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Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol

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Abstract

The monitoring of stress levels in humans has become increasingly relevant, given the recent incline of stress-related mental health disorders, lifestyle impacts, and chronic physiological diseases. Long-term exposure to stress can induce anxiety and depression, heart disease, and risky behaviors, such as drug and alcohol abuse. Biomarker molecules can be quantified in biological fluids to study human stress. Cortisol, specifically, is a hormone biomarker produced in the adrenal glands with biofluid concentrations that directly correlate to stress levels in humans. The rapid, real-time detection of cortisol is necessary for stress management and predicting the onset of psychological and physical ailments. Current methods, including mass spectrometry and immunoassays, are effective for sensitive cortisol quantification. However, these techniques provide only single measurements which pose challenges in the continuous monitoring of stress levels. Additionally, these analytical methods often require trained personnel to operate expensive instrumentation. Alternatively, low-cost electrochemical biosensors enable the real-time detection and continuous monitoring of cortisol levels while also providing adequate analytical figures of merit (e.g., sensitivity, selectivity, sensor response times, detection limits, and reproducibility) in a simple design platform. This review discusses the recent developments in electrochemical biosensor design for the detection of cortisol in human biofluids. Special emphasis is given to biosensor recognition elements, including antibodies, molecularly imprinted polymers (MIPs), and aptamers, as critical components of electrochemical biosensors for cortisol detection. Furthermore, the advantages and limiting factors of various electrochemical techniques and sensing in complex biofluid matrices are overviewed. Remarks on the current challenges and future perspectives regarding electrochemical biosensors for stress monitoring are provided, including matrix effects (pH dependence and biological interferences), wearability, and large-scale production.

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References

  1. Salleh MR. Life event, stress and illness. Malays J Med Sci. 2008;15:9–18.

    PubMed  PubMed Central  Google Scholar 

  2. Bethune S. More than a quarter of U.S. adults say they’re so stressed they can’t function. APA, American Psychological Association. 2022.

  3. Iqbal T, Simpkin AJ, Roshan D, Glynn N, Killilea J, Walsh J, et al. Stress monitoring using wearable sensors: a pilot study and stress-predict dataset. Sensors (Basel). 2022;22:8135.

    Article  PubMed  Google Scholar 

  4. Kirsch DL, Woodbury-Farina MA. Stress in health and disease, an issue of psychiatric clinics of North America: Elsevier; 2014.

  5. Zea M, Bellagambi FG, Ben Halima H, Zine N, Jaffrezic-Renault N, Villa R, et al. Electrochemical sensors for cortisol detections: almost there. TrAC Trends Anal Chem. 2020;132: 116058.

    Article  CAS  Google Scholar 

  6. Sekar M, Sriramprabha R, Sekhar PK, Bhansali S, Ponpandian N, Pandiaraj M, et al. Review-towards wearable sensor platforms for the electrochemical detection of cortisol. J Electrochem Soc. 2020;167: 067508.

    Article  CAS  Google Scholar 

  7. Rohleder N. Stress and inflammation – the need to address the gap in the transition between acute and chronic stress effects. Psychoneuroendocrinology. 2019;105:164–71.

    Article  PubMed  Google Scholar 

  8. Pruessner JC, Champagne F, Meaney MJ, Dagher A. Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [C-11]raclopride. J Neurosci. 2004;24:2825–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Jackson JA, Riordan HD, Neathery S, Revard C. Histamine levels in health and disease. J Orthomol Med. 1998;13:1947–60.

    Google Scholar 

  10. Hirsch D, Zukowska Z. NPY and stress 30 years later: the peripheral view. Cell Mol Neurobiol. 2012;32:645–59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Taves MD, Gomez-Sanchez CE, Soma KK. Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am J Physiol Endocrinol Metab. 2011;301:E11–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1526–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Kazakou P, Nicolaides NC, Chrousos GP. Basic concepts and hormonal regulators of the stress system. Horm Res Paediatr. 2023;96:8–16.

    Article  PubMed  CAS  Google Scholar 

  14. de Kloet ER, Joels M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005;6:463–75.

