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Project titleIntegrated optical nanosensors based on two-dimensional nanomaterials

Research area 09 - ENGINEERING SCIENCES, 09-708 - Laser-information technologies

KeywordsWaveguide, plasmonic waveguide, microring resonator, biosensor, microfluidics, two-dimensional materials, graphene, graphene oxide, boron nitride, tungsten disulfide, molybdenum disulfide

Annotation
Last years, an increasing interest of the scientific community is devoted to the development of highly compact chemical and biological sensors. This is explained by their potential applications in such areas as pharmaceuticals, medical diagnostics, veterinary medicine, food quality control, and environmental monitoring. At the same time, one of the main mechanisms to implement this class of devices is the use of the principles of nanophotonics and plasmonics [1-2]. It is assumed that these devices can replace biosensors based on the surface plasmon resonance which exploit the similar physical principles. The project is supposed to use the new two-dimensional nanomaterials such as graphene, graphene oxide, boron nitride, molybdenum disulfide, and tungsten disulfide for the implementation of biosensing schemes based on the detection of biomolecules in the near field of micro- and nanoscale optical waveguides and resonators. The optical and chemical properties of these materials are well understood and it is worth noting their unique characteristics such as high transparency, which can be regulated [3], as well as a high reactivity with respect to a broad class of chemical and biological molecules [4- 6]. At the moment, it is shown that a thin film of graphene and graphene oxide can be used as a linking layers for detecting surfaces of biosensors based on surface plasmon resonance and optical fiber technology, which improves the sensitivity of detection [7-9]. In the first phase of the project, we will develop and create integrated optical systems based on dielectric and plasmonic waveguides and optical resonators for compact optical biosensors. As part of this project, we will develop the coating methods of the surfaces of the waveguides by thin and uniform films based on two-dimensional nanomaterials: graphene, graphene oxide, boron nitride and molybdenum disulfide and tungsten disulfide. The following techniques will be used: airbrushing, spin-coating, and the direct transfer of films grown on other substrates by chemical vapor deposition. The flow cell based on polymer microfluidic system will be created to deliver solutions with test molecules. Biologically active layers will be adsorbed on the surfaces of the linking layers based on two-dimensional nanomaterials to determine the devices characteristics such as sensitivity, specificity and the ability to multiple-times measurements, and a series of experiments will be conducted to study the biochemical reactions involving DNA and protein molecules.. [1] M.S. Luchansky, R.C. Bailey, High-Q optical sensors for chemical and biological analysis // Anal. Chem. 84, 793-821 (2012). [2] M.-C. Estevez, M. Alvarez, L.M. Lechuga, Integrated optical devices for lab-on-a-chip biosensing applications // Laser & Photonics Reviews 6, 463-487 (2012). [3] G. Eda, G. Fanchini, M. Chhowalla, Large-area ultrathin films of reduced graphene oxide as a transparent and flexible electronic material // Nature Nanotech. 3, 270-274 (2008). [4] E. Morales-Narváez and A. Merkoçi, Graphene oxide as an optical biosensing platform // Adv. Mater. 24, 3298-3308 (2012). [5] W. Yang, K.R. Ratinac, S.P. Ringer, et. al., Carbon nanomaterials in biosensors: should you use nanotubes or graphene? // Angew. Chem. Int. Ed., 49, 2114-2138 (2010). [6] Yu Chen, C. Tan, H. Zhang and L. Wang, Two-dimensional graphene analogues for biomedical applications, Chem. Soc. Rev., 44, 2681-2701 (2015). [7] E. Wijaya, N. Maalouli, R. Boukherroub, et al., Graphene-based high-performance surface plasmon resonance biosensors, Proc. of SPIE, Vol. 8424, 84240R-1, 2012. [8] J. Ah Kim, T. Hwang, S.R. Dugasanic, et al., Graphene based fiber optic surface plasmon resonance for bio-chemical sensor applications, Sensors and Actuators B, 187, 426– 433, 2013. [9] Y. V. Stebunov, O. A. Aftenieva, A. V. Arsenin, and V. S. Volkov, “Highly Sensitive and Selective Sensor Chips with Graphene-Oxide Linking Layer,” ACS Appl. Mater. Interfaces, vol. 7, no. 39, pp. 21727–21734, 2015.

