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CMOS Circuits for Biological Sensing and Processing pp 77–100Cite as

CMOS Multimodal Sensor Array for Biomedical Sensing

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Abstract

Multimodal sensor arrays with potentiometric, amperometric, impedimetric, and photometric sensors have been designed and fabricated by standard CMOS process and post-CMOS process to form gold electrodes and microfluidics. Three types of sensor arrays, 64 × 64 potentiometric and photometric sensor array, 64 × 64 ASSP (application-specific standard product) sensor array, and 512 × 512 high-density sensor array, are implemented in 7 × 7.5 mm2 chip and total power consumption 10 mW using 0.6 μm CMOS technology. In potentiometric and photometric sensor array, electric potential is sensed and outputted as an analog signal by a cascode source-drain follower, and photocurrent is converted to digital signal by current-mode ADC (analog-to-digital converter). In ASSP sensor array, potentiometric, amperometric, impedimetric, and photometric sensors output electric currents which are processed by current mixers and current-mode ADCs in array peripheral circuits. In high-density sensor array, submicron gold electrodes are formed by electroless plating. These sensors are applied to enzyme sensor with redox mediator and counting bacteria/viruses one by one. Stand-alone portable diagnostic inspection system is constructed with 18 × 10 × 5.5 cm3 and 850 g. Power is 5 V 220 mA supplied from USB adapter.

Keywords

  • Complementary Metal Oxide Semiconductor (CMOS)
  • High-density Sensor Arrays
  • Standard CMOS Process
  • Application-specific Standard Product (ASSP)
  • Photometric Sensor

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. K. Nakazato, M. Ohura, S. Uno, CMOS cascode source-drain follower for monolithically integrated biosensor Array. IEICE Trans. Electron. E91-C(9), 1505–1515 (2008). https://doi.org/10.1093/ietele/e91-c.9.1505

    CrossRef  Google Scholar 

  2. J. Hasegawa, S. Uno, K. Nakazato, Amperometric electrochemical sensor Array for on-Chip simultaneous imaging: circuit and microelectrode design considerations. Jpn. J. Appl. Phys. 50, 04DL03 (2011). https://doi.org/10.1143/JJAP.50.04DL03

    CrossRef  Google Scholar 

  3. M. Bennati, F. Thei, M. Rossi, M. Crescentini, G. D’Avino, A. Baschirotto, M. Tartagni, A sub-pA ΔΣ current amplifier for single-molecule nanosensors. ISSCC Dig. Tech. Papers, 348–349 (2009). https://doi.org/10.1109/ISSCC.2009.4977451

  4. M.H. Nazari, H. Mazhab-Jafari, L. Leng, A. Guenther, R. Genov, CMOS neurotransmitter microarray: 96-channel integrated potentiostat with on-die microsensors. IEEE Trans. Biomed. Circuits Syst. 7(3), 338–348 (2013). https://doi.org/10.1109/TBCAS.2012.2203597

    CrossRef  Google Scholar 

  5. J. Rothe, O. Frey, A. Stettler, Y. Chen, A. Hierlemann, Fully integrated CMOS microsystems for electrochemical measurements on 32 × 32 working electrodes at 90 frames per second. Anal. Chem. 86, 6425–6432 (2014). https://doi.org/10.1021/ac500862v

    CrossRef  Google Scholar 

  6. M. Yang, S.C. Liu, T. Delbruck, A dynamic vision sensor with 1% temporal contrast sensitivity and in-pixel asynchronous delta modulator for event encoding. IEEE J. Solid State Circuits 50(9), 2149–2160 (2015). https://doi.org/10.1109/JSSC.2015.2425886

    CrossRef  Google Scholar 

  7. M. Takihi, K. Niitsu, K. Nakazato, Charge-conserved analog-to-time converter for a large-scale CMOS biosensor array. IEEE Int. Symp. Circuits Syst. (ISCAS 2014), 33–36 (2014). https://doi.org/10.1109/ISCAS.2014.6865058

  8. K. Ikeda, A. Kobayashi, K. Nakazato, K. Niitsu, Design and analysis of scalability in current-mode analog-to-time converter for an energy-efficient and high-resolution CMOS biosensor array. IEICE Trans. Electron (2017) (in press)

    Google Scholar 

  9. P. Georgiou, C. Toumazou, An adaptive ISFET chemical imager chip. IEEE Int. Symp. Circuits Syst. (ISCAS 2008), 2078–2081 (2008). https://doi.org/10.1109/ISCAS.2008.4541858

  10. P. Bergveld, Development of an ion-sensitive solid-state device for neurophysiological measurements. IEEE Trans. Biomed. Eng. BME-17, 70–71 (1970)

