graphene thesis title

Official URL: http://edoc.unibas.ch/diss/DissB_13681

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• DOI: 10.21608/ejchem.2019.15173.1919
• Corpus ID: 210795575

Graphene: Structure, Synthesis, and Characterization; a brief review

• S. Kamel , M. El-Sakhawy , +1 author H. S. Tohamy
• Published in Egyptian Journal of Chemistry 2 October 2019
• Materials Science, Physics, Chemistry, Engineering

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Graduate Thesis Or Dissertation

Graphene-semiconductor heterojunctions and devices public deposited.

In this thesis we explore the potential of versatile graphene-semiconductor heterojunctions in photodetection and field-effect transistor (FET) applications.

The first part of the thesis studies near-infrared photodiode (NIR PD) based on a graphene- n-Si heterojunction in which graphene is used as the absorbing medium. Graphene is chosen for its absorption in NIR wavelengths to which Si is not responsive. Most graphene detectors in the literature are photoconductors that have a high dark current. The graphene-Si heterojunction PD has a large Schottky barrier height that suppresses the dark current and enhances the current rectification and the photon detectivity.

The fabricated graphene-Si heterojunction PD under conventional telecommunication 1.3 (1.5)- μ m illumination exhibits a responsivity of 3 (0.2) mA/W, an internal quantum efficiency of 14 (0.6) %, a noise-equivalent power of 1.5 (30) pW/Hz 0.5 , and a specific detectivity of 3 (0.1)x10⁹ cm Hz 0.5 /W. An unexpected tunnel oxide is observed at the graphene-Si interface, further reducing the dark current. The performance in terms of sensitivity and noise is comparable to the commercially available discrete germanium NIR PDs due to its low dark current density on the order of 10 fA/ μ m 2 . The Si CMOS-compatible PD based on graphene-Si heterojunction provides a promising route to realize a critical component for monolithically integrated Si photonic interconnects.

The second part of the thesis focuses on a novel graphene junction FET (GJFET) gated by a graphene-semiconductor heterojunction. The majority of graphene transistors in the literature -- including MOSFETs, barristors, and tunneling FETs -- have a heavily-doped Si back gate separated from the graphene channel by a conventional or high-K dielectric layer. The threshold voltage of individual transistors cannot be tuned easily in such designs, and have an additional problem with shorted back gates. In GJFETs, a Schottky junction is formed as graphene is placed on a semi conductor, resulting in a depletion region inside the semiconductor that induces a complementary charge in the graphene. Changing the reverse bias across the graphene-semiconductor junction modulates the depletion region width and thereby changes the total charge in graphene. The charge density of the graphene is also modulated by the doping density of the semiconductor substrate. The GJFET structure provides a solution for Dirac voltage tuning and back gate isolation by location-specific doping on a single device wafer.

A detailed understanding of the device is obtained through the design, fabrication, and analysis of GJFETs with atmospheric pressure chemical-vapor deposited graphene on n-type Si and 4H-SiC substrates of various doping densities. A variable depletion width model is built to numerically simulate the performance. A representative n-Si (4.5x10 15 cm -3 ) GJFET exhibits an on-off ratio of 3.8, an intrinsic hole density of 8x10 11 cm -2 , and a Dirac voltage of 14.1 V. Fitting the transfer characteristic of the Si GJFET with our device model yields an electron and hole mobility of 300 and 1300 cm 2 /V·s respectively. The tunability of the threshold voltage by varying the substrate doping density is also demonstrated. With an increasing substrate doping from 8x10 14 to 2x10 16 cm -3 , the threshold of the Si GJFET decreases from 24.9 V to 3.8 V. With even higher doping density (5x10 18 cm -3 ) in n + -4H-SiC, the Dirac voltage of the GJFET is further reduced to 1.5 V. These results also demonstrate the feasibility of integrating GJFET with semiconductor substrates other than Si, widening their potential for use in high-frequency electronics.

• Ou, Tzu-Min
• Electrical, Computer and Energy Engineering (ECEE)
• Zeghbroeck, Bart Van
• Gopinath, Juliet
• Schibli, Thomas
• Moddel, Garret
• University of Colorado Boulder
• solar cells
• photodetector
• Dissertation
• In Copyright
• English [eng]

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• Published: 18 March 2022

Large-scale synthesis of graphene and other 2D materials towards industrialization

• Soo Ho Choi   ORCID: orcid.org/0000-0002-9927-0101 1 , 2   na1 ,
• Seok Joon Yun 1 , 2   na1 ,
• Yo Seob Won 2 ,
• Chang Seok Oh 2 ,
• Soo Min Kim 3 ,
• Ki Kang Kim   ORCID: orcid.org/0000-0003-1008-6744 1 , 2 &
• Young Hee Lee   ORCID: orcid.org/0000-0001-7403-8157 1 , 2  

Nature Communications volume  13 , Article number:  1484 ( 2022 ) Cite this article

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• Electronic devices
• Synthesis and processing
• Synthesis of graphene
• Two-dimensional materials

The effective application of graphene and other 2D materials is strongly dependent on the industrial-scale manufacturing of films and powders of appropriate morphology and quality. Here, we discuss three state-of-the-art mass production techniques, their limitations, and opportunities for future improvement.

Two-dimensional (2D) van der Waals (vdW) layered materials including graphene, transition metal dichalcogenides (TMDs), hexagonal boron nitride (hBN), and MXenes have attracted much attention in recent years. This is due to their distinctive physical and chemical properties, such as their quantum Hall effects and quantum valley Hall effects, indirect-to-direct bandgap transition, and strong spin-orbit coupling 1 , which have not been accessible with conventional 3D bulk materials. In addition, vertical vdW heterostructures constructed by layer-by-layer stacking enable interesting applications for atomically thin quantum wells, p-n junctions, Coulomb drag transistors, and twistronic devices 1 , 2 , 3 . However, applications based on such structures are limited by the fact that most vdW materials are currently only available with a lateral size of up to a few tens of micrometers. Techniques for the large-scale synthesis of 2D materials will therefore be required for industrialization. Moreover, since specific applications of these materials are strongly dependent on characteristics such as their morphology and quality, mass production techniques should also be developed that can accommodate such requirements (Fig.  1 ). In general, most applications rely on either films or powders of vdW materials. Films require high crystal quality, and can be used in the context of electronics, spintronics, optoelectronics, twistronics, or solar cells, whereas powders exhibit large surface areas and are employed in the construction of batteries, sensors, and catalysts. At present, only large-area graphene films and graphite oxide powders are currently available in the commercial market 4 . In this Comment, we briefly examine research trends in synthesis techniques and their associated challenges for the industrialization of 2D layered materials.

2D films and heterostructures require high crystal quality and homogeneous thickness for applications such as electronics and spintronics, whereas high-porosity powders with vast specific surface area can be used in contexts such as catalysts and energy storage.

Three representative synthesis techniques

There are currently three representative synthesis techniques available for the large-scale synthesis of 2D materials. The first is chemical vapor deposition (CVD); although a variety of thin-film deposition techniques have been investigated for growing large-area 2D films, including pulsed laser deposition (PLD) 5 , atomic layer deposition (ALD) 6 , and molecular beam epitaxy (MBE) 7 , CVD is most feasible for industrialization when one takes into account the uniformity and crystallinity of 2D films as well as requirements of high throughput, cost effectiveness, and scalability. The other two techniques being investigated for mass production are top-down liquid exfoliation of 2D materials and bottom-up wet chemical synthesis.

CVD for growing large-scale 2D thin films

There are multiple examples of CVD synthesis of thin films at wafer scale (Fig.  2a ). For example, wafer-scale polycrystalline monolayer and multilayer graphene films have been successfully synthesized by CVD on polycrystalline Cu and Ni foils since 2009 8 , 9 , 10 , 11 , and wafer-scale single-crystal monolayer graphene has been synthesized by using single-crystal substrates such as H–Ge (110) and Cu (111) 12 , 13 . Single-crystal multilayer graphene films have been also grown on Si–Cu alloys at wafer scale 14 . In 2012, centimeter-scale polycrystalline monolayers of hBN and TMDs were grown on polycrystalline Cu foils and SiO 2 /Si substrates, respectively 15 , 16 . And more recently, single-crystal hBN and TMD films were successfully synthesized on liquid Au, high-index single-crystal Cu surfaces, and atomic sawtooth Au surfaces 17 , 18 .

Lefthand panels show timelines of milestones for a chemical vapor deposition (CVD), b liquid exfoliation, and c wet chemical synthesis methods. The abbreviations correspond to: metal-organic CVD (MOCVD), graphene (Gr), graphite oxide (GO), reduced GO (rGO), and molybdenum disulfide (MoS 2 ). Righthand panels show the corresponding strengths and weaknesses of these methods in terms of mass production (MP), thickness controllability (THK), temperature variation (TEMP), uniformity (UNI), material diversity (MAT), crystal quality (QLTY), morphology (MORPH). Panel a reprinted from refs. 9 , 17 , American Association for the Advancement of Science, ref. 15 , Nature, refs. 7 , 10 , 12 , Wiley, ref. 5 , American Institute of Physics, ref. 6 , Royal Society of Chemistry, and ref. 11 , World Scientific. Panel b reprinted from refs. 26 , 27 , American Association for the Advancement of Science, refs. 22 , 23 , Wiley, refs. 19 , 20 , 21 , Elsevier, and ref. 24 , Institute of Electrical and Electronic Engineers. Panel c reprinted from ref. 28 , Elsevier, ref. 30 , American Chemical Society, ref. 31 , Elsevier, and ref. 32 , Royal Society of Chemistry.

CVD produces relatively high-quality 2D films under atmospheric or low pressure, and the size of the film can easily be scaled up by increasing the chamber size. However, high temperature reactions (above 500 °C) are required, which could be a drawback for industrialization. The growth of a vast range of 2D materials, including graphene, hBN, and TMDs, is still limited by the absence of appropriate precursors. Perhaps the most important technical challenge presented by this method is the poor control over the number of synthesized layers, because the absence of dangling bonds on the surface of 2D vdW materials makes epitaxial growth difficult.

Liquid exfoliation

Liquid exfoliation is a powerful process for the mass production of pristine 2D bulk materials by dispersing them into individual sheets. Bulk materials have been synthesized by chemical vapor transport (CVT) (Fig.  2b ) since the late 1960s, but most 2D bulk materials are currently only available in small quantities. Nanodispersion into monolayers is often required to manifest the unique 2D nature, but the strong vdW energy of micron-scale materials hinders facile exfoliation. Thus, two additional steps should be considered for liquid exfoliation processes: (i) weakening the layer-layer interaction by expanding the interlayer distance, and (ii) physical agitation for dispersion 19 , 20 . In 1958, it was demonstrated that the interlayer distance can be increased from 3.4 to 7.0 Å by the oxidation of graphite, known as “graphite oxide”, and such an expansion of the interlayer distance made it possible to disperse the individual graphite oxide layers by sonication. Graphite oxide layers can subsequently be reduced to graphene nanosheets through chemical treatment with reducing agents and thermal annealing treatment 21 , 22 , 23 .