Expected results
The analytical description and numerical simulation of integrated optical systems based on dielectric and plasmonic waveguides and optical resonators with the aim of creating a compact optical nanosensor. Optimization of parameters of integrated optical circuits for a highly sensitive biosensing. The technology of integrated optical systems development (systems of micro- and nanowaveguides and optical resonators) for the proposed nanosensors, which are characterized by the specified parameters depending on any particular application. Optical systems will be based on different types of waveguides, including dielectric plasmonic waveguides. An optical systems will later be used to create nanosensors. Protocols for producing biological layers on the surfaces of the optical biosensor systems, which will include the detection of particular substances, as well as their methods of deposition. Two-dimensional nanomaterials will be used as the linking layer between the optical system and biospecific layer. The protocols of bioactive layers deposition can be used to create the proposed optical biosensors, as well as for other devices or experiments requiring efficient and specific adsorption of biomolecules onto the surface. Experimental samples of compact integrated optical nanosensors, including optical and microfluidic systems based on different types of waveguides. Optimization of biosensing schemes. The typical dimensions of the optical system will be equal units of centimeters, instead of tens of centimeters, which, in particular, will reduce the volume of the flow cell and the minimum sample volume required for biosensing analysis by at least five times. The obtained results, which can be commercialized, will be used for patent applications. In the future, intellectual property can be used for commercialization of the developed sensors and building of a high-tech business, which will affect the economic, and social spheres. The results can be used in different industries such as medical diagnostics, pharmacy, veterinary science and others. The protocols for biomolecular reactions analysis involving various types of biomolecules. The significance of this result is primarily consists in characterization of the developed devices. The protocols can be also used to solve scientific problems related to the different areas of biology. The project results will be published in the leading scientific journals (eg, Nano Letters (impact factor of 12.712), Biosensors & Bioelectronics (7.780), Optics Express (3.307), Optics Letters (3.416), Nanotechnology (3.440), Biomedical Optics Express (3.337), Journal of Applied Physics (2.068), and others.) and presented at the leading scientific conferences (Biosensors, Graphene, IEEE Sensors, etc.). It is expected that at least two articles in a journals with impact factor of not less than 3 will be published in 2018. In 2019 and 2020, it is expected to publish at least 8 articles. The aim of the project is to obtain significant scientific results which can be published in the leading journals on the profile of the proposed research. Patent applications on the developed devices with commercial value are anticipated.

Annotation of the results obtained in 2020
The project is aimed at creating compact highly sensitive optical biosensors based on new nanomaterials (two-dimensional and quasi-two-dimensional materials) using technologies compatible with microelectronics technological processes. The efficiency of application of two-dimensional materials in the compact and highly sensitive bio-detection circuits developed within the project was evaluated, and the created devices with binding layers based on two-dimensional materials were tested. At the final stage of the project, new possibilities of increasing sensitivity of compact biological and chemical sensors by using new two-dimensional materials as binding layers were analyzed and functionalization of binding layers based on two-dimensional materials using 3-(ethyliminomethylamino)-N,N-dimethylpropane-1-amine for activation of carboxyl groups and crosslinking with biotin was perfected. As part of the stage the optical, electrical and structural properties of two-dimensional materials (graphene (chemical deposition from the gaseous phase, ultrasonic exfoliation) and graphene oxide with different functional groups) in relation to their use as binding layers in the optical (plasmonic) schemes of biodetection were determined. The evaluation of the optical sensitivity of biosensors with binding layers based on two-dimensional materials was performed. Numerical modeling of an integrated optical biosensor based on dielectric and plasmonic waveguides with binding layers based on two-dimensional materials has been performed. Efficient methods of applying binding layers based on two-dimensional materials have been developed: deposition from solutions, chemical and dry transfer of binding layers based on two-dimensional materials onto the surface of the integrated optical biosensor. The technology of low-temperature chemical deposition of graphene from the gas phase on the surface of the optical integrated system has been developed. Functional integrated optical biosensors with functionalized binding layers based on two-dimensional materials with bioselective layers containing streptavidin molecules, antibodies, and aptamers were created, and basic tests on different buffer solutions were performed. The sensitivity and selectivity of biodeactivation of compact optical biosensors during the following biochemical reactions: streptavidin with biotinylated ligands; antibodies with antigens, and aptamers with low molecular weight ligands were evaluated on the biosensor surface. Most of the obtained results were presented and discussed at the thematic workshops and international conferences (V International Conference on Metamaterials and Nanophotonics - METANANO 2020, September 14-18, 2020, ONLINE; International Conference Nanophotonics of 2D Materials (N2D 2020), ONLINE, September 13-14, 2020; International Conference Nanolight 2020, Benasque, Spain, March 08-14, 2020 and others). The main 2020 results have been published in highly ranked journals (Laser & Photonics Reviews (IF = 10.655, Q1), ACS Photonics (IF = 6.864, Q1), Nanomaterials (IF = 4.324, Q1), Sensors (IF = 3.275, Q1) and the Journal of Physics: Conference Series (with some results pending). More information on the results of the research can be found at: https://mipt.ru/en/science/labs/nano/

