Stress is a natural response of the body to threatening and challenging situations. Although stress can sometimes have positive impacts, such as enhanced alertness and improved performance, it can also cause harmful effects, such as sustained high blood pressure, anxiety, and depression, especially when prolonged. Continuous monitoring of stress-related molecules, known as stress biomarkers, could enable early diagnosis of stress conditions and therefore improve recovery and reduce healthcare costs and long absences from work. We present a highly sensitive grating-coupled surface plasmon resonance (SPR) sensor for detecting stress biomarkers. The gold-coated sensor chip operates with a tunable laser within the wavelength range of 1527 to 1565 nm. This sensing method is based on detecting a shift of the SPR wavelength, which occurs due to a change in the refractive index of the medium that is caused by the presence of analytes near the plasmonic grating. The sensor chip was tested with four stress-related biomarkers: glucose, creatinine, lactate, and cortisol. With the current version of the sensor, containing no recognition element, the achieved detection limits for these analytes were 5.9, 7.1, 36.9, and 10.7 mM, respectively, which are close to the physiological values of these analytes in body fluids, such as sweat. This proof-of-concept work demonstrates the sensitivity and physiologically relevant detection limits of the presented compact sensor chip and its potential for future healthcare applications, such as continuous stress monitoring, when developed further.
Stress is a widely spread phenomenon in the modern society. Only work-related stress was estimated to cost US companies more than $300 billion a year in healthcare costs, absences and decreased performance. Early diagnosis of stress conditions and therefore improved recovery and reduced costs could potentially be achieved with continuous monitoring of stress biomarkers using wearable devices. Compared to the conventional electrochemical and optical sensing methods used in current wearable devices, plasmonic sensing could offer higher sensitivity, better stability and faster data collection. Our developed plasmonic sensor chip represents a nanograting structured polymer on a silicon substrate, covered with gold. The sensing method is based on detecting a surface plasmon resonance wavelength shift due to refractive index change caused by presence of analytes in the vicinity of the plasmonic grating. The sensitivity of the chip was tested with two different stress-related biomarkers: cortisol and creatinine. With the tested range from 0 to 265 mM, in the current version of the system, without a receptor layer, the detection limits for cortisol and creatinine were 10.65 and 7.09 mM, respectively, which are close to the physiological ranges of these analytes in body fluids. When integrated into a wearable device, this approach has a potential in future healthcare applications paving the way to continuous stress monitoring.
Prism-based Surface Plasmon Resonance (SPR) sensor is a powerful label-free analytical technique used in food safety, medical diagnostics, and environmental monitoring. It is currently mainly used in centralized laboratories due to its size and price. Grating-based SPR sensors offer a cost-effective and miniaturized alternative for point-of-care applications. However, grating based SPR sensors have limited performance and robustness for practical use. In this study, we present a high-performance, robust, and compact grating based SPR sensor enabled by a tunable laser working at normal excitation and readout incidence. This configuration eliminates the spectral analysis and moving parts, thereby enhancing the robustness of the instrumentation. The sensor was designed, optimized, and analyzed using COMSOL Multiphysics, and then fabricated through nanoimprinting lithography. Both computationally and experimentally, we demonstrated the SPR dip splitting at non-zero incidence, which was lacking in previously reported grating-based SPR sensor studies. The sensor was tested with glucose solutions, achieving a sensitivity of 1101.6 m/RIU. The figure of merit of the sensor was 229.5 surpassing other reported grating-based SPR sensors by one order of magnitude. The experimental results were in good agreement with the simulations. We also demonstrate its performance in detecting low concentrations of glucose and creatinine with the limit of detection of 14.2 mM and 19.1 mM, respectively. These results show the potential of our high-performance, portable SPR sensor for point-of-care applications.
In stressful situations, concentrations of various molecules in the human body shift in response to the stressor. These molecules are measurable indicators of stress and are therefore called stress biomarkers. In many stress conditions, such as in overtraining syndrome, early detection of these biomarkers is highly important as the conditions are often not fully reversible. Early detection of the stress symptoms could be achieved with wearable sensors that would continuously monitor health information from different body fluids, such as sweat, urine, saliva, tears and blood. Compared to more conventional electrochemical or optical methods, plasmonic sensing could offer higher sensitivity, better stability and faster data collection while enabling implementation to compact devices. In this work, a sensor chip, based on grating-coupled surface plasmon resonance, is proposed for stress biomarker detection. In this work, we show a highly sensitive grating-based SPR sensor working in concert with a tunable laser within the wavelength range of 1528-1565 nm. The SPR sensor was designed using COMSOL Multiphysics software and was fabricated by means of UV nanoimprinting lithography. The implemented SPR sensor shows sensitivity close to 1200 nm/RIU, with a figure of merit (a ratio between the sensitivity and the full width at half maximum of the SPR dip) exceeding 400. The experimental results are strongly in agreement with COMSOL simulations. Such impressive characteristics of the fabricated sensor are among the best reported in the literature. The sensitivity of the chip was tested with two different stress-related biomarkers: glucose and lactate. With the tested range of 0 to 1.1 M, in the current version of the setup, without a receptor layer, the detection limits of glucose and lactate were 5.9 and 36.9 mM, respectively, which are close to the physiological ranges of these analytes in body fluids. The detection limit can be further improved with the sensor functionalization, thermal stabilization and mechanical isolation. When integrated into a wearable device, this approach has a potential in future healthcare applications, such as in continuous stress monitoring.
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