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JOURNAL OF CHROMATOGRAPHIC SCIENCE · 2022 ·Vol. 61 ·期 2 ·130-139 · IF 1.555

Simultaneous Determination of Cortisol and 6β-Hydroxycortisol in Human Plasma by Liquid Chromatography–Tandem Mass Spectrometry

Sun Lu-Ning,Shen Ye,Yang Yu-Qing,Chen Xiang-Long,Huang Feng-Ru,Wang Dun-Jian,Zhang Ye,Wang Da-Wei,Wang Yong-Qing

The feasibility of taking the ratio of 6β-hydroxycortisol (6β-OHCOR) to cortisol (COR) in plasma as a biomarker to reflect CYP3A4 activity needs to be verified, but the low concentration of 6β-OHCOR which is an endogenous substance in plasma presents a challenge for determination. In this study, a Liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was established to simultaneously quantify the COR and 6β-OHCOR in plasma with COR-d4 and 6β-OHCOR-d4 as internal standards (ISs). Plasma samples were treated by protein precipitation using acetonitrile. Separation with a gradient elution within 5 min was achieved on C18+ column utilizing 5 mM ammonium formate and methanol. An API 4,000 MS in multiple reaction monitoring mode with transitions of 407.1 → 361.1 and 423.1 → 347.1 was utilized. Albumin solution was used as a surrogate matrix, with good linearities over the concentration of 1.20–300 ng/mL for COR and 0.0400–10.0 ng/mL for 6β-OHCOR. The precisions for intrarun and interrun were < 6.8%, and the accuracy was fell in the interval of −5.2 to 3.5%. Matrix effect was not found. Recovery was close to 100.0%. Stability was confirmed under the storage and processing conditions. The validated method was applied to evaluate the inhibitory effect of voriconazole to CYP3A by the ratio of 6β-OHCOR to COR.

CAS / MDL: 64-18-6
研究领域: 分析化学 · 药理学 · 临床医学
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MICROCHEMICAL JOURNAL · 2022 · IF 5.304

Sweat cortisol determination utilizing MXene and multi-walled carbon nanotube nanocomposite functionalized immunosensor

Liang Tian,Mengyuan Jiang,Mengjie Su,Xiaoqing Cao,Qiyu Jiang,Quan Liu,Chunmei Yu

In this work, a highly selective and sensitive cortisol immunosensor based on MXene and multi-walled carbon nanotubes (MXene-MWCNTs) hybrid composite was proposed. The immunosensor was developed by screen printing technique on a flexible polyethyleneterephthalate (PET) substrate followed by modification of MXene-MWCNTs and anti-cortisol antibodies with EDC/NHS coupling agent. Owing to the large surface area and excellent conductivity of MXene-MWCNTs, the immunosensor exhibited a low detection limit and a wide linear range toward cortisol from 0.1 fg/mL to 1 µg/mL, which covered the normal range of free cortisol in sweat. Additionally, the immunosensor was applied to evaluate the cortisol level in human sweat samples, and the results were validated by a commercial chemiluminescence immunoassay (CLIA) assay. The present platform provides an effective method for non-invasive monitoring of human sweat cortisol levels, which may be well-suited for hormone screenings in healthy monitoring and medical diagnosis.

CAS / MDL: 7664-39-3
研究领域: 生物医学工程 · 分析化学 · 医疗诊断
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2023 · IF 4.4

Ag triangle nanoplates assembled on PVC/SEBS membrane as flexible SERS substrates for skin cortisol sensing

Guojun Weng,Jianming Yang,Jianjun Li,Jian Zhu,Junwu Zhao

Surface-enhanced Raman scattering (SERS) based on rigid substrates has been widely used in biomedical detection due to its high sensitivity and specificity. However, the tedious operation steps for preparing SERS rigid substrates limited their applications in real-world detection. Compared with general rigid substrate, the flexible substrate has the advantages of simple preparation and easy portability, which are suitable for rapid, wearable and personalized detection in the field of point-of-care test. Herein, the flexible SERS substrates employing copolymer were fabricated and used for detection of skin cortisol, a biomarker for evaluating psychological stress in sweat. Silver triangle nanoplates with sharp corner were used as enhanced particles, and transferred to polyvinyl chloride/styrene-ethylene-butene-styrene copolymer (PVC/SEBS) film through three-phase interface self-assembly. By adjusting the size of silver nanoparticles, the ratio of PVC to SEBS in the polymer film, and the number of transfers of self-assembled silver films, the enhancement effect of the flexible SERS substrate was maximized. In addition, functionalization of the flexible SERS substrate with cortisol antibodies is used to achieve specific detection of cortisol on the skin surface. Under the optimal conditions, the Raman peak intensities at 1268 and 1500 cm −1 of the cortisol had a good linear relationship with the logarithm of its concentration in the range of 10 −7 to 10 −3 M, and the detection limits were 5.47 × 10 −8 M and 5.51 × 10 −8 M, respectively. The flexible silver triangle nanoplates SERS substrate constructed by self-assembly in the three-phase interface has the characteristics of good specificity and high sensitivity, which has potential for transdermal cortisol wearable detection, providing a feasible method for the rapid evaluating psychological stress level.