Publications

1. Gubin M.Y., Leksin A.Y., Shesterikov A.V., Prokhorov A.V., Volkov V.S. All-plasmonic switching effect in the graphene nanostructures containing quantum emitters Nanomaterials, 10, 1, 122 (year - 2020) https://doi.org/10.3390/nano10010122

2. Novikov S.M., Boroviks S., Evlyukhin A.B., Tatarkin D.E., Arsenin A.V., Volkov V.S., Bozhevolnyi S.I. Fractal Shaped Periodic Metal Nanostructures Atop Dielectric-Metal Substrates for SERS Applications ACS Photonics, 7, 7, 1708-1715 (year - 2020) https://doi.org/10.1021/acsphotonics.0c00257

3. Novikov S.M., Popok V.N., Fiutowski J., Arsenin A.V., Volkov V.S. Plasmonic properties of nanostructured graphene with silver nanoparticles Journal of Physics: Conference Series, 1461, 012119 (year - 2020) https://doi.org/10.1088/1742-6596/1461/1/012119

4. Terekhov P.D., Evlyukhin A.B., Redka D., Volkov V.S., Shalin A.S., Karabchevsky A. Magnetic Octupole Response of Dielectric Quadrumers Laser & Photonics Reviews, 14, 4, 1900331 (year - 2020) https://doi.org/10.1002/lpor.201900331

5. Voronin K.V., Stebunov Y.V., Voronov A.A., Arsenin A.V., Volkov V.S. Vertically coupled plasmonic racetrack ring resonator for biosensor applications Sensors, 20, 1, 203 (year - 2020) https://doi.org/10.3390/s20010203

6. Zenin V.A., Garcia-Ortiz C.E., Evlyukhin A.B., Yang Y., Malureanu R., Novikov S.M., Coello V., Chichkov B.N., Bozhevolnyi S.I., Lavrinenko A.V., Mortensen N.A. Engineering Nanoparticles with Pure High-Order Multipole Scattering ACS Photonics, 7, 4, 1067-1075 (year - 2020) https://doi.org/10.1021/acsphotonics.0c00078

