全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

唾液皮质醇检测技术的研究进展与挑战
Salivary Cortisol Detection Technology: Current Investigations and Challenges

DOI: 10.12677/ojns.2026.141004, PP. 32-46

Keywords: 唾液皮质醇,生物传感器,即时检测,标准化
Salivary Cortisol
, Biosensor, Point-of-Care Testing, Standardization

Full-Text   Cite this paper   Add to My Lib

Abstract:

唾液皮质醇作为下丘脑–垂体–肾上腺轴(HPA轴)终端分泌的关键激素,是评估机体应激状态与内分泌功能的重要生物标志物。近年来,唾液皮质醇检测技术因其无创、便捷、能直接反映生物活性游离激素水平等优势,逐渐成为临床与科研中评估HPA轴功能的“黄金标准”。本文系统综述了唾液皮质醇的生理基础、采集与预处理方法、检测技术的研究进展及其面临的挑战。在检测技术方面,免疫学方法(如ELISA、LFIA、CLIA)和液相色谱–串联质谱法(LC-MS/MS)已广泛应用于实践,而微流控芯片、电化学生物传感器等新兴技术也展现出高灵敏度与即时检测潜力。然而,唾液皮质醇检测仍受多种因素影响,包括昼夜节律、年龄、性别、应激状态及外源性干扰等。未来研究需致力于提高检测技术的灵敏度与特异性,推动便携式即时检测设备的发展,并建立标准化的操作流程与临床参考范围,以促进其在健康监测与疾病诊断中的广泛应用。
As a key end-product of the hypothalamic-pituitary–adrenal (HPA) axis, salivary cortisol serves as a crucial biomarker for assessing stress status and endocrine function. In recent years, salivary cortisol detection technology has emerged as the “gold standard” for evaluating HPA axis function in clinical and research settings due to its non-invasive nature, convenience and ability to directly reflect free hormone levels. This article provides a systematic review of the physiological basis of salivary cortisol, its collection and pre-analytical processing methods, research and development in detection technologies, and the associated challenges. In terms of detection techniques, immunological methods such as ELISA, LFIA and CLIA, as well as liquid chromatography-tandem mass spectrometry (LC-MS/MS), have been widely adopted in practice. Meanwhile, emerging technologies such as microfluidic chips and electrochemical biosensors demonstrate high sensitivity and potential for point-of-care testing. However, salivary cortisol measurement is still influenced by various factors, including circadian rhythms, age, gender, stress status and exogenous interferences. Future research should focus on enhancing the sensitivity and specificity of detection technologies, advancing the development of portable, point-of-care testing devices and establishing standardized operational procedures and clinical reference ranges to facilitate their widespread application in health monitoring and disease diagnosis.