    Article  PubMed  Google Scholar 

  15. Levine A, Zagoory-Sharon O, Feldman R, Lewis JG, Weller A. Measuring cortisol in human psychobiological studies. Physiol Behav. 2007;90:43–53.

    Article  PubMed  CAS  Google Scholar 

  16. Mizoguchi K, Ishige A, Takeda S, Aburada M, Tabira T. Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function. J Neurosci. 2004;24:5492–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Papanicolaou DA, Mullen N, Kyrou I, Nieman LK. Nighttime salivary cortisol: a useful test for the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 2002;87:4515–21.

    Article  PubMed  CAS  Google Scholar 

  18. Corbalan-Tutau D, Madrid JA, Nicolas F, Garaulet M. Daily profile in two circadian markers “melatonin and cortisol” and associations with metabolic syndrome components. Physiol Behav. 2014;123:231–5.

    Article  PubMed  CAS  Google Scholar 

  19. Yehuda R, Teicher MH, Trestman RL, Levengood RA, Siever LJ. Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis. Biol Psychiatry. 1996;40:79–88.

    Article  PubMed  CAS  Google Scholar 

  20. Adam EK, Vrshek-Schallhorn S, Kendall AD, Mineka S, Zinbarg RE, Craske MG. Prospective associations between the cortisol awakening response and first onsets of anxiety disorders over a six-year follow-up. Psychoneuroendocrinology. 2014;44:47–59.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Russell E, Koren G, Rieder M, Van Uum SH. The detection of cortisol in human sweat: implications for measurement of cortisol in hair. Ther Drug Monit. 2014;36:30–4.

    Article  PubMed  CAS  Google Scholar 

  22. Khumngern S, Jeerapan I. Advances in wearable electrochemical antibody-based sensors for cortisol sensing. Anal Bioanal Chem. 2023;415:3863–77.

    Article  PubMed  CAS  Google Scholar 

  23. Kraan GP, Dullaart RP, Pratt JJ, Wolthers BG, Drayer NM, De Bruin R. The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different. J Clin Endocrinol Metab. 1998;83:1247–52.

  24. Kerrigan JR, Veldhuis JD, Leyo SA, Iranmanesh A, Rogol AD. Estimation of daily cortisol production and clearance rates in normal pubertal males by deconvolution analysis. J Clin Endocrinol Metab. 1993;76:1505–10.

    PubMed  CAS  Google Scholar 

  25. Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, et al. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab. 1991;72:39–45.

    Article  PubMed  CAS  Google Scholar 

  26. Novak MA, Menard MT, El-Mallah SN, Rosenberg K, Lutz CK, Worlein J, et al. Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta). Am J Primatol. 2017;79:1–8.

    Article  PubMed  CAS  Google Scholar 

  27. Incollingo Rodriguez AC, Epel ES, White ML, Standen EC, Seckl JR, Tomiyama AJ. Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: a systematic review. Psychoneuroendocrinology. 2015;62:301–18.

    Article  PubMed  CAS  Google Scholar 

  28. Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition. 2000;16:924–36.

    Article  PubMed  CAS  Google Scholar 

  29. Garcia-Blanco A, Diago V, Serrano De La Cruz V, Hervas D, Chafer-Pericas C, Vento M. Can stress biomarkers predict preterm birth in women with threatened preterm labor? Psychoneuroendocrinology. 2017;83:19–24.

  30. Baid SK, Sinaii N, Wade M, Rubino D, Nieman LK. Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary cortisol levels: a comparison of assays to establish hypercortisolism. J Clin Endocrinol Metab. 2007;92:3102–7.

    Article  PubMed  CAS  Google Scholar 

  31. Casals G, Hanzu FA. Cortisol measurements in Cushing’s syndrome: immunoassay or mass spectrometry? Ann Lab Med. 2020;40:285–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Cao ZT, Wemm SE, Han L, Spink DC, Wulfert E. Noninvasive determination of human cortisol and dehydroepiandrosterone sulfate using liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2019;411:1203–10.

    Article  PubMed  CAS  Google Scholar 

  33. Li C, Zhang Z, Liu X, Shen K, Gu P, Kang X. Simultaneous quantification of cortisol and cortisone in urines from infants with packed-fiber solid-phase extraction coupled to HPLC-MS/MS. J Chromatogr B: Analyt Technol Biomed Life Sci. 2017;1061:163–8.