    CrossRef  Google Scholar 

  11. K. Sawada, S. Mimura, K. Tomita, T. Nakanishi, H. Tanabe, M. Ishida, T. Ando, Novel CCD-based pH imaging sensor. IEEE Trans. Electron Devices 46(9), 1846–1849 (1999)

    CrossRef  Google Scholar 

  12. D.M. Garner, H. Bai, P. Georgiou, T.G. Constandinou, S. Reed, L.M. Shepherd, W. Wong Jr., K.T. Lim, C. Toumazou, A multichannel DNA SoC for rapid point-of-care gene detection. ISSCC Dig. Tech. Papers, 492–493 (2010). https://doi.org/10.1109/ISSCC.2010.5433834

  13. T. Sakata, Y. Miyahara, Direct transduction of allele-specific primer extension into electrical signal using genetic field effect transistor. Biosens. Bioelectron. 22, 1311–1316 (2007). https://doi.org/10.1016/j.bios.2006.05.031

    CrossRef  Google Scholar 

  14. J.M. Rothberg et al., An integrated semiconductor device enabling non-optical genome sequencing. Nature 475, 348–352 (2011). https://doi.org/10.1038/nature10242

    CrossRef  Google Scholar 

  15. M. Kamahori, K. Harada, H. Kambara, A new single nucleotide polymorphisms typing method and device by bioluminometric assay coupled with a photodiode array. Meas. Sci. Technol. 13, 1779–1785 (2002)

    CrossRef  Google Scholar 

  16. K. Gamo, K. Nakazato, K. Niitsu, A Current-integration-based CMOS amperometric sensor with 1024 × 1024 bacteria-sized microelectrode array for high-sensitivity bacteria counting. IEICE Trans. Electron (2017) (in press)

    Google Scholar 

  17. K. Niitsu, K. Ikeda, K. Muto, K. Nakazato, Design, experimental verification, and analysis of a 1.8-V-input-range voltage-to-current converter using source degeneration for low-noise multimodal CMOS biosensor array. Jpn. J. Appl. Phys 56, 01AH06 (2017). https://doi.org/10.7567/JJAP.56.01AH06

    CrossRef  Google Scholar 

  18. T. Kuno, K. Niitsu, K. Nakazato, Amperometric electrochemical sensor array for on-chip simultaneous imaging. Jpn. J. Appl. Phys 53, 04EL01 (2014). https://doi.org/10.7567/JJAP.53.04EL01

    CrossRef  Google Scholar 

  19. A. Manickam, A. Chevalier, M. McDermott, A.D. Ellington, A. Hassibi, A CMOS electrochemical impedance spectroscopy (EIS) biosensor array. IEEE Trans. Biomed. Circuits Syst. 4(6), 379–390 (2010). https://doi.org/10.1109/TBCAS.2010.2081669

    CrossRef  Google Scholar 

  20. S. Hwang, C.N. LaFratta, V. Agarwal, X.J. Yu, D.R. Walt, S. Sonkusale, CMOS microelectrode array for electrochemical lab-on-a-chip applications. IEEE Sensors J. 9(6), 609–615 (2009). https://doi.org/10.1109/JSEN.2009.2020193

    CrossRef  Google Scholar 

  21. M. Datta, S.A. Merritt, M. Dagenais, Electroless remetallization of aluminum bond pads on CMOS driver chip for flip-chip attachment to vertical cavity surface emitting lasers (VCEL’s). IEEE Trans. Compon. Pack. Technol. 22(2), 299–306 (1999)

    CrossRef  Google Scholar 

  22. Kanigen Technical Report No. 9. http://www.kanigen.co.jp/file/report9.pdf (in Japanese)

  23. M. Kamahori, Y. Ishige, M. Shimoda, Enzyme immunoassay using a reusable extended-gate field-effect-transistor sensor with a ferrocenylalkanethiol-modified gold electrode. Anal. Sci. 24, 1073–1079 (2008)

    CrossRef  Google Scholar 

  24. Y. Ishige, M. Shimoda, M. Kamahori, Extended-gate FET-based enzyme sensor with ferrocenyl-alkanethiol modified gold sensing electrode. Biosens. Bioelectron. 24, 1096–1102 (2009). https://doi.org/10.1016/j.bios.2008.06.012

    CrossRef  Google Scholar 

  25. H. Anan, M. Kamahori, Y. Ishige, K. Nakazato, Redox-potential sensor array based on extended-gate field-effect transistors with ω-ferrocenylalkanethiol-modified gold electrodes. Sensors Actuators B Chem. 187, 254–261 (2013). https://doi.org/10.1016/j.snb.2012.11.016

