Biomedical Integrated Instrumentation

  • Jordi Colomer-FarraronsEmail author
  • Pere Lluís Miribel-Català


This Chapter is focused on the development of an integrated instrumentation to work with three electrodes amperometric Biosensor. First of all, it is introduced the conception of three electrodes configuration and how it works. Moreover, some typical electrochemical techniques like Voltammetry, EIS and amperometry, are introduced to the reader. The instrumentation electronics is based on a potentiostat architecture, which is explained in detail and experimentally validated. The obtained results with the full-custom approach are compared with the ones obtained using a commercial potentiostat. In that way, the correct operation of the designed circuits is fully validated. Furthermore, this chapter explains the conception of a Lock-In amplifier circuit used to detect the real and imaginary components of the complex impedance measured from the Biosensor. This circuit is theoretically explained and some simulated results are shown. Finally, the conception of Biotelemetry or how to transmit information from the subcutaneous device to the external reader is introduced. Then, the implemented protocol in this work is detailed. In summary, this chapter presents the developed BioChip IC that is able to drive the sensor, process the measured data and transmit the data to the external side through an inductive link.


Analog integrated circuits Microelectronic implants Bioimpedance Amperometric sensors Electrochemical impedance spectroscopy Phase detection Active filters Biomedical telemetry 


  1. 1.
    P.H. King, R.C. Fries, Design of Biomedical Devices and Systems, 2nd edn. (CRC Press, Florida, USA, 2009), ISBN: 978-1-4200-6179-6Google Scholar
  2. 2.
    J.G. Webster, Medical Instrumentation Application and Design, 3rd edn. (Wiley, New York, USA, 1998), ISBN: 0-471-15368-0Google Scholar
  3. 3.
    R.P. Areny, Sensores y Acondicionadores de Señal. 3ª Edición, (Marcombo, Barcelona, Spain, 1998), ISBN 84-267-1171-5Google Scholar
  4. 4.
    C. Wen-Yaw, P. Arnold, W. Ying-Hsiang, T. Tseng, A 600 μW Readout Circuit with Potentiostat for Amperometric Chemical Sensors and Glucose Meter Applications, IEEE Conference on Electron Devices and Solid-State Circuits, EDSSC 2007, 20–22 (2007)Google Scholar
  5. 5.
    F.Z. Padmadinata, J.J. Veerhoek, G.J.A. van Dijk, J.H. Huijsing, Microelectronic skin electrode. Sens. Actuators B Chem. 1(1–6), 491–494 (1990)CrossRefGoogle Scholar
  6. 6.
    L. Ramasamy, ASIC System Development of MEMS Bio-chip Analyzer with Calibration, Signal Capture and Display Circuit, (University of Cincinnati, 2005) Available at:
  7. 7.
    S.K. Kailasa, S.H. Kang, Microchip-based capillary electrophoresis for DNA analysis in modern biotechnology: A review, Taylor. Francis. Sep. Purif. Rev. 38, 242–288 (2009)CrossRefGoogle Scholar
  8. 8.
    V.M. Ivama, S.H.P. Serrano, Rhodium – Prussian Blue modified carbon paste electrode (Rh – PBMCPE) for amperometric detection of0020hydrogen peroxide. J. Brazilin. Chem. Soc. 14(4), (Aug 2003). ISSN: 0103–5053Google Scholar
  9. 9.
    X. Ji, C.E. Banks, A. Crossley, R.G. Compton, Oxygenated edge plane sites slow the electron transfer of the ferro-/ferricyanide redox couple at graphite electrodes. Chem. Phys. Chem. 7, 1337–1344 (2006)CrossRefGoogle Scholar
  10. 10.
    F. Heer et al., CMOS microelectrode array for the monitoring of electrogenic cells. Biosens. Bioelecron 20, 358–366 (2004)CrossRefGoogle Scholar
  11. 11.
    S.M. Radke, E.C. Alocilja, A microfabricated biosensor for detecting foodborne bioterrorism agents. IEEE Sens. J. 5(4), 744–750 (2005)CrossRefGoogle Scholar
  12. 12.
    D.L. McCulloch, G.B. Boemel, M.S. Borchert, Comparison of contact lens, foil, fiber, and skin electrodes for patterns electroretinograms. Doc. Ophtalmol 94, 4 (1997)CrossRefGoogle Scholar
  13. 13.