    Article  PubMed  Google Scholar 

  34. Appel D, Schmid RD, Dragan CA, Bureik M, Urlacher VB. A fluorimetric assay for cortisol. Anal Bioanal Chem. 2005;383:182–6.

    Article  PubMed  CAS  Google Scholar 

  35. Posthuma-Trumpie GA, Korf J, van Amerongen A. Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal Bioanal Chem. 2009;393:569–82.

  36. Markossian S, Grossman A, Brimacombe K, Arkin M, Auld D, Austin C, et al. Immunoassay methods. The assay guidance manual. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004.

  37. Haq N, Araque KA, Kanegusuku ALG, Wei B, Soldin SJ. Are serum cortisol measurements by immunoassays reliable?: A case series. Med Res Arch. 2020;8:2128.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shimada M, Takahashi K, Ohkawa T, Segawa M, Higurashi M. Determination of salivary cortisol by ELISA and its application to the assessment of the circadian rhythm in children. Horm Res. 1995;44:213–7.

    Article  PubMed  CAS  Google Scholar 

  39. Stevens RC, Soelberg SD, Near S, Furlong CE. Detection of cortisol in saliva with a flow-filtered, portable surface plasmon resonance biosensor system. Anal Chem. 2008;80:6747–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Mejia-Salazar JR, Oliveira ON Jr. Plasmonic biosensing. Chem Rev. 2018;118:10617–25.

    Article  PubMed  CAS  Google Scholar 

  41. Choi J, Xue Y, Xia W, Ray TR, Reeder JT, Bandodkar AJ, et al. Soft, skin-mounted microfluidic systems for measuring secretory fluidic pressures generated at the surface of the skin by eccrine sweat glands. Lab Chip. 2017;17:2572–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Singh A, Kaushik A, Kumar R, Nair M, Bhansali S. Electrochemical sensing of cortisol: a recent update. Appl Biochem Biotechnol. 2014;174:1115–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Simoska O, Stevenson KJ. Electrochemical sensors for rapid diagnosis of pathogens in real time. Analyst. 2019;144:6461–78.

    Article  PubMed  CAS  Google Scholar 

  44. Renneberg R, Pfeiffer D, Lisdat F, Wilson G, Wollenberger U, Ligler F, et al. Frieder Scheller and the short history of biosensors. Adv Biochem Eng Biotechnol. 2008;109:1–18.

    PubMed  Google Scholar 

  45. Simoska O, Stevenson KJ. Electrochemical sensors for detection of Pseudomonas aeruginosa virulence biomarkers: principles of design and characterization. Sens Actuators Rep. 2022;4:100072.

  46. Karuppaiah G, Lee M-H, Bhansali S, Manickam P. Electrochemical sensors for cortisol detection: principles, designs, fabrication, and characterisation. Biosens Bioelectron 2023;239:115600.

  47. Grieshaber D, MacKenzie R, Voros J, Reimhult E. Electrochemical biosensors - sensor principles and architectures. Sensors (Basel). 2008;8:1400–58.

    Article  PubMed  CAS  Google Scholar 

  48. Ye J-S, Ottova A, Tien HT, Sheu F-S. Nanostructured platinum-lipid bilayer composite as biosensor. Bioelectrochemistry. 2003;59:65–72.

    Article  PubMed  CAS  Google Scholar 

  49. Nikolelis DP, Siontorou CG. Hemoglobin modified bilayer lipid membranes (BLMs) biosensor for carbon dioxide detection Bioelectrochem Bioenerg. 1997;42:71–5.

  50. Hazarika CS, D. Puzari, P. Medhi, T. Sharma, S. Use of cytochrome P450 enzyme isolated from Bacillus stratosphericus sp. as recognition element in designing schottky-based ISFET biosensor for hydrocarbon detection. IEEE Sens J 2018;18:6059–69.

  51. Divya KP, Keerthana S, Viswanathan C, Ponpandian N. MXene supported biomimetic bilayer lipid membrane biosensor for zeptomole detection of BRCA1 gene. Microchim Acta. 2023;190:116.