The lattice of graphene nanosheets is often severely damaged during oxidation and reduction processes. To prevent this, the interlayer distance can be increased by intercalating ions and molecules between layers. Electrochemistry enables effective intercalation of both cations and anions in an electrolyte solution by applying negative and positive bias, respectively 24 . Alkali metals, organic solvents, and surfactants with similar surface energies to those of the 2D materials can also be directly intercalated in liquid or vapor phase 25 , 26 . After intercalation, agitation methods such as sonication, homogenization, and microwave treatment can be employed to exfoliate materials into individual 2D layers 27 . Liquid exfoliation enables mass production of 2D nanosheets under atmospheric pressure at room temperature. However, this approach also leads to presumably unavoidable damage and non-uniform nanosheet thickness.

Wet chemical synthesis

Hydrothermal and solvothermal syntheses are representative wet chemical synthesis methods, in which materials are respectively solubilized in aqueous solution and organic solvent under high vapor pressure at elevated temperatures (~300 °C). A variety of nanomaterials have been synthesized in this fashion since the first report of hydrothermal synthesis of microscopic quartz crystals in 1845 (Fig.  2c ). The wet chemical synthesis of pure 2D materials such as graphene and MoS 2 surged in the early 21st century 28 , 29 , and more recently, doped 2D materials, nanocomposites, and their heterostructures have been synthesized in this fashion by adding various precursors and dopants in solvent to enhance the material properties for specific applications 30 , 31 , 32 , 33 . For example, the hydrogen evolution reaction in graphene oxide was dramatically enhanced by introducing boron dopants 33 .

The strengths of wet chemical synthesis include the controllability of surface morphology, crystallite size, and dopants in 2D materials for catalyst, energy storage, and chemical/biological sensor applications. Reaction temperatures, precursors, and additives have been optimized for various types of 2D materials and their composites, enabling essentially unlimited mass production. The direct synthesis of 2D materials on a desired substrate is also possible, although such synthesis takes a relatively longer time—up to a few days. Growth temperature is often limited to below 300 °C due to the limited durability of equipment under harsh conditions including high pressure and exposure to corrosive chemicals. It is worth noting that bottom-up synthesis tends to yield low-quality 2D materials with defects, but it is still possible to employ these for catalytic applications.

Perspectives and challenges toward industrialization

The abovementioned techniques enable mass production of 2D materials, but considerable further advances will be required for some specific applications. Single-crystal graphene films have been successfully synthesized at wafer scale with layer control, but the synthesis of other 2D materials such as hBN and TMDs are limited exclusively to single-crystal monolayer films. Thickness control of such materials is essential for tunneling barrier and high-performance electronics. The combination of tunable bandgap semiconductors, metals, and insulators in 2D systems can generate versatile heterostructures with remarkable physical properties. Several planar and vertical heterostructures have been generated to date, but these remain limited to micron scale 34 , 35 . More generally, the growth of various heterostructures at wafer scale is still challenging (Fig.  3a ). Atomic sawtooth surfaces could be ideal as a growth platform for single-crystal 2D materials including graphene, hBN, TMDs, and their heterostructures, but surface facet control remains elusive. The formation of wrinkles in 2D films after high temperature growth is another important issue, originating from the thermal expansion coefficient mismatch between 2D materials and growth substrate. Recently, the growth of fold-free single-crystal graphene films at 750 °C has been reported 36 , but further investigation will be required to see if this method is applicable for other 2D materials, and lower-temperature growth methods should be established.

a Single-crystal homo/heteroepitaxial growth, wrinkle formation by thermal expansion coefficient mismatch between 2D materials and growth substrates, and cracking/contamination during the transfer process are all issues presented by the CVD technique. b Inhomogeneous size and thickness of 2D nanosheets and poor production yield are problems associated with liquid exfoliation. c Low durability and instability of 2D materials by defects and environmental pollution remain challenges for wet chemical synthesis.

High temperature processes (above 400 °C) are not compatible with current Si technology, and 2D thin films grown by CVD at high temperature must therefore be transferred onto a target substrate. A conventional transfer process can give rise to serious problems such as folding and cracking of 2D films, ultimately degrading film homogeneity and device performance. Furthermore, the polymer contaminants that are commonly introduced as a supporting layer for the transfer process can give rise to unintentional doping and high contact resistance in heterostructure interfaces and devices. Therefore, methods for the direct growth of large-area 2D films by CVD or advanced roll-to-roll transfer technique would be highly desirable. For industrialization, the manufacturing process including scalable techniques (roll-to-roll, batch-to-batch, etc.), production capacity/cost, reproducibility, and large-area uniformity are further considered 37 .

Wet chemical processes including liquid exfoliation and wet chemical synthesis also face several challenges for the mass production of 2D materials. Liquid exfoliation employs pristine 2D bulk materials synthesized by CVT or flux methods for the mass production of 2D nanosheets. Those synthetic methods typically take at least one week, lowering the throughput of production, and companies need the capacity to provide these bulk materials at a larger scale. Additionally, the production yield of liquid exfoliation generally remains poor, and although some materials show relatively high yield, most 2D materials like hBN and telluride are not effectively exfoliated with current techniques. In addition, it is difficult to obtain 2D nanosheets of uniform size and thickness with this method (Fig.  3b ). In order to remedy this, improved techniques for sorting the synthesized nanosheets in terms of size and thickness (e.g., density gradient ultracentrifugation) are needed.

Bottom-up chemical synthesis typically produces 2D materials with low crystal quality. The defect sites (i.e., edges) often serve as active sites for 2D catalyst, but also give rise to low durability and instability issues. Moreover, 2D materials generated by chemical synthesis are not uniformly distributed in terms of size and thickness, requiring special care during synthesis. In addition, the byproducts frequently generated during chemical synthesis can inhibit catalytic activity. To resolve these material quality and byproduct issues, post-treatments such as thermal annealing and purification have been suggested, but a simple process without post-treatment would greatly improve productivity. Another important issue is the environmental pollution caused by the large amount of hazardous chemical wastes used in synthesis (Fig.  3c ), and the use of supercritical fluid regions could be considered as a shortcut to minimize chemical use 38 .

In addition, rapid and reliable non-destructive characterization tools are highly required to evaluate the wafer-scale 2D materials in terms of sample quality and uniformity. The current state-of-the-art terahertz image, phase-shift interferometry, and wide-field Raman imaging could be adopted to analyze the electrical and optical properties of 2D films with short acquisition time of a few seconds per mm 2 and high spatial resolution of an order of micrometers 39 , 40 , 41 . It still requires a prolonged period to thoroughly inspect 12-inch wafer-scale sample, and therefore, the development of advanced characterization tools is further desired.

From a materials point of view, there is plenty of room for unexplored novel 2D materials and their vdW heterostructures. Since it is almost impossible to explore all such materials experimentally, artificial intelligence-based material design could prove useful for the industrialization and large-scale manufacture of such newly-developed 2D materials 42 .

Novoselov, K. S., Mishchenko, A., Carvalho, A. & Neto, A. H. C. 2D materials and van der Waals heterostructures. Science 353 , aac9439 (2016).

Article   CAS   PubMed   Google Scholar  

Jin, Y. et al. Coulomb drag transistor using a graphene and MoS 2 heterostructure. Commun. Phys. 3 , 189 (2020).

Article   CAS   Google Scholar  

Cao, Y. et al. Unconventional superconductivity in magic-angle graphene superlattices. Nature 556 , 43–50 (2018).

Article   ADS   CAS   PubMed   Google Scholar  

Lin, L., Peng, H. L. & Liu, Z. F. Synthesis challenges for graphene industry. Nat. Mater. 18 , 520–524 (2019).

Koh, A. T. T., Foong, Y. M. & Chua, D. H. C. Cooling rate and energy dependence of pulsed laser fabricated graphene on nickel at reduced temperature. Appl. Phys. Lett. 97 , 114102 (2010).

Article   ADS   Google Scholar  

Tan, L. K. et al. Atomic layer deposition of a MoS 2 film. Nanoscale 6 , 10584–10588 (2014).

Park, J. et al. Epitaxial graphene growth by carbon molecular beam epitaxy (CMBE). Adv. Mater. 22 , 4140–4145 (2010).

Zhang, Y., Zhang, L. Y. & Zhou, C. W. Review of chemical vapor deposition of graphene and related applications. Acc. Chem. Res. 46 , 2329–2339 (2013).

Li, X. S. et al. Large-area synthesis of high-quality and uniform graphene films on copper foils. Science 324 , 1312–1314 (2009).

Chae, S. J. et al. Synthesis of large-area graphene layers on poly-nickel substrate by chemical vapor deposition: Wrinkle formation. Adv. Mater. 21 , 2328–2333 (2009).

Han, G. H. et al. Poly(ethylene co-vinyl acetate)-assisted one-step transfer of ultra-large graphene. Nano 6 , 59–65 (2011).

Nguyen, V. L. et al. Seamless stitching of graphene domains on polished copper (111) foil. Adv. Mater. 27 , 1376–1382 (2015).

Nguyen, V. L. & Lee, Y. H. Towards wafer-scale monocrystalline graphene growth and characterization. Small 11 , 3512–3528 (2015).

Nguyen, V. L. et al. Layer-controlled single-crystalline graphene film with stacking order via Cu–Si alloy formation. Nat. Nanotechnol. 15 , 861–867 (2020).

Kang, K. et al. High-mobility three-atom-thick semiconducting films with wafer-scale homogeneity. Nature 520 , 656–660 (2015).

Cai, Z. Y., Liu, B. L., Zou, X. L. & Cheng, H. M. Chemical vapor deposition growth and applications of two-dimensional materials and their heterostructures. Chem. Rev. 118 , 6091–6133 (2018).

Lee, J. S. et al. Wafer-scale single-crystal hexagonal boron nitride film via self-collimated grain formation. Science 362 , 817–821 (2018).

Choi, S. H. et al. Epitaxial single-crystal growth of transition metal dichalcogenide monolayers via the atomic sawtooth Au surface. Adv. Mater. 33 , 2006601 (2021).

Chen, G. H. et al. Preparation and characterization of graphite nanosheets from ultrasonic powdering technique. Carbon 42 , 753–759 (2004).

Stankovich, S., Piner, R. D., Nguyen, S. T. & Ruoff, R. S. Synthesis and exfoliation of isocyanate-treated graphene oxide nanoplatelets. Carbon 44 , 3342–3347 (2006).

Stankovich, S. et al. Synthesis of graphene-based nanosheets via chemical reduction of exfoliated graphite oxide. Carbon 45 , 1558–1565 (2007).

Shin, H. J. et al. Efficient reduction of graphite oxide by sodium borohydride and its effect on electrical conductance. Adv. Funct. Mater. 19 , 1987–1992 (2009).

Jin, M. H. et al. Facile physical route to highly crystalline graphene. Adv. Funct. Mater. 21 , 3496–3501 (2011).

Kozawa, A., Fujita, K., Sato, A. & Brodd, D. Recent new additives for electric vehicle lead-acid batteries for extending the cycle life and capacity. In Twelfth Annual Battery Conference on Applications and Advances . 277–282 (IEEE, 1997).

