Analytical and Bioanalytical Chemistry

, Volume 397, Issue 4, pp 1493–1502 | Cite as

3D nanogap interdigitated electrode array biosensors

  • Kanwar Vikas Singh
  • Allison M. Whited
  • Yaswanth Ragineni
  • Thomas W. Barrett
  • Jeff King
  • Raj Solanki
Original Paper


Three-dimensional interdigitated electrodes (IDEs) have been investigated as sensing elements for biosensors. Electric field and current density were simulated in the vicinity of these electrodes as a function of the electrode width, gap, and height to determine the optimum geometry. Both the height and the gap between the electrodes were found to have significant effect on the magnitude and distribution of the electric field and current density near the electrode surface, while the width of the electrodes was found to have a smaller effect on field strength and current density. IDEs were fabricated based on these simulations and their performance tested by detecting C-reactive protein (CRP), a stress-related protein and an important biomarker for inflammation, cardiovascular disease risk indicator, and postsurgical recuperation. CRP-specific antibodies were immobilized on the electrode surface and the formation of an immunocomplex (IC) with CRP was monitored. Electrochemical impedance spectroscopy (EIS) was employed as the detection technique. EIS data at various concentrations (1 pg/mL to 10 μg/mL) of CRP spiked in buffer or diluted human serum was collected and fitted into an equivalent electrical circuit model. Change in resistance was found to be the parameter most sensitive to change in CRP concentration. The sensor response was linear from 0.1 ng/mL to 1 μg/mL in both buffer and 5% human serum samples. The CRP samples were validated using a commercially available ELISA for CRP detection. Hence, the viability of IDEs and EIS for the detection of serum biomarkers was established without using labeled or probe molecules.


Interdigitated electrodes CRP Impedimetric biosensor EIS Impedance spectroscopy Device simulation Label-free 