    Article  CAS  Google Scholar 

  52. Li Y, Si S, Huang F, Wei J, Dong S, Yang F, et al. Ultrasensitive label-free electrochemical biosensor for detecting linear microcystin-LR using degrading enzyme MlrB as recognition element. Bioelectrochemistry. 2022;144: 108000.

    Article  PubMed  CAS  Google Scholar 

  53. Coronado-Apodaca KG, Gonzalez-Meza GM, Aguayo-Acosta A, Araujo RG, Gonzalez-Gonzalez RB, Oyervides-Muñoz MA, et al. Immobilized enzyme-based novel biosensing system for recognition of toxic elements in the aqueous environment. Top Catal. 2023;66:606–24.

    Article  CAS  Google Scholar 

  54. Lokar N, Pecar B, Mozek M, Vrtacnik D. Microfluidic electrochemical glucose biosensor with in situ enzyme immobilization. Biosensors (Basel). 2023;13:364.

    Article  PubMed  CAS  Google Scholar 

  55. Bhalla N, Jolly P, Formisano N, Estrela P. Introduction to biosensors. Essays Biochem. 2016;60:1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gillan L, Jansson E. Molecularly imprinted polymer on roll-to-roll printed electrodes as a single use sensor for monitoring of cortisol in sweat. Flex Print Electron. 2022;7: 025014.

    Article  Google Scholar 

  57. Singh NK, Chung S, Sveiven M, Hall DA. Cortisol detection in undiluted human serum using a sensitive electrochemical structure-switching aptamer over an antifouling nanocomposite layer. ACS Omega. 2021;6:27888–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Rice P, Upasham S, Jagannath B, Manuel R, Pali M, Prasad S. CortiWatch: watch-based cortisol tracker. Future Sci OA. 2019;5:FSO416.

  59. Sun K, Ramgir N, Bhansali S. An immunoelectrochemical sensor for salivary cortisol measurement. Sens Actuators B Chem. 2008;133:533–7.

    Article  CAS  Google Scholar 

  60. Zubarev A, Cuzminschi M, Iordache AM, Iordache SM, Rizea C, Grigorescu CEA, et al. Graphene-based sensor for the detection of cortisol for stress level monitoring and diagnostics. Diagnostics (Basel). 2022;12:2593.

    Article  PubMed  CAS  Google Scholar 

  61. Olgac N, Karakus E, Yucel S, Liv L. Electrochemical biosensing of cortisol in a hormone tablet and artificial bodily fluids. Diam Relat Mater. 2023;132:109622.

  62. Dhull N, Kaur G, Gupta V, Tomar M. Highly sensitive and non-invasive electrochemical immunosensor for salivary cortisol detection. Sens Actuators B Chem. 2019;293(281–288).

  63. Simoska O, Minteer SD. Techniques in electroanalytical chemistry. ACS Publications: American Chemical Society; 2022.

  64. Dhull N, Kaur G, Gupta V, Tomar M. Development of nanostructured nickel oxide thin film matrix by RF sputtering technique for the realization of efficient bioelectrode. Vacuum. 2018;158:68–74.

    Article  CAS  Google Scholar 

  65. Liu J, Xu N, Men H, Li S, Lu Y, Low SS, Li X, Zhu L, Cheng C, Xu G, Liu Q. Salivary cortisol determination on smartphone-based differential pulse voltammetry system. Sensors. 2020;20:1422.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Cheng C, Li X, Xu G, Lu Y, Low SS, Liu G, et al. Battery-free, wireless, and flexible electrochemical patch for in situ analysis of sweat cortisol via near field communication. Biosens Bioelectron. 2021;172: 112782.

    Article  PubMed  CAS  Google Scholar 

  67. Yamaguchi M, Matsuda Y, Sasaki S, Sasaki M, Kadoma Y, Imai Y, et al. Immunosensor with fluid control mechanism for salivary cortisol analysis. Biosens Bioelectron. 2013;41:186–91.

    Article  PubMed  CAS  Google Scholar 

  68. Sanghavi BJ, Moore JA, Chavez JL, Hagen JA, Kelley-Loughnane N, Chou CF, et al. Aptamer-functionalized nanoparticles for surface immobilization-free electrochemical detection of cortisol in a microfluidic device. Biosens Bioelectron. 2016;78:244–52.