References

[1]  Russell, G. and Lightman, S. (2019) The Human Stress Response. Nature Reviews Endocrinology, 15, 525-534.
https://doi.org/10.1038/s41574-019-0228-0
[2]  Xue, T., Chiao, B., Xu, T., Li, H., Shi, K., Cheng, Y., et al. (2022) The Heart-Brain Axis: A Proteomics Study of Meditation on the Cardiovascular System of Tibetan Monks. eBioMedicine, 80, Article ID: 104026.
https://doi.org/10.1016/j.ebiom.2022.104026
[3]  Dorn, L.D., Lucke, J.F., Loucks, T.L. and Berga, S.L. (2007) Salivary Cortisol Reflects Serum Cortisol: Analysis of Circadian Profiles. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 44, 281-284.
https://doi.org/10.1258/000456307780480954
[4]  Perogamvros, I., Keevil, B.G., Ray, D.W. and Trainer, P.J. (2017) Salivary Cortisone Is a Potential Biomarker for Serum Free Cortisol in Dynamic Function Testing. The Journal of Clinical Endocrinology & Metabolism, 102, 2384-2392.
[5]  Nieman, L.K., Biller, B.M.K., Findling, J.W., Murad, M.H., Newell-Price, J., Savage, M.O., et al. (2015) Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 100, 2807-2831.
https://doi.org/10.1210/jc.2015-1818
[6]  Stalder, T., Kirschbaum, C., Kudielka, B.M., Adam, E.K., Pruessner, J.C., Wüst, S., et al. (2016) Assessment of the Cortisol Awakening Response: Expert Consensus Guidelines. Psychoneuroendocrinology, 63, 414-432.
https://doi.org/10.1016/j.psyneuen.2015.10.010
[7]  Joseph, J.J. and Golden, S.H. (2016) Cortisol Dysregulation: The Bidirectional Link between Stress, Depression, and Type 2 Diabetes Mellitus. Annals of the New York Academy of Sciences, 1391, 20-34.
https://doi.org/10.1111/nyas.13217
[8]  Dooley, L.N., Kuhlman, K.R., Robles, T.F., Eisenberger, N.I., Craske, M.G. and Bower, J.E. (2018) The Role of Inflammation in Core and Peripheral Symptoms of Major Depressive Disorder: Protocol for a Pilot Clinical Trial. BMJ Open, 8, e021216.
[9]  Ahn, R.S., Lee, Y.J., Choi, J.Y., et al. (2022) The Salient Issues of Salivary Cortisol Measurements: A Comprehensive Review. Endocrinology and Metabolism (Seoul), 37, 71-81.
[10]  Heikenfeld, J., Jajack, A., Rogers, J., Gutruf, P., Tian, L., Pan, T., et al. (2018) Wearable Sensors: Modalities, Challenges, and Prospects. Lab on a Chip, 18, 217-248.
https://doi.org/10.1039/c7lc00914c
[11]  Gao, W., Emaminejad, S., Nyein, H.Y.Y., Challa, S., Chen, K., Peck, A., et al. (2016) Fully Integrated Wearable Sensor Arrays for Multiplexed in Situ Perspiration Analysis. Nature, 529, 509-514.
https://doi.org/10.1038/nature16521
[12]  Bariya, M., Nyein, H.Y.Y. and Javey, A. (2018) Wearable Sweat Sensors. Nature Electronics, 1, 160-171.
https://doi.org/10.1038/s41928-018-0043-y
[13]  El-Farhan, N., Rees, D.A. and Evans, C. (2017) Measuring Cortisol in Serum, Urine and Saliva—Are Our Assays Good Enough? Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 54, 308-322.
https://doi.org/10.1177/0004563216687335
[14]  Bellagambi, F.G., Lomonaco, T., Salvo, P., Vivaldi, F., Hangouët, M., Ghimenti, S., et al. (2020) Saliva Sampling: Methods and Devices. an Overview. TrAC Trends in Analytical Chemistry, 124, Article ID: 115781.
https://doi.org/10.1016/j.trac.2019.115781
[15]  Tonge, J.J., Keevil, B.G., Craig, J.N., Whitaker, M.J., Ross, R.J. and Elder, C.J. (2022) Salivary Steroid Collection in Children under Conditions Replicating Home Sampling. The Journal of Clinical Endocrinology & Metabolism, 107, 3128-3136.
https://doi.org/10.1210/clinem/dgac419
[16]  Ueland, G.Å., Kellmann, R., Jørstad Davidsen, M., Viste, K., Husebye, E.S., Almås, B., et al. (2021) Bedtime Salivary Cortisol as a Screening Test for Cushing Syndrome in Children. Journal of the Endocrine Society, 5, bvab033.