    CrossRef  Google Scholar 

  26. W. Guan, X. Duan, M.A. Reed, Highly specific and sensitive non-enzymatic determination of uric acid in serum and urine by extended gate field effect transistor sensors. Biosens. Bioelectron. 51, 225–231 (2014). https://doi.org/10.1016/j.bios.2013.07.061

    CrossRef  Google Scholar 

  27. M.J. Milgrew, D.R.S. Cumming, Matching the transconductance characteristics of CMOS ISFET arrays by removing trapped charge. IEEE Trans. Electron Devices 55(4), 1074–1079 (2008). https://doi.org/10.1109/TED.2008.916680

  28. H. Komori, K. Niitsu, J. Tanaka, Y. Ishige, M. Kamahori, K. Nakazato, An extended-gate CMOS sensor Array with enzyme-immobilized microbeads for redox-potential glucose detection. Proc. IEEE Biomed. Circuits Syst. Conf. (BioCAS 2014), 464–467 (2014). https://doi.org/10.1109/BioCAS.2014.6981763

  29. H. Ishihara, K. Niitsu, K. Nakazato, Analysis and experimental verification of DNA single-base polymerization detection using CMOS FET-based redox potential sensor array. Jpn. J. Appl. Phys. 54, 04DL05 (2015). https://doi.org/10.7567/JJAP.54.04DL05

    CrossRef  Google Scholar 

  30. H. Tanaka, P. Fiorini, S. Peeters, B. Majeed, T. Sterken, M. Op de Beeck, M. Hayashi, H. Yaku, I. Yamashita, Sub-micro-liter electrochemical single-nucleotide-polymorphism detector for lab-on-a-chip system. Jpn. J. Appl. Phys. 51, 04DL02 (2012). https://doi.org/10.1143/JJAP.51.04DL02

    CrossRef  Google Scholar 

  31. Y. Ishige, Y. Goto, I. Yanagi, T. Ishida, N. Itabashi, M. Kamahori, Feasibility study on direct counting of viruses and bacteria by using microelectrode array. Electroanalysis 24(1), 131–139 (2012). https://doi.org/10.1002/elan.201100482

    CrossRef  Google Scholar 

  32. K. Niitsu, S. Ota, K. Gamo, H. Kondo, M. Hori, K. Nakazato, Development of microelectrode arrays using electroless plating for CMOS-based direct counting of bacterial and HeLa cells. IEEE Trans. Biomed. Circuits Syst. 9(5), 607–619 (2015). https://doi.org/10.1109/TBCAS.2015.2479656

    CrossRef  Google Scholar 

  33. T. Satoh, J. Kato, N. Takiguchi, H. Ohtake, A. Kuroda, ATP amplification for ultrasensitive bioluminescence assay: detection of a single bacterial cell. Biosci. Biotechnol. Biochem. 68(6), 1216–1220 (2004). https://doi.org/10.1271/bbb.68.1216

    CrossRef  Google Scholar 

  34. M.A.G. Zevenbergen, P.S. Singh, E.D. Goluch, B.L. Wolfrum, S.G. Lemay, Stochastic sensing of single molecules in a nanofluidic electrochemical device. Nano Lett. 11, 2881–2886 (2011). https://doi.org/10.1021/nl2013423

    CrossRef  Google Scholar 

  35. C. Toumazou et al., Simultaneous DNA amplification and detection using a pH-sensing semiconductor system. Nat. Methods 10(7), 641–646 (2013). https://doi.org/10.1038/NMETH.2520

    CrossRef  Google Scholar 

  36. H. Norian, R.M. Field, I. Kymissis, K.L. Shepard, An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics. Lab Chip 14, 4076–4084 (2014). https://doi.org/10.1039/c4lc00443d

    CrossRef  Google Scholar 

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Acknowledgments

This research is financially supported by a Grant-in-Aid for Scientific Research (No. 25220906, 20226009) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by Adaptable and Seamless Technology Transfer Program through Target-Driven R&D (No. AS272S001b) from the Japan Science and Technology Agency, Japan.

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Authors and Affiliations

  1. Department of Electronic Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan

    Kazuo Nakazato

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  1. Kazuo Nakazato
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Correspondence to Kazuo Nakazato .

Editor information

Editors and Affiliations

  1. School of Engineering, University of Glasgow, Glasgow, United Kingdom

    Srinjoy Mitra

  2. School of Engineering, University of Glasgow, Glasgow, United Kingdom

    David R. S. Cumming

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Nakazato, K. (2018). CMOS Multimodal Sensor Array for Biomedical Sensing. In: Mitra, S., Cumming, D. (eds) CMOS Circuits for Biological Sensing and Processing. Springer, Cham. https://doi.org/10.1007/978-3-319-67723-1_4

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  • DOI: https://doi.org/10.1007/978-3-319-67723-1_4

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