ISSN 0027-1314, Moscow University Chemistry Bulletin, 2022, Vol. 77, No. 6, pp. 307–321. © Allerton Press, Inc.

, 2022.
Russian Text © The Author(s), 2022, published in Vestnik Moskovskogo Universiteta, Seriya 2: Khimiya, 2022, No. 6, pp. 375–394.

Biosensors Based on Graphene Nanomaterials

I. I. Kulakovaa, * and G. V. Lisichkina
a Department of Petroleum Chemistry and Organic Catalysis, Moscow State University, Moscow, 119991 Russia
*e-mail: [email protected]
Received March 16, 2022; revised April 12, 2022; accepted May 14, 2022

Abstract—This review is devoted to the development, properties, and application of biosensors based on
graphene nanomaterials. It is shown that such biosensors are characterized by their sensitivity, specificity of
detection of analytes, high speed, and small size. Examples of the use of graphene biosensors for the detection
of viruses, bacteria, markers of socially significant diseases, and various toxins are given.

Keywords: biosensors, grapheme, nanomaterials, viruses, bacteria, toxins

DOI: 10.3103/S0027131422060049

INTRODUCTION stantly reporting new achievements in the study of

In the 21st century a new scientific direction has graphene and its application in various fields of sci-
arisen and is successfully developing: nanobiotechnol- ence and technology [7–16]. Various measuring
ogy or biomolecular nanotechnology. This direction is devices, sensors, and sensor systems are considered to
based on the close cooperation of life sciences with be the main areas of application for graphene and
chemistry, physics, and engineering. One of the key related materials [14, 17]. For example, many
tasks of nanobiotechnology is the creation of biomed- graphene-based gas sensors are capable of reacting at
ical instruments and devices of the minimum (in the the limit of sensitivity to single acts of adsorp-
nanometer limit) size using special materials and tion/desorption of molecules (single-molecule detec-
interfaces. tion). The main trends in the improvement of biomed-
ical means of registration and measurement are a
Medical applications of nanobiotechnology have decrease in the size of sensor elements, as well as an
led to the emergence of a new branch of medicine, increase in their sensitivity and selectivity. It is
nanomedicine, one of the most promising areas of assumed that nanodevices that can be implanted in the
which is the early diagnosis of diseases and infections. human body for continuous monitoring of its parame-
Methods for the express diagnostics and monitor- ters will find mass application [18].
ing of the patient’s health status are being actively
developed, which allow obtaining the result of the The unique properties of graphene make it an ideal
analysis within a few minutes [1]. There are already candidate for one of the main roles in nanobiotech-
solutions for the express diagnostics of a person’s nologies [14–16, 19].
health status (the state of the cardio and immune sys- The aim of this review is to consider domestic and
tems, the presence of infections). These tests (point- foreign developments devoted to biochemical sensors
of-care (POC), i.e. studies near the patient) are used based on graphene materials and the creation of bio-
in the ambulance service, during hospitalization, and sensors for the express diagnostics of human health.
at home.
Biochemical sensors occupy an important place 1. BIOSENSOR DEVICES
among diagnostic devices. Such sensors can analyze
both biological fluids and analytes in a gaseous envi- In the past decade, there has been an increasingly
ronment, recognizing substances in low concentra- steady interest of scientists and engineers in the devel-
tions, up to single molecules [2, 3]. opment of public express methods of analysis that
Research is underway to develop biosensors based have high levels of sensitivity and selectivity.
on graphene and its derivatives. The possibility of miniaturization of such analyti-
Graphene is one of the youngest carbon materials cal devices is especially important. The most promi-
[4–6]; it is distinguished by exceptionally high con- nent representatives of analytical systems that com-
ductivity, mechanical strength, adjustable bandwidth, bine the listed qualities are biosensors [20, 21].
adjustable optical properties, and a large specific sur- Biosensors are a type of chemical sensors in which
face area. Research teams around the world are con- the recognition system has a biochemical nature and

307
308 KULAKOVA, LISICHKIN

uses the reactions of either individual biomolecules, or while the specific indication of microorganisms using
biological supramolecular structures [20, 22]. A enzyme immunoassay takes 3–4 h.
unique feature of biosensors, in contrast to chemical Biosensors can be classified according to the
ones, is the high specificity of the receptor element, as mechanism of biological recognition and according to
well as its ability to perform recognition without addi- the type of transducer used (a device that converts the
tional energy consumption. The authors of [20, 22] response of the recognition element into a measurable
believe that a necessary characteristic of both chemi- signal). According to the type of transducers, biosen-
cal and biological sensors should be the possibility of sors can be divided into electrochemical, optical, and
their miniaturization. gravimetric ones. Electrochemical biosensors, accord-
Among the areas of application of biosensors, the ing to the authors [22], occupy a priority position
most important place is occupied by clinical diagnos- among other types of sensors.
tics, whose area of interest includes, in particular, con- Electrochemical biosensors track any changes in the
tinuous monitoring of key metabolites of blood and electrical properties, size, shape, and charge distribu-
other biological fluids to monitor the patient’s condi- tion, for example, during the formation of an “anti-
tion. This problem can be solved by implanting spe- body–antigen” complex on the electrode surface.
cific sensors, among which biosensors have no equal. According to the method of measuring the analyti-
Biosensors as chemical sensors that include biolog- cal signal, electrochemical biosensors are divided into
ical material were first reported by L. Clark and amperometric, potentiometric, and conductometric
S. Lyons at the symposium of the New York Academy sensors and field-effect transistors. Such biosensors
of Sciences in 1962 [23]. are used to detect a wide range of biological targets,
They suggested using electrodes modified with glu- including proteins, biomarkers, and nucleic acids.
cose oxidase embedded in membranes to create more Optical biosensors are widely used; they allow direct
advanced electrochemical sensors. This results in sen- detection of biomolecules in real time. Optical detec-
sors that are specifically sensitive to certain substrates, tion systems use the power of the optical field and the
since they detect the formation of an enzymatic reac- biological recognition element, which allows the anal-
tion product or the consumption of one of the sub- ysis of macromolecules with a high degree of sensitiv-
stances involved in this reaction. Clark and his coau- ity directly in the body.
thors, using the idea mentioned above, developed bio-
Among the advantages of optical biosensors over
sensors for determining glucose and lactate in the
others, their high specificity, great sensitivity, cost-
blood [24, 25]
effectiveness, and small size can be singled out. The
The term biosensor has not yet been unambiguously disadvantages of an optical transducer include its sen-
defined. Some authors consider that this is an analyt- sitivity to various environmental parameters, includ-
ical system for working with biological matter; and oth- ing local temperature changes.
ers, that a biosensor is a system that itself contains a bio-
Piezoelectric biosensors track the change in mass on
logical substance.
the surface of a physical carrier (piezoelectric crystal—
Although experts have not yet reached a consensus resonator), density, viscosity of the medium, and fre-
view, there are more arguments in favor of the second quency of acoustic waves. Such biosensors are most
definition. Thus, a biosensor can be called an analyti- effective for detecting large molecules and particles:
cal device, in which the reactions of these compounds hormones, bacteria, cells, etc.
catalyzed by enzymes, immunochemical reactions, or
reactions taking place in organelles, cells, or tissues are In the classification according to the biochemical
used to determine chemical compounds. The main component, the following biosensors are distin-
part of the biosensor is the biological material guished:
(enzymes, cells, antibodies, antigens, DNA frag- enzyme, which include pure enzyme preparations
ments, etc.), with which the analyte interacts during or biological preparations (tissue homogenates or
the operation of the sensor. The signal about this reac- microbial cultures) and exhibit a certain biological
tion with the help of various physical and chemical activity;
methods (electrical, optical, etc.) is converted so that immunosensors use immunoglobulins, which are
it can be measured and the result displayed on the protective proteins secreted by the body’s immune sys-
device screen [20, 26]. tem in response to the intake of foreign biological
Biosensors that function without the addition of an compounds (antigens), as a biochemical receptor;
additional reagent are called reagentless. Biosensors DNA sensors, including nucleic acids as a biochem-
that can quickly and reproducibly recover are called ical component;
reusable, and biosensors that cannot be reproducibly microbial biosensors using microorganisms that can
and quickly restored are considered disposable, includ- convert a certain substance with the help of enzymes,
ing bioassays and bioindicators [22]. differing from enzyme sensors in that not one enzyme
Biosensors are characterized by their fast response but a combination of enzymes can participate in the
(response time ranges from several minutes to 1 h), conversion of the substrate; and

