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Label-Free Optical Detection of Multiple Biomarkers in Sweat, Plasma, Urine, and Saliva

Cite this: ACS Sens. 2019, 4, 5, 1346–1357
Publication Date (Web):March 22, 2019
https://doi.org/10.1021/acssensors.9b00301
Copyright © 2019 American Chemical Society

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    Abstract

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    We report a novel label-free quantitative detection of human performance “stress” biomarkers in different body fluids based on optical absorbance of the biomarkers in the ultraviolet (UV) region. Stress biomarker (hormones and neurotransmitters) concentrations in bodily fluids (blood, sweat, urine, saliva) predict the physical and mental state of the individual. The stress biomarkers primarily focused on in this manuscript are cortisol, serotonin, dopamine, norepinephrine, and neuropeptide Y. UV spectroscopy of stress biomarkers performed in the 190–400 nm range has revealed primary and secondary absorption peaks at near-UV wavelengths depending on their molecular structure. UV characterization of individual and multiple biomarkers is reported in various biofluids. A microfluidic/optoelectronic platform for biomarker detection is reported, with a prime focus toward cortisol evaluation. The current limit of detection of cortisol in sweat is ∼200 ng/mL (∼0.5 μM), which is in the normal (healthy) range. Plasma samples containing both serotonin and cortisol resulted in readily detectable absorption peaks at 203 (serotonin) and 247 (cortisol) nm, confirming feasibility of simultaneous detection of multiple biomarkers in biofluid samples. UV spectroscopy performed on various stress biomarkers shows a similar increasing absorption trend with concentration. The detection mechanism is label free, applicable to a variety of biomarker types, and able to detect multiple biomarkers simultaneously in various biofluids. A microfluidic flow cell has been fabricated on a polymer substrate to enable point-of-use/care UV measurement of target biomarkers. The overall sensor combines sample dispensing and fluid transport to the detection location with optical absorption measurements with a UV light emitting diode (LED) and photodiode. The biomarker concentration is indicated as a function of photocurrent generated at the target wavelength.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssensors.9b00301.

    • Spectral characterization (including signal deconvolution) in plasma, urine, and saliva for cortisol and serotonin; UV LED/PD characteristics (PDF)