    Article  PubMed  CAS  Google Scholar 

  69. Nong C, Yang B, Li X, Feng S, Cui H. An ultrasensitive electrochemical immunosensor based on in-situ growth of CuWO4 nanoparticles on MoS2 and chitosan-gold nanoparticles for cortisol detection. Microchem J 2022;179:107434.

  70. Lin KC, Jagannath B, Muthukumar S, Prasad S. Sub-picomolar label-free detection of thrombin using electrochemical impedance spectroscopy of aptamer-functionalized MoS2. Analyst. 2017;142:2770–80.

    Article  PubMed  CAS  Google Scholar 

  71. Khan MS, Dighe K, Wang Z, Srivastava I, Schwartz-Duval AS, Misra SK, et al. Electrochemical-digital immunosensor with enhanced sensitivity for detecting human salivary glucocorticoid hormone. Analyst. 2019;144:1448–57.

    Article  PubMed  CAS  Google Scholar 

  72. Daniels JS, Pourmand N. Label-free impedance biosensors: opportunities and challenges. Electroanalysis. 2007;19:1239–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Bertok T, Lorencova L, Chocholova E, Jane E, Vikartovska A, Kasak P, et al. Electrochemical impedance spectroscopy-based biosensors: mechanistic principles, analytical examples for assay of protein cancer biomarkers and challenges towards commercialization. ChemElectroChem. 2018;6:989–1003.

    Article  Google Scholar 

  74. Sim D, Brothers MC, Slocik JM, Islam AE, Maruyama B, Grigsby CC, et al. Biomarkers and detection platforms for human health and performance monitoring: a review. Adv Sci (Weinh). 2022;9:2104426.

    Article  PubMed  CAS  Google Scholar 

  75. Liu W, Lian Z, Deng Q. Use of mean skin temperature in evaluation of individual thermal comfort for a person in a sleeping posture under steady thermal environment. Indoor Built Environ. 2015;24:489–99.

    Article  CAS  Google Scholar 

  76. Benedek M, Kaernbach C. Physiological correlates and emotional specificity of human piloerection. Biol Psychol. 2011;86:320–9.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med. 2001;163:1693–722.

    Article  PubMed  CAS  Google Scholar 

  78. Ryter SW, Choi AM. Carbon monoxide in exhaled breath testing and therapeutics. J Breath Res. 2013;7: 017111.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Dhama K, Latheef S, Daear M, Samad HA, Munjal A, Khandia R, et al. Biomarkers in stress related diseases/disorders: diagnostic, prognostic, and therapeutic values. Front Mol Biosci. 2019;6:91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Pratico D, Rokach J, Lawson J, FitzGerald GA. F2-isoprostanes as indices of lipid peroxidation in inflammatory diseases. Chem Phys Lipids. 2004;128:165–71.

    Article  PubMed  CAS  Google Scholar 

  81. Venugopal M, Arya SK, Chornokur G, Bhansali S. A real-time and continuous assessment of cortisol in ISF using electrochemical impedance spectroscopy. Sens Actuators A Phys. 2011;172:154–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Pearlmutter P, DeRose G, Samson C, Linehan N, Cen Y, Begdache L, et al. Sweat and saliva cortisol response to stress and nutrition factors. Sci Rep. 2020;10:19050.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Sela-Culang I, Kunik V, Ofran Y. The structural basis of antibody-antigen recognition. Front Immunol. 2013;4:302.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Sharma S, Byrne H, O’Kennedy RJ. Antibodies and antibody-derived analytical biosensors. Essays Biochem. 2016;60:9–18.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Karachaliou CE, Koukouvinos G, Goustouridis D, Raptis I, Kakabakos S, Petrou P, et al. Cortisol immunosensors: a literature review. Biosensors (Basel). 2023;13:285.

    Article  PubMed  CAS  Google Scholar 

  86. Lee HB, Meeseepong M, Trung TQ, Kim BY, Lee NE. A wearable lab-on-a-patch platform with stretchable nanostructured biosensor for non-invasive immunodetection of biomarker in sweat. Biosens Bioelectron. 2020;156: 112133.