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 309

biosensors based on supramolecular structures of the Development of relatively simple methods for
cell, occupying an intermediate position between obtaining graphene and its derivatives, such as
enzyme and DNA sensors and microbial sensors, graphene oxide, fluorinated graphene, etc. [13, 16, 38,
since they are based on intracellular structures that 39], the implementation of syntheses of conjugates of
have a rather complex hierarchical structure. graphene nanomaterials with organic or bioorganic
To increase the selectivity of the sensor to certain compounds of any complexity [40, 41], and the above
molecules, the surface of the receptor is chemically complex of properties have made graphene nanomate-
modified so that these molecules can be immobilized rials (GNMs) attractive for biomedical application.
on it. GNMs are of interest as receptor elements for record-
Thus, a high level of sensitivity and selectivity of the ing the interaction of a surface with molecules in the
biosensor is achieved. gas and liquid phases. Achievements in the develop-
ment of gas sensors based on GNMs are considered in
[14, 42–44].
2. GRAPHENE AS THE RECEPTOR MATERIAL
As is well known, graphene is an allotropic modifi- 3. GRAPHENE NANOMATERIALS
cation of carbon, formed by a layer of sp2 carbon atoms IN BIOSENSORS
and representing a 2D crystal one atom thick. Less Over the past decade, a lot of work has been done
than two decades have passed since the discovery of to explore the possibilities of use of graphene nanoma-
graphene [4]; however, it is rapidly gaining a wide terials in biomedicine [11, 15]. It has been shown that
range of potential applications, in particular medicine. GNMs are promising for targeted drug delivery, visu-
Thus, in 2013, publications on the biomedical applica- alization of organs and tissues, the creation of antibac-
tions of graphene and its derivatives reached 63% [27]. terial materials, and the synthesis of a biocompatible
The structural features of the graphene sheet are scaffold for cell cultures [15]. Specialists are especially
such that it is a system in which charge carriers, having interested in the possibility of developing graphene
unlimited freedom of movement in the plane of the biosensors. The review [11] shows that GNM-based
sheet, are closed in a narrow space of one carbon layer. biosensors are capable of detecting biomarkers-indi-
This leads to the appearance of unique electrophysical cators of diseases, which is important for medical
characteristics and other unusual properties of diagnostics; in addition, they allow studying processes
graphene [8, 16, 27, 28], in particular, good electrical occurring in living cells at the molecular level, for
conductivity [4] due to the high concentration and example, the formation of reactive oxygen species.
mobility of the charge carriers. A common disadvantage of electrochemical sen-
Graphene has a record-high mechanical strength. sors is insufficient selectivity due to the simultaneous
Despite this, it has elasticity and can be subjected to 20% sorption of several substances. As applied to graphene
deformation without the network structure breaking electrochemical sensors, this drawback was eliminated
[30]. Monolayer graphene has a constant optical by using the antigen–antibody reaction. The compo-
transparency in the visible range (97.7%) and a trans- nents of this pair can only interact with each other.
mittance value that linearly decreases depending on They cannot interact with any other proteins. It is
the number of layers for n-layer graphene [31, 32]. The known that at certain stages of many human diseases,
monatomic thickness of a graphene sheet provides the antigens-markers specific for any one disease or for a
highest possible surface to volume ratio, a specific sur- group of diseases appear in the blood. These antigens
face area of ~2630 m2/g [16, 27, 33], and high sorption can interact with specific antibodies previously depos-
properties. In addition, it has biocompatibility [8], ited on the surface of the graphene sensor.
which is important for biomedical applications.
Graphene can be obtained using mechanical meth-
ods: exfoliation of carbon layers from the surface of 3.1. Graphene Materials for Biosensors
highly oriented pyrolytic graphite (the Scotch tape It follows from the analysis of the literature that,
method), splitting of graphite crystallites into individ- depending on the choice of the synthesis method and
ual plates when exposed to ultrasound in the presence the features of its implementation, it is possible to
of surfactants in solvents. Chemical methods are also obtain graphene materials with different properties
used: longitudinal catalytic oxidative cutting of carbon [13, 14, 45–47]. Thus, the CVD method allows us to
nanotubes, which contain rolled graphene layers; synthesize high-quality and large graphene samples
deposition from the gas phase of carbon-containing on the surface of various metals but monolayer films
compounds (CVD method); thermal decomposition are formed only on copper. The method is promising
of the surface layer of a single crystal of silicon carbide; for the large-scale production of graphene, but it is
reduction of graphene oxide or graphite oxide; etc. energy-consuming, which makes it economically
[13, 14, 16, 19]. Methods for obtaining 3D graphene unjustified for use where a significant amount of
materials (graphene foam, laser-induced graphene graphene is required. Synthesis of graphene monolay-
LIG) have been developed [12, 34–37]. ers by thermal decomposition of the surface layer of

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

310 KULAKOVA, LISICHKIN

CO2-laser
(a) (b) (c)

Polyamide film

Fig. 1. Formation of an electrode from LIG: (a) polyimide substrate, (b) creation of graphene electrodes, (c) formation of a recep-
tor window upon encapsulation in plastic [12].

single-crystal silicon carbide at a temperature of conductivity. Moreover, LIG can be used to design
~1000°C leads to the epitaxial growth of a structurally graphene patterns of any complexity (Fig. 1). To do
homogeneous high-quality graphene film on the SiC this, it is sufficient either to apply a pattern on the sub-
surface. However, the high cost of single-crystal SiC strate with a polymer solution and then apply laser
and its high decomposition temperature reduce the radiation, or to draw electrodes on the polymer sub-
attractiveness of the method for the production of strate (Fig. 1a) with a laser and attach Ag-contacts to
large amounts of graphene. them (Fig. 1b), and then encapsulate it in plastic, leav-
However, sensor developers have looked at these ing the receptor window open (Fig. 1c).
materials and compared their sensory characteristics. The stenciling and printing process, as well as the
The comparative study of epitaxial graphene films on useful properties of LIG, open up a new way to
SiC and graphene obtained by the CVD method as a develop miniature graphene devices. The use of LIGs
material for electrochemical biosensing was carried in sensor applications quickly moved from single
out in [48, 49]. For quantitative measurement, the experiments to the creation of an integrated intelligent
authors used the method of impedance spectroscopy system for detecting biological objects [11, 12].
using deionized water and saline (0.9% NaCl). Based
on the results obtained, it was concluded that single- Oxidized forms of graphene, such as graphene
layer epitaxial graphene on SiC has a higher sensitivity oxide and reduced graphene oxide (RGO), are among
than multilayer CVD-graphene. Biosensors based on the most promising GNMs for creating biosensors,
graphene films on SiC showed an extremely high sen- since, by controlling the conditions of their oxidation
sitivity to the detected substances. One of the latest or reduction, materials with the required ratio of oxy-
advances in the development of graphene biosensors is gen and carbon [13], as well as certain functional
related to the use of suspended graphene [50]. groups, can be obtained.
The authors deposited monolayer graphene from a The presence of oxygen-containing groups allows
suspension onto a preliminarily structured Si sub- us to carry out adsorption and covalent modification
strate. To increase the selectivity, graphene was chem- of the surface of these materials with both small mole-
ically modified. Selectivity was assessed by nanoscale cules and large biomolecules, such as enzymes, anti-
mechanical deflection of the sheet plane, as the bio- bodies, antigens, DNA fragments, and even cells.
marker generates a force that deforms planar graphene
into a dome shape, resulting in spectral shifts in optical The interaction of immobilized molecules with the
interference between graphene and silicon substrate. analyte is detected using the same principles as in the
Using the interference properties of light, the authors case of other sensors. For example, these can be the
estimated the magnitude of the deformation from the following biosensors:
change in color. — electrochemical (based on field-effect transis-
The sensitivity of biosensors can be increased by tors, the impedance spectroscopy method [48, 49]);
using laser-induced graphene (LIG). In 2014, it was
found that polymers, such as polyimide, can be — optical (biosensors using the phenomenon of
directly converted into porous three-dimensional surface plasmon resonance) [50];
graphene using an infrared CO2 laser [37]. The discov- — fluorescent [51]; and
ery of LIG has attracted a significant attention due to
its wide range of applications. The advantages of the — others.
technology for obtaining LIG compared to conven- The schematic diagram of the biosensor is shown in
tional methods for the synthesis of graphene are the Fig. 2. Designs of graphene biosensors differ depend-
environmental friendliness of the process and the pos- ing on the goals and objectives of sensing. They can be
sibility of controlling the morphology of samples. either wired or wireless. These are wearable, flexible,
LIG has high porosity, flexibility, and mechanical monoplex, and multiplex systems used in both clinical
strength, as well as excellent electrical and thermal and home settings.

