Development of a Sensitive Multiplexed Open Circuit Potential System for the Detection of Prostate Cancer Biomarkers

  • Lai Chun Caleb Wong
  • Pawan Jolly
  • Pedro Estrela
Article
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Abstract

We report the development of a sensitive label-free, cost-effective detection system with simultaneous multi-channel measurement of open circuit potential (OCP) variations for the detection of prostate specific antigen (PSA). We demonstrate a significant increase of 600 times in the sensitivity as compared to the reported literature. To accurately measure OCP variations, a complete monolithic field-effect transistor (FET)-input ultra-low input bias current instrumentation amplifier is used to form the electronic circuit to measure the variation between a working electrode and a reference electrode. This amplifier electronic system setup provides a differential voltage measurement with high input impedance and low input bias current. Since no current is applied to the electrochemical system, a true and accurate measurement of the variation can be performed. This is the first report on the use of DNA aptamers with an OCP system where we employed a DNA aptamer against PSA. An optimised ratio of anti-PSA DNA aptamer with 6-mercapto-1-hexanol (MCH) was used to fabricate the aptasensor using gold electrodes. The electrodes are hosted in a cell with an automated flow system. A wide range of concentrations of PSA (0.1 to 100 ng/mL) were injected through the system. The sensor could potentially differentiate 0.1 ng/mL PSA from blank measurement, which is well below the required clinical range (>1 ng/mL). The sensor was also challenged with 4% human serum albumin and human kallikrein2 as control proteins where the sensor demonstrated excellent selectivity. The developed system can be further generalised to various other targets using specific probes.

Graphical Abstract

Keywords

Aptamer Prostate cancer diagnosis Prostate specific antigen Open circuit potential 