    Article  PubMed  CAS  Google Scholar 

  87. Torrente-Rodriguez RM, Tu J, Yang Y, Min J, Wang M, Song Y, et al. Investigation of cortisol dynamics in human sweat using a graphene-based wireless mHealth system. Matter. 2020;2:921–37.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Demuru S, Kim J, El Chazli M, Bruce S, Dupertuis M, Binz PA, et al. Antibody-coated wearable organic electrochemical transistors for cortisol detection in human sweat. ACS Sens. 2022;7:2721–31.

    Article  PubMed  CAS  Google Scholar 

  89. Madhu S, Ramasamy S, Manickam P, Nagamony P, Chinnuswamy V. TiO2 anchored carbon fibers as non-invasive electrochemical sensor platform for the cortisol detection Mater Lett. 2022;308:131238.

  90. Gogotsi Y, Anasori B. The rise of MXenes. ACS Nano. 2019;18:8491–4.

    Article  Google Scholar 

  91. Laochai T, Yukird J, Promphet N, Qin J, Chailapakul O, Rodthongkum N. Non-invasive electrochemical immunosensor for sweat cortisol based on L-cys/AuNPs/MXene modified thread electrode. Biosens Bioelectron. 2022;203: 114039.

    Article  PubMed  CAS  Google Scholar 

  92. Tian L, Jiang M, Su M, Cao X, Jiang Q, Liu Q, et al. Sweat cortisol determination utilizing MXene and multi-walled carbon nanotube nanocomposite functionalized immunosensor. Microchem J. 2023;185:108172.

  93. Byrne B, Stack E, Gilmartin N, O’Kennedy R. Antibody-based sensors: principles, problems and potential for detection of pathogens and associated toxins. Sensors (Basel). 2009;9:4407–45.

    Article  PubMed  CAS  Google Scholar 

  94. Bonanno LM, Delouise LA. Steric crowding effects on target detection in an affinity biosensor. Langmuir. 2007;23:5817–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Tsekenis G, Chatzipetrou M, Massaouti M, Zergioti I. Comparative assessment of affinity based techniques for oriented antibody immobilization towards immunosensor performance optimization. J Sensors. 2019;2019:1–10.

    Google Scholar 

  96. Vasapollo G, Sole RD, Mergola L, Lazzoi MR, Scardino A, Scorrano S, et al. Molecularly imprinted polymers: present and future prospective. Int J Mol Sci. 2011;12:5908–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Yulianti ES, Rahman SF, Whulanza Y. Molecularly imprinted polymer-based sensor for electrochemical detection of cortisol. Biosensors (Basel). 2022;12:1090.

    Article  PubMed  CAS  Google Scholar 

  98. Parlak O, Keene ST, Marais A, Curto VF, Salleo A. Molecularly selective nanoporous membrane-based wearable organic electrochemical device for noninvasive cortisol sensing. Sci Adv. 2018;4:eaar2904.

  99. Mugo SM, Alberkant J. Flexible molecularly imprinted electrochemical sensor for cortisol monitoring in sweat. Anal Bioanal Chem. 2020;412:1825–33.

    Article  PubMed  CAS  Google Scholar 

  100. Yeasmin S, Wu B, Liu Y, Ullah A, Cheng LJ. Nano gold-doped molecularly imprinted electrochemical sensor for rapid and ultrasensitive cortisol detection. Biosens Bioelectron. 2022;206: 114142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Crapnell RD, Dempsey-Hibbert NC, Peeters M, Tridente A, Banks CE. Molecularly imprinted polymer based electrochemical biosensors: overcoming the challenges of detecting vital biomarkers and speeding up diagnosis. Talanta. 2020;2:100018.

  102. Daniels E, Mustafa YL, Herdes C, Leese HS. Optimization of cortisol-selective molecularly imprinted polymers enabled by molecular dynamics simulations. ACS Appl Bio Mater. 2021;4:7243–53.