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 311

3.2. Chemical Modification of Graphene Is a Necessary

Step in the Development of Biosensors Biosensor

An important step in the use of graphene nanoma-

Biological
terials in biomedicine (including the creation of bisen- Biological receptor Signal
converter
Signal
based
sors) is their chemical modification. Chemical modi- analyte on GNM (transducer) amplifier
fication can improve the solubility of nanoparticles of
these materials in water, ensure their biocompatibility,
and reduce their toxicity and the ability to interact Interaction Signal
with certain analytes. conditioning
GNMs are characterized by an extended polyaro-
matic system and the presence of oxygen-containing Fig. 2. Schematic diagram of a graphene biosensor.
groups localized both on the periphery of graphene
planes and on their surface. These groups make
graphene molecules active with respect to electro- that the carboxyl groups were uniformly distributed
philic and nucleophilic reagents. In recent years, over the graphene oxide plane.
methods for the chemical modification of graphene In [51], a fluorescent peptide labeled with pyrene
with functional groups and fragments of molecules fragments was immobilized on graphene oxide. The
have been actively developed. On the one hand, such authors suggested using the obtained material to study
modification allows us to control the electronic prop- protein-protein interactions.
erties and, consequently, the conductivity of graphene
over a wide range. Depending on the type of modifi- The formation of supramolecular complexes of
cation, the interaction energy between the adsorbed porphyrin derivatives with reduced graphene flakes is
molecule and graphene, as well as the charge transfer described in the review [59].
in the system, can vary greatly. On the other hand, The authors paid special attention to this material,
functional groups play the role of specific reaction since, in their opinion, the great possibilities of post-
centers during the adsorption and covalent bonding of synthetic modification in combination with the
various molecules with graphene and its derivatives unusual properties of graphene and its derivatives can
[13, 19, 45, 46]. be used to solve complex biomedical and environmen-
Phenyl and alkyl groups, a stable free radical tal problems.
4-amine-2,2,6,6-tetramethyl-1-piperidine oxide, and
dichlorocaben were covalently grafted to the surface of As an example, we present a scheme of chemical
graphene using organic synthesis methods [53]. Con- modification of an electrode in manufacturing a bio-
jugates of graphene and its derivatives with DNA mol- sensor based on LIG (Fig. 3).
ecules [54], porphyrins (as drug components) [55, 56], To stabilize the loosened LIG particles and obtain
poly-L-lysine [57], star-shaped polyethylene glycol more sensitive layers, the authors of [12] electrochemi-
(PEG) [58], etc. [13, 16], have been obtained. cally polymerized 3,4-ethylenedioxythiophene (EDOT)
The grafting of star-shaped PEG [58] to graphene to form polyEDOT (PTDOT) in the working elec-
oxide made it possible to obtain biocompatible mate- trode (Fig. 3a). Then, the electrode surface was ami-
rials for cell visualization and sorption of biomole- nated (Fig. 3b), a template was attached (Fig. 3c), and
cules, including drugs. Unlike other graphene materi- electropolymerization was performed in the presence
als, the resulting product forms stable dispersions in an of the template (Fig. 3d). After the template was
aqueous salt medium and in biological fluids. In addi- removed, a polymer with a molecular imprint was
tion, it exhibits fluorescent properties in the near-IR obtained (Fig. 3e)
region, which can be used to create optical biosensors.
The sensitivity and selectivity of the biosensor
Covalent modification of graphene oxide depos- based on molecularly imprinted LIGs were compara-
ited on a substrate with DNA molecules to create bio- ble to those of sensors fabricated using commercial
molecular devices was carried out in [54]. An oligode- graphene-based screen-printed electrodes.
oxynucleotide containing 20 links (amine-AAC TGC
CAG CCT AAGTCC AA) was involved in a reaction
with graphene oxide carboxyl groups in the presence 3.3. Application Examples of Graphene Biosensors
of an activator. It has been shown that DNA binds pre-
dominantly onto thicker regions of the crumpled Currently (March 2022), about two hundred bio-
graphene sheet, including graphene oxide folds, which sensor devices that use graphene nanomaterials have
follows from the observation of a higher fluorescence been described in the scientific and patent literature.
intensity in these regions. Since no increased fluores- Because the volume of the article is limited, we will
cence was observed at the edges of the graphene focus only on the most significant and illustrative
planes, where the carboxyl groups that bind DNA examples of the use of graphene biosensors in relation
molecules are supposed to be, the authors concluded to various classes of analytes.

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

312 KULAKOVA, LISICHKIN

(a) (b) (c) (d) (e)

NH2 NH2 NH2 NHNH NH NHNH NH NHNH NH

Precipitation Attaching Template

Amination Electropolymerization
PEDOT a template removal

1 2 3

Fig. 3. Scheme of chemical modification of an electrode based on LIG: (1) polyamide; (2) graphene; (3) PEDOT-polymer
(according to [12]).

3.3.1. Graphene Biosensors bimetallic Ag–ZnO nanoparticles and graphene oxide

for Detecting Bacteria and Viruses modified with a polymer with molecular imprints of
bacteria.
The work [60] reported on the fabrication, based
on graphene oxide or aminated graphene deposited on In [66], the authors summarized recent advances in
a silicon substrate, of new biological devices: with a electrochemical biosensing used to detect common
bacterium localized on the sensor (1) and bacterial foodborne pathogens. For example, labelless electro-
DNA (2). The bacterial biological device 1 is highly chemical biosensors have also been developed to
sensitive due to the attachment of Bacillus cereus bac- detect E. coli. Thus, a (rGO-CysCu) Gold electrode
teria generating approximately 1400 p-type charge car- was made from RGO modified with a chelate salt of
riers in graphene. Similarly, single-stranded DNA cysteine with Сu(II) and gold, which showed that
grafted to graphene in device 2 hybridizes with its E. coli O157: H7 cells can be differentiated from non-
complementary DNA strand, reversibly increasing the pathogenic E. coli and other bacterial cells.
hole density by 5.61 × 1012 cm–2. An electrochemical biosensor for the detection of
The authors showed that, by varying the nature and Staphylococcus aureus (S. Aureus) by the method of
content of surface functional groups, the sensitivity of impedance spectroscopy using single-stranded DNA
the device can be controlled. The specificity of the related to a reduced graphene oxide–gold nanoparti-
sensor is switched by changing the polarity of the sur- cle nanocomposite is also described. Clostridium per-
face; and immobilization of the DNA molecules fringens (C. perfringens) is the most common type of
occurs mainly in the thicker areas and wrinkles of the Clostridium among the causative agents of clinical
GNM layer. genital gangrene C. It can break down sugar in muscles
and connective tissue, and then release large amounts
According to the authors, the study will motivate of gas, leading to severe tissue emphysema and affect-
the development of the next generation of biodetec- ing the blood supply, and eventually there is a large
tion tools. area of tissue necrosis. The DNA biosensor was fabri-
The researchers [61, 62] have developed a graphene cated based on screen-printed electrodes modified
biosensor to detect the Helicobacter pylori bacteria (see with streptavidin aptamer.
Section 3.3.2 for details). The authors of [67] developed a biosensor in which
The authors of [63] created a biosensor based on a a specific DNAzyme (a DNA oligonucleotide that can
CVD graphene film with immobilized antibodies to enter into certain chemical reactions and achieve
detect Escherichia coli (E. coli). The biosensor pro- highly specific detection of bacteria) was immobilized
vided high levels of sensitivity and specificity. The by adsorption on a graphene surface. The fabrication
researchers claimed that their fast, label-free method of this biosensor made it possible to avoid time-con-
could also be used to detect other bacteria and patho- suming operations of functionalization or surface
gens, if the right antibodies are used. To detect E. coli modification. The authors developed a fluorescent
bacteria, another biosensor was developed using CVD biosensor with DNAzyme attached directly to colloi-
graphene coated with poly(methyl methacrylate) [64]. dal graphene to detect E. coli bacteria. DNAzyme acts
The sensor demonstrated a very low detection limit as a fluorescent producer and detection element, while
(10 CFU/mL) and high performance. graphene acts as a transducer, generating measurable
Good analytical performance was achieved in [65], signals upon contact with E. coli and creating changes
which describes a very economical, fast, sensitive, and in fluorescence.
specific electrochemical biosensor for the detection of Achievements in the field of creating biosensors
E. coli. The sensor is based on a nanocomposite of based on GNMs used to detect various types of

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 313

Table 1. Graphene biosensor materials and virus detection limits (according to [68])
Virus type Basic material Limit of detection
Bird influenza virus RGO 5 pM
Human influenza virus Graphene 1 ng/mL
Bird and human influenza viruses Graphene 130 pM (for humans) 600 nM (for birds)
Ebola virus RGO 2.4 pg/mL
Ebola virus RGO 1 ng/mL
Hepatitis B virus Graphene 0.1 fM
Hepatitis B virus RGO 50 aM
Human immunodeficiency virus HIV Graphene 1 pM
Human immunodeficiency virus HIV Graphene 10 fg/mL
Norovirus Graphene 0.1 mcg/mL
Human papillomavirus RGO 1.75 nM
Rotavirus RGO 4.5 ng
Zika virus Graphene 450 pM
SARS virus COVID-19 Graphene 1 fg/mL
Graphene 0.2 pM

viruses, such as Ebola, Zika, and influenza, are con- but also good selectivity and reproducibility. A mono-
sidered in the reviews [68, 69] and are partially pre- layer of graphene modified with 1-pyrenebutanoic
sented in Table 1. acid succinimidyl ester is a myrobiocide, and this is
By immobilizing a monoclonal antibody (anti- important because it can be produced on a large scale
Zika NS1) on the surface of commercially available from soybean seeds treated according to the known
CVD graphene, a cost-effective and ultraspecific industrial technologies.
graphene biosensor for detecting the Zika virus was The use of a graphene oxide film modified with
constructed [70]. pyrene derivatives and antibodies allowed us to
Ebola hemorrhagic fever is an extremely dangerous develop an electrochemical biosensor for detecting the
epidemic disease, and its early detection is vital to pre- rotavirus [74]. Later, these authors presented a modi-
vent serious outbreaks. To detect the Ebola virus, the fied and more sensitive model using a field-effect
authors of [71] used a biosensor with reduced transistor based on reduced graphene oxide with a
graphene oxide, on which antibodies against Ebola covalently bound antibody [75]. This made it possible
were immobilized. The authors were able to detect the to overcome the low reproducibility and some other
Zairian strain of the Ebola virus in real time with a shortcomings of their previous work. As a result, the
very low detection limit (up to 1 ng/mL). resulting biosensor was proposed for highly sensitive
A method for detecting the dengue fever virus using pathogen detection. Another biosensor based on
a graphene oxide–polymer composite [72] with a low graphene oxide for the detection of rotavirus is
detection limit of 12 PFU/mL has been described. described in [76].
(One PFU is equal to 10–4 m–2 st–1 s–1, where st is a
steradian). The surface of gold microelectrodes was coated
with graphene oxide, on which antibodies were immo-
A graphene-based biosensor that is selective for bilized. To increase the specificity of the sensor, the
recombinant cyanovirin-N (cV-N), an antiviral pro- electrodes were additionally treated with bovine serum
tein that has proven to be an effective microbiocide for albumin to block the remaining free surface so that
HIV replication suppression, has been developed [73]. only antibodies determined the selectivity of the sen-
The graphene monolayer was modified with 1-pyren- sor. The resulting biosensor provided rapid and spe-
ebutanoic acid succinimidyl ester, which interacts cific detection of rotavirus. The authors of [77] devel-
both with graphene and with primary and secondary oped an immunobiosensor based on graphene oxide
antibody amines. By monitoring the change in the for the detection of rotavirus, which has high levels of
electrical resistance of the developed device, the sensitivity and selectivity.
authors were able to detect rCV-N in solutions in the
concentration range from 0.01 to 10 ng/mL and Several viral biodetectors have been proposed to
showed that the limit of detection was 0.45 pg/mL, improve performance based on graphene modified
which was much lower than of currently available with aptamers. Aptasensors are biosensors based on
methods. The sensor showed not only high sensitivity aptamers, which are oligonucleotides capable of bind-

