|Article title||METHODS OF PRELIMINARY BIOLOGICAL SENSOR SIGNAL PROCESSING IN ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY SYSTEMS|
|Authors||L. K. Samoilov, E. A. Zhebrun|
|Section||SECTION II. THE DESIGN OF THE CIRCUITRY|
|Month, Year||02, 2018 @en|
|Abstract||The possibilities of creating specialized microelectronic systems of electrochemical impedance spectroscopy (EIS) as part of software and hardware systems based on biological sensors (BS) are considered. To increase the accuracy of the final value in such systems, a large (about 500) number of BS parallel channels are ensured. Users desire of obtaining a reliable result leading to the need to simultaneously conduct up to 500 analyzes of one substance. The question of the possibilities and limitations of EIS systems in the context of modern technological advances has been explored. The paper shows that effective multi-channel EIS systems can be built in the form of systems on a chip within the framework of standard CMOS process technology. In EIS systems with a comparatively low frequency of BS operating signals (up to 20 kHz) integrating ADCs are widely used. Its input circuits are optimally combined with the BS outputs and allow the operation of digital multiplication to be performed on a digital signal. In integrating ADCs, according to the limiting factors considered in the work, it is possible to optimize the characteristics depending on the final requirements. Within the framework of the modern 90 nm process technology, the main blocks of the integrating ADCs – integrator and the comparator are designed. The circuit solutions allow us to expand the freedom of parameters choice in the space of the variable clock frequency, conversion speed and conversion accuracy. So, for example, it is possible to create an analog signals input device based on an integrating converter with an accuracy of 10 bits at 1 MHz frequency conversion at a clock frequency of 5 GHz. At the same time, for one channel of BS analog interface, the power is reduced to tens of microwatts and the area on the crystal is up to 0.05 mm2, that allows to reach high integration in multi-channel EIS systems based on integrating ADSs with a large number of BSs. The used technological process is provided by one of the leaders of the homeland microelectronics market PJSC "Mikron" (Moscow). This allows us to use the demonstrated circuit engineering developments in import substitution programs.|
|Keywords||Data processing module; biological sensor; impedance spectroscopy; analog-to-digital converter; integrator; comparator.|
|References||1. Normanov D.D., Atkin E.V., Osipov D.L. Effektivnyy po ploshchadi blok malomoshchnogo ATsP. Nauchnaya sessiya NIYaU MIFI-20 14 [Effective area unit low-power ADC. Scientific session of niyau MEPhI-20 14], Annotatsii dokladov [Annotations of reports]: in 3 vol. O.N. Golotyuk ((responsible editor), 2014, pp. 68.
2. Osipov D., Malankin E., Shumikhin V. Linearity analysis of single-ended SAR ADC with split capacitive DAC, IOP Conference Series: Materials Science and Engineering, IOP Publishing, 2016, Vol. 151, No. 1, pp. 012014.
3. Evgenij Barsoukov, J. Ross Macdonald. Impedance Spectroscopy: Theory, Experiment, and Applications. 2nd Edition. Wiley Interscience Publications, April 2005, 616 p. ISBN: 978-0-471-64749-2.
4. Evtugyn G. Biosensors: Essentials. Springer-Verlag, New York, 2014, 265 p. ISBN: 978-3-642-40240-1. DOI: 10.1007/978-3-642-40241-8.
5. Biosensory: osnovy i prilozheniya [Biosensors: fundamentals and applications]: translation from English, ed. by E. Ternera, I. Karube, Dzh. Uilsona. Moscow: Mir, 1992. ISBN 5-03-001186-2.
6. Santos A. et al. Fundamentals and Applications of Impedimetric and Redox Capacitive Biosensors, J. of Anal. & Bioanal. Tech., 2014, S7:016.
7. Ghindilis A.L. et al. Sensor array: Impedimetric label-free sensing of DNA hybridization in real time for rapid, PCR-based detection of microorganisms, Electroanalysis, 2009, Vol. 21, issue 13, pp. 1459-1468.
