A realtime and continuous assessment of cortisol in ISF using electrochemical impedance spectroscopy

Abstract

This study describes the functioning of a novel sensor to measure cortisol concentration in the interstitial fluid (ISF) of a human subject. ISF is extracted by means of vacuum pressure from micropores created on the stratum corneum layer of the skin. The pores are produced by focusing a near infrared laser on a layer of black dye material attached to the skin. The pores are viable for approximately three days after skin poration. Cortisol measurements are based on electrochemical impedance (EIS) technique. Gold microelectrode arrays functionalized with Dithiobis (succinimidyl propionate) self-assembled monolayer (SAM) have been used to fabricate an ultrasensitive, disposable, electrochemical cortisol immunosensor. The biosensor was successfully used for in-vitro measurement of cortisol in ISF. Tests in a laboratory setup show that the sensor exhibits a linear response to cortisol concentrations in the range 1 pm to 100 nM. A small pilot clinical study showed that in-vitro immunosensor readings, when compared with commercial evaluation using enzyme-linked immunoassay (ELISA) method, correlated well with cortisol levels in saliva and ISF. Further, circadian rhythm could be established between the subject's ISF and the saliva samples collected over 24 hours time-period. Cortisol levels in ISF were found reliably higher than in saliva. This Research establishes the feasibility of using impedance based biosensor architecture for a disposable, wearable cortisol detector. The projected commercial in-vivo real-time cortisol sensor device, besides being minimally invasive, will allow continuous ISF harvesting and cortisol monitoring over 24 hours even when the subject is asleep. Forthcoming, this sensor could be interfaced to a wireless health monitoring system that could transfer sensor data over existing wide-area networks such as the internet and a cellular phone network to enable real-time remote monitoring of subjects.

Quantification of cortisol in human eccrine sweat by liquid chromatography – tandem mass spectrometry

“…It has also been detected in interstitial fluid (ISF) [20] and hair [21–22]. Among these, blood and ISF sampling is invasive, and can thus trigger stress, thereby introducing artifacts and erroneous results.…”

Electrochemical Sensing of Cortisol: A Recent Update

“…3) based biosensor can accurately detect cortisol in the range of 0.36 pg mL −1 to 0.36 ng mL −1 with the detection limit of 0.36 pg mL −1 in ISF. ISF was extracted through micropores created on the stratum corneum layer of the skin by means of vacuum pressure for detection of cortisol via EA/C-Mab/DTSP/Au based immunosensor [7]. The performance of this EIS based immunosensor was validated using ELISA.…”

“…It is known that cortisol levels vary throughout the day in a circadian rhythm with highest levels during daybreak and reaching its lowest level by night [2,3]. Thus understanding of abnormal levels of cortisol is important [4–7,1]. Abnormalities in cortisol are indicator of chronic conditions such as Cushing’s disease [8] due to excess cortisol levels, Addison’s disease [9] due to decreased cortisol levels, and adrenal insufficiencies [10–13].…”

“…In the recent years, electrochemical immunosensing has emerged as the promising technology for simple, cost-effective, and label free POC detection of cortisol in bio-fluids. Interstitial Fluid (ISF) [7], Blood [11], Urine [32], Sweat [33], and Saliva [34] are the sources of cortisol. Urine and saliva are relevant bio-fluids for detection of cortisol because only free cortisol is found in urine and 90% of free cortisol is in saliva.…”

Electrochemical Immunosensing of Saliva Cortisol

“…[1][2][3][4][5] Moreover, cortisol abnormalities are often a good indicator of chronic conditions such as Addison's disease, Cushing's syndrome, and adrenal insufficiencies. Cortisol is often called the "stress hormone", but it also plays an important role in the homeostasis of physiological processes e.g., adrenal, immune, circulatory, metabolic etc.…”