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

314 KULAKOVA, LISICHKIN

ing to a specific molecule with a high degree of speci- form developed by them, will allow self-testing at
ficity. home for telemedicine diagnosis and monitoring of
Aptasensors are very promising: they are quite COVID-19 and get the result in less than 10 minutes.
accessible and selective to the most diverse figurative Such sensors can monitor conditions such as gout and
analysts. For example, an aptasensor based on a stress levels by detecting extremely low levels of certain
microfluidic platform was described in [78] in which compounds in blood, saliva, or sweat. A graphene-
the carbon electrode was modified with a composite of based wireless device has been developed for the
gold nanoparticles with graphene particles. Detection detection of the SARS-CoV-2 virus in human bioflu-
of norovirus (causative agent of acute intestinal infec- ids [81], which allows for fast and highly sensitive self-
tion) is based on the interaction of the aptamer with testing for COVID-19 with high accuracy at a low cost,
the target. The aptamer was labeled with ferrocene as i.e., to provide sensitive, rapid, and inexpensive dis-
a redox probe. When the norovirus binds to the ease monitoring.
aptamer, an increase in the capacitance of the elec-
trode results in detection of the virus in the blood sam- 3.3.2. Graphene Biosensors for the Detection
ple within 35 minutes (total time). of Markers of Socially Significant Diseases
The COVID-19 pandemic has become a major
global challenge to public health systems. To prevent a To diagnose many diseases, it is necessary to be
wider spread of COVID-19 infections, sensitive, rapid, able to detect disease markers, protein molecules spe-
and inexpensive detection of infection in presymp- cific for each specific pathology, which are usually
tomatic and asymptomatic patients is important. The expressed in very small quantities.
use of biosensors contributes to the solution of this GNM-based biosensors for probing protein mole-
problem. The introduction of nanomaterials improves cules can significantly increase the efficiency of diag-
the performance of the biosensor, and the addition of nosing a wide range of diseases affecting both humans
graphene increases the sensitivity to a very high level. and animals.
Among various biosensor circuits, the graphene-based
field-effect transistor stands out for its unique ability
of ultra-sensitive and low-noise detection, which Cardiovascular Diseases
facilitates instantaneous measurements even in the An aptasensor for determining the myoglobin car-
presence of a small amount of analytes [79]. diomarker, an oxygen-binding protein in skeletal mus-
COVID-19 diagnostics based on Real-time poly- cles and heart muscle, whose function is to create an
merase chain reaction (RT-PCR) is the main, most oxygen reserve in the muscles, was proposed [82, 83].
sensitive, and selective method. However, it is costly, The myoglobin-specific aptamer was immobilized
requires qualified personnel, takes a lot of time, and on the surface of a printed electrode and modified
can only be carried out in laboratory medical institu- with graphene oxide and carbon nanotubes. The sen-
tions. Worse still, the RT-PCR method showed a high sor provides a low detection limit (34 ng/L) in the lin-
false negative rate (ranging from 20 to 67%) due to poor earity range (1–4000 ng/mL).
sampling, insufficient sample quality, low sensitivity of
the diagnostic kits, and long duration (4–5 h). The Troponins I, T, and C are involved in the calcium-
authors of [80] describe a multiplex portable wireless dependent regulation of the act of the contraction-
electro-chemical device based on graphene electrodes relaxation of the heart and are specific markers of
with laser engraving for ultrafast detection of COVID- myocardial damage. In a number of medical tests, tro-
19: Rapid Plex SARS-CoV-2. In this sensor, graphene ponins are used as biomarkers for various heart dis-
structures are connected to antibodies and immune eases. Acute myocardial infarction (AMI) is one of the
system molecules that are sensitive to specific pro- leading causes of death among patients with cardio-
teins, such as those found on the surface of the vascular disease, prompting researchers in this field to
COVID virus. When connected to auxiliary electron- develop POC biosensors to quickly detect an AMI epi-
ics, the sensor can transmit data wirelessly to the user’s sode. Over the years, various detection methods have
mobile phone via Bluetooth. It can be used for highly emerged to evaluate cardiac troponins. Review [84]
selective, supersensitive, and fast electrochemical summarizes various biosensor methods for detecting
detection of the nucleocapsid protein of the viral anti- these markers of myocardial injury.
gen, lgM, and lgG antibodies in physiologically sig- To detect troponin I, the authors of [85] developed
nificant ranges, as well as the biomarker of inflamma- an electrochemical labelless biosensor based on a
tion: the C-reactive protein. glassy carbon electrode coated with nanoporous
The applicability of the Rapid Plex SARS-CoV-2 graphene oxide. The biosensor is inexpensive, and due
platform with positive and negative blood and saliva to the use of porous graphene, has good electrochem-
samples in COVID-19 has been successfully evalu- ical properties and a large active surface area.
ated. Based on the results of the pilot study, the The sensor showed good selectivity and high sensi-
authors claim that the multiplex immunosensor plat- tivity: the limit of detection was 0.07 ng/mL.

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 315

Oncology and the possibility of remote wireless sensing. Thus,

It is known that early diagnosis of oncological dis- the “tattoo on the tooth” warns of bacteria in saliva.
eases plays a key role for subsequent treatment in many
cases. However, the level of tumor markers in the Diabetes
patient’s blood at the initial stages of the disease does
not exceed a few pmol; thus, only a few methods and Diabetes is a common chronic disease in which the
sensors can detect them [61, 83]. In recent years, var- body’s ability to absorb glucose is impaired. Constant
ious biosensors have been proposed for diagnosing monitoring of the concentration of glucose in the
various types of cancer, including breast [86], prostate blood of diabetic patients is necessary to assess the
[87, 88], lung [89], liver, stomach, and intestine cancer condition of patients. Various glucometers are used for
[90]. Let us give specific examples. measurements, primarily enzymatic electrochemical
The authors of [89] developed a highly sensitive biosensors. The latter have satisfactory selectivity and
graphene biosensor capable of identifying signs of lung sensitivity, are based on the use of glucose dehydroge-
cancer, i.e., to detect (sniff out) in the respiratory nase or glucose oxidase enzymes, and are commer-
products of a human molecules of the most common cially available. However, the use of biological materi-
biomarkers of lung cancer (ethanol, isopropanol, and als such as enzymes, antibodies, etc., is limited by the
acetone) in a range of different concentrations. The complexity of their manufacture and low service life
sensor is able to detect molecules of specific lung can- due to the decrease and loss of the biological activity of
cer markers at the earliest stage of the disease. the enzyme over time. The commonly used glucose
oxidase enzyme has insufficient stability and requires
Detection of the prostate tumor marker PSA was
complex immobilization processes on the sensor sur-
performed by the authors of [87] using graphene field-
face. It does not withstand even a slight heating, which
effect transistors modified with polyethylene glycol
narrows the range of application of biosensors.
(PEG)/ethanolamine. The study demonstrated the
possibility of real-time biomarker detection. In addi- An alternative to enzymatic biosensors are sensors
tion, studies using graphene devices modified with a without enzymes that detect glucose through its oxi-
PEG/DNA aptamer have shown specific binding and dation. In this case, it is important to develop suitable
detection of PSA in solutions at pH 7.4. The receptor efficient catalysts for the detection of glucose in bio-
of aptamer-modified graphene devices can be regen- logical samples under physiological conditions with-
erated for the purpose of multiple selective determina- out any pre/post treatment. The main advantages of
tion of PSA. enzyme-free biosensors are their low cost, high stabil-
Helicobacter pylori (H. Pylori) bacteria attack the ity, fast response, and low detection limit. The devices
stomach lining and cause ulcers and stomach cancer. directly detect glucose and are based on its oxidation
To detect them, a graphene biosensor was developed reaction catalyzed by various electrocatalysts, which
in [61, 62]. Graphene was adsorptively modified by are atoms on the surface of the material. Here, a signif-
antibodies. When bacteria interact with the biosensor, icant role is assigned to nanomaterials, such as
chemical reactions are triggered, which are fixed by nanoparticles of Au, Ag, Ni, Cu, and Co, as well as
graphene. The researchers used microfluidics to their oxides and sulfides.
ensure the detection of reaction products occurring In [92], the authors compared the latest develop-
with bacteria in the presence of certain chemicals that ments in nonenzymatic glucose biosensors based on
the authors added to a tiny drop of water. copper nanoparticles (NPs), copper oxides, their
Microfluidics allows bacteria to be localized in alloys, and their composites. Copper and its oxides are
microdroplets near the sensor surface. The biosensor widely used as components of nonenzymatic glucose
quite quickly (in less than 30 min), highly sensitively, sensors due to their low cost, good sensitivity, and cur-
and quantitatively detects H. Pylori bacteria, and the rent response in alkaline media, and also because of
concentration of the reaction products can be moni- the practical and simple methods for preparing nano-
tored in real time. materials based on them. In addition, they have high
A wireless nanosensor based on graphene was electrocatalytic activity, economy, nontoxicity, and
developed to detect bacteria in saliva [91]. The stability. Combining copper with graphene signifi-
graphene sensing element was adsorbed onto a silk cantly increases the sensitivity of nonenzymatic glu-
film (fibroin) and then transferred to the tooth sur- cose sensors, which is probably due to the synergistic
face, followed by dissolution of the supporting silk effect between the two components leading to an
film. The detection specificity was ensured by using increase in the electrocatalytic active area and an
self-assembling antimicrobial peptides (odorranin- increase in electron transfer for glucose oxidation.
HP) on a graphene monolayer. When the system rec- Information about some biosensors is given in Table 2.
ognizes and binds the target bacteria (H. pylori), the It follows from the data presented in Table 2 that
electrical conductivity of the graphene film changes the developed enzyme-free electrochemical glucose
and the data are transmitted wirelessly. The developed biosensor based on LIG decorated with Cu or Cu–
nanosensor has a low detection limit (100 CFU/mL) Cu2O nanoparticles showed the highest sensitivity