Wan, J. Y. et al. Tuning two-dimensional nanomaterials by intercalation: Materials, properties, and applications. Chem. Soc. Rev. 45 , 6742–6765 (2016).

Viculis, L. M., Mack, J. J. & Kaner, R. B. A chemical route to carbon nanoscrolls. Science 299 , 1361–1361 (2003).

Coleman, J. N. et al. Two-dimensional nanosheets produced by liquid exfoliation of layered materials. Science 331 , 568–571 (2011).

Zhan, J. H. et al. Solvothermal synthesis of nanocrystalline MoS 2 from MoO 3 and elemental sulfur. J. Solid State Chem. 141 , 270–273 (1998).

Article   ADS   CAS   Google Scholar  

Yang, L. S., Chen, W. J., Yu, Q. M. & Liu, B. L. Mass production of two-dimensional materials beyond graphene and their applications. Nano Res 14 , 1583–1597 (2021).

Deng, D. H. et al. Toward N-doped graphene via solvothermal synthesis. Chem. Mater. 23 , 1188–1193 (2011).

Wang, J. et al. Ni 3 S 2 @MoS 2 core/shell nanorod arrays on Ni foam for high-performance electrochemical energy storage. Nano Energy 7 , 151–160 (2014).

Deng, J. et al. Triggering the electrocatalytic hydrogen evolution activity of the inert two-dimensional MoS 2 surface via single-atom metal doping. Energy Environ. Sci. 8 , 1594–1601 (2015).

Sathe, B. R., Zou, X. X. & Asefa, T. Metal-free B-doped graphene with efficient electrocatalytic activity for hydrogen evolution reaction. Catal. Sci. Technol. 4 , 2023–2030 (2014).

Article   Google Scholar  

Duong, D. L., Yun, S. J. & Lee, Y. H. van der Waals layered materials: Opportunities and challenges. ACS Nano 11 , 11803–11830 (2017).

Li, M. Y., Chen, C. H., Shi, Y. M. & Li, L. J. Heterostructures based on two-dimensional layered materials and their potential applications. Mater. Today 19 , 322–335 (2016).

Wang, M. et al. Single-crystal, large-area, fold-free monolayer graphene. Nature 596 , 519–524 (2021).

Lin, L. & Liu, Z. Synthesis challenges for graphene industry. Nat. Mater. 18 , 520–524 (2019).

Takahashi, Y., Nakauasu, Y., Iwase, K., Kobayashi, H. & Honma, I. Supercritical hydrothermal synthesis of MoS 2 nanosheets with controllable layer number and phase structure. Dalton Trans. 49 , 9377–9384 (2020).

Lee, U. et al. Facile morphological qualification of transferred graphene by phase-shifting interferometry. Adv. Mater. 32 , 2002854 (2020).

Havener, R. W. et al. High-throughput graphene imaging on arbitrary substrates with widefield Raman spectroscopy. ACS Nano 6 , 373–380 (2012).

Scarfe, S., Cui, W., Luican-Mayer, A. & Ménard, J.-M. Systematic THz study of the substrate effect in limiting the mobility of graphene. Sci. Rep. 11 , 8729 (2021).

Article   ADS   CAS   PubMed   PubMed Central   Google Scholar  

Cai, J. Z., Chu, X., Xu, K., Li, H. B. & Wei, J. Machine learning-driven new material discovery. Nanoscale Adv. 2 , 3115–3130 (2020).

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Acknowledgements

K.K.K. acknowledges support by Samsung Research Funding & Incubation Center of Samsung Electronics under Project Number SRFC-MA1901-04, the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2018R1A2B2002302 and 2020R1A4A3079710). K.S.M. acknowledges support by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2022R1A2C2009292). Y.S.J., C.S.H., K.K.K., and L.Y.H. acknowledge support by the Institute for Basic Science (IBS-R011-D1).

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These authors contributed equally: Soo Ho Choi, Seok Joon Yun.

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Center for Integrated Nanostructure Physics, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea

Soo Ho Choi, Seok Joon Yun, Ki Kang Kim & Young Hee Lee

Department of Energy Science, Sungkyunkwan University, Suwon, 16419, Republic of Korea

Soo Ho Choi, Seok Joon Yun, Yo Seob Won, Chang Seok Oh, Ki Kang Kim & Young Hee Lee

Department of Chemistry, Sookmyung Women’s University, Seoul, 14072, Republic of Korea

Soo Min Kim

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C.S.H., Y.S.J., K.S.M., K.K.K., and L.Y.H. designed and developed this work. W.Y.S., O.C.S., Y.S.J., and C.S.H. investigated the history and technical issues of the various production methods. All authors participated in the writing manuscript.

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Correspondence to Soo Min Kim , Ki Kang Kim or Young Hee Lee .

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Choi, S.H., Yun, S.J., Won, Y.S. et al. Large-scale synthesis of graphene and other 2D materials towards industrialization. Nat Commun 13 , 1484 (2022). https://doi.org/10.1038/s41467-022-29182-y

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DOI : https://doi.org/10.1038/s41467-022-29182-y

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Biosensors Based on Graphene Nanomaterials

• Published: 20 September 2022
• Volume 77 , pages 307–321, ( 2022 )

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• I. I. Kulakova 1 &
• G. V. Lisichkin 1  

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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.

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INTRODUCTION

In the 21st century a new scientific direction has arisen and is successfully developing: nanobiotechnology or biomolecular nanotechnology . This direction is based on the close cooperation of life sciences with chemistry, physics, and engineering. One of the key tasks of nanobiotechnology is the creation of biomedical instruments and devices of the minimum (in the nanometer limit) size using special materials and interfaces.

Medical applications of nanobiotechnology have led to the emergence of a new branch of medicine, nanomedicine , one of the most promising areas of which is the early diagnosis of diseases and infections.

Methods for the express diagnostics and monitoring of the patient’s health status are being actively developed, which allow obtaining the result of the analysis within a few minutes [ 1 ]. There are already solutions for the express diagnostics of a person’s health status (the state of the cardio and immune systems, the presence of infections). These tests (point-of-care (POC), i.e. studies near the patient) are used in the ambulance service, during hospitalization, and at home.

Biochemical sensors occupy an important place among diagnostic devices. Such sensors can analyze both biological fluids and analytes in a gaseous environment, recognizing substances in low concentrations, up to single molecules [ 2 , 3 ].

Research is underway to develop biosensors based on graphene and its derivatives.

Graphene is one of the youngest carbon materials [ 4 – 6 ]; it is distinguished by exceptionally high conductivity, mechanical strength, adjustable bandwidth, adjustable optical properties, and a large specific surface area. Research teams around the world are constantly reporting new achievements in the study of graphene and its application in various fields of science and technology [ 7 – 16 ]. Various measuring devices, sensors, and sensor systems are considered to be the main areas of application for graphene and related materials [ 14 , 17 ]. For example, many graphene-based gas sensors are capable of reacting at the limit of sensitivity to single acts of adsorption/desorption of molecules ( single-molecule detection ). The main trends in the improvement of biomedical means of registration and measurement are a decrease in the size of sensor elements, as well as an increase in their sensitivity and selectivity. It is assumed that nanodevices that can be implanted in the human body for continuous monitoring of its parameters will find mass application [ 18 ].

The unique properties of graphene make it an ideal candidate for one of the main roles in nanobiotechnologies [ 14 – 16 , 19 ].

The aim of this review is to consider domestic and foreign developments devoted to biochemical sensors based on graphene materials and the creation of biosensors for the express diagnostics of human health.

1 BIOSENSOR DEVICES

In the past decade, there has been an increasingly steady interest of scientists and engineers in the development of public express methods of analysis that have high levels of sensitivity and selectivity.

The possibility of miniaturization of such analytical devices is especially important. The most prominent representatives of analytical systems that combine the listed qualities are biosensors [ 20 , 21 ].

Biosensors are a type of chemical sensors in which the recognition system has a biochemical nature and uses the reactions of either individual biomolecules, or biological supramolecular structures [ 20 , 22 ]. A unique feature of biosensors, in contrast to chemical ones, is the high specificity of the receptor element, as well as its ability to perform recognition without additional energy consumption. The authors of [ 20 , 22 ] believe that a necessary characteristic of both chemical and biological sensors should be the possibility of their miniaturization.

Among the areas of application of biosensors, the most important place is occupied by clinical diagnostics, whose area of interest includes, in particular, continuous monitoring of key metabolites of blood and other biological fluids to monitor the patient’s condition. This problem can be solved by implanting specific sensors, among which biosensors have no equal.

Biosensors as chemical sensors that include biological material were first reported by L. Clark and S. Lyons at the symposium of the New York Academy of Sciences in 1962 [ 23 ].

They suggested using electrodes modified with glucose oxidase embedded in membranes to create more advanced electrochemical sensors. This results in sensors that are specifically sensitive to certain substrates, since they detect the formation of an enzymatic reaction product or the consumption of one of the substances involved in this reaction. Clark and his coauthors, using the idea mentioned above, developed biosensors for determining glucose and lactate in the blood [ 24 , 25 ]

The term biosensor has not yet been unambiguously defined. Some authors consider that this is an analytical system for working with biological matter ; and others, that a biosensor is a system that itself contains a biological substance.

Although experts have not yet reached a consensus view, there are more arguments in favor of the second definition. Thus, a biosensor can be called an analytical device, in which the reactions of these compounds catalyzed by enzymes, immunochemical reactions, or reactions taking place in organelles, cells, or tissues are used to determine chemical compounds. The main part of the biosensor is the biological material (enzymes, cells, antibodies, antigens, DNA fragments, etc.), with which the analyte interacts during the operation of the sensor. The signal about this reaction with the help of various physical and chemical methods (electrical, optical, etc.) is converted so that it can be measured and the result displayed on the device screen [ 20 , 26 .

Biosensors that function without the addition of an additional reagent are called reagentless . Biosensors that can quickly and reproducibly recover are called reusable , and biosensors that cannot be reproducibly and quickly restored are considered disposable , including bioassays and bioindicators [ 22 ].

Biosensors are characterized by their fast response (response time ranges from several minutes to 1 h), while the specific indication of microorganisms using enzyme immunoassay takes 3–4 h.

Biosensors can be classified according to the mechanism of biological recognition and according to the type of transducer used (a device that converts the response of the recognition element into a measurable signal). According to the type of transducers, biosensors can be divided into electrochemical, optical, and gravimetric ones. Electrochemical biosensors, according to the authors [ 22 ], occupy a priority position among other types of sensors.

Electrochemical biosensors track any changes in the electrical properties, size, shape, and charge distribution, for example, during the formation of an “antibody–antigen” complex on the electrode surface.

According to the method of measuring the analytical signal, electrochemical biosensors are divided into amperometric, potentiometric, and conductometric sensors and field-effect transistors. Such biosensors are used to detect a wide range of biological targets, including proteins, biomarkers, and nucleic acids.