  1. 1.
    Wang J (2006) Electrochemical biosensors: towards point-of-care cancer diagnostics. Biosens Bioelectron 21:1887–1892CrossRefGoogle Scholar
  2. 2.
    Sadik OA, Aluoch AO, Zhou A (2009) Status of biomolecular recognition using electrochemical techniques. Biosens Bioelectron 24:2749–2765CrossRefGoogle Scholar
  3. 3.
    Gizeli E, Lowe CR (1996) Immunosensors. Curr Opin Biotechnol 7:66–71CrossRefGoogle Scholar
  4. 4.
    Killard AJ, Sequeira M, Diamond D, Smyth MR (2000) Electroanalysis and Biosensors in Clinical Chemistry. In: Meyers RA (ed) The Encyclopedia of Analytical Chemistry. John Wiley & Sons Ltd., New York, pp 173–207Google Scholar
  5. 5.
    Yoon HC, Yang H, Byun SY (2004) Ferritin immunosensing on microfabricated electrodes based on the integration of immunoprecipitation and electrochemical signaling reactions. Anal Sci 20:1249–1253CrossRefGoogle Scholar
  6. 6.
    Chen H, Jiang C, Yu C, Zhang S, Liu B, Kong J (2009) Protein chips and nanomaterials for application in tumor marker immunoassays. Biosens Bioelectron 24:3399–3411CrossRefGoogle Scholar
  7. 7.
    Baldrich E, Campo FJ, Munoz FX (2009) Biosensing at disk microelectrode arrays. Inter-electrode functionalization allows formatting into miniaturized sensing platforms of enhaced sensitivity. Biosens Bioelectron 25:920–926CrossRefGoogle Scholar
  8. 8.
    Chen X, Wang Y, Zhou J, Yan W, Li X, Zhu JJ (2008) Electrochemical impedance immunosensor based on three-dimensionally ordered macroporous goldfilm. Anal Chem 80:2133–2140CrossRefGoogle Scholar
  9. 9.
    Bothara M, Venkatraman V, Reddy R, Barrett T, Carruthers J, Prasad S (2008) Nanomonitors: electrochemical immunoassays for protein biomarker profiling. Nanomedicine 3:423–436CrossRefGoogle Scholar
  10. 10.
    Suri CR, Boro R, Nangia Y, Gandhi S, Sharma P, Wangoo N, Rajesh K, Shekhawat GS (2009) Immunoanalytical techniques for analyzing pesticides in the environment. Trends Anal Chem 28:29–39CrossRefGoogle Scholar
  11. 11.
    Kim SK, Hesketh PJ, Li C, Thomas JH, Halsall HB, Heineman WR (2004) Fabrication of comb interdigitated electrodes array (IDA) for a microbead-based electrochemical assay system. Biosens Bioelectron 20:887–894Google Scholar
  12. 12.
    Albers J, Grunwald T, Nebling E, Piechotta G, Hintsche R (2003) Electrical biochip technology – a tool for microarrays and continuous monitoring. Anal Bioanal Chem 377:521–527CrossRefGoogle Scholar
  13. 13.
    Lisdat F, Schafer D (2008) The use of electrochemical impedance spectroscopy for biosensing. Anal Bioanal Chem 391:1555–1567CrossRefGoogle Scholar
  14. 14.
    Dharuman V, Grunwald T, Nebling E, Albers J, Blohm L, Hintsche R (2005) Label-free impedance detection of oligonucleotide hybridisation on interdigitated ultramicroelectrodes using electrochemical redox probes. Biosens Bioelectron 21:645–654CrossRefGoogle Scholar
  15. 15.
    Valera E, Azcon JR, Rodrıguez A, Castaner LM, Sanchez FJ, Marco MP (2007) Impedimetric immunosensor for atrazine detection using interdigitated μ-electrodes (IDμE’s). Sens Actuators B Chem 125:526–537CrossRefGoogle Scholar
  16. 16.
    Brewood GP, Rangineni Y, Fish DJ, Bhandiwad AS, Evans DR, Solanki R, Benight AS (2008) Electrical detection of the temperature induced melting transition of a DNA hairpin covalently attached to gold interdigitated microelectrodes. Nucleic Acids Res 36:e98CrossRefGoogle Scholar
  17. 17.
    Montelius L, Tegenfeldt JO, Ling TG (1995) Fabrication and characterization of a nanosensor for admittance spectroscopy of biomolecules. J Vac Sci Technol A 13:1755–1760CrossRefGoogle Scholar
  18. 18.
    Van Gerwen P, Laureyn W, Laureys W, Huyberechts G, Beeck M, Baert K, Suls J, Sansen W, Jacobs P, Hermans L, Mertens R (1998) Nanoscaled interdigitated electrode arrays for biochemical sensors. Sens Actuators B Chem 49:73–80CrossRefGoogle Scholar
  19. 19.
    Singh KV, Kaur J, Raje M, Varshney GC, Suri CR (2003) An ELISA bsed approach to optimize elution conditions for screening antibodies against hapten. Anal Bioanal Chem 377:220–224CrossRefGoogle Scholar
  20. 20.
    Finot E, Bourillot E, Prest RM, Lacroute Y, Legay G, Malki MC, Latruffe N, Siri O, Braunstein P, Dereux A (2003) Performance of interdigitated nanoelectrodes for electrochemical DNA biosensor. Ultramicroscopy 97:441–449CrossRefGoogle Scholar
  21. 21.
    Hintsche R, Möller B, Dransfeld I, Wollenberger U, Scheller F, Hoffmann B (1991) biosensors on thin-film metal electrodes. Sens Actuators B Chem 4:287–291CrossRefGoogle Scholar
  22. 22.
    Hou YX, Helali S, Zhang AD, Renault NJ, Martelet C, Minic J, Gorojankina T, Persuy MA, Augy EP, Salesse R, Bessueille F, Samitier J, Errachid A, Akimov V, Reggiani L, Pennetta C, Alfinito E (2006) Immobilization of rhodopsin on a self-assembled multilayer and its specific detection by electrochemical impedance spectroscopy. Biosens Bioelectron 21:1393–1402CrossRefGoogle Scholar
  23. 23.
    Katz E, Willner I (2003) Probing biomolecular interactions at conductive and semiconductive surfaces by impedance spectroscopy: routes to impedimet ric immunosensors, DNA-sensors, and enzyme biosensors. Electroanalysis 15:913–947CrossRefGoogle Scholar
  24. 24.
    Berney H, Alderman J, Lane W, Collins JK (1997) A differential capacitive biosensor using polyethylene glycol to overlay the biolayer. Sens Actuators B Chem 44:578–584CrossRefGoogle Scholar
  25. 25.
    Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC, Taubert K, Tracy RP, Vinicor F (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for health-care professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511CrossRefGoogle Scholar
  26. 26.
    Black S, Kushner I, Samols D (2004) C-reactive protein. J Biol Chem 279:48487–48490CrossRefGoogle Scholar
  27. 27.
    Azzaroni O, Vela ME, Fonticelli M, Benitez G, Carro P, Blum B, Salvarezza RC (2003) Electrodesorption potentials of self-assembled alkanethiolate monolayers on copper electrodes. An experimental and theoretical study. J Phys Chem B 107:13446–13454CrossRefGoogle Scholar
  28. 28.
    Castro BR, Fachini E, Hernandez J, Davis MP, Cabrera C (2006) Electrochemical and Surface Characterization of 4-Aminothiophenol Adsorption at Polycrystalline Platinum Electrodes. Langmuir 22:6102–6108CrossRefGoogle Scholar
  29. 29.
    Akinaga Y, Nakajima T, Hirao K (2001) A density functional study on the adsorption of methanethiolate on the (111) surfaces of noble metals. J Chem Phys 114:8555–8564CrossRefGoogle Scholar
  30. 30.
    Dent AH, Aslam M (1998) The functional chemistry of Proteins and Proetin coupling. In: Aslam M, Dent AH (eds) Bioconjugation: Protein Coupling Techniques for the Biomedical Sciences. MacMillan Refrences Ltd, London, pp 50–100Google Scholar
  31. 31.
    Carrigan SD, Scott G, Tabrizian M (2005) Rapid three-dimensional biointerfaces for real-time immunoassay using hIL-18BPa as a model antigen. Biomaterials 26:7514–7523CrossRefGoogle Scholar
  32. 32.
    Haycock JW (1993) Polyvinylpyrrolidone as a blocking agent in immunochemical studies. Anal Biochem 208:397–399CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Kanwar Vikas Singh
    • 1
  • Allison M. Whited
    • 1
  • Yaswanth Ragineni
    • 1
  • Thomas W. Barrett
    • 2
  • Jeff King
    • 3
  • Raj Solanki
    • 1
  1. 1.Department of PhysicsPortland State UniversityPortlandUSA
  2. 2.Veterans Affairs and MedicineOregon Health and Science University (OHSU)PortlandUSA
  3. 3.Flash SensortechVirogenomics TigardTigardUSA

Personalised recommendations