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

316 KULAKOVA, LISICHKIN

Table 2. Analytical characteristics of non-enzymatic graphene biosensors for glucose based on Cu nanoparticles, copper
oxides, alloys/composites (according to [92])
Sensitivity, Limit of detection Linear detection
Sensor type
μA mM–1 cm–2 (LOD), μM range
Sensor based on Cu nanoparticles on laser-induced graphene
495 0.39 0.10–400 μM
(Cu NPs–LIG)
Porous structure consisting of three-dimensional graphene (3DG)
230.86 16.00 0.8–10 mM
based on Cu or Cu-Cu2O nanoparticles (Cu-Cu2O NPs @ 3DG)
Graphene modified Cu2O–Cu nanocomposite electrodes 371 and 400 5.5 and 2.0 2 μM–12 mM

(495 μA mM–1 cm–2) and 1086 _uc2s 10 mM. A and stretching. In vivo tests using a live rabbit, includ-
graphene-modified Cu2O nanocomposite was synthe- ing monitoring the temperature changes in the eye of a
sized by microwave irradiation of an aqueous solution rabbit, showed the promise of such contact lenses for
of copper compounds and studied as an enzymeless noninvasive monitoring.
glucose biosensor. The biosensor showed a broad lin- The development of effective biosensors for deter-
ear response to glucose detection in the concentration mining the concentration of glucose in a patient’s blood
range from 2 μM to 12 mM with a detection limit of continues to be an urgent task, since it is necessary to
2 μM. In addition, it ensured the selectivity of glucose increase reliability and reduce the cost of analysis.
determination at high concentrations of ascorbic acid
and dopamine. The results of these studies have shown
that these materials can be used to create inexpensive 3.3.3. Graphene Biosensors for Toxins
nonenzymatic electrochemical glucose sensors. Mycotoxins
The authors of [93] created a wearable, noninva- Mycotoxins produced by microscopic molds are a
sive, low-cost LIG-based device that allows us to mea- common type of toxin found in food and feed. The
sure blood glucose levels without piercing the skin, in problem of mycotoxin contamination has recently
contrast to the currently used tests. The problem was become more acute due to the increased complexity of
that graphene is inert to glucose; thus, the authors had transport chains from farm to store, which entails neg-
to look for workarounds. They found that LIG modi- ative consequences for human and animal health.
fied with nickel-gold alloy nanoparticles could detect Consumption of products contaminated with
low concentrations of glucose in sweat on the surface mycotoxins leads to acute and chronic diseases (myco-
of the skin. The concentration of glucose in sweat is toxicosis, chronic gastrointestinal diseases, hemor-
lower by a factor of about 100 than the concentration rhagic necrosis, liver cancer, etc.). It is highly desirable
in blood, but there is a strong correlation between to establish easy to use, in situ, and rapid monitoring
sweat and blood glucose levels. The sensor works on a of mycotoxins in food and feed.
small area of the skin containing at least one hair folli- Consumption of products contaminated with
cle. It detects glucose by drawing it out of the fluid that mycotoxins leads to acute and chronic diseases (myco-
is present between cells. The new device is sufficiently toxicosis, chronic gastrointestinal diseases, hemor-
sensitive to accurately measure glucose in sweat and rhagic necrosis, liver cancer, etc.). It is highly desirable
estimate blood concentrations. The researchers to establish easy to use in situ and rapid monitoring of
demonstrated the device by attaching it to a person’s mycotoxins in food and feed.
arm 1 and 3 h after a meal.
In [80], the authors reported on the creation of an
The sugar levels detected by this device and com- improved bioelectronic sensor for mycotoxin ochra-
mercial glucometers matched each other. toxin A (OTA) based on graphene field-effect transis-
A group of Korean researchers [94] developed a tors integrated on a silicon chip. The OTA-specific
method for manufacturing biosensors in the form of aptamer was attached to graphene via a covalent bond
soft contact lenses that can monitor tear glucose levels with a pyrene-based linker. This device has demon-
to indicate real-time diabetic status through a wireless strated a high degree of sensitivity to OTA with a low
display. For this smart lens, the electronic components detection limit of 1.4 pM with a response time of 10 s
(glucose sensor, LED pixel, rectifier circuit, and in a phosphate buffer and up to 50 s in the case of real
stretchable transparent antenna) were integrated into a samples, which is superior to any other assay method.
stress-tunable hybrid substrate with well-matched Grafting several aptamers specific for different myco-
refractive indices for high optical transparency and low toxins can provide the simultaneous detection of sev-
haze. After shaping the soft contact lens into a round eral targets.
shape, the built-in electronic system worked reliably To detect food contaminants such as mycotoxins
under mechanical deformations, including bending (including OTA), the authors of [96] developed a non-

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 317

enzymatic electrochemical aptasensor based on the ish peroxidase. They showed a high level of sensitivity
use of cerium oxide and graphene oxide nanoparticles to atrazine (28.9 na/μm) with little difference from
on a screen-printed electrode. other common herbicides (glyphosate, dicamba and
Changes in the optical properties of cerium nanoo- 2,4-dichlorophenoxyacetic acid).
xide upon interaction with phenols and H2O2 were
used to manufacture portable colorimetric sensors for
the detection of food antioxidants and glucose. Biogenic Amines
Biogenic amines (BAs) are nitrogenous com-
Pesticides and Chemical Warfare Agents pounds, the concentration of which in food products
is directly related to food safety and, consequently, to
The intensive development of printed electronics human health. The presence of a large amount of BAs
methods (the field of electronics involved in the cre- in food can lead to severe poisoning. In food, BAs are
ation of electronic circuits using printing equipment) formed by endogenous enzymatic activity or microbial
has allowed us to develop methods for printing metabolism, leading either to the decarboxylation of
graphene-based electrodes, which has recently amino acids or to the amination of aldehydes and
become an attractive, inexpensive, and scalable tech- ketones. The properties of individual BAs (e.g., hista-
nology for the production of field electrochemical mine, tyramine, cadaverine) vary depending on the
biosensors. For example, in [97], the authors report on amino acid precursor (histidine, tyrosine, lysine) and
a graphene-based electrode obtained by maskless ink- chemical structure (aliphatic, aromatic, or heterocy-
jet lithography for direct and rapid monitoring of clic). The total BA content in any food product
organophosphorus compounds—chemical warfare depends on the specific biochemical composition, as
agents and pesticides. well as the type and number of microorganisms pres-
The graphene electrode has a microstructure with ent. For example, fermented foods such as cheese,
laser engraving and electrochemically deposited plati- wine, sausage, and pickled vegetables that use lactic
num nanoparticles (diameter ~25 nm) to improve its acid bacteria communities for fermentation may con-
electrical conductivity (sheet resistance is reduced tain high concentrations of histamine, cadaverine,
from ~10000 to 100 Ohm per m2 of surface area). The tyramine, and/or putrescine. Fermented fish products
enzyme phosphotriesterase is covalently immobilized are particularly susceptible to high levels of BA due to
on the electrode by cross-linking through glutaralde- a combination of high microbial load and high content
hyde. The resulting biosensor was able to quickly of amino acid precursors. Since the accumulation of
(response 5 s) detect the model insecticide paraoxon histamine, putrescine, cadaverine, tyramine, trime-
with a low detection limit (3 nM) and high sensitivity thylamine, and dimethylamine can be related to
(370 nA/μM) with little interference from similar microbial contamination, the total concentration of
nerve agents. BAs is commonly used to assess quality and safety
In addition, the biosensor demonstrated reusability indicators, as well as the overall shelf life of fish, fish
(decrease in sensitivity by 0.3% on average per mea- products, and shellfish.
surement), stability (90% preservation of the anode Graphene biosensors can be used in the food
current signal for 1000 s), durability (after 8 weeks, industry to analyze histamine and other toxins. For
sensitivity is maintained at 70%) and the ability to biosensing food safety (in particular, the presence of
selectively determine organophosphorus in real soil biogenic amines) without the use of additional
and water samples. Thus, in [97], a scalable technol- reagents, graphene electrodes with laser engraving
ogy for manufacturing a printed graphene electrode is were developed [83, 99]. In the manufacture of bio-
presented, which can be used to create biosensors suit- sensors, the graphene surface was functionalized with
able for field use. diamine oxidase and copper microparticles. The devel-
A printed electrochemical sensor has been pro- oped biosensor showed good electrochemical character-
posed for the in situ determination of methyl para- istics: average sensitivity to histamine 23.3 μA/mm, as
thion (an insecticide containing an organothiophos- well as a lower detection limit of 11.6 μm and response
phate group) and nitrite in foodstuffs [83, 97]. The time 7.3 s. The authors demonstrated the use of the
electrodes were made from a mixture of chitosan, biosensor by testing the total concentration of BAs in
graphene, and silver powders. The porous structure of fish paste samples fermented with lactic acid bacteria.
the sensors allows the analysis to be carried out with- The concentration of biogenic amines before fermen-
out prior removal of the analyte. The sensor has been tation with lactic acid was below the detection limit of
tested on simulation systems and real objects (Fuji the biosensor, while after fermentation, the concen-
apples, Chinese onions and cabbages). The limit of tration of histamine was 19.24 ± 8.21 mg/kg. These
detection was 15 ng and 18.4 μg for methyl parathion results confirm that the sensor was selective in a com-
and nitrite, respectively. plex food matrix. An inexpensive, fast, and accurate
Biosensors for pesticides were created [98] by func- device is a promising tool for assessing biogenic
tionalizing LIG electrodes with the enzyme horserad- amines in food samples, especially in situations where