Optical biosensors are widely used; they allow direct detection of biomolecules in real time. Optical detection systems use the power of the optical field and the biological recognition element, which allows the analysis of macromolecules with a high degree of sensitivity directly in the body.

Among the advantages of optical biosensors over others, their high specificity, great sensitivity, cost-effectiveness, and small size can be singled out. The disadvantages of an optical transducer include its sensitivity to various environmental parameters, including local temperature changes.

Piezoelectric biosensors track the change in mass on the surface of a physical carrier (piezoelectric crystal—resonator), density, viscosity of the medium, and frequency of acoustic waves. Such biosensors are most effective for detecting large molecules and particles: hormones, bacteria, cells, etc.

In the classification according to the biochemical component, the following biosensors are distinguished:

enzyme , which include pure enzyme preparations or biological preparations (tissue homogenates or microbial cultures) and exhibit a certain biological activity;

immunosensors use immunoglobulins, which are protective proteins secreted by the body’s immune system in response to the intake of foreign biological compounds (antigens), as a biochemical receptor;

DNA sensors , including nucleic acids as a biochemical component;

microbial biosensors using microorganisms that can convert a certain substance with the help of enzymes, differing from enzyme sensors in that not one enzyme but a combination of enzymes can participate in the conversion of the substrate; and

biosensors based on supramolecular structures of the cell , occupying an intermediate position between enzyme and DNA sensors and microbial sensors, since they are based on intracellular structures that have a rather complex hierarchical structure.

To increase the selectivity of the sensor to certain molecules, the surface of the receptor is chemically modified so that these molecules can be immobilized on it.

Thus, a high level of sensitivity and selectivity of the biosensor is achieved.

2 GRAPHENE AS THE RECEPTOR MATERIAL

As is well known, graphene is an allotropic modification of carbon, formed by a layer of sp 2 carbon atoms and representing a 2D crystal one atom thick. Less than two decades have passed since the discovery of graphene [ 4 ]; however, it is rapidly gaining a wide range of potential applications, in particular medicine. Thus, in 2013, publications on the biomedical applications of graphene and its derivatives reached 63% [ 27 ].

The structural features of the graphene sheet are such that it is a system in which charge carriers, having unlimited freedom of movement in the plane of the sheet, are closed in a narrow space of one carbon layer. This leads to the appearance of unique electrophysical characteristics and other unusual properties of graphene [ 8 , 16 , 27 , 28 ], in particular, good electrical conductivity [ 4 ] due to the high concentration and mobility of the charge carriers.

Graphene has a record-high mechanical strength. Despite this, it has elasticity and can be subjected to 20% deformation without the network structure breaking [ 30 ]. Monolayer graphene has a constant optical transparency in the visible range (97.7%) and a transmittance value that linearly decreases depending on the number of layers for n -layer graphene [ 31 , 32 ]. The monatomic thickness of a graphene sheet provides the highest possible surface to volume ratio, a specific surface area of ~2630 m 2 /g [ 16 , 27 , 33 ], and high sorption properties. In addition, it has biocompatibility [ 8 ], which is important for biomedical applications.

Graphene can be obtained using mechanical methods: exfoliation of carbon layers from the surface of highly oriented pyrolytic graphite (the Scotch tape method), splitting of graphite crystallites into individual plates when exposed to ultrasound in the presence of surfactants in solvents. Chemical methods are also used: longitudinal catalytic oxidative cutting of carbon nanotubes, which contain rolled graphene layers; deposition from the gas phase of carbon-containing compounds (CVD method); thermal decomposition of the surface layer of a single crystal of silicon carbide; reduction of graphene oxide or graphite oxide; etc. [ 13 , 14 , 16 , 19 ]. Methods for obtaining 3D graphene materials (graphene foam, laser-induced graphene LIG) have been developed [ 12 , 34 – 37 ].

Development of relatively simple methods for obtaining graphene and its derivatives, such as graphene oxide, fluorinated graphene, etc. [ 13 , 16 , 38 , 39 ], the implementation of syntheses of conjugates of graphene nanomaterials with organic or bioorganic compounds of any complexity [ 40 , 41 ], and the above complex of properties have made graphene nanomaterials (GNMs) attractive for biomedical application. GNMs are of interest as receptor elements for recording the interaction of a surface with molecules in the gas and liquid phases. Achievements in the development of gas sensors based on GNMs are considered in [ 14 , 42 – 44 ].

3 GRAPHENE NANOMATERIALS IN BIOSENSORS

Over the past decade, a lot of work has been done to explore the possibilities of use of graphene nanomaterials in biomedicine [ 11 , 15 ]. It has been shown that GNMs are promising for targeted drug delivery, visualization of organs and tissues, the creation of antibacterial materials, and the synthesis of a biocompatible scaffold for cell cultures [ 15 ]. Specialists are especially interested in the possibility of developing graphene biosensors. The review [ 11 ] shows that GNM-based biosensors are capable of detecting biomarkers-indicators of diseases, which is important for medical diagnostics; in addition, they allow studying processes occurring in living cells at the molecular level, for example, the formation of reactive oxygen species.

A common disadvantage of electrochemical sensors is insufficient selectivity due to the simultaneous sorption of several substances. As applied to graphene electrochemical sensors, this drawback was eliminated by using the antigen–antibody reaction. The components of this pair can only interact with each other. They cannot interact with any other proteins. It is known that at certain stages of many human diseases, antigens-markers specific for any one disease or for a group of diseases appear in the blood. These antigens can interact with specific antibodies previously deposited on the surface of the graphene sensor.

3.1 Graphene Materials for Biosensors

It follows from the analysis of the literature that, depending on the choice of the synthesis method and the features of its implementation, it is possible to obtain graphene materials with different properties [ 13 , 14 , 45 – 47 ]. Thus, the CVD method allows us to synthesize high-quality and large graphene samples on the surface of various metals but monolayer films are formed only on copper. The method is promising for the large-scale production of graphene, but it is energy-consuming, which makes it economically unjustified for use where a significant amount of graphene is required. Synthesis of graphene monolayers by thermal decomposition of the surface layer of single-crystal silicon carbide at a temperature of ~1000°C leads to the epitaxial growth of a structurally homogeneous high-quality graphene film on the SiC surface. However, the high cost of single-crystal SiC and its high decomposition temperature reduce the attractiveness of the method for the production of large amounts of graphene.

However, sensor developers have looked at these materials and compared their sensory characteristics. The comparative study of epitaxial graphene films on SiC and graphene obtained by the CVD method as a material for electrochemical biosensing was carried out in [ 48 , 49 ]. For quantitative measurement, the authors used the method of impedance spectroscopy using deionized water and saline (0.9% NaCl). Based on the results obtained, it was concluded that single-layer epitaxial graphene on SiC has a higher sensitivity than multilayer CVD-graphene. Biosensors based on graphene films on SiC showed an extremely high sensitivity to the detected substances. One of the latest advances in the development of graphene biosensors is related to the use of suspended graphene [ 50 ].

The authors deposited monolayer graphene from a suspension onto a preliminarily structured Si substrate. To increase the selectivity, graphene was chemically modified. Selectivity was assessed by nanoscale mechanical deflection of the sheet plane, as the biomarker generates a force that deforms planar graphene into a dome shape, resulting in spectral shifts in optical interference between graphene and silicon substrate. Using the interference properties of light, the authors estimated the magnitude of the deformation from the change in color.

The sensitivity of biosensors can be increased by using laser-induced graphene (LIG). In 2014, it was found that polymers, such as polyimide, can be directly converted into porous three-dimensional graphene using an infrared CO 2 laser [ 37 ]. The discovery of LIG has attracted a significant attention due to its wide range of applications. The advantages of the technology for obtaining LIG compared to conventional methods for the synthesis of graphene are the environmental friendliness of the process and the possibility of controlling the morphology of samples.

LIG has high porosity, flexibility, and mechanical strength, as well as excellent electrical and thermal conductivity. Moreover, LIG can be used to design graphene patterns of any complexity ( Fig. 1 ). To do this, it is sufficient either to apply a pattern on the substrate with a polymer solution and then apply laser radiation, or to draw electrodes on the polymer substrate ( Fig. 1a ) with a laser and attach Ag-contacts to them ( Fig. 1b ), and then encapsulate it in plastic, leaving the receptor window open ( Fig. 1c ).

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

The stenciling and printing process, as well as the useful properties of LIG, open up a new way to develop miniature graphene devices. The use of LIGs in sensor applications quickly moved from single experiments to the creation of an integrated intelligent system for detecting biological objects [ 11 , 12 ].

Oxidized forms of graphene, such as graphene oxide and reduced graphene oxide (RGO), are among the most promising GNMs for creating biosensors, since, by controlling the conditions of their oxidation or reduction, materials with the required ratio of oxygen and carbon [ 13 ], as well as certain functional groups, can be obtained.

The presence of oxygen-containing groups allows us to carry out adsorption and covalent modification of the surface of these materials with both small molecules and large biomolecules, such as enzymes, antibodies, antigens, DNA fragments, and even cells.

The interaction of immobilized molecules with the analyte is detected using the same principles as in the case of other sensors. For example, these can be the following biosensors:

— electrochemical (based on field-effect transistors, the impedance spectroscopy method [ 48 , 49 ]);

— optical (biosensors using the phenomenon of surface plasmon resonance) [ 50 ];

— fluorescent [ 51 ]; and

The schematic diagram of the biosensor is shown in Fig. 2 . Designs of graphene biosensors differ depending on the goals and objectives of sensing. They can be either wired or wireless. These are wearable, flexible, monoplex, and multiplex systems used in both clinical and home settings.

Schematic diagram of a graphene biosensor.

3.2 Chemical Modification of Graphene Is a Necessary Step in the Development of Biosensors

An important step in the use of graphene nanomaterials in biomedicine (including the creation of bisensors) is their chemical modification. Chemical modification can improve the solubility of nanoparticles of these materials in water, ensure their biocompatibility, and reduce their toxicity and the ability to interact with certain analytes.

GNMs are characterized by an extended polyaromatic system and the presence of oxygen-containing groups localized both on the periphery of graphene planes and on their surface. These groups make graphene molecules active with respect to electrophilic and nucleophilic reagents. In recent years, methods for the chemical modification of graphene with functional groups and fragments of molecules have been actively developed. On the one hand, such modification allows us to control the electronic properties and, consequently, the conductivity of graphene over a wide range. Depending on the type of modification, the interaction energy between the adsorbed molecule and graphene, as well as the charge transfer in the system, can vary greatly. On the other hand, functional groups play the role of specific reaction centers during the adsorption and covalent bonding of various molecules with graphene and its derivatives [ 13 , 19 , 45 , 46 ].

Phenyl and alkyl groups, a stable free radical 4‑amine-2,2,6,6-tetramethyl-1-piperidine oxide, and dichlorocaben were covalently grafted to the surface of graphene using organic synthesis methods [ 53 ]. Conjugates of graphene and its derivatives with DNA molecules [ 54 ], porphyrins (as drug components) [ 55 , 56 ], poly-L-lysine [ 57 ], star-shaped polyethylene glycol (PEG) [ 58 ], etc. [ 13 , 16 ], have been obtained.