    Article  PubMed  CAS  Google Scholar 

  103. Zamora-Galvez A, Ait-Lahcen A, Mercante LA, Morales-Narvaez E, Amine A, Merkoci A. Molecularly imprinted polymer-decorated magnetite nanoparticles for selective sulfonamide detection. Anal Chem. 2016;88:3578–84.

    Article  PubMed  CAS  Google Scholar 

  104. Ansari S. Combination of molecularly imprinted polymers and carbon nanomaterials as a versatile biosensing tool in sample analysis: recent applications and challenges. TrAC Trends Anal Chem. 2017;93:134–51.

    Article  CAS  Google Scholar 

  105. Nawaz N, Abu Bakar NK, Muhammad Ekramul Mahmud HN, Jamaludin NS. Molecularly imprinted polymers-based DNA biosensors. Anal Bioanal Chem. 2021;630:114328.

  106. Ali GK, Omer KM. Molecular imprinted polymer combined with aptamer (MIP-aptamer) as a hybrid dual recognition element for bio(chemical) sensing applications. Review. Talanta. 2022;236: 122878.

    Article  PubMed  CAS  Google Scholar 

  107. Roushani M, Farokhi S, Rahmati Z. Development of a dual-recognition strategy for the aflatoxin B1 detection based on a hybrid of aptamer-MIP using a Cu2O NCs/GCE. Microchem J. 2022;178: 107328.

    Article  CAS  Google Scholar 

  108. Pellitero MA, Shaver A, Arroyo-Curras N. Critical review—approaches for the electrochemical interrogation of DNA-based sensors: a critical review. J Electrochem Soc. 2020;167: 037529.

    Article  CAS  Google Scholar 

  109. Liu Y, Canoura J, Alkhamis O, Xiao Y. Immobilization strategies for enhancing sensitivity of electrochemical aptamer-based sensors. ACS Appl Mater Interfaces. 2021;13:9491–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Jayasena SD. Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem. 1999;45:1628–50.

    Article  PubMed  CAS  Google Scholar 

  111. Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249:505–10.

    Article  PubMed  CAS  Google Scholar 

  112. Ganguly A, Lin KC, Muthukumar S, Prasad S. Autonomous, real-time monitoring electrochemical aptasensor for circadian tracking of cortisol hormone in sub-microliter volumes of passively eluted human sweat. ACS Sens. 2021;6:63–72.

    Article  PubMed  CAS  Google Scholar 

  113. Pusomjit P, Teengam P, Thepsuparungsikul N, Sanongkiet S, Chailapakul O. Impedimetric determination of cortisol using screen-printed electrode with aptamer-modified magnetic beads. Microchim Acta. 2021;188:41.

    Article  CAS  Google Scholar 

  114. Mugo SM, Alberkant J, Bernstein N, Zenkina OV. Flexible electrochemical aptasensor for cortisol detection in human sweat. Anal Methods. 2021;13:4169–73.

    Article  PubMed  CAS  Google Scholar 

  115. Pali M, Jagannath B, Lin K-C, Upasham S, Sankhalab D, Upashama S. CATCH (cortisol Apta WATCH): ‘bio-mimic alarm’ to track anxiety, stress, immunity in human sweat. Electrochim Acta. 2021;390: 138834.

    Article  CAS  Google Scholar 

  116. Wang B, Zhao C, Wang Z, Yang KA, Cheng X, Liu W, et al. Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring. Sci Adv. 2022;8:1–15.

    Google Scholar 

  117. Sharma V, Sharma TK, Kaur I. Electrochemical detection of cortisol using a structure-switching aptamer immobilized on gold nanoparticles-modifed screen-printed electrodes. J Appl Electrochem. 2023;53:1765–76.

    Article  CAS  Google Scholar 

  118. Singh NK, Chung S, Chang A-Y, Wang J, Hall DA. A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer. Biosens Bioelectron. 2023;227:115097.

  119. Su T, Mi Z, Xia Y, Jin D, Xu Q, Hu X, et al. A wearable sweat electrochemical aptasensor based on the Ni-Co MOF nanosheet-decorated CNTs/PU film for monitoring of stress biomarker. Talanta. 2023;260: 124620.