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

318 KULAKOVA, LISICHKIN

the standard laboratory methods are not available or CONCLUSIONS

too expensive. The high sensitivity, fast action, and small size of
Electrochemical biosensors for the detection of graphene biosensors, combined with the record speci-
histamine based on graphene with electrodes fabri- ficity achieved by modifying graphene with antibodies
cated using aerosol inkjet printing are described in [83, and/or aptamers, make such sensors extremely prom-
100, 101]. These sensors detect BAs in foods much ising devices for use in various fields of biomedicine.
faster than the standard laboratory tests. Their use for The first, but promising results have been obtained in
these purposes is more expedient. Commercial elec- important areas such as diagnosing autoimmune dis-
trochemical sensors are disposable; thus, it is too eases, monitoring and diagnosing oncological diseases
expensive to use them all the time. Low-temperature in the early stages, monitoring intrauterine genetic
abnormalities of the fetus during pregnancy, and con-
chemical vapor deposition graphene devices used for
trolling the appearance of dangerous metabolites
food monitoring are too expensive for such applica- during surgical operations.
tions. At the same time, inexpensive alternative meth-
ods, such as screen printing and inkjet printing, are not The biosensors created based on the GNM allow us
able to provide sufficient control of the electrode not only to detect biomarkers but also to study the pro-
geometry to obtain suitable electrochemical charac- cesses occurring in cells (formation of reactive oxygen
teristics of the sensor. When applying specially species in living cells and in vivo expression of genes
designed aerosol-jet ink [100, 101], it is possible to contained in chromosomes).
change the geometry of the template using software In modern genetic engineering, it is promising to
control. New graphene-based biosensors detect sub- use CRISPR/Cas9, a new technology for editing the
stances hazardous to health in food faster and more genomes of higher organisms based on the immune
efficiently than classical biosensors. Also, airjet sen- system of bacteria, which is based on special sections
sors apply the right material only where it is needed, of bacterial DNA, short palindromic cluster repeats,
minimizing production waste and making the devices or CRISPR (Clustered Regularly Interspaced Short
inexpensive and easy to manufacture. Because of this, Palindromic Repeats). Since 2016, molecular biolo-
they can be used where constant monitoring of food gists have been widely using approaches based on
samples is important in order to assess the quality of CRISPR/Cas systems.
products. In the course of the study [100], interdigital It is believed that in the foreseeable future these
flexible electrodes were created from graphene on a approaches will be used in medicine for the treat-
substrate, after which they were converted into hista- ment of hereditary diseases, https://ru.wikipe-
mine biosensors by covalent modification of the dia.org/wiki/CRISPR: cite_note-3. CRISPR/Cas is
graphene surface with monoclonal antibodies. The important for the targeted delivery of drugs and their
operation of biosensors was tested not only in a model release under external influence. For the discovery of
buffer solution but also in fish broth to ensure the this method in 2020, the Nobel Prize in Chemistry was
effectiveness of histamine detection. It was found that awarded.
the graphene biosensor is able to detect histamine in a Most nucleic acid detection methods require large
buffer solution and fish broth in toxicologically signif- amounts of reagents, expensive and bulky devices, and
icant amounts (6.25–100 and 6.25–200 ppm with in addition, are related to a violation of gene material.
limits of 2.52 and 3.41 ppm, respectively). For exam- The advantage of the CRISPR method is that it allows
ple, histamine levels in fish that exceed 50 ppm cause us to directly observe DNA, instead of isolating DNA,
severe allergies in some people and even food poison- destroying, amplifying, labeling, and directing an
ing. It is also important that the biosensor demon- optical laser at it to detect the label. It is important that
strates a short response time: 33 minutes is sufficient the graphene CRISPR chips developed in [103, 104]
and no pretreatment of product samples is required. make it possible to study DNA in its natural state and
immediately signal the presence of a specific muta-
Similar laboratory tests take longer and require tion, protein, or other component.
prior labeling and sample processing. In addition, the It can be argued that the use of graphene nanoma-
sensitivity of the sensor was not affected by the adsorp- terials in biosensors is a very relevant and promising
tion of large protein molecules, which often act as a direction in the development of this field.
blocking agent. A new type of biosensor created from
graphene can be used in food processing plants, ports,
and stores where constant on-site monitoring of sam- FUNDING
ples is required. Its use will avoid sending samples to This study was carried out as part of state task
the laboratory, save time, and reduce the cost of test- no. 121031300092-6.
ing for the content of histamine and toxins in prod-
ucts. Achievements in the design and development of
graphene biosensors for food safety assessment are CONFLICT OF INTEREST
summarized in the review [102]. The authors declare that they have no conflicts of interest.

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 319

REFERENCES 18. Rybakov, V., Komponenty Tekhnol., 2009, no. 3, p. 21.