The grafting of star-shaped PEG [ 58 ] to graphene oxide made it possible to obtain biocompatible materials for cell visualization and sorption of biomolecules, including drugs. Unlike other graphene materials, the resulting product forms stable dispersions in an aqueous salt medium and in biological fluids. In addition, it exhibits fluorescent properties in the near-IR region, which can be used to create optical biosensors.

Covalent modification of graphene oxide deposited on a substrate with DNA molecules to create biomolecular devices was carried out in [ 54 ]. An oligodeoxynucleotide containing 20 links (amine-AAC TGC CAG CCT AAGTCC AA) was involved in a reaction with graphene oxide carboxyl groups in the presence of an activator. It has been shown that DNA binds predominantly onto thicker regions of the crumpled graphene sheet, including graphene oxide folds, which follows from the observation of a higher fluorescence intensity in these regions. Since no increased fluorescence was observed at the edges of the graphene planes, where the carboxyl groups that bind DNA molecules are supposed to be, the authors concluded that the carboxyl groups were uniformly distributed over the graphene oxide plane.

In [ 51 ], a fluorescent peptide labeled with pyrene fragments was immobilized on graphene oxide. The authors suggested using the obtained material to study protein-protein interactions.

The formation of supramolecular complexes of porphyrin derivatives with reduced graphene flakes is described in the review [ 59 ].

The authors paid special attention to this material, since, in their opinion, the great possibilities of postsynthetic modification in combination with the unusual properties of graphene and its derivatives can be used to solve complex biomedical and environmental problems.

As an example, we present a scheme of chemical modification of an electrode in manufacturing a biosensor based on LIG ( Fig. 3 ).

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

To stabilize the loosened LIG particles and obtain more sensitive layers, the authors of [ 12 ] electrochemically polymerized 3,4-ethylenedioxythiophene (EDOT) to form polyEDOT (PTDOT) in the working electrode ( Fig. 3a ). Then, the electrode surface was aminated ( Fig. 3b ), a template was attached ( Fig. 3c ), and electropolymerization was performed in the presence of the template ( Fig. 3d ). After the template was removed, a polymer with a molecular imprint was obtained ( Fig. 3e )

The sensitivity and selectivity of the biosensor based on molecularly imprinted LIGs were comparable to those of sensors fabricated using commercial graphene-based screen-printed electrodes.

3.3 Application Examples of Graphene Biosensors

Currently (March 2022), about two hundred biosensor devices that use graphene nanomaterials have been described in the scientific and patent literature. Because the volume of the article is limited, we will focus only on the most significant and illustrative examples of the use of graphene biosensors in relation to various classes of analytes.

3.3.2 Graphene Biosensors for the Detection of Markers of Socially Significant Diseases

To diagnose many diseases, it is necessary to be able to detect disease markers, protein molecules specific for each specific pathology, which are usually expressed in very small quantities.

GNM-based biosensors for probing protein molecules can significantly increase the efficiency of diagnosing a wide range of diseases affecting both humans and animals.

Cardiovascular Diseases

An aptasensor for determining the myoglobin cardiomarker, an oxygen-binding protein in skeletal muscles and heart muscle, whose function is to create an oxygen reserve in the muscles, was proposed [ 82 , 83 ].

The myoglobin-specific aptamer was immobilized on the surface of a printed electrode and modified with graphene oxide and carbon nanotubes. The sensor provides a low detection limit (34 ng/L) in the linearity range (1–4000 ng/mL).

Troponins I, T, and C are involved in the calcium-dependent regulation of the act of the contraction-relaxation of the heart and are specific markers of myocardial damage. In a number of medical tests, troponins are used as biomarkers for various heart diseases. Acute myocardial infarction (AMI) is one of the leading causes of death among patients with cardiovascular disease, prompting researchers in this field to develop POC biosensors to quickly detect an AMI episode. Over the years, various detection methods have emerged to evaluate cardiac troponins. Review [ 84 ] summarizes various biosensor methods for detecting these markers of myocardial injury.

To detect troponin I, the authors of [ 85 ] developed an electrochemical labelless biosensor based on a glassy carbon electrode coated with nanoporous graphene oxide. The biosensor is inexpensive, and due to the use of porous graphene, has good electrochemical properties and a large active surface area.

The sensor showed good selectivity and high sensitivity: the limit of detection was 0.07 ng/mL.

It is known that early diagnosis of oncological diseases plays a key role for subsequent treatment in many cases. However, the level of tumor markers in the patient’s blood at the initial stages of the disease does not exceed a few pmol; thus, only a few methods and sensors can detect them [ 61 , 83 ]. In recent years, various biosensors have been proposed for diagnosing various types of cancer, including breast [ 86 ], prostate [ 87 , 88 ], lung [ 89 ], liver, stomach, and intestine cancer [ 90 ]. Let us give specific examples.

The authors of [ 89 ] developed a highly sensitive graphene biosensor capable of identifying signs of lung cancer, i.e., to detect (sniff out) in the respiratory products of a human molecules of the most common biomarkers of lung cancer (ethanol, isopropanol, and acetone) in a range of different concentrations. The sensor is able to detect molecules of specific lung cancer markers at the earliest stage of the disease.

Detection of the prostate tumor marker PSA was performed by the authors of [ 87 ] using graphene field-effect transistors modified with polyethylene glycol (PEG)/ethanolamine. The study demonstrated the possibility of real-time biomarker detection. In addition, studies using graphene devices modified with a PEG/DNA aptamer have shown specific binding and detection of PSA in solutions at pH 7.4. The receptor of aptamer-modified graphene devices can be regenerated for the purpose of multiple selective determination of PSA.

Helicobacter pylori (H. Pylori) bacteria attack the stomach lining and cause ulcers and stomach cancer. To detect them, a graphene biosensor was developed in [ 61 , 62 ]. Graphene was adsorptively modified by antibodies. When bacteria interact with the biosensor, chemical reactions are triggered, which are fixed by graphene. The researchers used microfluidics to ensure the detection of reaction products occurring with bacteria in the presence of certain chemicals that the authors added to a tiny drop of water.

Microfluidics allows bacteria to be localized in microdroplets near the sensor surface. The biosensor quite quickly (in less than 30 min), highly sensitively, and quantitatively detects H. Pylori bacteria, and the concentration of the reaction products can be monitored in real time.

A wireless nanosensor based on graphene was developed to detect bacteria in saliva [ 91 ]. The graphene sensing element was adsorbed onto a silk film (fibroin) and then transferred to the tooth surface, followed by dissolution of the supporting silk film. The detection specificity was ensured by using self-assembling antimicrobial peptides (odorranin-HP) on a graphene monolayer. When the system recognizes and binds the target bacteria ( H. pylori ), the electrical conductivity of the graphene film changes and the data are transmitted wirelessly. The developed nanosensor has a low detection limit (100 CFU/mL) and the possibility of remote wireless sensing. Thus, the “tattoo on the tooth” warns of bacteria in saliva.

Diabetes is a common chronic disease in which the body’s ability to absorb glucose is impaired. Constant monitoring of the concentration of glucose in the blood of diabetic patients is necessary to assess the condition of patients. Various glucometers are used for measurements, primarily enzymatic electrochemical biosensors. The latter have satisfactory selectivity and sensitivity, are based on the use of glucose dehydrogenase or glucose oxidase enzymes, and are commercially available. However, the use of biological materials such as enzymes, antibodies, etc., is limited by the complexity of their manufacture and low service life due to the decrease and loss of the biological activity of the enzyme over time. The commonly used glucose oxidase enzyme has insufficient stability and requires complex immobilization processes on the sensor surface. It does not withstand even a slight heating, which narrows the range of application of biosensors.

An alternative to enzymatic biosensors are sensors without enzymes that detect glucose through its oxidation. In this case, it is important to develop suitable efficient catalysts for the detection of glucose in biological samples under physiological conditions without any pre/post treatment. The main advantages of enzyme-free biosensors are their low cost, high stability, fast response, and low detection limit. The devices directly detect glucose and are based on its oxidation reaction catalyzed by various electrocatalysts, which are atoms on the surface of the material. Here, a significant role is assigned to nanomaterials, such as nanoparticles of Au, Ag, Ni, Cu, and Co, as well as their oxides and sulfides.

In [ 92 ], the authors compared the latest developments in nonenzymatic glucose biosensors based on copper nanoparticles (NPs), copper oxides, their alloys, and their composites. Copper and its oxides are widely used as components of nonenzymatic glucose sensors due to their low cost, good sensitivity, and current response in alkaline media, and also because of the practical and simple methods for preparing nanomaterials based on them. In addition, they have high electrocatalytic activity, economy, nontoxicity, and stability. Combining copper with graphene significantly increases the sensitivity of nonenzymatic glucose sensors, which is probably due to the synergistic effect between the two components leading to an increase in the electrocatalytic active area and an increase in electron transfer for glucose oxidation. Information about some biosensors is given in Table 2 .

It follows from the data presented in Table 2 that the developed enzyme-free electrochemical glucose biosensor based on LIG decorated with Cu or Cu–Cu 2 O nanoparticles showed the highest sensitivity (495 μA mM –1 cm –2 ) and 1086 _uc2s 10 mM. A graphene-modified Cu 2 O nanocomposite was synthesized by microwave irradiation of an aqueous solution of copper compounds and studied as an enzymeless glucose biosensor. The biosensor showed a broad linear response to glucose detection in the concentration range from 2 μM to 12 mM with a detection limit of 2 μM. In addition, it ensured the selectivity of glucose 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 nonenzymatic electrochemical glucose sensors.

The authors of [ 93 ] created a wearable, noninvasive, low-cost LIG-based device that allows us to measure blood glucose levels without piercing the skin, in contrast to the currently used tests. The problem was that graphene is inert to glucose; thus, the authors had to look for workarounds. They found that LIG modified with nickel-gold alloy nanoparticles could detect low concentrations of glucose in sweat on the surface of the skin. The concentration of glucose in sweat is lower by a factor of about 100 than the concentration in blood, but there is a strong correlation between sweat and blood glucose levels. The sensor works on a small area of the skin containing at least one hair follicle. It detects glucose by drawing it out of the fluid that is present between cells. The new device is sufficiently sensitive to accurately measure glucose in sweat and estimate blood concentrations. The researchers demonstrated the device by attaching it to a person’s arm 1 and 3 h after a meal.

The sugar levels detected by this device and commercial glucometers matched each other.

A group of Korean researchers [ 94 ] developed a method for manufacturing biosensors in the form of soft contact lenses that can monitor tear glucose levels to indicate real-time diabetic status through a wireless display. For this smart lens, the electronic components (glucose sensor, LED pixel, rectifier circuit, and stretchable transparent antenna) were integrated into a stress-tunable hybrid substrate with well-matched refractive indices for high optical transparency and low haze. After shaping the soft contact lens into a round shape, the built-in electronic system worked reliably under mechanical deformations, including bending and stretching. In vivo tests using a live rabbit, including monitoring the temperature changes in the eye of a rabbit, showed the promise of such contact lenses for noninvasive monitoring.