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    14. Pushan Guha Roy, Sayantani Sen, Anirban Bhattacharyya. Wavelength-switchable ultraviolet light-emitting diodes. Optics Letters 2023, 48 (11) , 3099. https://doi.org/10.1364/OL.490036
    15. Dang Du Nguyen, Seho Lee, Inki Kim. Recent Advances in Metaphotonic Biosensors. Biosensors 2023, 13 (6) , 631. https://doi.org/10.3390/bios13060631
    16. Jingjing Li, Sang Hyuk Lee, Dong Kyu Yoo, Ho Chul Woo, Sung Hwa Jhung, Milica Jović, Hubert Girault, Hye Jin Lee. A spatially multiplexed voltammetric magneto-sandwich assay involving Fe3O4/Fe-based metal-organic framework for dual liver cancer biomarkers. Sensors and Actuators B: Chemical 2023, 380 , 133313. https://doi.org/10.1016/j.snb.2023.133313
    17. Ayman Negm, Matiar M.R. Howlader, Mohamed Bakr, Shirook Ali. Biomarker detection using GST-based permittivity-asymmetric metasurface. Materials & Design 2023, 227 , 111747. https://doi.org/10.1016/j.matdes.2023.111747
    18. Yanke Zhang, Qingteng Lai, Wei Chen, Chi Zhang, Long Mo, Zhengchun Liu. Recent Advance in Cortisol Immunosensing Technologies and Devices. Chemosensors 2023, 11 (2) , 90. https://doi.org/10.3390/chemosensors11020090
    19. Xin Zhang, Zhiheng Zhang, Weize Diao, Chuangxin Zhou, Yetong Song, Renzhi Wang, Xiaoguang Luo, Guozhen Liu. Early-diagnosis of major depressive disorder: From biomarkers to point-of-care testing. TrAC Trends in Analytical Chemistry 2023, 159 , 116904. https://doi.org/10.1016/j.trac.2022.116904
    20. Annalisa Scroccarello, Flavio Della Pelle, Michele Del Carlo, Dario Compagnone. Optical plasmonic sensing based on nanomaterials integrated in solid supports. A critical review. Analytica Chimica Acta 2023, 1237 , 340594. https://doi.org/10.1016/j.aca.2022.340594
    21. Michael Breitenbach, Elisabeth Kapferer, Clemens Sedmak. Wie misst man Stress?. 2023, 109-130. https://doi.org/10.1007/978-3-031-23697-6_6
    22. Mahdi Bahadoran, Abbas Kalate Seyfari, Parisa Sanati, Lee Suan Chua. Label free identification of the different status of anemia disease using optimized double-slot cascaded microring resonator. Scientific Reports 2022, 12 (1) https://doi.org/10.1038/s41598-022-09504-2
    23. Parijat Deshpande, Bharath Ravikumar, Siddharth Tallur, Debjani Paul, Beena Rai. Development of an insilico model of eccrine sweat using molecular modelling techniques. Scientific Reports 2022, 12 (1) https://doi.org/10.1038/s41598-022-24440-x
    24. Hui ZHENG, MengYuan LIU, XianQing YANG, Yun CAO, WeiRong NIE, ShuQi WANG, Ting ZHANG. Preparation of the artificial “skin” uniform sweating simulation device. SCIENTIA SINICA Technologica 2022, 52 (11) , 1769-1776. https://doi.org/10.1360/SST-2022-0114
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    26. Kazuma Hashimoto, Paul Ben Ishai, Erik Bründermann, Saroj R. Tripathi. Dielectric property measurement of human sweat using attenuated total reflection terahertz time domain spectroscopy. Biomedical Optics Express 2022, 13 (9) , 4572. https://doi.org/10.1364/BOE.467450
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    35. Kazuma Hashimoto, Hikaru Sakata, Saroj R. Tripathi. Measurement of dielectric properties of human sweat in terahertz frequency region. 2021, 1-2. https://doi.org/10.1109/IRMMW-THz50926.2021.9567344
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    40. Michael Breitenbach, Elisabeth Kapferer, Clemens Sedmak. Measuring Stress. 2021, 95-113. https://doi.org/10.1007/978-3-030-77738-8_6
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    45. Daewoo Han, Prajokta Ray, Shima Dalirirad, Andrew Steckl. Novel point of care strategies for biomarker detection. 2020, 1-2. https://doi.org/10.1109/RAPID49481.2020.9195654
    46. Rares Drula, Leonie Florence Ott, Ioana Berindan-Neagoe, Klaus Pantel, George A. Calin. MicroRNAs from Liquid Biopsy Derived Extracellular Vesicles: Recent Advances in Detection and Characterization Methods. Cancers 2020, 12 (8) , 2009. https://doi.org/10.3390/cancers12082009
    47. Timothy Shay, Tamoghna Saha, Michael D. Dickey, Orlin D. Velev. Principles of long-term fluids handling in paper-based wearables with capillary–evaporative transport. Biomicrofluidics 2020, 14 (3) https://doi.org/10.1063/5.0010417
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    50. Sajal Shrivastava, Tran Quang Trung, Nae-Eung Lee. Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing. Chemical Society Reviews 2020, 49 (6) , 1812-1866. https://doi.org/10.1039/C9CS00319C
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    52. Ying Zhang, Wang Ren, Yu Zhu Fan, Hong Qun Luo, Nian Bing Li. Chemically-modulated turn-on fluorescence for rapid and visual discrimination of norepinephrine and epinephrine and its application for dopamine-β-hydroxylase detection. Sensors and Actuators B: Chemical 2020, 305 , 127463. https://doi.org/10.1016/j.snb.2019.127463
    53. Junning Qian, Hui Xu. Insight into optical properties of carbazole-supported on CeO 2 /TiO 2 composite. Materials Research Express 2019, 6 (11) , 116206. https://doi.org/10.1088/2053-1591/ab47cb

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