https://doi.org/10.1210/jendso/bvab033
[17]  Şemsi, R., Kökbaş, U., Arslan, B., Ergünol, E., Kayrın, L. and Sepici Dinçel, A. (2021) The Saliva Cortisol and Amylase Levels Related with Stress Response Compared by Different Analytical Methods. Applied Biochemistry and Biotechnology, 194, 1166-1177.
https://doi.org/10.1007/s12010-021-03676-9
[18]  Fan, X., Peters, B.A., Min, D., Ahn, J. and Hayes, R.B. (2018) Comparison of the Oral Microbiome in Mouthwash and Whole Saliva Samples. PLOS ONE, 13, e0194729.
https://doi.org/10.1371/journal.pone.0194729
[19]  Justino, A.B., Teixeira, R.R., Peixoto, L.G., Jaramillo, O.L.B. and Espindola, F.S. (2017) Effect of Saliva Collection Methods and Oral Hygiene on Salivary Biomarkers. Scandinavian Journal of Clinical and Laboratory Investigation, 77, 415-422.
https://doi.org/10.1080/00365513.2017.1334261
[20]  Li, Y., Ou, Y., Fan, K. and Liu, G. (2024) Salivary Diagnostics: Opportunities and Challenges. Theranostics, 14, 6969-6990.
https://doi.org/10.7150/thno.100600
[21]  Al Habobe, H., Haverkort, E.B., Nazmi, K., Van Splunter, A.P., Pieters, R.H.H. and Bikker, F.J. (2024) The Impact of Saliva Collection Methods on Measured Salivary Biomarker Levels. Clinica Chimica Acta, 552, Article ID: 117628.
https://doi.org/10.1016/j.cca.2023.117628
[22]  Peres, J.C., Rouquette, J.L., Miočević, O., Warner, M.C., Slowey, P.D. and Shirtcliff, E.A. (2015) New Techniques for Augmenting Saliva Collection: Bacon Rules and Lozenge Drools. Clinical Therapeutics, 37, 515-522.
https://doi.org/10.1016/j.clinthera.2015.02.015
[23]  Paré-Ruel, M., Brendgen, M., Ouellet-Morin, I., Lupien, S., Vitaro, F., Dionne, G., et al. (2022) Unique and Interactive Associations of Proactive and Reactive Aggression with Cortisol Secretion. Hormones and Behavior, 137, Article ID: 105100.
https://doi.org/10.1016/j.yhbeh.2021.105100
[24]  Puglisi, S., Pizzuto, A., Laface, B., Panero, F., Aprà, F., Palmas, E., et al. (2019) Determination of Salivary Cortisol to Assess Time-Related Changes of the Adrenal Response to Stress in Critically Ill Patients. European Journal of Internal Medicine, 68, 66-70.
https://doi.org/10.1016/j.ejim.2019.08.001
[25]  藤林他. 人唾液中皮质醇含量的简易测定法[J]. 日本卫生学杂志, 1988, 88(1): 402.
[26]  魏东, 黄智, 刘丽丽. 浅析ELISA的基本原理与注意事项[J]. 安徽农业科学, 2009, 37(6): 2357-2358.
[27]  Gupta, B.D., Pathak, A. and Shrivastav, A.M. (2022) Optical Biomedical Diagnostics Using Lab-on-Fiber Technology: A Review. Photonics, 9, Article No. 86.
https://doi.org/10.3390/photonics9020086
[28]  上海茁彩生物科技有限公司. 人唾液皮质醇(SC)定量检测试剂盒(ELISA)说明书[EB/OL].
https://elisa.oss-cn-shanghai.aliyuncs.com/%E4%BA%BAELISA/ZC-54504Human%20SC%20ELISA%20Kit.pdf?versionId=null, 2014-11-25.
[29]  Apilux, A., Rengpipat, S., Suwanjang, W., et al. (2018) Development of Competitive Lateral Flow Immunoassay Coupled with Silver Enhancement for Simple and Sensitive Salivary Cortisol Detection. EXCLI Journal, 17, 1198-1209.
[30]  李辉, 盈盈, 曹振, 刘广洋, 王静. 基于智能手机拍照判读的侧流免疫层析快速检测技术研究进展[J]. 分析化学, 2022, 50(1): 9-25.
[31]  Dalirirad, S., Han, D. and Steckl, A.J. (2020) Aptamer-Based Lateral Flow Biosensor for Rapid Detection of Salivary Cortisol. ACS Omega, 5, 32890-32898.
https://doi.org/10.1021/acsomega.0c03223
[32]  Abdulsattar, J.O. and Greenway, G.M. (2019) A Sensitive Chemiluminescence Based Immunoassay for the Detection of Cortisol and Cortisone as Stress Biomarkers. Journal of Analytical Science and Technology, 10, Article No. 34.
https://doi.org/10.1186/s40543-019-0196-y
[33]  Balasamy, S., Atchudan, R., Arya, S., Gunasekaran, B.M., Nesakumar, N. and Sundramoorthy, A.K. (2024) Cortisol: Biosensing and Detection Strategies. Clinica Chimica Acta, 562, Article ID: 119888.
https://doi.org/10.1016/j.cca.2024.119888