The development of effective biosensors for determining the concentration of glucose in a patient’s blood continues to be an urgent task, since it is necessary to increase reliability and reduce the cost of analysis.

3.3.3 Graphene Biosensors for Toxins

Mycotoxins produced by microscopic molds are a common type of toxin found in food and feed. The problem of mycotoxin contamination has recently become more acute due to the increased complexity of transport chains from farm to store, which entails negative consequences for human and animal health.

Consumption of products contaminated with mycotoxins leads to acute and chronic diseases (mycotoxicosis, chronic gastrointestinal diseases, hemorrhagic necrosis, liver cancer, etc.). It is highly desirable to establish easy to use, in situ, and rapid monitoring of mycotoxins in food and feed.

Consumption of products contaminated with mycotoxins leads to acute and chronic diseases (mycotoxicosis, chronic gastrointestinal diseases, hemorrhagic necrosis, liver cancer, etc.). It is highly desirable to establish easy to use in situ and rapid monitoring of mycotoxins in food and feed.

In [ 80 ], the authors reported on the creation of an improved bioelectronic sensor for mycotoxin ochratoxin A (OTA) based on graphene field-effect transistors integrated on a silicon chip. The OTA-specific aptamer was attached to graphene via a covalent bond with a pyrene-based linker. This device has demonstrated a high degree of sensitivity to OTA with a low detection limit of 1.4 pM with a response time of 10 s in a phosphate buffer and up to 50 s in the case of real samples, which is superior to any other assay method. Grafting several aptamers specific for different mycotoxins can provide the simultaneous detection of several targets.

To detect food contaminants such as mycotoxins (including OTA), the authors of [ 96 ] developed a nonenzymatic electrochemical aptasensor based on the use of cerium oxide and graphene oxide nanoparticles on a screen-printed electrode.

Changes in the optical properties of cerium nanooxide upon interaction with phenols and H 2 O 2 were used to manufacture portable colorimetric sensors for the detection of food antioxidants and glucose.

Pesticides and Chemical Warfare Agents

The intensive development of printed electronics methods (the field of electronics involved in the creation of electronic circuits using printing equipment) has allowed us to develop methods for printing graphene-based electrodes, which has recently become an attractive, inexpensive, and scalable technology for the production of field electrochemical biosensors. For example, in [ 97 ], the authors report on a graphene-based electrode obtained by maskless inkjet lithography for direct and rapid monitoring of organophosphorus compounds—chemical warfare agents and pesticides.

The graphene electrode has a microstructure with laser engraving and electrochemically deposited platinum nanoparticles (diameter ~25 nm) to improve its electrical conductivity (sheet resistance is reduced from ~10 000 to 100 Ohm per m 2 of surface area). The enzyme phosphotriesterase is covalently immobilized on the electrode by cross-linking through glutaraldehyde. The resulting biosensor was able to quickly (response 5 s) detect the model insecticide paraoxon with a low detection limit (3 nM) and high sensitivity (370 nA/μM) with little interference from similar nerve agents.

In addition, the biosensor demonstrated reusability (decrease in sensitivity by 0.3% on average per measurement), stability (90% preservation of the anode current signal for 1000 s), durability (after 8 weeks, sensitivity is maintained at 70%) and the ability to selectively determine organophosphorus in real soil and water samples. Thus, in [ 97 ], a scalable technology for manufacturing a printed graphene electrode is presented, which can be used to create biosensors suitable for field use.

A printed electrochemical sensor has been proposed for the in situ determination of methyl parathion (an insecticide containing an organothiophosphate group) and nitrite in foodstuffs [ 83 , 97 ]. The electrodes were made from a mixture of chitosan, graphene, and silver powders. The porous structure of the sensors allows the analysis to be carried out without prior removal of the analyte. The sensor has been tested on simulation systems and real objects (Fuji apples, Chinese onions and cabbages). The limit of detection was 15 ng and 18.4 μg for methyl parathion and nitrite, respectively.

Biosensors for pesticides were created [ 98 ] by functionalizing LIG electrodes with the enzyme horseradish peroxidase. They showed a high level of sensitivity to atrazine (28.9 na/μm) with little difference from other common herbicides (glyphosate, dicamba and 2,4-dichlorophenoxyacetic acid).

Biogenic Amines

Biogenic amines (BAs) are nitrogenous compounds, the concentration of which in food products is directly related to food safety and, consequently, to human health. The presence of a large amount of BAs in food can lead to severe poisoning. In food, BAs are formed by endogenous enzymatic activity or microbial metabolism, leading either to the decarboxylation of amino acids or to the amination of aldehydes and ketones. The properties of individual BAs (e.g., histamine, tyramine, cadaverine) vary depending on the amino acid precursor (histidine, tyrosine, lysine) and chemical structure (aliphatic, aromatic, or heterocyclic). The total BA content in any food product depends on the specific biochemical composition, as well as the type and number of microorganisms present. For example, fermented foods such as cheese, wine, sausage, and pickled vegetables that use lactic acid bacteria communities for fermentation may contain high concentrations of histamine, cadaverine, tyramine, and/or putrescine. Fermented fish products are particularly susceptible to high levels of BA due to a combination of high microbial load and high content of amino acid precursors. Since the accumulation of histamine, putrescine, cadaverine, tyramine, trimethylamine, and dimethylamine can be related to microbial contamination, the total concentration of BAs is commonly used to assess quality and safety indicators, as well as the overall shelf life of fish, fish products, and shellfish.

Graphene biosensors can be used in the food industry to analyze histamine and other toxins. For biosensing food safety (in particular, the presence of biogenic amines) without the use of additional reagents, graphene electrodes with laser engraving were developed [ 83 , 99 ]. In the manufacture of biosensors, the graphene surface was functionalized with diamine oxidase and copper microparticles. The developed biosensor showed good electrochemical characteristics: average sensitivity to histamine 23.3 μA/mm, as well as a lower detection limit of 11.6 μm and response time 7.3 s. The authors demonstrated the use of the biosensor by testing the total concentration of BAs in fish paste samples fermented with lactic acid bacteria. The concentration of biogenic amines before fermentation with lactic acid was below the detection limit of the biosensor, while after fermentation, the concentration of histamine was 19.24 ± 8.21 mg/kg. These results confirm that the sensor was selective in a complex food matrix. An inexpensive, fast, and accurate device is a promising tool for assessing biogenic amines in food samples, especially in situations where the standard laboratory methods are not available or too expensive.

Electrochemical biosensors for the detection of histamine based on graphene with electrodes fabricated using aerosol inkjet printing are described in [ 83 , 100 , 101 ]. These sensors detect BAs in foods much faster than the standard laboratory tests. Their use for these purposes is more expedient. Commercial electrochemical sensors are disposable; thus, it is too expensive to use them all the time. Low-temperature chemical vapor deposition graphene devices used for food monitoring are too expensive for such applications. At the same time, inexpensive alternative methods, such as screen printing and inkjet printing, are not able to provide sufficient control of the electrode geometry to obtain suitable electrochemical characteristics of the sensor. When applying specially designed aerosol-jet ink [ 100 , 101 ], it is possible to change the geometry of the template using software control. New graphene-based biosensors detect substances hazardous to health in food faster and more efficiently than classical biosensors. Also, airjet sensors apply the right material only where it is needed, minimizing production waste and making the devices inexpensive and easy to manufacture. Because of this, they can be used where constant monitoring of food samples is important in order to assess the quality of products. In the course of the study [ 100 ], interdigital flexible electrodes were created from graphene on a substrate, after which they were converted into histamine biosensors by covalent modification of the graphene surface with monoclonal antibodies. The operation of biosensors was tested not only in a model buffer solution but also in fish broth to ensure the effectiveness of histamine detection. It was found that the graphene biosensor is able to detect histamine in a buffer solution and fish broth in toxicologically significant amounts (6.25–100 and 6.25–200 ppm with limits of 2.52 and 3.41 ppm, respectively). For example, histamine levels in fish that exceed 50 ppm cause severe allergies in some people and even food poisoning. It is also important that the biosensor demonstrates a short response time: 33 minutes is sufficient and no pretreatment of product samples is required.

Similar laboratory tests take longer and require prior labeling and sample processing. In addition, the sensitivity of the sensor was not affected by the adsorption of large protein molecules, which often act as a 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 samples is required. Its use will avoid sending samples to the laboratory, save time, and reduce the cost of testing for the content of histamine and toxins in products. Achievements in the design and development of graphene biosensors for food safety assessment are summarized in the review [ 102 ].

CONCLUSIONS

The high sensitivity, fast action, and small size of graphene biosensors, combined with the record specificity achieved by modifying graphene with antibodies and/or aptamers, make such sensors extremely promising devices for use in various fields of biomedicine. The first, but promising results have been obtained in important areas such as diagnosing autoimmune diseases, monitoring and diagnosing oncological diseases in the early stages, monitoring intrauterine genetic abnormalities of the fetus during pregnancy, and controlling the appearance of dangerous metabolites during surgical operations.

The biosensors created based on the GNM allow us not only to detect biomarkers but also to study the processes occurring in cells (formation of reactive oxygen species in living cells and in vivo expression of genes contained in chromosomes).

In modern genetic engineering, it is promising to use CRISPR/Cas9, a new technology for editing the genomes of higher organisms based on the immune system of bacteria, which is based on special sections of bacterial DNA, short palindromic cluster repeats, or CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). Since 2016, molecular biologists have been widely using approaches based on CRISPR/Cas systems.

It is believed that in the foreseeable future these approaches will be used in medicine for the treatment of hereditary diseases, https://ru.wikipedia.org/wiki/CRISPR : cite_note-3. CRISPR/Cas is important for the targeted delivery of drugs and their release under external influence. For the discovery of this method in 2020, the Nobel Prize in Chemistry was awarded.

Most nucleic acid detection methods require large amounts of reagents, expensive and bulky devices, and in addition, are related to a violation of gene material. The advantage of the CRISPR method is that it allows us to directly observe DNA, instead of isolating DNA, destroying, amplifying, labeling, and directing an optical laser at it to detect the label. It is important that the graphene CRISPR chips developed in [ 103 , 104 ] make it possible to study DNA in its natural state and immediately signal the presence of a specific mutation, protein, or other component.

It can be argued that the use of graphene nanomaterials in biosensors is a very relevant and promising direction in the development of this field.

Popov, V.P., Tropin, A.V, Glukhov, A.V., and Ivanov, Yu.D., Innovatsii, 2014, no. 3, p. 94.

Schedin, F., Geim, A.K., Morozov, S.V., Hil, E.W.L., Blake, P., and Katsnelson, M.I., Nat. Mater. , 2007, vol. 6, p. 652.

Article   CAS   PubMed   Google Scholar  

Lu, C.H., Li, J., Liu, J.J., Chen, X., Yang, H.H., and Zhu, C.L., Chem. Commun. , 2010, vol. 46, p. 3116.

Article   CAS   Google Scholar  

Novoselov, K.S., Geim, A.K., Morozov, S.V., Jiang, D., Zhang, Y., Dubonos, S.V., Grigorieva, I.V., and Firsov, A.A., Science , 2004, vol. 306, p. 666.

