Direct Surface Enhanced Raman Spectroscopic Detection of Cortisol at Physiological Concentrations

Abstract

Cortisol is an important steroid hormone in human physiology. Variations or abnormalities in the physiological cortisol levels control acute and chronic stress response, as well as contribute to diseases and syndromes including Addison's disease and Cushing syndrome. The ability to monitor cortisol levels in the physiological range is key in diagnosis and monitoring of these conditions, where current methodology for determination of cortisol levels relies on instrumentation that requires extensive sample preparation, long run times, and is destructive to the sample. Raman spectroscopy provides rapid sample analysis with relatively simple instrumentation; however, Raman spectroscopy is an inherently weak technique. To provide an enhanced Raman signal, we use surface enhanced Raman spectroscopy (SERS) which utilizes oscillating electric fields of metal nanoparticles, enhancing the overall electric field and therefore resulting in an enhanced signal. We demonstrate SERS-based detection of cortisol in the physiologically relevant range using colloidal silver nanoparticles in ethanolic solutions and bovine serum albumin. The SERS spectra obtained in an ethanol matrix demonstrate a sigmoidal concentration response over the physiologically relevant concentration range, with a limit of detection established at 177 nM. Analysis of cortisol solutions in a complex matrix (bovine serum albumin in phosphate buffered saline) is also demonstrated through the use of principal components analysis, a multivariate technique, which shows the separation of cortisol in a linear fashion with respect to cortisol concentration.

Ultrasensitive Stress Biomarker Detection Using Polypyrrole Nanotube Coupled to a Field-Effect Transistor

“…Normally, an antibody is an amphoteric electrolyte composed of many carboxyl and amino bases. The isoelectric point (pI) of IgG, including its anti-cortisol antibody, is approximately pH 5.0-5.5 [10]. Hence, the charge state of the IgG became negative at pH 7.4 in our measurements [11].…”

“…Conventional methods to detect stress levels include interviews and counseling, self-questionnaires, electroencephalograms, and electrocardiograms. Recently, cortisol levels have been measured by radioimmunoassay, enzyme-linked immunosorbent assays, surface-enhanced Raman spectroscopy, ultraviolet spectroscopy, gas chromatography-mass spectrometry, and electrochemical sensors [10][11][12]. These techniques provide qualitative or quantitative determinations for use in diagnosis, although some result in bias [13].…”

Biomarkers and biosensors for the diagnosis of noncompliant pH, dark cutting beef predisposition, and welfare in cattle

“…Moreover, negligible interference of cortisone, progesterone, and testosterone was reported (Figure 5c) (Parlak et al., 2018). Recently, SERS was used to detect cortisol without a recognition element (Moore & Sharma, 2020) with an LOD of 64 ppb reached in an ethanolic solution. Experiments were also conducted in a phosphate‐buffered saline solution containing bovine serum albumin to represent a more complex matrix; however, significant signal suppression was observed, and linear regression could not be performed.…”

“…Moreover, negligible interference of cortisone, progesterone, and testosterone was reported (Figure 5c) (Parlak et al, 2018). Recently, SERS was used to detect cortisol without a recognition element (Moore & Sharma, 2020) with an F I G U R E 5 (a) A 3D printed smartphone attachment and chemiluminescent assay used for cortisol detection in saliva. Image adapted with permission from (Zangheri et al, 2015).…”

Hand-Held Raman Spectrometer-Based Dual Detection of Creatinine and Cortisol in Human Sweat Using Silver Nanoflakes

“…For example, cortisol-related, stress-induced mood disorders cause such mental illnesses as Cushing's syndrome, Addison's disease, bipolar disorders, and depression. 6 Historically, several conventional methods, including colorimetric assays, 4 fluorescence analysis, 7 and chemiluminescence immunoassays, 8 have been used to detect creatinine and cortisol. In addition, updated analytical methods involving localized surface plasmon resonance-based refractive-index analysis, 9 chemiresistors, 10 and electrochemical sensors 11 have been employed for creatinine and cortisol detection.…”