[34]  Zhang, T., Zhao, H., Li, M., Zeng, J., Wang, J., Long, Q., et al. (2020) Development and Validation of a Candidate Reference Method for Serum Cortisol by Isotope Dilution Liquid Chromatography-Tandem Mass Spectrometry Combined with Dextran Sulfate-Mg2+ Precipitation. Analytical and Bioanalytical Chemistry, 412, 1325-1333.
https://doi.org/10.1007/s00216-019-02356-2
[35]  Carrozza, C., Lapolla, R., Gervasoni, J., Rota, C.A., Locantore, P., Pontecorvi, A., et al. (2012) Assessment of Salivary Free Cortisol Levels by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) in Patients Treated with Mitotane. Hormones, 11, 344-349.
https://doi.org/10.14310/horm.2002.1363
[36]  Kataoka, H., Matsuura, E. and Mitani, K. (2007) Determination of Cortisol in Human Saliva by Automated In-Tube Solid-Phase Microextraction Coupled with Liquid Chromatography-Mass Spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 44, 160-165.
https://doi.org/10.1016/j.jpba.2007.01.023
[37]  陆优丽, 龚晓霖, 李水军. 液相色谱-串联质谱法检测唾液皮质醇和可的松进展及临床应用[J]. 临床检验杂志, 2020, 38(9): 688-691.
[38]  Vignesh, V., Castro-Dominguez, B., James, T.D., Gamble-Turner, J.M., Lightman, S. and Reis, N.M. (2024) Advancements in Cortisol Detection: From Conventional Methods to Next-Generation Technologies for Enhanced Hormone Monitoring. ACS Sensors, 9, 1666-1681.
https://doi.org/10.1021/acssensors.3c01912
[39]  Frasconi, M., Mazzarino, M., Botrè, F. and Mazzei, F. (2009) Surface Plasmon Resonance Immunosensor for Cortisol and Cortisone Determination. Analytical and Bioanalytical Chemistry, 394, 2151-2159.
https://doi.org/10.1007/s00216-009-2914-6
[40]  Pinto, V., Sousa, P., Catarino, S.O., Correia-Neves, M. and Minas, G. (2017) Microfluidic Immunosensor for Rapid and Highly-Sensitive Salivary Cortisol Quantification. Biosensors and Bioelectronics, 90, 308-313.
https://doi.org/10.1016/j.bios.2016.11.067
[41]  Yamaguchi, M., Matsuda, Y., Sasaki, S., Sasaki, M., Kadoma, Y., Imai, Y., et al. (2013) Immunosensor with Fluid Control Mechanism for Salivary Cortisol Analysis. Biosensors and Bioelectronics, 41, 186-191.
https://doi.org/10.1016/j.bios.2012.08.016
[42]  Zhang, M., Li, C. and Huang, C. (2024) A Facile Electrochemical Cortisol Sensing Based on Zinc Oxide Nanostructures for Monitoring Stress and Recovery in High-Performance Athletes. Alexandria Engineering Journal, 88, 145-154.
https://doi.org/10.1016/j.aej.2023.12.068
[43]  Dhull, N., Kaur, G., Gupta, V. and Tomar, M. (2019) Highly Sensitive and Non-Invasive Electrochemical Immunosensor for Salivary Cortisol Detection. Sensors and Actuators B: Chemical, 293, 281-288.
https://doi.org/10.1016/j.snb.2019.05.020
[44]  Stevens, R.C., Soelberg, S.D., Near, S. and Furlong, C.E. (2008) Detection of Cortisol in Saliva with a Flow-Filtered, Portable Surface Plasmon Resonance Biosensor System. Analytical Chemistry, 80, 6747-6751.
https://doi.org/10.1021/ac800892h
[45]  Ahmed, T., Powner, M.B., Qassem, M. and Kyriacou, P.A. (2024) Rapid Optical Determination of Salivary Cortisol Responses in Individuals Undergoing Physiological and Psychological Stress. Scientific Reports, 14, Article No. 31578.
https://doi.org/10.1038/s41598-024-69466-5
[46]  Malon, R.S.P., Sadir, S., Balakrishnan, M. and Córcoles, E.P. (2014) Saliva-Based Biosensors: Noninvasive Monitoring Tool for Clinical Diagnostics. BioMed Research International, 2014, Article ID: 962903.
https://doi.org/10.1155/2014/962903
[47]  Løvås, K., Thorsen, T.E. and Husebye, E.S. (2006) Saliva Cortisol Measurement: Simple and Reliable Assessment of the Glucocorticoid Replacement Therapy in Addison’s Disease. Journal of Endocrinological Investigation, 29, 727-731.
https://doi.org/10.1007/bf03344183