Novoselov, K.S., Jiang, D., Schedin, F., Khotkevich, V.V., Morozov, S.V., and Geim, A.K., Proc. Natl. Acad. Sci. U. S. A. , 2005, vol. 102, no. 30, p. 10451.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Geim, A.K., Nobel lecture. http://www.nobelprize.org/ nobel_prizes/physics/laureates/2010/geim_lecture.pdf.

Randviir, E.P., Brownson, D.A.C., and Banks, C.E., Mater. Today , 2014, vol. 17, no. 9, p. 426.

Ferrari, A.C., Bonaccorso, F., Fal’ko, V., Novoselov, K.S., Roche, S., Bøggild, P., Borini, S., L.Koppens, F.H., Palermo, V., Pugno, N., Garrido, J.A., Sordan, R., Bianco, A., Ballerini, L., Prato, M., Lidorikis, E., Kivioja, J., Marinelli, C., Ryhänen, T., Morpurgo, A., Coleman, J.N., Nicolosi, V., Colombo, L., Fert, A., Garcia-Hernandez, M., Bachtold, A., Schneider, G.F., Guinea, F., Dekker, C., Barbone, M., Sun, Z., Galiotis, C., Grigorenko, A.N., Konstantatos, G., Kis, A., Katsnelson, M., Vandersypen, L., Loiseau, A., Morandi, V., Neumaier, D., Treossi, E., Pellegrini, V., Polini, M., Tredicucci, A., Williams, G.M., Hong, B.H., Ahn, J.-H., Kim, J.M., Zirath, H., van, Wees, B.J., Vander, Zant, H., Occhipinti, L., DiMatteo, A., Kinloch, I.A., Seyller, T., Quesnel, E., Feng, X., Teo, K., Rupesinghe, N., Hakonen, P., Neil, S.R.T., Tannock, Q., Löfwander, T., and Kinaret, J., Nanoscale , 2015, vol. 7, p. 4598.

Fadeel, B., Bussy, C., Merino, S., Vázquez, E., Flahaut, E., Mouchet, F., Evariste, L., Gauthier, L., Koivisto, A.J., Vogel., Martín, C., Delogu, L.G., Buerki-Thurnherr, T., Wick, P., Beloin-Saint-Pierre, D., Hischier, R., Pelin, M., Carniel, F.C., Tretiach, M., Cesca, F., Benfenati, F., Scaini, D., Ballerini, L., Kostarelos., Prato, M., and Bianco, A., ACS Nano , 2018, vol. 12, no. 11, p. 10582.

Ye, E. and Tour, J.M., ACS Nano , vol. 13, no. 10, p. 10872.

Garg, R., Roman, D.S., and Cohen-Karni, T., Appl. Mater. , 2020, vol. 8, no. 10.

Huang, L., Su, J., Song, Y., and Ye, R., Nano-Micro Lett. , 2020, vol. 12, p. 157.

Kulakova, I.I. and Lisichkin, G.V., Russ. J. Gen. Chem. , 2020, vol. 90, no. 10, p. 16013.

Article   Google Scholar  

Kulakova, I.I. and Lisichkin, G.V., Russ. J. Appl. Chem. , 2021, vol. 94, no. 9, p. 1077.

Lisichkin, G.V. and Kulakova, I.I., Uglerodnye nanochastitsy, in Lisichkin, G.V., Olenin, A.Yu., and Kulakova, I.I., Khimiya poverkhnosti neorganicheskikh nanochastits (Surface Chemistry of Inorganic Nanoparticles), Moscow: Technosfera, 2021.

Google Scholar  

Lisichkin, G.V. and Kulakova, I.I., Pharm. Chem. J. , 2022, vol. 56, no. 1, p. 1.

Pumera, M., Mater. Today , 2011, vol. 14, no. 7, p. 308.

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

Gubin, S.P. and Tkachev, S.V., Grafen i rodstvennye nanoformy ugleroda (Graphene and Related Nanoforms of Carbon), Moscow: URSS, 2019.

Karyakin, A.A., Biosensors , Amsterdam: Springer, 2009.

Aksenova, E.I., Kamynina, N.N., and Maklakova, Yu.A., in Ekspertnyi obzor: biosensornye sistemy v meditsine (Scientific Review: Biosensor Systems in Medicine), Moscow, 2020.

Karyakin, A.A., Ulasova, E.A., Vagin, M.Yu., and Karyakina, E.E., Sensor , 2002, no. 1, p. 16.

Clark, Ir L.C. and Lyons, C., Ann. N. Y. Acad. Sci. , 1962, vol. 102, p. 29.

Clark, L.C. and Sache, G., Ann. N. Y. Acad. Sci. , 1968, vol. 148, p. 133.

Clark, Ir L.C., Noves, L.R., Grooms, T.A., and Moore, M.S., Crit. Care Med. , 1984, vol. 12, p. 461.

Article   PubMed   Google Scholar  

Biokhimicheskie metody analiza (Biochemical Methods of Analysis), Dzantiev, B.B., Ed., vol. 12 of Problemy analiticheskoi khimii (Problems of Analytical Chemistry), Moscow: Nauka, 2010.

Mao, H.Y., Laurent, S., Chen, W., Akhavan, O., and Imani, M., Chem. Rev. , 2013, vol. 113, no. 5, p. 3407.

Banerje, A.N., Glob. J. Nano , 2016, vol. 1, no. 1, 555552.

Aleksenko, A.G., Grafen (Graphene) , Moscow: Laboratoriya Znanii, 2014.

Lee, C., Wei, X.D., Kysar, J.W., and Hone, J., Science , 2008, vol. 321, p. 385.

Nair, R.R., Blake, P., Grigorenko, A.N., Novoselov, K.S., Booth, T.J., Stauber, T., Peres, N.M.R., and Geim, A.K., Science , 2006, vol. 320, no. 5881, p. 1308.

Kumar, R., Mehta, B.R., Bhatnagar, M., Ravi, S., Mahapatra Salkalachen, S., and Jhawar, P., Nanoscale Res. Lett. , 2014, vol. 9, 349.

Article   PubMed   PubMed Central   CAS   Google Scholar  

Stoller, M.D., Park, S., Zhu, Y., An J., and Ruoff, R.S., Nano Lett ., 2008, vol. 8, no. 10, p. 3498.

Chabot, V., Higgins, D., Yu, A., Xiao, X., Chena, Z., and Zhang, J., Energy Environ. Sci. , 2014, no. 7, p. 15564.

Yan, Y., Ruan, G., Xiang, C., Wang, G., and Tour, J.M., J. Am. Chem. Soc. , 2014, vol. 136, p. 6187.

Zhang, S., Jiang, S.-F., Huan, B.-C.G., Shen, X.-C., Chen, W.-J., Zhou, T.-P., Cheng, H.-Y., Cheng, B.-H., Wu, C.-Z., Li, W.-W., Jiang, H., and Yu, H.-Q., Nat. Sustainability , 2020, vol. 3, p. 753.

Lin, J., Peng, Z., Liu, Y., Ruiz-Zepeda, F., and Yeetal, R., Nat. Commun. , 2014, vol. 5, no. 1, 5714.

Inagaki, M. and Kang, F., Mater. Chem. A, 2014, vol. 2, p. 13193.

Peng, Q., Dearden, A.K., Crean, J., Han, L., Liu, S., Wen, X., and De, S., Nanotechnol., Sci. Appl. , 2014, vol. 7, p. 1.

Liu, Z., Robinson, J.T., Sun, X.M., and Dai, H., J. Am. Chem. Soc. , 2008, vol. 130, no. 33, p. 10876.

Jiang, H., Small , 2011, vol. 7, no. 17, p. 2413.

CAS   PubMed   Google Scholar  

Wang, T., Huang, D., Yang, Z., Xu, S., He, G., Li, X., Hu, N., Yin, G., He, D., and Zhang, L., Nano-Micro Lett. , 2016, vol. 8, no. 2, p. 95.

Varghese, S.S., Lonkar, S., Singh, K.K., Swaminathan, S., and Abdala, A., Sens. Actuators, B , 2015, vol. 218, pp. 160–183.

Hosseingholipourasl, A., Ariffin, S.H.S., Al-Otaibi, Y.D., Akbari, E., Hamid, F.K.H., and Koloor, S.S.R., Sensors , 2020, vol. 20, no. 5, p. 1506.

Article   CAS   PubMed Central   Google Scholar  

Gubin, S.P. and Tkachev, S.V., Radioelektron. Nanosist. Inf. Tekhnol. , 2010, vol. 2, nos. 1–2, p. 99.

Graifer, E.D., Makotchenko, V.G., Nazarov, A.S., Kim, S.Dzh., and Fedorov, V.E., Russ. Chem. Rev. , 2011, vol. 80, no. 8, p. 751.

Liu, J., Tang, J., and Gooding, G., J. Mater. Chem. , 2012, vol. 22, no. 25, p. 12435.

Sleptsuk, N., Land, R., Toompuu, J., Lebedev, A., Davydov, V., Eliseyev, I., Kalinina, E., Korolkov, O., and Rang, T., Proc. 6th Int. Symp. on Graphene Devices (ISGD-6) , 2018, ePoster.

Sleptsuk, N., Lebedev, A.A., Eliseyev, I., Korolkov, O., Toompuu, J., Land, R., Mikl, V.I., Zubov, A., and Rang, T., Key Eng. Mater. , 2019, no. 799, p. 185.

Kidane, S., Ishida, H., Sawada, K., and Takahash, K., Nanoscale Adv. , 2020, vol. 2, no. 4, p. 1431.

Lu, C.-H., Li, J., Zhang, X.-L., Zheng, A.-X., Yang, H.-H., Chen, X., and Chen, G.-N., Anal. Chem. , 2011, vol. 83, no. 19, p. 7271.

Lebedev, S.P., Davydov, V.Yu., Usachov, D.Yu., Smirnov, A.N., Levitskii, V.S., Eliseyev, I.A., Guschina, E.V., Dunaevsckiy, M.S., Vilkov, O.Yu., Rybkin, A.G., Lebedev, A.A., Novikov, S.N., and Makarov, Yu.N., Nanosyst.: Phys., Chem., Math. , 2018, vol. 9, no. 1, p. 95.

CAS   Google Scholar  

Cui, Y., Kim, S.N., Jones, Sh.E., Wissler, L.L., Naik, R.R., and McAlpine, M.C., Nano Lett. , 2010, vol. 10, p. 4559.

Rabchinskii, M., Ryzhkov, S., Kirilenko, D., Lin, N., Baidakova, M., Shnitov, V., Pavlov, S., Chumakov, R., Stolyarova, D., Brzhezinskaya, M., Lebedev, O., Melnikov, V., and Brunkov, P., Sci. Rep. , 2020, vol. 10, p. 10.

Shan, C., Yang, H., Han, D., Zhang, Q., Ivaska, A., and Niu, L., Langmuir , 2009, vol. 25, p. 12030.