    O. Chailapakul, J. Promnil, M. Somasundrum, M. Tanticharoen, Immobilized K3Fe(CN)6 and glucose oxidase in polypyrrole on a gold micro-electrode and the it application as a glucose sensor. J. Sci. Res. Chula. Unit. 25, 1 (2006)Google Scholar
  14. 14.
    S.V. Dzyadevych et al., Electrochem. Enzyme. Biosens. (2006). ISBN: 966-02-4200-XGoogle Scholar
  15. 15.
    F. Mizutani, E. Yamanaka, Y. Tanabe, K. Tsuda, An enzyme electrode for L-lactate with chemically amplified electrode. Anal. Chem. Acta. 117, 153–166 (1985)CrossRefGoogle Scholar
  16. 16.
    P.N. Bartlett, R.G. Whitaker, Strategies for the development of amperometric enzyme electrodes. Biosensors 3, 359–379 (1987)CrossRefGoogle Scholar
  17. 17.
    L.E. Morrison, Time resolved detection of energy transfer: Theory and application to immunoassays. Anal. Biochem. 174, 101–120 (1988)CrossRefGoogle Scholar
  18. 18.
    H.A. Lee, M.R.A. Morgan, Food immunoassay: Application of polyclonal, monoclonal and remobinant antibodies. Trends Food Sci. Technol. 3, 129–134 (1993)Google Scholar
  19. 19.
    C. Dumschat et al., Pesticide-sensitive ISFET based on enzyme inhibition. Anal. Chim. Acta. 252, 7–9 (1991)CrossRefGoogle Scholar
  20. 20.
    P. Bergveld, Thirty years of ISFETOLOGY. What happened in the past 30 years and what may happen in the next 30 years. Sens. Actuators B 88, 1–20 (2003)CrossRefGoogle Scholar
  21. 21.
    E. Lorenzo et al., Analytical strategies for amperometric biosensors based on chemically modified electrodes. Biosens. Bioelectron 13, 319–332 (1998)CrossRefGoogle Scholar
  22. 22.
    D.B. Kell, C.L. Dave, Conductimetric and Impediometric Devices in Biosensors. A Practical Approach, (IRL Press, Oxford, 1990)Google Scholar
  23. 23.
    D.C. Cullen et al., Multi-analyte miniature conductance biosensor. Anal. Chim. Acta. 231, 33–40 (1990)CrossRefGoogle Scholar
  24. 24.
    J. Colomer-Farrarons, P. Miribel-Català, A. Saiz-Vela, J. Samitier, in Proceeding of the 16th IEEE International Conference on Very Large Scale Integration VLSI – SOC, A 50 μW low-voltage CMOS Biopotentiostat for low frequency Capacitive Biosensor, 2008Google Scholar
  25. 25.
    A. Gore, S. Chakrabartty, S. Pal, E. Alocilja, A multi-channel femtoampere-sensitivity conductometric array for biosensing applications. IEEE Transactions on Circuits and Systems I: Regular Papers, 53(11), 2357–2363 (2006)Google Scholar
  26. 26.
    L.Y. Woo, L.P. Martin, R. Glass, R.J. Gorte. Impedance characterization of a model Au/Yttria-Stabilized Zirconia/Au electrochemical cell in variying oxygen and NOx concentrations. J. Electrochem. Soc. 154(4), 129–135 (2007)CrossRefGoogle Scholar
  27. 27.
    J.M. Flores, R.D. Romero, J.G. Llongueras, Espectroscopía de impedancia electroquímica en corrosión, Instituto Mexicano del Petróleo, UNAM, Available at: Scholar
  28. 28.
    A. Lasia. Electrochemical Impedance Spectroscopy and Its Applications. Modern Aspects of Electrochemistry, vol. 32. (Kluwer Academic/Plenum Publisher, New York, USA, 1999),  Chapter 2, p. 143
  29. 29.
    R.J. Reay, S.P. Kounaves, G.T.A. Kovacs, An integrated CMOS potentiostat for miniaturized electroanalytical instrumentation, IEEE International 41st ISSCC Solid-State Circuits Conference, pp. 162–163 (1994)Google Scholar
  30. 30.
    C. Berggren, B. Bjarnason, G. Johansson, Capacitive biosensors, Electroanalysis 13(3), 173–180 (2001)CrossRefGoogle Scholar
  31. 31.
    S. Grimnes, O.G. Martinsen, Bioimpedance and Bioelectricity Basics, 2nd edn. (Academic Press, Elseiver, London, UK, 2008). ISBN: 0-12-303260-1Google Scholar
  32. 32.