研究领域: 生物医学工程 · 分析化学 · 材料科学 · 可穿戴技术
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2025 · IF 3.8

Development and clinical application of a novel urinary cortisol extraction agent

Wang Chengxue,Wang Qian,Yuan Wenting,Jia Zichao,Dong Lizhen,Chai Yamin,Cai Qinzhen,Yuan Chunhui,Cao MingFeng,Luo Wei

Dichloromethane (DCM), a traditional extractant for 24-h urine free cortisol (UFC) testing, poses significant occupational hazards. This study aimed to explore a novel extractant, evaluate its performance in replacing DCM, and establish the biological reference range for UFC detection using the new extractant. Comparative analyses of extraction efficiency were conducted between ethyl acetate (EA) and DCM. A stabilized EA-based formulation (named EEG) was developed by incorporating anhydrous ethanol and gallic acid as anti-hydrolysis and volatility-reducing agents. Recovery rates were assessed using a control product. Stability was tested through delayed detection. Biological reference intervals were determined via chemiluminescence immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) following EEG extraction, and determined the reference interval using mean ± 1.96 standard deviation. EA demonstrated superior extraction efficiency, yielding significantly higher median cortisol levels (6.27 (IQR 4.68–8.68) µg/dL) versus DCM (3.96 (IQR 2.41–5.07) µg/dL, p  = 0.002). Recovery tests confirmed EA’s enhanced performance (mean recovery 95.3% vs. DCM’s 65.4%, p  = 0.011). The EEG formulation exhibited improved stability with unchanged extraction efficacy. Established reference intervals (95% range) were 14.58~136.62 µg/24 h (CLIA) and 0.81~60.55 µg/24 h (LC–MS/MS). EA extraction surpasses DCM in recovery and safety. The optimized EEG formulation demonstrates enhanced stability while maintaining analytical reliability. The newly established reference intervals provide method-specific benchmarks for clinical UFC assessment. This innovation offers a safer, more efficient alternative for routine laboratory practice. The findings underscore the feasibility of replacing hazardous solvents in endocrine diagnostics without compromising analytical performance.

CAS / MDL: 149-91-7
研究领域: 临床化学 · 内分泌学 · 分析化学 · 诊断检测 · 职业健康
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Analytical Methods · 2024 · IF 2.7

Aptamer-aided plasmonic nano-urchins for reporter-free surface-enhanced Raman spectroscopy analysis of cortisol

Chengyu Li,Jing Hu,Nan Hu,Jianjun Zhao,Qianwen Li,Yanhui Han,Yanxiong Liu,Xufang Hu,Liyan Zheng,Qiue Cao

Cortisol is a vital glucocorticoid hormone reflecting stress levels and related disease processes. In this study, we report an aptamer-functionalized plasmonic nano-urchin (α-FeOOH@Au-aptamer)-aided cortisol-capturing and surface-enhanced Raman spectroscopy (SERS) analysis approach. The designed α-FeOOH@Au-aptamer exhibits a well-patterned plasma structure, which combines the good SERS enhancement ability of reduced nanogaps between the Au plasma and the hot spot–favored structure of anisotropic tips from α-FeOOH urchins, with the high affinity of the aptamer towards cortisol molecules. The α-FeOOH@Au-aptamer achieved reporter-free SERS quantification for cortisol with good sensitivity (limit of detection <0.28 μmol L−1), robust salt (1.0 mol per L NaCl) and protein (5.0 mg per mL bovine serum protein) tolerance, favorable reproducibility, as well as good reusability. We further demonstrated the good cortisol-capturing ability and SERS efficacy of the α-FeOOH@Au-aptamer profiling in the serum and urine samples. Our approach provides an alternative tool for cortisol analysis and a reference strategy for report-free SERS detection of small molecules.