8. Yang C., Jadhav S.R., Worden R.M., and Mason A.J. Compact low-power impedance-to-digital converter for sensor array Microsystems, IEEE J. Solid-State Circuits, 2009, Vol. 44, No. 10, pp. 2844-2855.
9. Liu X., Li L., Mason A.J. High Throughput Impedance Spectroscopy Biosensor Array Chip, Phil. Trans. R. Soc. A, 2014, Vol. 372. DOI: 10.1098/rsta.2013.0107.
10. Daniels, J.S. An Integrated Impedance Biosensor Array, PhD thesis, Stanford University. 2010, 240 p. Available at: https://stacks.stanford.edu/file/druid:dn968xz4219/thesis_toplevel-augmented.pdf (Accessed 27 June 2016).
11. Samoylov L.K., Zhebrun E.A., Titov A.E. Mikroskhemotekhnika analogovykh interfeysov sistem elektrokhimicheskoy impedansnoy spektroskopii [The analog circuitry of system interfaces of electrochemical impedance spectroscopy], Problemy razrabotki perspektivnykh mikro- i nanoelektronnykh sistem – 2016: Sb. trudov [Problems of Perspective Micro- and Nanoelectronic Systems Development - 2016. Proceedings], under the General ed. of acad. RAS A.L. Stempkovskogo. Moscow: IPPM RAN, 2016. Part III, pp. 79-86.
12. Tarasov S.E., Emets V.V., Gutorov M.A., Reshetilov A.N. Impedansnaya spektroskopiya v sovremennykh elektrokhimicheskikh DNK-biosensorakh [Impedance spectroscopy in modern electrochemical DNA biosensors], Vestnik biotekhnologii [Bulletin of Biotechnology], 2014, Vol. 10, No. 3, pp. 43-50.
13. Grenier K., Dubuc D., Chen T., et al. Recent advances in microwave-based dielectric spectroscopy at the cellular level for cancer investigations, IEEE Trans. Microwave Theory Techniques, May 2013, Vol. 6 1, No. 5, pp. 2023-2030.
14. Jafari H., Soleymani L., and Genov R. 16-Channel CMOS Impedance Spectroscopy DNA Analyzer With Dual-Slope Multiplying ADCs, IEEE Transactions on Biomedical Circuits and Systems, Oct. 2012, Vol. 6, No. 5, pp. 468-478.
15. Wu W., Staszewski R.B., Long J.R. Millimeter-Wave Digitally Intensive Frequency Generation in CMOS. Academic Press, 2015, 200 p.
16. Sergey Krutchinsky, Vasiliy Bespyatov, Alexander Korolev, Eugeniy Zhebrun, Anton Zolotarev. Circuitry design feature of stages with high-gain coefficient on field-effect transistors, Advanced Materials Research. Vol. 320. Trans Tech Publications, Swizerland, 2011,
pp. 589-596. DOI: 10.4028/www.scientific.net/AMR.320.589.
17. Holberg D., Allen P. CMOS Analog Circuit Design. 3rd Edition. Oxford University Press, 2011, 783 p.
18. Tittse U., Shenk K. Poluprovodnikovaya skhemotekhnika [Semiconductor circuitry]. Moscow: DMK Press, 2008. Vol. 1: 832 p. Vol. 2: 942 p.
19. Bonetti A. Low Power and Compact Successive Approximation ADC for Bioelectronic Chips. Master thesis, Politecnico di Milano, 2012, 70 p. Available at:https://www.politesi.polimi.it/ bitstream/10589/44562/1/2012_04_Bonetti.PDF (Accessed: 27 June 16).
20. Levine P., Gong P., Levicky R., Shepard K. Active CMOS biochip for electrochemical DNA assays. In E. Lagally, & K. Iniewski (Eds.). Microfluidics and nanotechnology for biosensing to the single molecule limit [Chapter 2]. New York: Taylor and Francis, 2014, pp. 19-80.