  33. 33.
    M.N. Latto, The Electrochemistery of Diamon, (University of Bristol, Bristol, UK, Sep 2001),
  34. 34.
    C.G. Zoski, Handbook of Electrochemistery, (Elsevier, The Netherlands, 2007), ISBN: 0-444-51958-0Google Scholar
  35. 35.
  36. 36.
    GAMRY Instruments App. Note, Electrochemical Impedance Spectroscopy,
  37. 37.
    J. Braz, Rhodium–prussian blue modified carbon paste electrode (Rh-PBMCPE) for amperometric detection of hydrogen peroxide. J. Brazilian Chem. Soc. 14, 4 (2003). ISSN 0103–5053Google Scholar
  38. 38.
    A.J. Bard, L.R. Faulkner, Electrochemical Methods. Fundamentals and Applications, 2nd edn. (Wiley, New York, NY, 2001). ISBN 0-471-04372-9Google Scholar
  39. 39.
    S.M. Martin, F.H. Gebara, T.D. Strong, R.B. Brown, A low.voltage, chemical sensor interface for system-on-chip: The fully-differential potentiostat, Proceeding of the 2004 International Symposium on Circuits and Systeems ISCAS’02, vol. 4, pp. IV–892–895, (2004)Google Scholar
  40. 40.
    E. Lauwers, J. Suls, W. Gumbrecht, D. Maes, G. Gielen, W. Sansen, A CMOS multiparameter biochemical microsensor with temperature control and signal interfacing. IEEE J. Solid-State Circuits 36, 12 (2001)CrossRefGoogle Scholar
  41. 41.
    S.M.R. Hasan, Stability analysis and novel compensation of a CMOS current-feedback potentiostat circuit for electrochemical sensors. Sens. J. IEEE. 7(5), 814–824 (May 2007)CrossRefGoogle Scholar
  42. 42.
    J. Colomer-Farrarons, P. Miribel-Català, A. Saiz-Vela, I. Rodriguez, J. Samitier, in Proceedings of the IEEE MWSCAS Conference, A low power CMOS Biopotentiostat in a Low-Voltage 0.13 μm Digital technology, Cancún, Mexico, 2009Google Scholar
  43. 43.
    J. Colomer-Farrarons, P. Miribel-Català, I. Rodriguez, J. Samitier, in Proceedings of the XX IECON Conference, CMOS Front-end Architecture for In-Vivo Biomedical Implantable devices, Porto, Portugal, 2009Google Scholar
  44. 44.
    J. Colomer-Farrarons, P. Miribel-Català, A. Saiz-Vela, M. Puig, J. Samitier, A. Errachid, A 50 μW low-voltage CMOS Biopotentiostat for low-frequenciy Capacitive Biosensor, Proceedings of the XX IEEE VLSI Conference, Rhodes, Greece, 2008Google Scholar
  45. 45.
    S.M. Martin, F.H. Gebara, B.J. Larivee, R.B. Brown, A CMOS-integrated microinstrument for trace detection of heavy metals. IEEE J. Solid-State Circuits 40(12), 2777–2786 (2005)CrossRefGoogle Scholar
  46. 46.
    T.D. Strong, S.M. Martin, R.F. Franklin, R.B. Brown, in Proceedings of the IEEE International Symposium on Circuits and Systems, Integrated electrochemical neurosensors, 2006, pp. 4110–4113Google Scholar
  47. 47.
    R. Jacob Baker, CMOS: Circuit Design, Layout, and Simulation, Revised 2nd edn. (Wiley – Interscience, NJ, USA, 2008). ISBN 978–0-470-22941-5Google Scholar
  48. 48.
    R. Gregorian, Introduction to CMOS Op-Amps and Comparators, (Wiley, New York, USA, 1999). ISBN 0-471-31778-0Google Scholar
  49. 49.
    J.H. Huijsing, Operational Amplifiers, Theory and Design, (Kluwer Academic Publishers, Dordrecht, The Netherlands, 2001). ISBN: 0-7923-7284-0Google Scholar
  50. 50.
    F. Maloberti, Analog Design for CMOS VLSI Systems, (Kluwer Academic Publishers, The Netherlands, 2001). ISBN: 0-7923-7550-5Google Scholar
  51. 51.
    A.C. Patil, F. Xiao, M. Mehregany, S.L. Garverick, Fully-monolithic, 600°C differential amplifier in 6H-SiC JFET IC technology, Custom Integrated Circuits Conference, CICC’09, pp. 73–76, (2009)Google Scholar
  52. 52.
