The channel conductivity determines the
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Figure 7. (a) Target receptors for biosensing, (b) Schematic display for
biosensors[30]Copyright 2018, Springer Nature.
presence of targets and thus gets recorded in an electrical signal. The FETs are divided
into two based on the detection techniques, i.e n-type (it uses electrons as carrier
charge) and p-type (it uses holes as carrier charge). For a typical, n-type FET, if the
target molecules have a positive charge and get attached to the channel then it leads to
increase in channel conductivity, while if the target molecules have negative charge
then it will lead to decrease in channel
Figure 8.The schematic diagram for the 2D material based channel FET biosensor
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-conductivity and vice-versa for p-type FET[71-72]. It can be inferred that all the
anchoring, detection, and signal transmission part has been controlled by the channel
path.

Change in the channel resistance of the FET device reveals the information about the
analyte. This state of the art is currently being used for wearable devices and neural
interfacing technology. Li et al. [73] demonstrated graphene-based FET (G-FET), in

which the channel length was made up of micro mechanically exfoliated graphene sheet
integrated with mercury ions. Graphene known for high mobility and conductivity has
detected 0.1 parts per billion (ppb) of mercury. Surprisingly, the graphene-based
channel length overpass the World Health Organization tolerance limit of 1 ppb and in
comparison to commercially available ISEs devices for detection of mercury, the
sensitivity has been increased by a factor or more than 1000 times [74-75]. Unlike
graphene, other 2D materials such as MoS2, black phosphorus, and h-BN are also
integrated on FET devices for channel length [76-78]. Lee et al. have demonstrated the
use of MoS2 based channel length for detection of DNA hybridization [79]. In
comparison to the PCR detection technique, which requires continuous amplification
during the testing cycle, FET based devices give low detection of targeted nucleic acid,
without pre-amplification [80]. Carbon nanotubes (CNTs) and Silicon (Si) nanowires
have also been used as channel length in FET devices, however, the difficulty in
fabrication of nanowires and nanotubes along with the reproducibility as well as the cost
of production limits their use in FET devices [81-84]. Mannoor et al. demonstrated
whole-cell bacterial detection using chemical vapour deposition (CVD) grown graphene
as a channel for sensing [85]. They used CVD grown layers of graphene sheet
anchored with antimicrobial peptides as well as coil micro antenna on biocompatible silk
to detect a single E. coli bacterium [85]. More, such evidence of graphene and
functionalized graphene for whole-cell detection has been reported by Guarnieri et al.
[86] and Pandey et al. [87] for the detection of human intestinal epithelial cells and E.
coli respectively.
Materials for channels are, therefore, the most crucial components which need to be
evenly considered and designed. 2D materials, such as graphene, borophene, alpha
lead oxide etc. not only provides high conductivity, mobility and enhanced mechanical
strength but also helps in anchoring with the target molecules due to high surface to
volume ratio and rapid, accurate, and early diagnosis of the molecules. FET based on
2D material platform have outnumbered all the conventional materials (as roughness in
the morphology of the channel is bound to give errors and unrealizable outputs from the
device due to scattering effect) used in FET. The most advantageous role of 2D
materials in FETS are that they provide a rapid, economical, and ease of use because
the real-time analysis is being monitored accompanied by low-cost meters which can
eventually be calibrated or anchored for different end-user applications.
Although FET based biosensors have many advantages over other sensors, charge
screening is the most common problem faced by FET devices for biological media
detection. As charge screening is mainly associated with electrolytes and the Debye
length (λD) and both factors are inversely related, one of the possible solutions is to
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avoid it, can be by diluting the sample into less concentration [87-89]. However, this
may lead to surface functionalization of the targeted molecules or analyte. The next
possible approach is to make targeted analyte within the size of the Debye length, but,

seems to be less feasible considering the size of the target and functional groups. Many
new innovative and upcoming way to avoid charge screening still need to be
investigated and creates a new area of futuristic research based on biomolecules
targeted FET devices [88-91].
Surface-Enhanced Raman Scattering (SERS) based sensing