CAS / MDL: 7647-14-5
研究领域: 生物化学 · 分析化学 · 纳米技术
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ACS Sensors · 2024 · IF 8.2

Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat

Yanan Luan,Yuting Zhou,Canjuan Li,Hongqiang Wang,Yuan Zhou,Qing Wang,Xiaoxiao He,Jin Huang,Jianbo Liu,Xiaohai Yang,Kemin Wang

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

CAS / MDL: 50-21-5
研究领域: 生物医学工程 · 分析化学
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OPTIK · 2023 · IF 3.1

Plasmonic dual-parameter optical fiber sensor for cortisol and glucose detection

Xingyu Wang,Xiaoyan Sun,Youwang Hu,Li Zeng,Ji’an Duan

The concentration of cortisol in the human body is related to health. Research has shown that the cortisol level in the body correlates with glucose. Therefore, simultaneously and sensitively measuring cortisol and glucose levels is very important for diabetic patients. A combination of biomolecules and metal nanoparticle surfaces can change the refractive index and induce a shift in the surface plasmon resonance (SPR) wavelength. Therefore, a sensor for cortisol and glucose detection is designed and fabricated. The logarithmic sensitivity of cortisol and glucose concentrations reach 5.267 nm/log(ng ml -1 ) and 9.878 nm/log(mM), respectively. The limits of detection (LODs) for the cortisol and glucose concentrations reach 0.0126 ng ml -1 and 1.136 × 10 −3 mM respectively. The detection range covers a concentration variation range of human saliva. The proposed sensor has a compact structure. In this work, it is proven that the sensor has good specificity and selectivity through experiments, and the technical methods of the sensor can be extended to applications in medical, biological and environmental detection.

研究领域: 生物医学工程 · 传感技术 · 光学检测
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ANALYTICA CHIMICA ACTA · 2024 · IF 5.7

Ultrasensitive cortisol electrochemical immunosensor amplifying by Au single-atom nanozymes and HRP enzymes

Yongling Du,Min Guo,Yan Chen,Xiaohui Mo,Junlei Cao,Fangdi Hu

Cortisol, a corticosteroid hormone as a primary stress hormone response to internal and external stress, has been regarded as a gold standard reliable biomarker to evaluate human mental stress. The double enzymes strategy, using nanozyme and enzyme amplifying the electrochemical signal, has been widely used to improve the performance of electrochemical biosensors. An ultra-sensitive electrochemical cortisol sensor based on Au single-atom nanozymes had been fabricated through HRP labeled anti-cortisol antibody binding with Au by Au-S bond. Based on the high catalytic activity of Au single-atom nanozymes and the high selectivity of HRP-labeled anti-cortisol antibodies, the cortisol electrochemical sensor-based Au single-atom nanozymes had an excellent response to cortisol, such as high electrochemical activity, high sensitivity, high selectivity, and wide linear range (0.15–300 ng.mL −1 ) and low detection (0.48 pg.mL −1 ) through the four-parameter logistic model with 95% confidence. The electrochemical cortisol sensor was used to determine the cortisol concentration of human saliva at different times.

研究领域: 生物医学工程 · 分析化学 · 纳米技术
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Biosensors-Basel · 2025 ·Vol. 15 ·期 3 ·194 · IF 5.6

A Wearable Molecularly Imprinted Electrochemical Sensor for Cortisol Stable Monitoring in Sweat

Yitao Chen,Zidong He,Yuanzhao Wu,Xinyu Bai,Yuancheng Li,Weiwei Yang,Yiwei Liu,Run-Wei Li

Cortisol, a steroid hormone, is closely associated with human mental stress. The rapid, real-time, and continuous detection of cortisol using wearable devices offers a promising approach for individual mental health. These devices must exhibit high sensitivity and long-term stability to ensure reliable performance. This study developed a wearable electrochemical sensor based on molecularly imprinted polymer (MIP) technology for real-time and dynamic monitoring of cortisol in sweat. A flexible gold (Au) electrode with interfacial hydrophilic treatment was employed to construct a highly stable electrode. The integration of a silk fibroin/polyvinylidene fluoride (SF/PVDF) composite membrane facilitates directional sweat transport, while liquid metal bonding enhances electrode flexibility and mechanical anti-delamination capability. The sensor exhibits an ultrawide detection range (0.1 pM to 5 μM), high selectivity (over 100-fold against interferents such as glucose and lactic acid), and long-term stability (less than 3.76% signal attenuation over 120 cycles). Additionally, a gradient modulus design was implemented to mitigate mechanical deformation interference under wearable conditions. As a flexible wearable device for cortisol monitoring in human sweat, the sensor’s response closely aligns with the diurnal cortisol rhythm, offering a highly sensitive and interference-resistant wearable solution for mental health monitoring and advancing personalized dynamic assessment of stress-related disorders.