    J.P. Close, F. Santos, in Proceeding of the Bipolar/BiCMOS Circuits and Technology Meeting. A JFET input single supply operational amplifier with rail-to-rail output, pp. 149–152, (1993)Google Scholar
  53. 53.
    F. Serra-Graells, A. Rueda, J.L. Huertas, Low-Voltage CMOS Log Companding Analog Design, (Springer, Netherlands, 2003). ISBN: 978-1-4020-7445-5Google Scholar
  54. 54.
    R.J. Baker, CMOS: Mixed-Signal Circuit Design, 2nd edn. (Wiley – IEEE Press Series on Microelectronic Systems, NJ, USA, 2008). ISBN: 978-0-470-29026-2Google Scholar
  55. 55.
    National Instruments, Lab View software,
  56. 56.
    X. Gan, Y. Wu, L. Liu, W. Hu, Effects of K4Fe(CN)6 on electroless copper plating using hypophospite as reducing agent. J. Appl. Electrochem. 37, 899–904 (Springer, Apr 2007)Google Scholar
  57. 57.
  58. 58.
    BVT Technologies,
  59. 59.
    N.I. Bojorge Ramírez, M.Fortes, A.M. Salgado, B. Valdman, Construction of an Amperometric Immunosensor Using Solanum Tuberosum Potato Apyrase for the Detection of Schistosomiasis. Información Tecnológica 20, 3 (2009). ISSN: 0718–0764Google Scholar
  60. 60.
    K.K. Kasem, S. Jones, Platinum as a reference electrode in electrochemical measurements, Platinum Metal Rev. 52, 100–106 (Apr 2008)CrossRefGoogle Scholar
  61. 61.
    H.E.A. Ferreira, D. Daniel, M. Bertotti, E.M. Richter, A novel disposable electrochemical microcell construction and characterization, J. Brazilian Chem. Soc. 19, 8 (2008)CrossRefGoogle Scholar
  62. 62.
    I. Bontidean, C. Berggren, G. Johansson, E. Csöregi, B. Mattiasson, J.R. Lloyd, K.J. Jakeman, N.L. Brown, Detection of heavy metal ions at femtomolar levels using protein-based biosensors. Anal. Chem. 70(19), 4162–4169 (1998)CrossRefGoogle Scholar
  63. 63.
    E. Katz, I. Willner, Probing biomolecular interactions at conductive and semiconductive surfaces by impedance spectroscopy:Routes to impedimetric immunosensors, DNA-sensors, and enzyme biosensors, Electroanalysis 15(11), 913–947 (2003)Google Scholar
  64. 64.
    L. Yang, Y. Li, C.L. Griffis, M.G. Johnson, Interdigitated microelectrode (IME) impedance sensor for the detection of ciable Salmonella typhimurium, Biosens. Bioelectron 19, (10), 1139–1147 (2004)CrossRefGoogle Scholar
  65. 65.
    B. Robert, C. Northrop, in Analysis and Application of Analog Electronic Circuits to Biomedical Instrumentation, ed. by M.R. Neuman. The Biomedical Engineering Series (CRC Press, Florida, USA, 2004)Google Scholar
  66. 66.
    A. De Marcellis, G. Ferri, M. Patrizi, V. Stornelli, A.D’ Amico, C. Di Natale, E. Martinelli, A. Alimelli, R. Paolesse, An integrated analog lock-in amplifier for low-voltage low-frequency sensor interface, in Proceddings of the Interational Workshop on Advances in Sensors and Interface, IWASI, pp. 1–5 June 2007Google Scholar
  67. 67.
    D. Rairigh, A. Mason, C. Yang, Analysis of on-chip impedance spectroscopy methodologies for sensor arrays. Sensor. Lett. 4(4), 398–402 (2006)CrossRefGoogle Scholar
  68. 68.
    A.E. Moe, S.R. Marx, I. Bhinderwala, D.M. Wilson, A miniaturuzed lock-in amplifier design suitable for impedance measurements in cells. Proc. IEEE Sens. 1(24–27), 215–218 (AUTRICHE 2004)Google Scholar
  69. 69.
    W. Xu, E.G. Friedman, Clock Feedthrough in CMOS analog transmission gate switches. Anal. Int. Circuits and Signal Process 44, 271–281 (2005)CrossRefGoogle Scholar
  70. 70.