SERS is amongst one of the techniques in bioelectronics that uses the change in
frequency to provide a rapid, non-invasive way to detect the signature of biological
samples with ultrahigh sensitivity. Moreover, it does not involve a complex process or
skill hand to obtain the result. However, in earlier days for a SERS platform complex
and complicated substrate are required. SERS techniques using nanostructured
surfaces, use localized electromagnetic field (EMF) near to the surface zone and results
in the enhancement of the signal by an order of typically 106 times. Usually, gold or
silver nanoparticles having different sizes and shapes, composite/hybrid nanoparticles
having core-shell structures or periodic structures are used for SERS platform. Lim et al.
[92] utilize the SERS platform for detection of influenza virus. Moreover, a different
strain of influenza virus was easily detected through SERS. Yeh et. al [93] detected
avian influenza A viruses using the SERS platform. In addition, it was claimed that the
virus such as rhinovirus, influenza virus, and parainfluenza viruses, can also be get
detected with their unmodified structure and with new strains. It was also revealed that
SERS can give selectivity when there is a presence of more than two viruses. More
reports for active detection of influenza virus can see through the results by Park et al.
and Kukushkin et al. [94-95].
Figure 9.The schematic diagram for the 2D material based SERS platform.
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Graphene was the first amongst all 2D materials family which was used for SERS

application and a variety of organic dyes (phthalocyanine (Pc), rhodamine 6G (R6G),
PPP, and crystal violet (CV)) molecules have been used for detection using graphene
[96-98]. Early-stage detection of viral infection is the key to cure and at a very early
stage, SERS signal due to test molecules are very weak. To enhance the signal,
therefore, one needs to enhance the laser intensity of the incident beam and at that
intensity, unfortunately, test molecules get degraded. Interestingly, the high thermal
conductivity of graphene comes to the rescue and helps remove interfacial heat
generated upon laser exposure and thus acts as a laser shield for underlying plasmonic
nanostructures on the one hand and prevents bond breaking and carbonization of test
molecules on the surface on the other hand [99,100]. Atomic-scale integration of
plasmonic nanostructure and graphene has been proposed and implemented earlier for
effortless removal of heat during SERS measurement [101-102]. 2D materials hetero
layers have designer materials behaviour such as mobility enhancement of graphene
when placed on boron nitride (BN). Inter-layer coupling amongst atomic sheets can be
exploited to manipulate out-of-plane tunnelling behaviour [103] in these heterolayer
stacks and thus they can be implemented to attain functional fast biochips. The
inception of 2D materials has completely revolutionized this field of research by
providing a simple, scalable, low-cost platform. The absence of a dangling bond in (out-
of-plane) 2D material makes them the most suitable platform to explore the chemical
enhancement mechanism (see Fig. 9). However, 2D materials are yet to be used for the
detection of viruses or microbes.
Challenges and Alternative Approaches
Control over the transmission of the contagious infection or the pandemic requires in-
depth basic knowledge, skill and anti-viral research to overcome the outbreak. Material
science broadens and opens up a plethora of opportunity to support antiviral research,
treatment and investigation. In the present pandemic, the SARS-CoV-2 virus needs to
be investigated from the structure, size, lifetime, transmission rate and its response to
various antiviral drugs. These challenges need to be properly addressed to avoid any
more upcoming pandemic in the future. The alternating approach to overcome any of
the present pandemics is to use technology such as advance research machine and AI.
To begin, with centrifuge machine powered with batteries would be an ideal solution to
separate viral-strain from saliva or blood. The structure of the virus can be analyzed via
environmental scanning electron microscopy or any confocal microscopy with high
magnification. Time-Resolved Photoluminescence, Ultraviolet, Raman and Fourier
Transform Infrared spectroscopy are few techniques which can be used to study the
binding of the protein/shell of the virus as well the for the interaction between the drugs
and virus. Alternatively, 3D printers can be used to produce a large number of masks,
gloves, personal protective kit etc. without engaging labours. Electro-spinning is yet
another technique which can help design and fabricate nanofibres. Artificial Intelligence
will be a boon for the scientist in their research if data from the infected person can be
monitored and tracked. These databases can be of utmost importance while designing
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and manufacturing anti-viral drugs or vaccines. Scalability of the drugs can be meet
using the robotics or microfluidic technology and effectiveness can further be monitored
by using AI. In short, multi-disciplinary research should be encouraged and

collaboration between industries, research labs and scientist should be established.
Future Work and Perspective

Immediate detection of the Covid-19 virus is the need of the hour. Moreover, lack of
time and available technology, as well as the basic knowledge of this unknown new
virus, is a threat and a bigger challenge to answer. As the virus is continuously
modifying its strain, size, structure and spread rate, and the development of vaccination
seems to be in its nascent stage, and out of the box, the solution needs to think of.
Material science, especially 2D materials based devices are amongst one of the ways to
detect and prevent the community from widespread of the virus. Also, early and rapid
detection can prevent severe organ failure as well as the death rate. Though several
portable, less expensive, invasive devices are present in the market for testing, they
take time to give result for an infected person. Yet, after consuming time and delaying
the treatment one infected person needs at that hour, these tests are not reliable
everywhere as they need an expert hand and skilled labour.
Figure 10. 2D material based devices for detection of Covid-19.