研究领域: 生物医学工程 · 传感器技术 · 健康监测
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LAB ON A CHIP · 2024 ·Vol. 24 ·期 24 ·5384-5397 · IF 6.1

SERS-based pump-free microfluidic chip sensor for highly sensitive competitive immunoassay of cortisol in human sweat

Siyue Xiong,Chushu Zhu,Chengxuan Wang,Peitao Dong,Xuezhong Wu

Cortisol, known as the “stress hormone”, is secreted by the adrenal cortex. Measuring cortisol levels in body fluids is essential for evaluating stress levels, adrenal function, hormone imbalance, and psychological well-being. Early diagnosis and management of related conditions depend on this measurement. A rapid detection method that combines immunoassay and surface-enhanced Raman scattering (SERS) technology has become widely used in bioanalysis, offering benefits such as fast detection, high throughput, integrated microsystems, and high specificity. This study introduces a pump-free microfluidic chip integrating a solid-state SERS substrate to detect trace amounts of cortisol in bodily fluids through immunoassay. The method relies on a competitive reaction between cortisol and SERS tags with cortisol antigens immobilized on gold nanostructured substrates in a microfluidic environment. Two detection channels are used to provide controls and enhance measurement efficiency and accuracy. Solid-state gold nanostructured substrates offer a larger surface area for antibody capture and act as SERS-active substrates, which significantly enhance the Raman signal and improve the microsystem's sensitivity and applicability. Driven by a capillary pump, the sample can be loaded within 60 seconds, with the entire detection process taking less than 10 min, significantly reducing the detection time. Results indicate that the detection limit for cortisol is 10 pg mL−1, meeting clinical biomarker thresholds. The integrated SERS microfluidic chip shows great promise as an analytical tool for the rapid and sensitive diagnosis of cortisol in bodily fluids.

研究领域: 生物医学工程 · 分析化学 · 传感器技术
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npj Flexible Electronics · 2024 ·Vol. 8 ·期 1 ·1-10 · IF 12.3

High-precision flexible sweat self-collection sensor for mental stress evaluation

Wang Chenhao,Wang Zhengyu,Wei Wei,Zhang Zhenjie,Li Anne Ailina,Huang Guanghao,Li Xian,Ge Shuzhi Sam,Zhou Lianqun,Kong Hui

As a stress hormone existing in the human body, cortisol can reflect the psychological stress and health status in daily life, and is a potential biomarker of the body’s stress response. To effectively collect sweat and accurately identify the target, this paper reports a flexible wearable cortisol detection device with outstanding reliability and sensitivity. Molecular imprinted polymer (MIP) ensures cortisol specificity. And carbon nanotubes (CNT) on electrodes increase sensitivity, expanding the detection range to 10 −3 to 10 4  nM, with sensitivity at 189.2 nA/lg(nM). In addition, porous chitosan hydrogel (PCSH) collects sweat effectively, its adhesive properties and 80% swelling rate offer a low-cost alternative to microfluidics. Flexible printed circuit board (FPCB) and serpentine electrode (SE) ensure device durability. This non-invasive, highly sensitive device offers a novel method for mental stress monitoring and clinical diagnosis, advancing human physiological state monitoring.

研究领域: 生物医学工程 · 材料科学 · 生理学
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ANALYTICA CHIMICA ACTA · 2024 · IF 5.7

A low-fouling electrochemical biosensor based on BSA hydrogel doped with carbon black for the detection of cortisol in human serum

Xiaohang Yu,Weichen Meng,Yang Li,Xiliang Luo

Electrochemical biosensors with high sensitivity can detect low concentrations of biomarkers, but their practical detection applications in complex biological environments such as human serum and sweat are severely limited by the biofouling. Herein, a conductive hydrogel based on bovine serum albumin (BSA) and conductive carbon black (CCB) was prepared for the construction of an antifouling biosensor. The BSA hydrogel (BSAG) was doped with CCB, and the prepared composite hydrogel exhibited good conductivity originated from the CCB and antifouling capability owing to the BSA hydrogel. An antifouling biosensor for the sensitive detection of cortisol was fabricated by drop-coating the conductive hydrogel onto a poly(3,4-ethylenedioxythiophene) (PEDOT) modified electrode and further immobilizing the cortisol aptamer. The constructed biosensor showed a linear range of 100 pg mL −1 - 10 μg mL −1 and a limit of detection of 26.0 pg mL −1 for the detection of cortisol, and it was capable of assaying cortisol accurately in complex human serum. This strategy of preparing antifouling and conductive hydrogels provides an effective way to develop robust electrochemical biosensors for biomarker detection in complex biological media.

CAS / MDL: 126213-50-1
研究领域: 生物传感器 · 电化学 · 分析化学 · 生物医学工程
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