    Article  PubMed  CAS  Google Scholar 

  120. Huang Z, Chen H, Ye H, Chen Z, Jaffrezic-Renault N, Guo Z. An ultrasensitive aptamer-antibody sandwich cortisol sensor for the noninvasive monitoring of stress state. Biosens Bioelectron. 2021;190: 113451.

    Article  PubMed  CAS  Google Scholar 

  121. Ran J, Luo D, Liu B. A dual-mode biosensor for salivary cortisol with antibody-aptamer sandwich pattern and enzyme catalytic amplification. J Solid State Electrochem. 2023;27:399–408.

    Article  CAS  Google Scholar 

  122. Schoen I, Krammer H, Braun D. Hybridization kinetics is different inside cells. PNAS. 2009;106:21649–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Watkins Z, Karajic AY, Young T, White R, Heikenfeld J. Week-long operation of electrochemical aptamer sensors: new insights into self-assembled monolayer degradation mechanisms and solutions for stability in serum at body temperature. ACS Sens. 2023;8:1119–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Dunn MR, Jimenez RM, Chaput JC. Analysis of aptamer discovery and technology. Nat Rev Chem. 2017;1:0076.

    Article  CAS  Google Scholar 

  125. Downs AM, Plaxco KW. Real-time, in vivo molecular monitoring using electrochemical aptamer based sensors: opportunities and challenges. ACS Sens. 2022;7:2823–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Shaver A, Curtis SD, Arroyo-Curras N. Alkanethiol monolayer end groups affect the long-term operational stability and signaling of electrochemical, aptamer-based sensors in biological fluids. ACS Appl Mater Interfaces. 2020;12:11214–23.

    Article  PubMed  CAS  Google Scholar 

  127. Santos-Cancel M, White RJ. Collagen membranes with ribonuclease inhibitors for long-term stability of electrochemical aptamer-based sensors employing RNA. Anal Chem. 2017;89:5598–604.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Clark V, Pellitero MA, Arroyo-Curras N. Explaining the decay of nucleic acid-based sensors under continuous voltammetric interrogation. Anal Chem. 2023;95:4974–83.

    Article  PubMed  CAS  Google Scholar 

  129. Pellitero MA, Nandini K, Sczepanski J, Arroyo-Curras N. Os(ii/iii) complex supports pH-insensitive electrochemical DNA-based sensing with superior operational stability than the benchmark methylene blue reporter. Analyst. 2023;148:806–13.

    Article  Google Scholar 

  130. Li S, Ferrer-Ruiz A, Dai J, Ramos-Soriano J, Du X, Zhu M, et al. A pH-independent electrochemical aptamer-based biosensor supports quantitative, real-time measurement in vivo. Chem Sci. 2022;13:8813–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Arroyo-Currás N, Dauphin-Ducharme P, Scida K, Chávez JL. From the beaker to the body: translational challenges for electrochemical, aptamer-based sensors. Anal Methods. 2020;12:1288–310.

    Article  Google Scholar 

  132. Ricci F, Zari N, Caprio F, Recine S, Amine A, Moscone D, et al. Surface chemistry effects on the performance of an electrochemical DNA sensor. Bioelectrochemistry. 2009;76:208–13.

    Article  PubMed  CAS  Google Scholar 

  133. Castiglione V, Aimo A, Vergaro G, Saccaro L, Passino C, Emdin M. Biomarkers for the diagnosis and management of heart failure. Heart Fail Rev. 2022;27:625–43.

    Article  PubMed  CAS  Google Scholar 

  134. Shajari S, Salahandish R, Zare A, Hassani M, Moossavi S, Munro E, et al. MicroSweat: a wearable microfluidic patch for noninvasive and reliable sweat collection enables human stress monitoring. Adv Sci (Weinh). 2023;10:2204171.

    Article  PubMed  CAS  Google Scholar 

  135. Mirica KA. Materials matter: adsvancing sensor science through innovation in materials chemistry. ACS Sens. 2022;7:3580–1.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge financial support from the University of South Carolina.

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This work was supported by start-up funding (to O.S.) from the University of South Carolina.

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Weber, C.J., Clay, O.M., Lycan, R.E. et al. Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol. Anal Bioanal Chem 416, 87–106 (2024). https://doi.org/10.1007/s00216-023-05047-1

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