Annotation of the results obtained in 2018
The project aims to develop highly sensitive compact optical nanosensors. The use of highly-integrated optical systems to convert biological signals into digital ones will allow creating a compact device on a chip that is compatible with conventional technological processes of microelectronics. This will eventually be used for the implementation of mass production of these devices. Within the framework of the declared work-plan (at the initial stage of the project) a review of modern literature was performed and the most effective (in terms of the sensor sensitivity) schemes of compact optical biosensors were identified. The main technological approaches for their practical implementation were also estimated. Various configurations of optical systems (including photonic and plasmonic waveguides) are considered. The analytical description and modeling of the long-range surface plasmon polariton (SPP)-based biosensor are performed. By use of the approximate theories (for describing electrodynamic systems) and varying the basic geometric parameters and material constants, the analytical estimates are obtained for the critical optical sensitivity of the biosensors under consideration. The proposed schemes open the way for the realization of biosensors with a sensitivity of about 0.5 μm/RIU, which allows measurement of changes in refractive index up to 10e-5. At the same time, the geometrical dimensions of the proposed integrated optical scheme (used in calculations and modeling) do not exceed 1 mm. A detailed theoretical and numerical study of optical biosensors based on plasmon/dielectric waveguides and resonators is performed. The main characteristics of such biosensors are analyzed in terms of sensitivity (and its dependence on system parameters i.e., geometrical dimensions and materials). The proposed integrated biosensor circuits (based on plasmon and dielectric waveguides and resonators) are carefully optimized, allowing to achieve record sensitivity values for this type of biosensing devices. A comparative analysis of photonic and plasmonic biosensors has been carried out. Despite the fact that SPP-based resonators are characterized by lower quality factor Q (especially in comparison with photonic schemes), it has been shown that a sensitivity of about 1.2 μm/RIU is achievable for the SPP waveguide resonator based biosensors. Such a device can be used to measure the change in the refractive index to 5*10e-6 whereas the typical sensitivity of biosensors based on photonic resonators does not exceed 0.5 μm/RIU. An experimental implementation of hybrid plasmonic waveguides based on metals with low optical losses is performed. Hybrid plasmonic waveguides, characterized by a high propagation length and a high localization of the SPP mode, are experimentally fabricated. It is demonstrated that the use of standard technological processes and materials compatible with CMOS (complementary metal-oxide-semiconductor structure) technology allows one to realize in practice highly efficient plasmonic waveguides. The output characteristics of these SPP waveguides allow one to implement them as working elements of highly-integrated optical biosensing schemes based on waveguides and nano-resonators. These results will smooth the path to the practical implementation of not only planar waveguide structures, but also more complex (multi-level) SPP-based devices that can be integrated on a chip with various components, such as optical signal input and output circuits and microfluidics systems. Most of the results presented here are reported and discussed at thematic scientific seminars and international conferences (for example, International Conference on Metamaterials and Nanophotonics (METANANO), 17 - 21 September 2018, Sochi, Russia; Developments in Protein Interaction Analysis (DIPIA), 17-20 June 2018, Boston, MA, USA and Russian Seminar on Fiber Lasers 2018, September 3-7, 2018, Novosibirsk, Akademgorodok). The results are published in journals indexed by the Web of Science and Scopus (Nanomaterials (3.504, Q1) and Journal of Physics: Conference Series). More information about the results of research can be found at: https://mipt.ru/en/science/labs/nano/

Publications

1. Volkov V.S., Yakubovsky D.I., Stebunov Y.V., Kirtaev R.V., Voronin K.V., Arsenin A.V. Hybrid graphene-nanometallic structures Journal of Physics: Conference Series, 1092, 012161 (year - 2018) https://doi.org/10.1088/1742-6596/1092/1/012161

2. Voronin K.V., Stebunov Y.V., Arsenin A.V., Volkov V.S. Integrated plasmonic biosensors based on microring resonators Journal of Physics: Conference Series, 1092, 012162 (year - 2018) https://doi.org/10.1088/1742-6596/1092/1/012162

3. Yakubovsky D.I., Stebunov Yu.V., Kirtaev R.V., Voronin K.V., Voronov A.A., Arsenin A.V., Volkov V.S. Graphene-supported thin metal films for nanophotonics and optoelectronics Nanomaterials, - (year - 2018)