Georgakilas, V., Otyepka, M., Bourlinos, A.B., Chandra, V., Kim, N., Kemp, K.C., Hobza, P., Zboril, R., and Kim, K.S., Chem. Rev. , 2012, vol. 112, p. 6156.

Yu, J.W., Jung, J., Choi, Y.-M., Choi, J.H., Yu, J., Lee, J.K., You, N.-H., and Goh, M., Polym. Chem. , 2016, no. 7, p. 36.

Loh, K.P., Bao, Q., Ang, P.K., and Yang, J., J. Mater. Chem. , 2010, vol. 20, p. 2277.

Arslanov, V.V., Kalinina, M.A., Ermakova, E.V., Raitman, O.A., Gorbunova, Yu.G., Aksyutin, O.E., Ishkov, A.G., Grachev, V.A., and Tsivadze, A.Yu., Russ. Chem. Rev. , 2019, vol. 88, no. 8, p. 775.

Mohanty, N. and Berry, V., Nano Lett. , 2008, vol. 8, no. 12, p. 4469.

Ono, T., Kanai, Y., Inoue, K., Watanabe, Y., Nakata, S., Kuwahara, T., Suzuki, Y., and Matsumoto, K., Nano Lett. , 2019, vol. 19, no. 6, p. 4004.

Science Daily. http://www.sciencedaily.com/releases/ 2019/06/190620100019.htm.

Huang, Y., Dong, X., Liu, Y., Li, L.-J., and Chen, P., J. Mater. Chem. , 2011, vol. 21, p. 12358.

Akbari, E., Nikoukar, A., Buntat, Z., Afroozeh, A., and Zeinalinezhad, A., IET Nanobiotechnol. , 2015, vol. 9, p. 273.

Roy, E., Patra, S., Tiwari, A., Madhuri, R., and Sharma, P.K., Biosens. Bioelectron. , 2017, vol. 89, p. 620.

Zhang, Z., Zhou, J., and Du, X., Micromachines , 2019, vol. 10, no. 4, p. 222.

Article   PubMed Central   Google Scholar  

Liu, M., Zhang, Q., Brennan, J.D., and Li, Y., MRC Commun. , 2018, vol. 8, no. 3, p. 687.

Sengupta, J., Adhikari, A., and Hussain, C.M., Carbon Trends , 2021, vol. 4, 100072. https://scholar.google.ru/ citations?view_op=view_citation&hl=ru&user=XoZ9dUsAAAAJ&citation_for_view=XoZ9dUsAAAAJ:_kc_bZDykSQC.

Moutaouakil, A.E.A., Poovathy, S., Belmoubarik, M., and Peng, W.K., Project: Molecular Medicine and Spin Physics, 2020. https://www.researchgate.net/publication/342378039_Review_Graphene-based_biosensor_ for_Viral_Detection.

Kosack, C.S., Page, A.-L., and Klatser, P.R., Bull. World Health Org. , 2017, vol. 95, p. 639.

Article   PubMed   PubMed Central   Google Scholar  

Chen, Y., Ren, R., Pu, H., Guo, X., Chang, J., Zhou, G., Mao, S., Kron, M., and Chen, J., Sci. Rep. , 2017, vol. 7, p. 10974.

Navakul, K., Warakulwit, C., Yenchitsomanus, P., Panya, A., Lieberzeit, P.A., and Sangma, C., Nanomed.: Nanotechnol., Biol. Med. , 2017, vol. 13, p. 549.

Campos, R., Borme, J., Guerreiro, J.R., Machado, G., Jr., Cerquerrac, M.A., Petrovykh, D.Y., and Alpium, P., ACS Sens. , 2019, vol. 4, p. 286.

Liu, F., Choi, K.S., Park, T.J., Lee, S.Y., and Seo, T.S., Bio Chip J. , 2011, vol. 5, p. 123.

Liu, F., Kim, Y.H., Cheon, D.S., and Seo, T.S., Sens. Actuators, B , 2013, vol. 186, p. 252.

Pant, M., Kharkwal, H., Singh, K.P., and Joshi, H.C., Biosens J. , 2017, vol. 6, no. 2, 1000148.

Afsahi, S., Lerner, M.B., Goldstein, J.M., Lee, J., Tang, X., Bagarozzi, D.A., Pan, D., Locascio, L., Walker, A., Barron, F., and Goldsmith, B.R., Biosens. Bioelectron. , 2018, vol. 100, p. 85.

Chand, R. and Neethirajan, S., Biosens. Bioelectron. , 2017, vol. 98, p. 47.

Sengupta, J. and Hussain, C.M., Carbon Trends , 2021, vol. 2, 100019.

Torrente-Rodriguez, R.M., Lukas, H., Tu, J., Min, J., Yang, Y., Xu, C., Rossiter, H.B., and Gao, W., Matter , 2020, vol. 3, no. 6, p. 1981.

Zhang, Z., Tang, Z., Farokhzad, N., Chen, T., and Tao, W., Matter , 2020, vol. 3, no. 6, p. 1818.

Kumar, V., Shorie, M., Ganguli, A.K., and Sabherwal, P., Biosens. Bioelectron. , 2015, vol. 72, p. 56.

Kozitsina, A.N., Svalova, T.S., Malysheva, N.N., Okhokhonin, A.V., Vidrevich, M.B., and Brainina, K.Z., Biosensors , 2018, vol. 8, no. 2, p. 35.

Article   PubMed Central   CAS   Google Scholar  

Upasham, S., Tanak, A., and Prasad, S., Adv. Health Care Technol. , 2018, vol. 4, p. 1.

Kazemi, S.H., Ghodsi, E., Abdollahi, S., and Nadri, S., Mater. Sci. Eng., C , 2016, vol. 69, p. 447.

Novodchuk, I., Bajcsy, M., and Yavuz, M., Carbon , 2021, vol. 72, no. 4, p. 471.

Xu, L., Wen, Y., Pandit, S., Mokkapati, V.R.S.S., Mijakovic, I., Li, Y., Ding, M., Ren, S., Li, W., and Liu, G., BMC Chem. , 2019, vol. 13, no. 1, p. 1.

Gao, N., Gao, T., Yang, X., Dai, X., Zhou, W., Zhang, A., and Lieber, C.M., Proc. Natl. Acad. Sci. U. S. A. , 2016, vol. 5, no. 113, p. 1.

Kovalskaya, E., Lesonger, P., Hogan, B.T., and Baldycheva, A., Nanoscale , 2019, vol. 11, no. 5, p. 2476.

Biosensor Based Advanced Cancer Diagnostics: From Lab to Clinics , Khan, R., Parihar, A., and Sanghi, S.K., Eds., New York: Academic, 2021.

Mannoor, M.S., Tao, H., Clayton, J.D., Sengupta, A., Kaplan, D.L., Naik, R.R., Verma, N., Omenetto, F.G., and McAlpine, M.C., Nat. Commun. , 2012, vol. 3, p. 763.

Article   PubMed   CAS   Google Scholar  

Makhmutov, B.B. and Kim, Yu.A., Mezhdunar. Zh. Prikl. Fundam.Issled. , 2021, no. 4, p. 17.

Zhu, J., Liu, S., Hu, Z., Zhang, X., Yi, N., Tang, K., Dexheimer, M.G., Lian, X., Wang, Q., Yang, J., Gray, J., and Cheng, H., Biosens. Bioelectron. , 2021, vol. 193, 113606.

Park, J., Kim, J., Kim, S.-Y., Cheong, W.H., Jang, J., Park, Y.-G., Na, K., Kim, Y.-T., Heo, J.H., Lee, C.Y., Lee, J.H., Bien, F., and Park, J.-U., Sci. Adv. , 2018, vol. 4, no. 1, eaap9841.

Nekrasov, N., Jaric, S., Kiree, D.V., Emelianov, A.V., Orlov, A., Gadjanski, I., Nikitin, P., Akinwande, D., and Bobrinetskiy, I., arXiv:2104.10551[cond-mat.mtrl-sci], 2021.

Bulbul, G., Hayat, A., and Andreescu, S., Sensors , 2015, vol. 15, p. 30736.

Hondred, J.A., Breger, J.C., Alves, N.J., Trammell, S.A., Walper, S.A., Medintz, I.L., and Claussen, J.C., ACS Appl. Mater. Interfaces , 2018, vol. 10, no. 13, p. 11125.

Kucherenko, I., Chen, B., Johnson, Z., Wilkins, A., Sanborn, D., Figueroa-Felix, N., Mendivelso-Perez, D., Smith, E.A., Gomes, C.L., and Claussen, J., Anal. Bioanal. Chem. , 2021, vol. 413, p. 17.

Vanegas, D., Patino, L., Mendez, C., Oliveira, D., Torres, A., Gomes, C., and McLamore, E., Biosensors , 2018, vol. 8, no. 2, p. 42.

Parate, K., Pola, C.C., Rangnekar, S.V., Mendivelso-Perez, D.L., Smith, E.A., Hersam, M.C., Gomes, C.L., and Claussen, C., 2D Mater. , 2020, vol. 7, no. 3, 034002.

Parate, K., Rangnekar, S.V., Jing, D., Mendivelso-Perez, D.L., Ding, S., Secor, E.B., Smith Hostetter, J.M., Hersam, MC., and Claussen, J.C., ACS Appl. Mater. Interfaces , 2020, vol. 12, no. 7, p. 8592.

Song, Y., Luo, Y., Zhu, Y., Li, C., and Du, H., D. lin y, Biosens. Bioelectron. , 2016, vol. 76, no. 15, p. 195.

Hajian, R., Balderston, S., Tran, T., Deboer, T., Etienne Sandhu, M., Wauford, N., Chung, J.-Y., Nokes, J., Athaiya, M., Paredes, J., Peytavi, R., Goldsmith, B., Murthy, N., Conboy, I.M., and Aran, K., Nat. Biomed. Eng. , 2019, vol. 3, no. 5, p. 427.

Balderston, S., Taulbee, J.J., Celaya, E., Fung, K.W., Jiao, A., Smith, K., Hajian, R., Gasiunas, G., Kutanovas, S., Kim, D., Parkinson, J., Dickerson, K., Ripoll, J.J., Peytavi, R., Lu, H.-W., Barron, F.E., Goldsmith, B., Collins, P.G., Conboy, I.M., Siksnys, V., and Aran, K., Nat. Biomed. Eng. , 2021, vol. 5, no. 7, p. 713.

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This study was carried out as part of state task no. 121031300092-6.

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Department of Petroleum Chemistry and Organic Catalysis, Moscow State University, 119991, Moscow, Russia

I. I. Kulakova & G. V. Lisichkin

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Translated by P. Kuchina

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Kulakova, I.I., Lisichkin, G.V. Biosensors Based on Graphene Nanomaterials. Moscow Univ. Chem. Bull. 77 , 307–321 (2022). https://doi.org/10.3103/S0027131422060049

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Received : 16 March 2022

Revised : 12 April 2022

Accepted : 14 May 2022

Published : 20 September 2022

Issue Date : December 2022

DOI : https://doi.org/10.3103/S0027131422060049

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