[48]  de Weerth, C., Graat, G., Buitelaar, J.K. and Thijssen, J.H.H. (2003) Measurement of Cortisol in Small Quantities of Saliva. Clinical Chemistry, 49, 658-660.
https://doi.org/10.1373/49.4.658
[49]  Raff, H., Raff, J.L. and Findling, J.W. (1998) Late-Night Salivary Cortisol as a Screening Test for Cushing’s Syndrome. Journal of Clinical Endocrinology & Metabolism, 83, 2681-2686.
https://doi.org/10.1210/jc.83.8.2681
[50]  Laudenslager, M.L., Noonan, C., Jacobsen, C., Goldberg, J., Buchwald, D., Bremner, J.D., et al. (2009) Salivary Cortisol among American Indians with and without Posttraumatic Stress Disorder (PTSD): Gender and Alcohol Influences. Brain, Behavior, and Immunity, 23, 658-662.
https://doi.org/10.1016/j.bbi.2008.12.007
[51]  Smeets, M.M., Vandenbossche, P., Duijst, W.L., Mook, W.N.v. and Leers, M.P.G. (2021) Validation of a New Method for Saliva Cortisol Testing to Assess Stress in First Responders. Emergency Medicine Journal, 38, 297-302.
https://doi.org/10.1136/emermed-2019-209205
[52]  Xing, K., Shan, S., Liu, D. and Lai, W. (2020) Recent Advances of Lateral Flow Immunoassay for Mycotoxins Detection. TrAC Trends in Analytical Chemistry, 133, Article ID: 116087.
https://doi.org/10.1016/j.trac.2020.116087
[53]  刘晓东, 乔荷, 孟祥娟, 等. 唾液中皮质醇测定的液相色谱-质谱法[J/OL]. 中华劳动卫生职业病杂志, 2019, 37(2): 143-146.
[54]  Jönsson, B.A.G., Malmberg, B., Amilon, Å., Helene Garde, A. and Ørbæk, P. (2003) Determination of Cortisol in Human Saliva Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry. Journal of Chromatography B, 784, 63-68.
https://doi.org/10.1016/s1570-0232(02)00753-5
[55]  Rezapoor-Fashtali, Z., Ganjali, M.R. and Faridbod, F. (2022) A Novel Electrochemical Aptasensor Based on a New Platform of Samarium Molybdate Flower-Like Nanoparticles@poly(pyrrole) for Non-Invasive Determination of Saliva Cortisol. Biosensors, 12, Article No. 720.
https://doi.org/10.3390/bios12090720
[56]  Domsicova, M., Korcekova, J., Poturnayova, A. and Breier, A. (2024) New Insights into Aptamers: An Alternative to Antibodies in the Detection of Molecular Biomarkers. International Journal of Molecular Sciences, 25, Article 6833.
https://doi.org/10.3390/ijms25136833
[57]  Ran, J., Luo, D. and Liu, B. (2022) A Dual-Mode Biosensor for Salivary Cortisol with Antibody-Aptamer Sandwich Pattern and Enzyme Catalytic Amplification. Journal of Solid State Electrochemistry, 27, 399-408.
https://doi.org/10.1007/s10008-022-05313-9
[58]  Kusov, P.A., Kotelevtsev, Y.V. and Drachev, V.P. (2023) Cortisol Monitoring Devices toward Implementation for Clinically Relevant Biosensing in Vivo. Molecules, 28, Article No. 2353.
https://doi.org/10.3390/molecules28052353
[59]  Ronkainen, N. and Okon, S. (2014) Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers. Materials, 7, 4669-4709.
https://doi.org/10.3390/ma7064669
[60]  Li, C., Hu, J., Hu, N., Zhao, J., Li, Q., Han, Y., et al. (2024) Aptamer-Aided Plasmonic Nano-Urchins for Reporter-Free Surface-Enhanced Raman Spectroscopy Analysis of Cortisol. Analytical Methods, 16, 3067-3073.
https://doi.org/10.1039/d4ay00401a
[61]  Hulett, J.M., Fessele, K.L., Clayton, M.F. and Eaton, L.H. (2019) Rigor and Reproducibility: A Systematic Review of Salivary Cortisol Sampling and Reporting Parameters Used in Cancer Survivorship Research. Biological Research for Nursing, 21, 318-334.
https://doi.org/10.1177/1099800419835321
[62]  Tanaka, Y. and Naruishi, N. (2008) Development of an On-Site Measurement System for Salivary Stress-Related Substances Based on Microchip Capillary Electrophoresis Technology. Yakugaku Zasshi, 128, 1595-1604.
https://doi.org/10.1248/yakushi.128.1595

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133