1. Popov, V.P., Tropin, A.V, Glukhov, A.V., and 19. Gubin, S.P. and Tkachev, S.V., Grafen i rodstvennye
Ivanov, Yu.D., Innovatsii, 2014, no. 3, p. 94. nanoformy ugleroda (Graphene and Related Nano-
forms of Carbon), Moscow: URSS, 2019.
2. Schedin, F., Geim, A.K., Morozov, S.V., Hil, E.W.L.,
Blake, P., and Katsnelson, M.I., Nat. Mater., 2007, 20. Karyakin, A.A., Biosensors, Amsterdam: Springer,
vol. 6, p. 652. 2009.
3. Lu, C.H., Li, J., Liu, J.J., Chen, X., Yang, H.H., and 21. Aksenova, E.I., Kamynina, N.N., and Maklakova, Yu.A.,
Zhu, C.L., Chem. Commun., 2010, vol. 46, p. 3116. in Ekspertnyi obzor: biosensornye sistemy v meditsine
(Scientific Review: Biosensor Systems in Medicine),
4. Novoselov, K.S., Geim, A.K., Morozov, S.V., Jiang, D., Moscow, 2020.
Zhang, Y., Dubonos, S.V., Grigorieva, I.V., and
Firsov, A.A., Science, 2004, vol. 306, p. 666. 22. Karyakin, A.A., Ulasova, E.A., Vagin, M.Yu., and
Karyakina, E.E., Sensor, 2002, no. 1, p. 16.
5. Novoselov, K.S., Jiang, D., Schedin, F., Khotkevich, V.V.,
Morozov, S.V., and Geim, A.K., Proc. Natl. Acad. Sci. 23. Clark, Ir L.C. and Lyons, C., Ann. N. Y. Acad. Sci.,
U. S. A., 2005, vol. 102, no. 30, p. 10451. 1962, vol. 102, p. 29.
6. Geim, A.K., Nobel lecture. http://www.nobelprize.org/ 24. Clark, L.C. and Sache, G., Ann. N. Y. Acad. Sci., 1968,
nobel_prizes/physics/laureates/2010/geim_lecture.pdf. vol. 148, p. 133.
7. Randviir, E.P., Brownson, D.A.C., and Banks, C.E., 25. Clark, Ir L.C., Noves, L.R., Grooms, T.A., and
Mater. Today, 2014, vol. 17, no. 9, p. 426. Moore, M.S., Crit. Care Med., 1984, vol. 12, p. 461.
8. Ferrari, A.C., Bonaccorso, F., Fal’ko, V., Novoselov, K.S., 26. Biokhimicheskie metody analiza (Biochemical Methods
Roche, S., Bøggild, P., Borini, S., L.Koppens, F.H., of Analysis), Dzantiev, B.B., Ed., vol. 12 of Problemy
Palermo, V., Pugno, N., Garrido, J.A., Sordan, R., Bi- analiticheskoi khimii (Problems of Analytical Chemis-
anco, A., Ballerini, L., Prato, M., Lidorikis, E., Kivio- try), Moscow: Nauka, 2010.
ja, J., Marinelli, C., Ryhänen, T., Morpurgo, A., Cole- 27. Mao, H.Y., Laurent, S., Chen, W., Akhavan, O., and
man, J.N., Nicolosi, V., Colombo, L., Fert, A., Garcia- Imani, M., Chem. Rev., 2013, vol. 113, no. 5, p. 3407.
Hernandez, M., Bachtold, A., Schneider, G.F., 28. Banerje, A.N., Glob. J. Nano, 2016, vol. 1, no. 1,
Guinea, F., Dekker, C., Barbone, M., Sun, Z., Galio- 555552.
tis, C., Grigorenko, A.N., Konstantatos, G., Kis, A., 29. Aleksenko, A.G., Grafen (Graphene), Moscow: Labo-
Katsnelson, M., Vandersypen, L., Loiseau, A., Mo- ratoriya Znanii, 2014.
randi, V., Neumaier, D., Treossi, E., Pellegrini, V., 30. Lee, C., Wei, X.D., Kysar, J.W., and Hone, J., Science,
Polini, M., Tredicucci, A., Williams, G.M., Hong, B.H., 2008, vol. 321, p. 385.
Ahn, J.-H., Kim, J.M., Zirath, H., van, Wees, B.J.,
Vander, Zant, H., Occhipinti, L., DiMatteo, A., Kin- 31. Nair, R.R., Blake, P., Grigorenko, A.N., Novoselov, K.S.,
loch, I.A., Seyller, T., Quesnel, E., Feng, X., Teo, K., Booth, T.J., Stauber, T., Peres, N.M.R., and Geim, A.K.,
Rupesinghe, N., Hakonen, P., Neil, S.R.T., Tannock, Q., Science, 2006, vol. 320, no. 5881, p. 1308.
Löfwander, T., and Kinaret, J., Nanoscale, 2015, vol. 7, 32. Kumar, R., Mehta, B.R., Bhatnagar, M., Ravi, S., Ma-
p. 4598. hapatra Salkalachen, S., and Jhawar, P., Nanoscale Res.
9. Fadeel, B., Bussy, C., Merino, S., Vázquez, E., Fla- Lett., 2014, vol. 9, 349.
haut, E., Mouchet, F., Evariste, L., Gauthier, L., 33. Stoller, M.D., Park, S., Zhu, Y., An J., and Ruoff, R.S.,
Koivisto, A.J., Vogel., Martín, C., Delogu, L.G., Buer- Nano Lett., 2008, vol. 8, no. 10, p. 3498.
ki-Thurnherr, T., Wick, P., Beloin-Saint-Pierre, D., 34. Chabot, V., Higgins, D., Yu, A., Xiao, X., Chena, Z.,
Hischier, R., Pelin, M., Carniel, F.C., Tretiach, M., and Zhang, J., Energy Environ. Sci., 2014, no. 7,
Cesca, F., Benfenati, F., Scaini, D., Ballerini, L., Ko- p. 15564.
starelos., Prato, M., and Bianco, A., ACS Nano, 2018, 35. Yan, Y., Ruan, G., Xiang, C., Wang, G., and Tour, J.M.,
vol. 12, no. 11, p. 10582. J. Am. Chem. Soc., 2014, vol. 136, p. 6187.
10. Ye, E. and Tour, J.M., ACS Nano, vol. 13, no. 10, p. 10872. 36. Zhang, S., Jiang, S.-F., Huan, B.-C.G., Shen, X.-C.,
11. Garg, R., Roman, D.S., and Cohen-Karni, T., Appl. Chen, W.-J., Zhou, T.-P., Cheng, H.-Y., Cheng, B.-H.,
Mater., 2020, vol. 8, no. 10. Wu, C.-Z., Li, W.-W., Jiang, H., and Yu, H.-Q., Nat.
12. Huang, L., Su, J., Song, Y., and Ye, R., Nano-Micro Sustainability, 2020, vol. 3, p. 753.
Lett., 2020, vol. 12, p. 157. 37. Lin, J., Peng, Z., Liu, Y., Ruiz-Zepeda, F., and Yeetal, R.,
13. Kulakova, I.I. and Lisichkin, G.V., Russ. J. Gen. Chem., Nat. Commun., 2014, vol. 5, no. 1, 5714.
2020, vol. 90, no. 10, p. 16013. 38. Inagaki, M. and Kang, F., Mater. Chem. A, 2014, vol. 2,
14. Kulakova, I.I. and Lisichkin, G.V., Russ. J. Appl. p. 13193.
Chem., 2021, vol. 94, no. 9, p. 1077. 39. Peng, Q., Dearden, A.K., Crean, J., Han, L., Liu, S.,
15. Lisichkin, G.V. and Kulakova, I.I., Uglerodnye nano- Wen, X., and De, S., Nanotechnol., Sci. Appl., 2014,
chastitsy, in Lisichkin, G.V., Olenin, A.Yu., and Kula- vol. 7, p. 1.
kova, I.I., Khimiya poverkhnosti neorganicheskikh nano- 40. Liu, Z., Robinson, J.T., Sun, X.M., and Dai, H., J. Am.
chastits (Surface Chemistry of Inorganic Nanoparti- Chem. Soc., 2008, vol. 130, no. 33, p. 10876.
cles), Moscow: Technosfera, 2021. 41. Jiang, H., Small, 2011, vol. 7, no. 17, p. 2413.
16. Lisichkin, G.V. and Kulakova, I.I., Pharm. Chem. J., 42. Wang, T., Huang, D., Yang, Z., Xu, S., He, G., Li, X.,
2022, vol. 56, no. 1, p. 1. Hu, N., Yin, G., He, D., and Zhang, L., Nano-Micro
17. Pumera, M., Mater. Today, 2011, vol. 14, no. 7, p. 308. Lett., 2016, vol. 8, no. 2, p. 95.

