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Critical Reviews™ in Biomedical Engineering
SJR: 0.26 SNIP: 0.375 CiteScore™: 1.4

ISSN Imprimir: 0278-940X
ISSN En Línea: 1943-619X

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Critical Reviews™ in Biomedical Engineering

DOI: 10.1615/CritRevBiomedEng.2019026109
pages 207-215

Toward a Label-Free Electrochemical Impedance Immunosensor Design for Quantifying Cortisol in Tears

Brittney A. Cardinell
School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ
Mark L. Spano
School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287
Jeffrey T. La Belle
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona


Cortisol is a viable biomarker for monitoring physiological, occupational, and emotional stress and is normally present in tear fluid at approximately 40 nM, or higher as a result of stress. We present characterization and quantification of cortisol via several electrochemical methods versus the standard enzyme-linked immunosorbent assay, commonly known as ELISA. We also present a prototyped design of a disposable test strip and handheld sensor based on label-free electrochemical impedance spectroscopy to quantify cortisol levels in tear fluid within approximately 90 seconds. Electrochemical characterization of the cortisol molecule was conducted using cyclic voltammetry, amperometric i-t, and square wave voltammetry. Lower limits of detection for these techniques were not sufficient to quantify cortisol and phycological tear ranges: 0.1 M, 0.23 M, and 193 M for cyclic voltammetry, amperometric i-t, and square wave voltammetry, respectively. However, electrochemical impedance spectroscopy (EIS) was to be the best mode of cortisol quantification and comparison to ELISA technique (detection range of ~ 138 pM – 552 nM). The initial EIS biosensor obtained a lower limit of detection of 59.76 nM with an approximate 10% relative standard deviation. The cortisol assay and tear collection prototype presented here offer a highly reproducible and ultra-low level of detection with a label-free and rapid response.


  1. Lazzarino AI, Hamer M, Gaze D, Collinson P, Steptoe A. , The association between cortisol response to mental stress and high-sensitivity cardiac troponin T plasma concentration in healthy adults. J Am Coll Cardiol. 2013; 62:1694–701.

  2. Clays E, De Bacquer D, Delanghe J, Kittel F, Van Renterghem L, De Backer G. , Associations between dimensions of job stress and biomarkers of inflammation and infection. J Occup Environ Med. 2005;47:878–883.

  3. Labad J, Stojanovic-Pérez A, Montalvo I, Solé M, Cabezas A, Ortega L, Moreno I, Vilella E, Martorell L, Reynolds RM, Gutiérrez-Zotes A., Stress biomarkers as predictors of transition to psychosis in at-risk mental states: roles for cortisol, prolactin and albumin. J Psychiatr Res. 2014;60C:163–169.

  4. Jergović M, Bendelja K, Savić Mlakar A, Vojvoda V, Aberle N, Jovanovic T, Rabatić S, Sabioncello A, Vidović A., Circulating levels of hormones, lipids, and immune mediators in post-traumatic stress disorder—a 3-month follow-up study. Front Psychiatr. 2015;6:1–13.

  5. Van Haeringen NJ. , Clinical biochemistry of tears. Survey Ophthalmol. 1981;26:84–96.

  6. Fullard R, Snyder C. , Protein levels in nonstimulated and stimulated tears of normal human subjects. Invest Ophthalmol Vis Sci. 1990.

  7. Banbury LK. , Stress biomarkers in the tear film [dissertation]. Lismore, NSW, Australia: Southern Cross University; 2009.

  8. Cusabio Technical Services. Goat Cortisol ELISA Kit. 2013.

  9. Lan K, McAferty K, Shah P, Lieberman E, Patel DR, Cook CB, LaBelle JT. , A disposable tear glucose biosensor. Part III: Assessment of enzymatic specificity. J Diabetes Sci Technol. 2011;5:1108–15.

  10. Bishop DK, LaBelle JT, Vossler SR, Patel DR, Cook CB. , A disposable tear glucose biosensor. Part I: Design and concept testing. J Diabetes Sci Technol. 2010;4:299–306.

  11. Thévenot DR, Toth K, Durst RA, Wilson GS. , Electrochemical biosensors: recommended definitions and classification. Biosens Bioelectr. 2001;16:121–131.

  12. Haselwood B, LaBelle J. , Development of electrochemical methods to enzymatically detect traumatic brain injury biomarkers. Biosens Bioelectr. 2015 May 15; 67: 752–6.

  13. Gonzalez SI, La Belle JT. , The development of an at-risk biosensor for cardiovascular disease. Biosens J. 2012; 1:1–5.

  14. Fairchild A, McAferty K, Demirok U, La Belle J. , A label-free, rapid multimarker protein impedance-based immunosensor. In: IEEE International Conference on Complex Medical Engineering. New York: IEEE; 2009. DOI: doi:10.1109/ICCME.2009.4906678

  15. Adamson TL, Eusebio FA, Cook CB, LaBelle JT. , The promise of electrochemical impedance spectroscopy as novel technology for the management of patients with diabetes mellitus. Analyst. 2012;137:4179.

  16. Adamson T, Cook C, LaBelle J. , Detection of 1, 5-anhydroglucitol by electrochemical impedance spectroscopy. J Diabetes Sci Technol. 2014;8:350–355.

  17. Arya SK, Dey A, Bhansali S. , Polyaniline protected gold nanoparticles based mediator and label free electrochemical cortisol biosensor. Biosens Bioelectr. 2011;28: 166–173.

  18. Nandakumar V, Bishop D, Alonas E, LaBelle J, Joshi L, Alford TL. , A low-cost electrochemical biosensor for rapid bacterial detection. IEEE Sens J. 2011;11:210–216.

  19. Bard AJ, Faulkner LR. , Electrochemical methods: fundamentals and applications. New York: Wiley; 2001. DOI: doi:10.1016/j.aca.2010.06.020

  20. LaBelle J, Fairchild A, Demirok U, Verma A. , Method for fabrication and verification of conjugated nanoparticle- antibody tuning elements for multiplexed electrochemical biosensors. Methods. 2013;61:39–51.

  21. LaBelle JT, Demirok UK, Patel DR, Cook CB. , Development of a novel single sensor multiplexed marker assay. Analyst. 2011;136:1496–1501.

  22. Baumstark A, Pleus S, Schmid C, Link M, Haug C, Freckmann G., Lot-to-lot variability of test strips and accuracy assessment of systems for self-monitoring of blood glucose according to ISO 15197. J Diabetes Sci Technol. 2012;6:1076–1086.

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