Heat and Mass Transfer

, Volume 49, Issue 11, pp 1647–1658 | Cite as

Three dimensional simulation on binding efficiency of immunoassay for a biosensor with applying electrothermal effect

  • Kuan-Rong HuangEmail author
  • Jeng-Shian Chang


In this work, we perform three dimensional finite element simulations on the binding reaction kinetics of the commonly used analyte–ligand protein pairs, namely, C-reactive protein (CRP) and anti-CRP, in a reaction chamber (microchannel) of a biosensor. For the diffusion limited binding biomolecular pairs, due to the slower transport speed of the analyte and the faster reaction rate of analyte–ligand complex, diffusion boundary layers often develop on the reaction surface. To enhance the performance of a biosensor by accelerating the transport speed, a non-uniform AC electric field is applied to induce the electrothermal force to stir the flow field. The swirling flow in the fluid can accelerate the transport of the analyte to and from the reaction surface and hence enhance the association and dissociation of analyte–ligand complex. Four types of biosensors with different arrangements of the geometric locations of the electrode pair and the reaction surface are designed to study the effects of varying geometric configuration on the binding efficiency. The simulation results show that the performance of a biosensor can be better improved by placing the electrodes and the reaction surface on the same side of the microchannel against the opposite side. For the best case studied in this work, the maximum initial slope of the binding curve can be raised up to 6.94 times (with respect to the field-free value) in the association phase, under applying AC field of 15 Vrms and operating frequency of 100 kHz. Another important result with applying electrothermal effect is that it is feasible to use the slower sample flow in the microchannel to save a lot of sample consumption without sacrificing the performance of a biosensor. Several control factors not studied in our previous works such as the thermal boundary condition and the effect of electrical conductivity are also discussed.


Applied Voltage Reaction Surface Protein Pair Binding Reaction Electrode Pair 
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.



This research was supported by the National Science Council in Taiwan through NSC 97-2221-E-002-017-MY3 and National Taiwan University CQSE 97R0066-69. We thank the NCHC in Taiwan for providing computing resources.