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

320 KULAKOVA, LISICHKIN

43. Varghese, S.S., Lonkar, S., Singh, K.K., Swaminathan, S., 64. Akbari, E., Nikoukar, A., Buntat, Z., Afroozeh, A., and
and Abdala, A., Sens. Actuators, B, 2015, vol. 218, Zeinalinezhad, A., IET Nanobiotechnol., 2015, vol. 9,
pp. 160–183. p. 273.
44. Hosseingholipourasl, A., Ariffin, S.H.S., Al-Otaibi, Y.D., 65. Roy, E., Patra, S., Tiwari, A., Madhuri, R., and Shar-
Akbari, E., Hamid, F.K.H., and Koloor, S.S.R., Sen- ma, P.K., Biosens. Bioelectron., 2017, vol. 89, p. 620.
sors, 2020, vol. 20, no. 5, p. 1506. 66. Zhang, Z., Zhou, J., and Du, X., Micromachines, 2019,
45. Gubin, S.P. and Tkachev, S.V., Radioelektron. Nano- vol. 10, no. 4, p. 222.
sist. Inf. Tekhnol., 2010, vol. 2, nos. 1–2, p. 99. 67. Liu, M., Zhang, Q., Brennan, J.D., and Li, Y., MRC
46. Graifer, E.D., Makotchenko, V.G., Nazarov, A.S., Commun., 2018, vol. 8, no. 3, p. 687.
Kim, S.Dzh., and Fedorov, V.E., Russ. Chem. Rev., 68. Sengupta, J., Adhikari, A., and Hussain, C.M., Carbon
2011, vol. 80, no. 8, p. 751. Trends, 2021, vol. 4, 100072. https://scholar.google.ru/
47. Liu, J., Tang, J., and Gooding, G., J. Mater. Chem., citations?view_op=view_citation&hl=ru&user=XoZ9-
2012, vol. 22, no. 25, p. 12435. dUsAAAAJ&citation_for_view=XoZ9dUsAAAAJ:_k-
48. Sleptsuk, N., Land, R., Toompuu, J., Lebedev, A., c_bZDykSQC.
Davydov, V., Eliseyev, I., Kalinina, E., Korolkov, O., 69. Moutaouakil, A.E.A., Poovathy, S., Belmoubarik, M.,
and Rang, T., Proc. 6th Int. Symp. on Graphene Devices and Peng, W.K., Project: Molecular Medicine and Spin
(ISGD-6), 2018, ePoster. Physics, 2020. https://www.researchgate.net/publica-
49. Sleptsuk, N., Lebedev, A.A., Eliseyev, I., Korolkov, O., tion/342378039_Review_Graphene-based_biosensor_
Toompuu, J., Land, R., Mikl, V.I., Zubov, A., and for_Viral_Detection.
Rang, T., Key Eng. Mater., 2019, no. 799, p. 185. 70. Kosack, C.S., Page, A.-L., and Klatser, P.R., Bull.
50. Kidane, S., Ishida, H., Sawada, K., and Takahash, K., World Health Org., 2017, vol. 95, p. 639.
Nanoscale Adv., 2020, vol. 2, no. 4, p. 1431. 71. Chen, Y., Ren, R., Pu, H., Guo, X., Chang, J., Zhou, G.,
51. Lu, C.-H., Li, J., Zhang, X.-L., Zheng, A.-X., Yang, H.-H., Mao, S., Kron, M., and Chen, J., Sci. Rep., 2017, vol. 7,
Chen, X., and Chen, G.-N., Anal. Chem., 2011, vol. 83, p. 10974.
no. 19, p. 7271. 72. Navakul, K., Warakulwit, C., Yenchitsomanus, P., Pa-
52. Lebedev, S.P., Davydov, V.Yu., Usachov, D.Yu., nya, A., Lieberzeit, P.A., and Sangma, C., Nanomed.:
Smirnov, A.N., Levitskii, V.S., Eliseyev, I.A., Gus- Nanotechnol., Biol. Med., 2017, vol. 13, p. 549.
china, E.V., Dunaevsckiy, M.S., Vilkov, O.Yu., Ryb- 73. Campos, R., Borme, J., Guerreiro, J.R., Machado, G., Jr.,
kin, A.G., Lebedev, A.A., Novikov, S.N., and Ma- Cerquerrac, M.A., Petrovykh, D.Y., and Alpium, P.,
karov, Yu.N., Nanosyst.: Phys., Chem., Math., 2018, ACS Sens., 2019, vol. 4, p. 286.
vol. 9, no. 1, p. 95. 74. Liu, F., Choi, K.S., Park, T.J., Lee, S.Y., and Seo, T.S.,
53. Cui, Y., Kim, S.N., Jones, Sh.E., Wissler, L.L., Naik, R.R., Bio Chip J., 2011, vol. 5, p. 123.
and McAlpine, M.C., Nano Lett., 2010, vol. 10, p. 4559. 75. Liu, F., Kim, Y.H., Cheon, D.S., and Seo, T.S., Sens.
54. Rabchinskii, M., Ryzhkov, S., Kirilenko, D., Lin, N., Actuators, B, 2013, vol. 186, p. 252.
Baidakova, M., Shnitov, V., Pavlov, S., Chumakov, R., 76. Pant, M., Kharkwal, H., Singh, K.P., and Joshi, H.C.,
Stolyarova, D., Brzhezinskaya, M., Lebedev, O., Mel- Biosens J., 2017, vol. 6, no. 2, 1000148.
nikov, V., and Brunkov, P., Sci. Rep., 2020, vol. 10, p. 10. 77. Afsahi, S., Lerner, M.B., Goldstein, J.M., Lee, J.,
55. Shan, C., Yang, H., Han, D., Zhang, Q., Ivaska, A., Tang, X., Bagarozzi, D.A., Pan, D., Locascio, L.,
and Niu, L., Langmuir, 2009, vol. 25, p. 12030. Walker, A., Barron, F., and Goldsmith, B.R., Biosens.
56. Georgakilas, V., Otyepka, M., Bourlinos, A.B., Chan- Bioelectron., 2018, vol. 100, p. 85.
dra, V., Kim, N., Kemp, K.C., Hobza, P., Zboril, R., 78. Chand, R. and Neethirajan, S., Biosens. Bioelectron.,
and Kim, K.S., Chem. Rev., 2012, vol. 112, p. 6156. 2017, vol. 98, p. 47.
57. Yu, J.W., Jung, J., Choi, Y.-M., Choi, J.H., Yu, J., 79. Sengupta, J. and Hussain, C.M., Carbon Trends, 2021,
Lee, J.K., You, N.-H., and Goh, M., Polym. Chem., vol. 2, 100019.
2016, no. 7, p. 36. 80. Torrente-Rodriguez, R.M., Lukas, H., Tu, J., Min, J.,
58. Loh, K.P., Bao, Q., Ang, P.K., and Yang, J., J. Mater. Yang, Y., Xu, C., Rossiter, H.B., and Gao, W., Matter,
Chem., 2010, vol. 20, p. 2277. 2020, vol. 3, no. 6, p. 1981.
59. Arslanov, V.V., Kalinina, M.A., Ermakova, E.V., Rait- 81. Zhang, Z., Tang, Z., Farokhzad, N., Chen, T., and
man, O.A., Gorbunova, Yu.G., Aksyutin, O.E., Ish- Tao, W., Matter, 2020, vol. 3, no. 6, p. 1818.
kov, A.G., Grachev, V.A., and Tsivadze, A.Yu., Russ. 82. Kumar, V., Shorie, M., Ganguli, A.K., and Sabherwal, P.,
Chem. Rev., 2019, vol. 88, no. 8, p. 775. Biosens. Bioelectron., 2015, vol. 72, p. 56.
60. Mohanty, N. and Berry, V., Nano Lett., 2008, vol. 8, 83. Kozitsina, A.N., Svalova, T.S., Malysheva, N.N.,
no. 12, p. 4469. Okhokhonin, A.V., Vidrevich, M.B., and Brainina, K.Z.,
61. Ono, T., Kanai, Y., Inoue, K., Watanabe, Y., Nakata, S., Biosensors, 2018, vol. 8, no. 2, p. 35.
Kuwahara, T., Suzuki, Y., and Matsumoto, K., Nano 84. Upasham, S., Tanak, A., and Prasad, S., Adv. Health
Lett., 2019, vol. 19, no. 6, p. 4004. Care Technol., 2018, vol. 4, p. 1.
62. Science Daily. http://www.sciencedaily.com/releases/ 85. Kazemi, S.H., Ghodsi, E., Abdollahi, S., and Nadri, S.,
2019/06/190620100019.htm. Mater. Sci. Eng., C, 2016, vol. 69, p. 447.
63. Huang, Y., Dong, X., Liu, Y., Li, L.-J., and Chen, P., 86. Novodchuk, I., Bajcsy, M., and Yavuz, M., Carbon,
J. Mater. Chem., 2011, vol. 21, p. 12358. 2021, vol. 72, no. 4, p. 471.

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022

 BIOSENSORS BASED ON GRAPHENE NANOMATERIALS 321

87. Xu, L., Wen, Y., Pandit, S., Mokkapati, V.R.S.S., Mija- 97. Hondred, J.A., Breger, J.C., Alves, N.J., Trammell, S.A.,
kovic, I., Li, Y., Ding, M., Ren, S., Li, W., and Liu, G., Walper, S.A., Medintz, I.L., and Claussen, J.C., ACS
BMC Chem., 2019, vol. 13, no. 1, p. 1. Appl. Mater. Interfaces, 2018, vol. 10, no. 13, p. 11125.
88. Gao, N., Gao, T., Yang, X., Dai, X., Zhou, W., Zhang, A., 98. Kucherenko, I., Chen, B., Johnson, Z., Wilkins, A.,
and Lieber, C.M., Proc. Natl. Acad. Sci. U. S. A., 2016, Sanborn, D., Figueroa-Felix, N., Mendivelso-Perez, D.,
vol. 5, no. 113, p. 1. Smith, E.A., Gomes, C.L., and Claussen, J., Anal. Bio-
anal. Chem., 2021, vol. 413, p. 17.
89. Kovalskaya, E., Lesonger, P., Hogan, B.T., and Baldy- 99. Vanegas, D., Patino, L., Mendez, C., Oliveira, D., Tor-
cheva, A., Nanoscale, 2019, vol. 11, no. 5, p. 2476. res, A., Gomes, C., and McLamore, E., Biosensors,
90. Biosensor Based Advanced Cancer Diagnostics: From Lab 2018, vol. 8, no. 2, p. 42.
to Clinics, Khan, R., Parihar, A., and Sanghi, S.K., 100. Parate, K., Pola, C.C., Rangnekar, S.V., Mendivelso-
Eds., New York: Academic, 2021. Perez, D.L., Smith, E.A., Hersam, M.C., Gomes, C.L.,
91. Mannoor, M.S., Tao, H., Clayton, J.D., Sengupta, A., and Claussen, C., 2D Mater., 2020, vol. 7, no. 3,
Kaplan, D.L., Naik, R.R., Verma, N., Omenetto, F.G., 034002.
and McAlpine, M.C., Nat. Commun., 2012, vol. 3, 101. Parate, K., Rangnekar, S.V., Jing, D., Mendivelso-Pe-
p. 763. rez, D.L., Ding, S., Secor, E.B., Smith Hostetter, J.M.,
Hersam, MC., and Claussen, J.C., ACS Appl. Mater.
92. Makhmutov, B.B. and Kim, Yu.A., Mezhdunar. Zh. Interfaces, 2020, vol. 12, no. 7, p. 8592.
Prikl. Fundam.Issled., 2021, no. 4, p. 17. 102. Song, Y., Luo, Y., Zhu, Y., Li, C., and Du, H., D. lin y,
93. Zhu, J., Liu, S., Hu, Z., Zhang, X., Yi, N., Tang, K., Biosens. Bioelectron., 2016, vol. 76, no. 15, p. 195.
Dexheimer, M.G., Lian, X., Wang, Q., Yang, J., Gray, J., 103. Hajian, R., Balderston, S., Tran, T., Deboer, T., Eti-
and Cheng, H., Biosens. Bioelectron., 2021, vol. 193, enne Sandhu, M., Wauford, N., Chung, J.-Y., Nokes, J.,
113606. Athaiya, M., Paredes, J., Peytavi, R., Goldsmith, B.,
94. Park, J., Kim, J., Kim, S.-Y., Cheong, W.H., Jang, J., Murthy, N., Conboy, I.M., and Aran, K., Nat.
Park, Y.-G., Na, K., Kim, Y.-T., Heo, J.H., Lee, C.Y., Biomed. Eng., 2019, vol. 3, no. 5, p. 427.
Lee, J.H., Bien, F., and Park, J.-U., Sci. Adv., 2018, 104. Balderston, S., Taulbee, J.J., Celaya, E., Fung, K.W.,
vol. 4, no. 1, eaap9841. Jiao, A., Smith, K., Hajian, R., Gasiunas, G., Kuta-
novas, S., Kim, D., Parkinson, J., Dickerson, K., Rip-
95. Nekrasov, N., Jaric, S., Kiree, D.V., Emelianov, A.V., oll, J.J., Peytavi, R., Lu, H.-W., Barron, F.E., Gold-
Orlov, A., Gadjanski, I., Nikitin, P., Akinwande, D., smith, B., Collins, P.G., Conboy, I.M., Siksnys, V.,
and Bobrinetskiy, I., arXiv:2104.10551[cond-mat.mtrl- and Aran, K., Nat. Biomed. Eng., 2021, vol. 5, no. 7,
sci], 2021. p. 713.
96. Bulbul, G., Hayat, A., and Andreescu, S., Sensors,
2015, vol. 15, p. 30736. Translated by P. Kuchina

MOSCOW UNIVERSITY CHEMISTRY BULLETIN Vol. 77 No. 6 2022