Annotation of the results obtained in 2019
The project aims to create highly sensitive compact optical biosensors based on new materials and using technologies compatible with CMOS processes. It also considers the effectiveness of the use of two-dimensional materials in the highly sensitive biodetection schemes developed as part of the project. At the first stage of the project, the main approaches and technologies were identified for the practical implementation of highly efficient (highly sensitive) compact optical (plasmon) biosensors. Various configurations of optical systems have been proposed, including photonic and plasmon waveguides, which make it possible to achieve a sensitivity of about 0.5 μm / RIU. In this case, the characteristic geometric dimensions of the integrated optical circuit do not exceed 1 mm. It has been demonstrated that the use of standard technological processes and materials compatible with CMOS processes makes it possible in practice to create highly efficient plasmon waveguides, the output characteristics of which allow their use as elements of optical biodetection schemes based on waveguides and resonators. At the second stage of the project, prototypes of compact optical biosensors based on symmetric and asymmetric long-range plasmon waveguides have been proposed and realized. The proposed planar waveguide structure consists of a multilevel vertical waveguide - micro-ring resonator circuit integrated with the optical signal input and output circuit and microfluidics system. The proposed technology for the manufacture of waveguides and resonators that form the basis of the biosensor is compatible with CMOS processes and has the necessary potential for scaling and integration in microelectronic devices. The developed microresonator devices are combined with a microfluidics system and optical signal input and output circuit, which is processed by a spectral analyzer. The developed technologies for producing ultrathin metal films are used to create long-range plasmon waveguide structures with metal thicknesses less than 10 nm. In order to evaluate the sensitivity and effectiveness of the developed sensors, modeling and testing of devices based on salt solutions with different refractive indices were carried out. The stability of the created devices was estimated by pumping alkaline, acidic solutions of various concentrations (up to 20 mM), as well as solutions with a high concentration of sodium chloride and potassium chloride (1 mol/liter) through the flow chamber. The possibility of multiple uses of the developed sensor for the analysis of biomolecular interactions is demonstrated. Due to the small volume of the flow cell, the analysis time is limited only by the kinetics of the chemical interaction of the analyte with the biospecific surface. The proposed biosensors can be used to study the kinetics of biochemical interactions. Most of the results presented here are reported and discussed at thematic scientific workshops and international conferences (IV International Conference on Metamaterials and Nanophotonics - METANANO 2019, 15 - 19 July 2019, St. Petersburg, Russia; International Congress on Graphene, 2D Materials and Applications - 2D MATERIALS 2019, 30 September - 04 October 2019, Sochi, Russia; 2nd International Symposium on "Low Dimensional Materials for Optoelectronics", 12-15 December 2019, Shenzhen, China; DIPC - MIPT Workshop, 6 - 7 November, 2019 - Donostia - San Sebastian (Spain) etc.). The results are published in top-rated journals indexed by the Web of Science and Scopus: Physical Review B (IF = 3.736, Q1), Applied Surface Science (IF = 5.155, Q1) and Journal of Vacuum Science and Technology B (IF = 1.351, Q2)). More information about the results of the research can be found at https://mipt.ru/en/science/labs/nano/

Publications

1. Álvarez-Pérez G., Voronin K.V., Volkov V.S., Alonso-González P., Nikitin A.Y. Analytical approximations for the dispersion of electromagnetic modes in slabs of biaxial crystals Physical Review B, 23, 100, 235408 (year - 2019) https://doi.org/10.1103/PhysRevB.100.235408

2. Ermolaev G., Yakubovsky D., Stebunov Y., Arsenin A., Volkov V. Spectral ellipsometry of monolayer transition metal dichalcogenides: analysis of excitonic peaks in dispersion Journal of Vacuum Science & Technology B, - (year - 2020) https://doi.org/10.1116/1.5122683

3. Gubin M.Yu., Leksin A.Yu., Shesterikov A.V., Volkov V.S., Prokhorov A.V. Nonlinear plasmonic switching in graphene-based stub nanoresonator loaded with core-shell nanowire Applied Surface Science, 144814 (year - 2019) https://doi.org/10.1016/j.apsusc.2019.144814

4. Volkov V.S., Yakubovsky D.I., Stebunov Y.V., Kirtaev R.V., Ermolaev G.A., Mironov M.S., Novikov S.M., Voronin K.V., Arsenin A.V. Ultra-thin gold films: towards 2D metals for photonic and optoelectronic applications Journal of Physics: Conference Series, - (year - 2020)

5. Novikov S., Boroviks S., Tatarkin D., Arsenin A., Volkov V., Bozhevolnyi S. Fractal shaped periodic metal nanostructures for SERS applications XXVIII International Materials Research Congress 2019, - (year - 2019)