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2D materials based detection techniques, such as SERS, Bio-FET, Electrochemical

sensing, and Photo-Luminescence spectroscopy (see Fig. 10) is currently seems to be
one of the upcoming technology for detection of Covid-19 virus. The absence of the

dangling bond, high conductivity, mobility, luminescence
Figure 11.Size of different viruses.

(size dependent), weak van der Waals of attraction between layers as well as their
anchoring capability (in case of graphene, borophene, phosphorene and transition metal
dichalcogenides) makes them the desired futuristic material for detection of microbes.
The unprecedented physical and chemical properties of 2D materials make them a
platform for high sensitivity, specificity and selectivity for different virus detection and
ensure the early detection, effectiveness, as well as rapid testing of microbes. Even in
the short period, 2D materials have outperformed several existing and well-recognized
methods for spreading of the Covid-19 virus. 2D materials (graphene) coated fabrics
such as masks, PPE kit, gloves and shoes are currently being used at the commercial
level. This is possible because the inter-atomic distance of two atoms in graphene is
0.14 nm, which is far small than almost each harmful microbes, apart from their
mechanical flexibility. A size comparison of all harmful, fatal and mostly communicable
viruses with Covid-19 has been depicted in Fig. 11. Graphene can even be embedded
inside the polymer fabric and at filler level higher than a threshold; the fabric will be
electrically conducting which then can be used for viral removal from its surface in an
electrically controlled manner [104]. In case of rapid detection of any virus or analyte
mobility and charge carriers plays a huge role. The electronic mobility of 2D material
relies on size, shape, strain, valancy of an atom, crystalinity and chemical bonds.
Therefore, the electronic mobility is an intrinsic characteristic of a material.
View Article Online
DOI: 10.1039/D1TB00071C

Figure 12. Bandgap versus mobility of various 2D materials [69].

Amongst the Xene family, graphene and borophene have the electronic mobilities of
180000 and 280000 cm2/Vs respectively. These values are the highest amongst 2D
materials. Cousins of graphene viz. silicene, germanene, stanene and phosphorene
however have moderate mobilities 2100 cm2/Vs, 2800 cm2/Vs, 3000 cm2/Vs, 1000
cm2/Vs respectively [63, 69]. In general, semiconductor 2D materials from Transition
Metal Dichalcogenides (TMDCs) family have low mobility, however compensated by
carrier concentration [63, 69]. Thus, even though these 2D semiconductors may not be
apt for ultrafast detection, electrical signal will be enhanced as conductivity is the
product of mobility and carrier concentration.
View Article Online
DOI: 10.1039/D1TB00071C
Figure 13. 2D material heterostructures as active materials in FET devices.

Even though Boron Nitride (BN) is an insulator and have lowest mobility 0.05 cm2/Vs
[69], 2D semi metals such as graphene, metals such as borophene and
semiconductors such as MoS2 exhibit excellent mobility enhancement when placed on
atomically smooth, dangling bond free and charge passivated BN layer. With the recent
surge in 2D materials Moire’ super lattices as a tunable metamaterials, varieties of
heterolayers composed of 2D materials are proposed as active surfaces for authentic
COVID 19 detection via two probe, 4 probe, FET measurements as well as SERS
based molecular sensing in liquid phase containing blood, tears, sweat or saliva. (see
Fig. 13). Nanomaterials in general and atomic sheets in particular are thus proposed to
have tremendous potential in prompt detection and prevention of COVID 19. Research
in this direction has just commenced worldwide and as a materials platform, 2D
materials are destined to bestow best performances in times to come. Even though
recent literature on usage of nanotechnology motivates research along these directions
and due implementation, the present review on employing two dimensional materials
along with its doped and hybrid versions would inspire on-demand prompt diagnosis
and treatments [105-114].
Conclusion
Systematic investigation of SARS-CoV-2 virus indicates similarity in the pathogenicity
and genome sequence to SARS-CoV-1. Speculation of the transmission of the disease
by animals such as bats or pigs seems un-authentic. No scientific evidence has been
found to date. SARS-CoV-2 has two kinds of S protein namely S1 and S2. The severity
of the disease and its effect relies on the age, gender and kind of personal medical
history. Asymptomatic patients may or may not be the only reason behind spreading the
virus. The symptoms include dry cough, loss of taste and smell, body pain, fatigues,
breathlessness, and failures of organs leading to death. PCR test is the most effective
way found to date to detect the virus. Use of medicine such as Remdesivir, Favipiravir,
and HCQ is under investigation. Biosensing using 2D materials can be used for rapid
detection, analysis and research on the SARS-CoV-2 virus. Materials like graphene,
MXene, borophene and their hybrids are the futuristic material for developing a testing
kit to detect any alien virus.
Author Contributions: All authors involved in literature data collection,
conceptualization of review, writing, editing and proof reading of this manuscript.
Conflict of interest: Authors declare no conflict of interests.
Acknowledgments: We acknowledge Indian Institute of Technology Patna for
providing research facilities. VT acknowledges the financial support by P42-ES027723-
01A1 from National Institute of Environmental Health Sciences (NIEHS) Superfund
program grant. The contents of this paper are solely the responsibility of the authors and
do not necessarily represent the official views of US National Institutes of Health (NIH).
View Article Online
DOI: 10.1039/D1TB00071C
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2D Materials As Diagnostic Platform For Detection and Sensing of SARS-CoV-2 Virus A Bird-Eye View