  1. 1.
    Yallow RS, Berson S (1959) Assay of plasma insulin in human subjects by immunological methods. Nature 184:1648–1649CrossRefGoogle Scholar
  2. 2.
    Auroux PA, Iossifidis D, Reyes DR, Manz A (2002) Micro total analysis systems. 2. Analytical standard operations and applications. Anal Chem 74:2637–2652CrossRefGoogle Scholar
  3. 3.
    Tillet WS, Francis T (1930) Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med 52:561–571CrossRefGoogle Scholar
  4. 4.
    Camillone N (2004) Diffusion-limited thiol adsorption on the gold (111) surface. Langmuir 20:1199–1206CrossRefGoogle Scholar
  5. 5.
    Deen WM (1998) Analysis of transport phenomena. Oxford University Press, New YorkGoogle Scholar
  6. 6.
    Hibbert DB, Gooding JJ (2002) Kinetics of irreversible adsorption with diffusion: application to biomolecule immobilization. Langmuir 18:1770–1776CrossRefGoogle Scholar
  7. 7.
    Yang CK, Chang JS, Chao SD, Wu KC (2008) Effects of diffusion boundary layer on reaction kinetics of immunoassay in a biosensor. J Appl Phys 103, article # 084702CrossRefGoogle Scholar
  8. 8.
    Sigurdson M, Wang D, Meinhart CD (2005) Electro-thermal stirring for heterogeneous immunoassays. Lab Chip 5:1366–1373CrossRefGoogle Scholar
  9. 9.
    Ramos HM, Castellanos A (1998) AC electrokinetics: a review of forces in microelectrode structures. J Phys D Appl Phys 31:2338–2353CrossRefGoogle Scholar
  10. 10.
    Pethig R (1996) Dieletrophoresis: using inhomogeneous AC electrical fields to separate and manipulate cells. Crit Rev Biotechnol 16:331–348CrossRefGoogle Scholar
  11. 11.
    Ramos A, Green N, Gonzalez AC, Morgan H (2000) Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes, II. A linear double-layer analysis. Phys Rev 61–4:4019–4028Google Scholar
  12. 12.
    Green N, Ramos A, Gonzalez A, Morgan H, Castellanos A (2000) Fluid flow induced by nonuniform ac electric fields in electrolytes on microelectrodes, I. Experimental measurements. Phys Rev 61(4):4011–4018Google Scholar
  13. 13.
    Meinhart C, Wang D, Turner K (2003) Measurement of ac electrokinetic flows. Biomed Microdevices 5–2:139–145CrossRefGoogle Scholar
  14. 14.
    Wang XB, Huang Y, Gascoyne PRC, Becker FF (1997) Dielectrophoretic manipulation of particles. IEEE Trans Ind Appl 33:660–669CrossRefGoogle Scholar
  15. 15.
    Morgan H, Hughes MP, Green NG (1999) Separation of submicron bioparticles by dielectrophoresis. Biophys J 77:516–525CrossRefGoogle Scholar
  16. 16.
    Washizu M, Suzuki S (1994) Molecular dielectrophoresis of biopolymers. IEEE Trans Ind Appl 30:835–843CrossRefGoogle Scholar
  17. 17.
    Wang D, Sigurdson M, Meinhart CD (2005) Experimental analysis of particle and fluid motion in ac electrokinetics. Exp Fluid 38:1–10CrossRefGoogle Scholar
  18. 18.
    Feldman HC, Sigurdson M, Meinhart CD (2007) AC electrothermal enhancement of heterogeneous assays in microfluidics. Lab Chip 7:1553–1559CrossRefGoogle Scholar
  19. 19.
    Huang KR, Chang JS, Chao SD, Wu KC, Yang CK, Lai CY, Chen SH (2008) Simulation on binding efficiency of immunoassay for a biosensor with applying electrothermal effect. J Appl Phys 104:064702/11CrossRefGoogle Scholar
  20. 20.
    Yang CK, Chang JS, Chao SD, Wu KC (2007) Two dimensional simulation on immunoassay for a biosensor with applying electrothermal effect. Appl Phys Lett 91 article # 113904Google Scholar
  21. 21.
    Stratton JA (1941) Electromagnetic theory. McGraw Hill, New YorkzbMATHGoogle Scholar
  22. 22.
    Landau LD, Lifshitz EM (1959) Fluid mechanics. Pergamon, OxfordGoogle Scholar
  23. 23.
    Langmuir I (1918) The adsorption of gases on plane surfaces of glass, mica and platinum. J Am Chem Soc 40:1361–1403CrossRefGoogle Scholar
  24. 24.
    Green NG, Ramos A, Gonzalez A, Castellanos A, Morgan H (2001) Electrothermally induced fluid flow on microelectrodes. J Electrost 53:71–87CrossRefGoogle Scholar
  25. 25.
    Hokama Y, Coleman MK, Riley RF (1965) An agar interaction in immunodiffusion. J Immunol 95:156–161Google Scholar
  26. 26.
    Behravesh E, Sikavitsas VI, Mikos AG (2003) Quantification of ligand surface concentration of bulk-modified biomimetic hydrogels. Biomaterials 24:4365–4374CrossRefGoogle Scholar
  27. 27.
    Chou C, Hsu HY, Wu HT, Tseng KY, Chiou A, Yu CJ, Lee ZY, Chan TS (2007) Fiber optic biosensor for the detection of C-reactive protein and the study of protein binding kinetics. J Biomed Opt 12:024025-1–024025-9CrossRefGoogle Scholar
  28. 28.
    (2008) Comsol Multiphysics Version 3.4, COMSOL Ltd., Stokhelm, SwedenGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Mechanical and System Engineering ProgramInstitute of Nuclear Energy ResearchTaoyuanTaiwan
  2. 2.Institute of Applied MechanicsNational Taiwan UniversityTaipeiTaiwan

Personalised recommendations