Stress Biomarkers in Biological Fluids and Their Point-of-Use Detection

Hormones produced by glands in the endocrine system and neurotransmitters produced by the nervous system control many bodily functions. The concentrations of these molecules in the body are an indication of its state, hence the use of the term biomarker. Excess concentrations of biomarkers, such as cortisol, serotonin, epinephrine, and dopamine, are released by the body in response to a variety of conditions, for example, emotional state (euphoria, stress) and disease. The development of simple, low-cost modalities for point-of-use (PoU) measurements of biomarkers levels in various bodily fluids (blood, urine, sweat, saliva) as opposed to conventional hospital or lab settings is receiving increasing attention. This paper starts with a review of the basic properties of 12 primary stress-induced biomarkers: origin in the body (i.e., if they are produced as hormones, neurotransmitters, or both), chemical composition, molecular weight (small/medium size molecules and polymers, ranging from ∼100 Da to ∼100 kDa), and hydro- or lipophilic nature. Next is presented a detailed review of the published literature regarding the concentration of these biomarkers found in several bodily fluids that can serve as the medium for determination of the condition of the subject: blood, urine, saliva, sweat, and, to a lesser degree, interstitial tissue fluid. The concentration of various biomarkers in most fluids covers a range of 5-6 orders of magnitude, from hundreds of nanograms per milliliter (∼1 μM) down to a few picograms per milliliter (sub-1 pM). Mechanisms and materials for point-of-use biomarker sensors are summarized, and key properties are reviewed. Next, selected methods for detecting these biomarkers are reviewed, including antibody- and aptamer-based colorimetric assays and electrochemical and optical detection. Illustrative examples from the literature are discussed for each key sensor approach. Finally, the review outlines key challenges of the field and provides a look ahead to future prospects.