References

  1. 1.
    marketsandmarkets.com, (2016) Label-Free Detection Market by Technology (Surface Plasmon Resonance, Bio-Layer Interferometry), Products (Consumables, Microplates, Biosensor Chips), Applications (Binding Kinetics, Binding Thermodynamics, Lead Generation)—Global Forecasts to 2020, USA.
  2. 2.
    Nagel, M., Bolivar, P. H., Brucherseifer, M., Kurz, H., Bosserhoff, A., & Buttner, R. (2002). Integrated THz technology for label-free genetic diagnostics. Applied Physics Letters, 80, 154–156.CrossRefGoogle Scholar
  3. 3.
    Grow, A. E., Wood, L. L., Claycomb, J. L., & Thompson, P. A. (2003). New biochip technology for label-free detection of pathogens and their toxins. Journal of Microbiological Methods, 53, 221–233.CrossRefGoogle Scholar
  4. 4.
    Estrela, P., Stewart, A. G., Yan, F., & Migliorato, P. (2005). Field effect detection of biomolecular interactions. Electrochimica Acta, 50, 4995–5000.CrossRefGoogle Scholar
  5. 5.
    Wang, W. U., Chen, C., Lin, K. H., Fang, Y., & Lieber, C. M. (2005). Label-free detection of small-molecule-protein interactions by using nanowire nanosensors. Proceedings of the National Academy of Sciences of the United States of America, 102, 3208–3212.CrossRefGoogle Scholar
  6. 6.
    Kukol, A., Li, P., Estrela, P., Ko-Ferrigno, P., & Migliorato, P. (2008). Label-free electrical detection of DNA hybridization for the example of influenza virus gene sequences. Analytical Biochemistry, 374, 143–153.CrossRefGoogle Scholar
  7. 7.
    Vollmer, F., & Arnold, S. (2008). Whispering-gallery-mode biosensing: label-free detection down to single molecules. Nature Methods, 5, 591–596.CrossRefGoogle Scholar
  8. 8.
    Sorgenfrei, S., Chiu, C. Y., Gonzalez, R. L., Yu, Y. J., Kim, P., Nuckolls, C., et al. (2011). Label-free single-molecule detection of DNA-hybridization kinetics with a carbon nanotube field-effect transistor. Nature Nanotechnology, 6, 125–131.CrossRefGoogle Scholar
  9. 9.
    Estrela, P., Paul, D., Li, P., Keighley, S. D., Migliorato, P., Laurenson, S., et al. (2008). Label-free detection of protein interactions with peptide aptamers by open circuit potential measurement. Electrochimica Acta, 53, 6489–6496.CrossRefGoogle Scholar
  10. 10.
    Estrela, P., & Migliorato, P. (2007). Chemical and biological sensors using polycrystalline silicon TFTs. Journal of Materials Chemistry, 17, 219–224.CrossRefGoogle Scholar
  11. 11.
    Mello, H. J. N. P. D., Heimfarth, T., & Mulato, M. (2015). Influence of the physical-chemical properties of polyaniline thin films on the final sensitivity of varied field effect sensors. Materials Chemistry and Physics, 160, 257–263.CrossRefGoogle Scholar
  12. 12.
    Harb, S. V., Pulcinelli, S. H., Santilli, C. V., Knowles, K. M., & Hammer, P. (2016). A comparative study on graphene oxide and carbon nanotube reinforcement of PMMA-siloxane-silica anticorrosive coatings. ACS Applied Materials & Interfaces, 8, 16339–16350.CrossRefGoogle Scholar
  13. 13.
    Bruno, J. G. (2015). Predicting the uncertain future of aptamer-based diagnostics and therapeutics. Molecules, 20, 6866–6887.CrossRefGoogle Scholar
  14. 14.
    Lee, J. W., Kim, H. J., & Heo, K. (2015). Therapeutic aptamers: developmental potential as anticancer drugs. BMB Reports, 48, 234–237.CrossRefGoogle Scholar
  15. 15.
    Mairal, T., Ozalp, V. C., Sanchez, P. L., Mir, M., Katakis, I., & O’Sullivan, C. K. (2008). Aptamers: molecular tools for analytical applications. Analytical and Bioanalytical Chemistry, 390, 989–1007.CrossRefGoogle Scholar
  16. 16.
    Jeong, S., Han, S. R., Lee, Y. J., & Lee, S. W. (2010). Selection of RNA aptamers specific to active prostate-specific antigen. Biotechnology Letters, 32, 379–385.CrossRefGoogle Scholar
  17. 17.
    Catalona, W. J., Smith, D. S., Ratliff, T. L., Dodds, K. M., Coplen, D. E., Yuan, J. J. J., et al. (1991). Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. New England Journal of Medicine, 324, 1156–1161.CrossRefGoogle Scholar
  18. 18.
    Healy, D. A., Hayes, C. J., Leonard, P., McKenna, L., & O’Kennedy, R. (2007). Biosensor developments: application to prostate-specific antigen detection. Trends in Biotechnology, 25, 125–131.CrossRefGoogle Scholar
  19. 19.
    Savory, N., Abe, K., Sode, K., & Ikebukuro, K. (2010). Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application to sensing. Biosensors & Bioelectronics, 26, 1386–1391.CrossRefGoogle Scholar
  20. 20.
    Jolly, P., Formisano, N., Tkac, J., Kasak, P., Frost, C. G., & Estrela, P. (2015). Label-free impedimetric aptasensor with antifouling surface chemistry: a prostate specific antigen case study. Sensors and Actuators B, 209, 306–312.CrossRefGoogle Scholar
  21. 21.
    Formisano, N., Jolly, P., Bhalla, N., Cromhout, M., Flanagan, S. P., Fogel, R., et al. (2015). Optimisation of an electrochemical impedance spectroscopy aptasensor by exploiting quartz crystal microbalance with dissipation signals. Sensors and Actuators B, 220, 369–375.CrossRefGoogle Scholar
  22. 22.
    Hong, S. K. (2014). Kallikreins as biomarkers for prostate cancer. BioMed Research International, 2014, 526341.Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Electronic & Electrical EngineeringUniversity of BathBathUK

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