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Bio-nanomechanical Detection of Diabetic Marker HbA1c

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Abstract

We report the development of an ultrasensitive immunosensor system for the detection of specific diabetic biomarker glycated hemoglobin (HbA1c) using specific antibody functionalized micromechanical cantilever chips. The biomolecules-induced deflection of the cantilever beam reflects the interplay between the strain energy increase of the cantilever and the free energy reduction of the interaction, providing a unique system for investigating the connection between the nanomechanics and the chemistry of antibody–antigen interaction at very low concentration. Cantilevers were functionalized with specific antibodies using site-directed antibody immobilization technique which was adopted to attach antibody on to the gold substrate. The antibody immobilized cantilevers were used to detect the level of the expressed biomarker in standard samples by adopting direct immunoassay format without using any labels. The assay exhibited an excellent sensitivity for HbA1c in the dynamic range from 0.147 to 1.47 pM. This label-free detection method could be used for fast, high-throughput screening of specific biomarkers for the therapeutic management of diabetes mellitus in clinical diagnostic at a very low cost.

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References

  1. Iberg, N., & Flückiger, R. (1986). Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites. The Journal of Biological Chemistry, 261, 13542–13545.

    Google Scholar 

  2. Abbreviated Report of a WHO Consultation (2011). Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. WHO, Geneva.

  3. Du, B. A., Li, Z. P., Liu, C. H. (2006). One-step homogeneous detection of DNA hybridization with gold nanoparticle probes by using a linear light-scattering technique. Angewandte Chemie, International Edition, 45, 8022–8025.

    Article  Google Scholar 

  4. Kokko, T., Kokko, L., Soukka, T., Lovgren, T. (2007). Homogeneous non-competitive bioaffinity assay based on fluorescence resonance energy transfer. Analytica Chimica Acta, 585, 120–125.

    Article  Google Scholar 

  5. Warnick, G. R., Nauck, M., Rifai, N. (2001). Evolution of methods for measurement of HDL-cholesterol: from ultracentrifugation to homogeneous assays. Clinical Chemistry, 47, 1579–1596.

    Google Scholar 

  6. Weigum, S. E., Floriano, P. N., Christodoulides, N., McDevitt, J. T. (2007). Cell-based sensor for analysis of EGFR biomarker expression in oral cancer. Lab on a Chip, 7, 995–1003.

    Article  Google Scholar 

  7. Xu, X., Georganopoulou, D. G., Hill, H. D., Mirkin, C. A. (2007). Homogeneous detection of nucleic acids based upon the light scattering properties of silver-coated nanoparticle probes. Analytical Chemistry, 79, 6650–6654.

    Article  Google Scholar 

  8. DCCT Research Group. (1993). The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin dependent diabetes mellitus. The New England Journal of Medicine, 329, 977–986.

    Article  Google Scholar 

  9. The DCCT/EDIC Study Research Group. (2005). Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. The New England Journal of Medicine, 353, 2643–2653.

    Article  Google Scholar 

  10. UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet, 352, 837–851.

    Article  Google Scholar 

  11. American Diabetes Association. (2010). Diagnosis and classification of diabetes mellitus. Diabetes Care, Suppl 1, S62–S69.

    Article  Google Scholar 

  12. Guntinas, C., Wissiack, R., Bordin, G., Rodrıguez, A. R. (2003). Determination of haemoglobin A(1c) by liquid chromatography using a new cation-exchange column. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 791, 73–83.

    Article  Google Scholar 

  13. Buchmeiser, M. R. (2001). New synthetic ways for the preparation of high performance liquid chromatography supports. Journal of Chromatography. A, 918, 233–266.

    Article  Google Scholar 

  14. Scott, M. G., Hoffman, J. W., Meltzer, V. N., Siegfried, B. A., Chan, K. M. (1984). Effects of azotemia on results of the boronate-agarose affinity and ion-exchange methods for glycated hemoglobin. Clinical Chemistry, 30, 896–898.

    Google Scholar 

  15. Menard, L., Dempsey, M. E., Blankstein, L. A., Aleyassine, H., Wacks, M., Soeldner, J. S. (1980). Quantitative determination of glycosylated hemoglobin A1 by agar gel electrophoresis. Clinical Chemistry, 26, 1598–1602.

    Google Scholar 

  16. Thienpont, L. M., Uytfanghe, K. V., Leenheer, A. P. (2002). Reference measurement systems in clinical chemistry. Clinica Chimica Acta, 323, 73–87.

    Article  Google Scholar 

  17. Das, J., Aziz, M. A., Yang, H. (2006). A nanocatalyst based assay for proteins: DNA-free ultrasensitive electrochemical detection using catalytic reduction of p-nitro phenyl gold nanoparticle labels. Journal of the American Chemical Society, 128, 16022–16023.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  19. Yu, F., Persson, B., Lofas, S., Knoll, W. (2004). Surface plasmon fluorescence immunoassay of free prostate-specific antigen in human plasma at the femtomolar level. Analytical Chemistry, 76, 6765–6770.

    Article  Google Scholar 

  20. Yanagisawa, K., Makita, Z., Shiroshita, K., Ueda, T., Fusegawa, T., Kuwajima, S., et al. (1998). Specific fluorescence assay for advanced glycation end products in blood and urine of diabetic patients. Metabolism, 47, 1348–1353.

    Article  Google Scholar 

  21. Arntz, Y., Seelig, J. D., Lang, H. P., Zhang, J., Hunziker, P., Ramseyer, J. P., et al. (2003). Label-free protein assay based on a nanomechanical cantilever array. Nanotechnology, 14, 86–90.

    Article  Google Scholar 

  22. Stoney, G. G. (1909). The tension of metallic films deposited by electrolysis. Proceedings of the Royal Society A, 82, 172–175.

    Article  Google Scholar 

  23. Suri, C. R., Kaur, J., Gandhi, S., Shekhawat, G. (2008). Label-free ultra-sensitive detection of atrazine based on nanomechanics. Nanotechnology, 19, 235502–235507.

    Article  Google Scholar 

  24. San Paulo, A., & Garcıa, R. (2000). High-resolution imaging of antibodies by tapping-mode atomic force microscopy: attractive and repulsive tip-sample interaction regimes. Biophysical Journal, 78, 1599–1605.

    Article  Google Scholar 

  25. Zhang, J., Lang, H. P., Huber, F., Bietsch, A., Grange, W., Certa, U., et al. (2006). Rapid and label-free nanomechanical detection of biomarker transcripts in human RNA. Nature Nanotechnology, 1, 214–220.

    Article  Google Scholar 

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Acknowledgments

University Grant Commission India is gratefully acknowledged for the financial support for awarding Senior Research fellowship to PS and AC. Authors greatly acknowledge Dr. G Shekhawat for optical detection measurements and Dr. Gina Mustata for AFM imaging at NUANCE, Northwestern University.

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Correspondence to C. Raman Suri.

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Priyanka Sharma and Adity Chopra have contributed equally to this study.

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Sharma, P., Chopra, A., Chaudhary, S. et al. Bio-nanomechanical Detection of Diabetic Marker HbA1c. BioNanoSci. 2, 179–184 (2012). https://doi.org/10.1007/s12668-012-0055-4

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