SOI-FET Snsors for Virus Detection

Abstract

The recent outbreak of coronavirus disease caused by the respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the urgent need to develop fast and highly sensitive analytical tools and diagnostic devices to detect and study of the fundamental properties viruses and their nucleic acid and protein components [1]. Silicon-on-insulator field-effect transistors (SOI-FETs) based sensors provide the versatile platform for direct detection of biological species as excellent electrical signal converters. These devices have demonstrated applications for label-free, ultra-sensitive, and selective real-time detection of a wide range of biological species, including nucleic acids, proteins and viruses in either single-element or multiplexed formats [2-5]. Dielectrophoresis (DEP) and electro-hydrodynamic techniques are well known as the methods of selection and delivery of analytes to overcome limitations of diffusive transport to sensor elements without additional processing or labeling steps [6]. The aim of this study was to investigate the features of the behavior of the viruses when they are indicated by SOI-FET sensors with DEF-control. For this, SOI-FET sensors with lateral DEP-electrodes and multichannel sensors, for comparison, were used. Top-down technology with using optical lithography was applied for sensor fabrication. Devices manufacturing details are described elsewhere [3]. As an analyte, we used nuclear polyhedrosis viruses (NPVs), coronavirus virus-like particles (CVP) and suspension of specific antibodies to the virus created in the Federal research center of Virology and biotechnology "Vector" of Rospotrebnadzor. The results showed that the sensors used in the study provide the subatomolar level of virus detection. DEP-concentration of viruses increase the response of the sensors by factors of 2 to 9 (compared to the response of sensors without DEP control) and allows the false positives can be eliminated. NPVs lose their mobility with prolonged exposure to an alternating field in the sub-MHz range. The DEP-concentration of CVP leads to the formation of crystal-like structures (Fig.1). This study was supported by grant no. 18-29-02091 of the Russian Foundation for Basic Research. Sample preparation of biological materials was done within the framework of the State Task of Rospotrebnadzor. Referencies: WHO Director-General's opening remarks at the media briefing on COVID-19 – 23 April 2021 23 апреля 2021 г.https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-23-april-2021. Patolsky F., Zheng G., Hayden O., Lakadamyali M., Zhuang X., Lieber C. M. Electrical detection of single viruses // Proc. Natl. Acad. Sci. 2004, v. 101. p. 14017-14022. O. V. Naumova, V. M. Generalov, E. G. Zaitseva, A. V. Latyshev, A. L. Aseev, S. A. Pyankov, I. V. Kolosov, G. G. Ananko, A. P. Agafonov, E. V. Gavrilova, R. A. Maksyutov, and A. S. Safatov. Biosensors Based on Soi Nanowire Transistors for Biomedicine and Virusology. Russian Microelectronics, 2021, v. 50, N3, p. 137–145. Ivanov Y.D., Pleshakova T.O., Kozlov A.F., Malsagova K.A., Krohin N.V., Shumyantseva V.V., Shumov I.D., Popov V.P., Naumova O.V., Fomin B.I., Nasimov D.A., Aseev A.L., Archakov A.I. SOI nanowire for the high-sensitive detection of HBsAg and a-fetoprotein. Lab Chip. 2012, v. 12, p. 5104-5111. Dmitrienko E., Naumova O., Fomin B., Kupryushkin M., Volkova A., Amirkhanov N., Semenov D., Pyshnaya I., Pyshnyi D. Surface modification of SOI FET sensors for label-free and specific detection of short RNA analyte. Nanomedicine 2016, v. 11, N 16, p. 2073-2082. Lee S., Roh S.M., Lee E., Park Y., Lee B.C., Kwon Y., Kim H.J., Kim J. Applications of converged various forces for detection of biomolecules and novelty of dielectrophoretic force in the applications(Review). Sensors, 2020, v.20, p.3242. Fig.1 – Optical image of sensor with lateral DEP electrodes after CVP detection. In the left - CVP organized in crystal-like structures under DEP-concentration, in the right (green dots on dark field) - viruses with luminescent labels. S - source, D - drain. G1, G2 - lateral DEP electrodes. Figure 1