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You can find more information about Accepted Manuscripts in the

or omissions in this Accepted Manuscript or any consequences arising

2D Materials as diagnostic platform for detection and sensing of

Journal of Materials Chemistry B Accepted Manuscript

Introduction to COVID 19 infection:

Journal of Materials Chemistry B Accepted Manuscript

Figure 1. Family of Coronaviridae virus

Journal of Materials Chemistry B Accepted Manuscript

Figure 2. Fatality and Transmission rate of viruses.

Journal of Materials Chemistry B Accepted Manuscript

Figure 3. Sensitivity and time of detection for COVID-19.

Journal of Materials Chemistry B Accepted Manuscript

Figure 4. CT-imaging of a COVID person recorded over a while.[30]

Journal of Materials Chemistry B Accepted Manuscript

Figure 5. COVID-19 detection techniques

Journal of Materials Chemistry B Accepted Manuscript

Figure 6. Sensitivity and time of detection for COVID-19.

Journal of Materials Chemistry B Accepted Manuscript

have been used in photodynamic and photothermal therapy. Transition metal

Journal of Materials Chemistry B Accepted Manuscript

detection of molecules (such as germs or microbes) integrate many branches of science

Field-effect transistor based sensing

Journal of Materials Chemistry B Accepted Manuscript

Journal of Materials Chemistry B Accepted Manuscript

interfacing technology. Li et al. [73] demonstrated graphene-based FET (G-FET), in

Journal of Materials Chemistry B Accepted Manuscript

targeted FET devices [88-91].

Surface-Enhanced Raman Scattering (SERS) based sensing

Journal of Materials Chemistry B Accepted Manuscript

Journal of Materials Chemistry B Accepted Manuscript

Future Work and Perspective

Figure 10. 2D material based devices for detection of Covid-19.

2D materials based detection techniques, such as SERS, Bio-FET, Electrochemical

Journal of Materials Chemistry B Accepted Manuscript

Figure 11.Size of different viruses.

Journal of Materials Chemistry B Accepted Manuscript

Figure 12. Bandgap versus mobility of various 2D materials [69].

Figure 13. 2D material heterostructures as active materials in FET devices.

Journal of Materials Chemistry B Accepted Manuscript

Journal of Materials Chemistry B Accepted Manuscript

2. A. E. Gorbalenya, S. C. Baker, R. S. Baric, R. J. d. Groot, C. Drosten, A. A.

23. A. Lorussoa, P. Calistria, M. T. Mercantea, F. Monacoa, O. Portanti, M. Marcacci

Journal of Materials Chemistry B Accepted Manuscript

26. A. T. Xiao, Y. X. Tong, C. Gao, L. Zhu, Y. J. Zhang, S. Zhang, Journal of Clinical

Journal of Materials Chemistry B Accepted Manuscript

67. P. Ranjan, R. Laha, J. Balakrishnan, Journal of Raman Spectroscopy, 2017, 48,

Journal of Materials Chemistry B Accepted Manuscript

90. C. H. Chu, I. Sarangadharan, A. Regmi, Y. W. Chen, C. P. Hsu, W. H. Chang, G.

Journal of Materials Chemistry B Accepted Manuscript

Y. Choi, Anal. Chem. 2015, 87, 23, 11652–11659.

111. S. Sharma, S. Saini, M, Khangembam, V. Singh, IEEE Sensors Journal,

Journal of Materials Chemistry B Accepted Manuscript

Kumar, S. Kumar, Materials Today Chemistry, 2020, 18, 100385.

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