    R. Hogervost, J.P. Tero, R.G.H. Eschauzier, J.H. Huijsin. A compact power-efficient 3 V CMOS rail-to-rail input/ouput omperational amplifier for VLSI cell libraries. IEEE J. Solid-State Circuits 29, 1505–1513 (1994)CrossRefGoogle Scholar
  71. 71.
    A. Veeravalli, E. Sánchez-Sinencio. J. Silva-Martínez, Transconductance amplifiers with very small transconductances: A comparative design approach. IEEE J. Solid-State Circuits 37(6), 770–775 (June 2002)CrossRefGoogle Scholar
  72. 72.
    A. Arnaud, R. Fiorelli, C. Galup-Montoro, Nanowatt, sub-nS OTAs, with Sub-10-mV input offset, using series-parallel current mirrors. IEEE J. Solid-State Circuits 41(9), 2009–2018 (Sept 2006)CrossRefGoogle Scholar
  73. 73.
    J.M. Fiore, in Amplificadores Operacionales y Circuitos Integrados Lineales, ed. by Thomson. (Mohawk Valley Community College, Ed. Paraninfo, Madrid, Spain, 2002)Google Scholar
  74. 74.
    R.S. Machay, Bio–Medical Telemetry, 2nd edn. (Wiley, New York, NY, 1970)Google Scholar
  75. 75.
    H.P. Kimmich, in Biotelemetry, eds. by J.G. Webster. Encyclopedia of Medical Devices and Instrumentation, (Wiley, New York, NY, 1980)Google Scholar
  76. 76.
    A. Santic, M.R. Neuman, A low-power infrared biotelemetry system, Biotelemetry VIII, (Kimmich/Klewe, Netherlands, 1984)Google Scholar
  77. 77.
    S.A.P. Haddad, W.A. Serdijn, Ultra low-power biomedical signal processing: An analog wavelet filter approach for pacemakers, Anal. Circuits and Signal Process. (Springer 2009). ISBN: 978-1-4020-9072-1Google Scholar
  78. 78.
    M.R. Haider, S.K. Islam, M. Zhang, A low-power signal processing unit for in vivo monioring and transmission of sensor signals. Sens. Trans. J. 84(10), 1625–1632 (2007)Google Scholar
  79. 79.
    Positive ID/Verichip White Paper, Development of an Implantable Glucose Sensor,
  80. 80.
    K. Van Schuylengergh, R. Puers, Inductive Powering. Basic Theory and Application to Biomedical Systems, (Springer, The Netherlands, 2009). ISBN: 978-90-481-2411-4Google Scholar
  81. 81.
    B. Lenaerts, R. Puers, Omnidirectional Inductive Powering for Biomedical Implants, (Springer, The Netherlands, 2009). ISBN: 978-1-4020-9074-5Google Scholar
  82. 82.
    W.C. Lin, S.K. Pillay, A micropower pulsewidht-modulation-pulse-position-modulation two-channel telemetry system for biomedical applications. IEEE Trans. Biomed. Eng. BME – 21, 273–280 (1974)CrossRefGoogle Scholar
  83. 83.
    C. Weller, Electrocardiography by infrared telemetry. J. Physiol. (London) 267, 11–12 (1977)ADSGoogle Scholar
  84. 84.
    Z. Tang, B. Smith, J.H. Schild, P.H. Peckham, Data transmission from an implantable biotelemeter by load-shift keying using circuit configuration modulator. IEEE Trans. Biomed. Eng. BME-42, 524–528 (1995)CrossRefGoogle Scholar
  85. 85.
    A. Santic, M.R. Neuman, A low-power infrared biotelemetry system, Biotelemetry VIII, (Kimmich/Klewe, Netherlands, 1984)Google Scholar
  86. 86.
    H.P. Kimmich, Biotelemetry, Enciclopedia of Medical Devices and Instrumentation, (Willey, New York, USA, 1988), pp. 409–425Google Scholar
  87. 87.
    N. Donaldson, Passive signalling via inductive coupling. Med. Biol. Eng. Comput. 24, 223–224 (1986)MathSciNetCrossRefGoogle Scholar
  88. 88.
    D. Gajski, Principios de Diseño Digital, (Prentice Hall, Madrid, España, 2000). ISBN: 84-8322-004-0Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Jordi Colomer-Farrarons
    • 1
    Email author
  • Pere Lluís Miribel-Català
    • 1
  1. 1.Electronics DepartmentUniversity of BarcelonaBarcelonaSpain

Personalised recommendations