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Hakeem MK, Sallabi S, Ahmed R, Hamdan H, Mameri A, Alkaabi M, Alsereidi A, Elangovan SK, Shah I. A Dual Biomarker Approach to Stress: Hair and Salivary Cortisol Measurement in Students via LC-MS/MS. ANALYTICAL SCIENCE ADVANCES 2025; 6:e70003. [PMID: 39991187 PMCID: PMC11845309 DOI: 10.1002/ansa.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/23/2025] [Accepted: 02/01/2025] [Indexed: 02/25/2025]
Abstract
Stress is a significant issue among students, affecting both their mental and physical health. In this study, we investigated cortisol levels, a key biomarker for stress, in students at the United Arab Emirates University (UAEU) during their exam period. Using a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology we measured cortisol concentrations in hair and saliva samples and explored the potential correlation between exam-induced stress and cortisol levels. The results revealed an increase in cortisol levels during the exam period, with male students showing an average hair cortisol concentration of 150.625 pg/mg and female students displaying an average of 77.756 pg/mg. Salivary cortisol levels ranged from 0.002 to 9.189 ng/mL, with an overall average of 4.505 ng/mL. Statistical analysis revealed significant differences in cortisol levels between male and female students, underscoring the impact of exam-related stress on both acute and chronic stress markers. This study underscores the importance of addressing academic stress and suggests targeted strategies to mitigate its impact on student health ultimately fostering an environment encouraging both academic success and psychological well-being within the student community. Future research directions include exploring additional clinical parameters and expanding the study population to further understand the long-term effects of academic stress.
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Affiliation(s)
- Muhammad K. Hakeem
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Sundas Sallabi
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Raghda Ahmed
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Hana Hamdan
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Amel Mameri
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Mariam Alkaabi
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Asmaa Alsereidi
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Sampath K. Elangovan
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
| | - Iltaf Shah
- Department of ChemistryCollege of ScienceUnited Arab Emirates University (UAEU)Al AinUAE
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Sharma A, Hossain NI, Thomas A, Sonkusale S. Saliva-Sensing Dental Floss: An Innovative Tool for Assessing Stress via On-Demand Salivary Cortisol Measurement with Molecularly Imprinted Polymer and Thread Microfluidics Integration. ACS APPLIED MATERIALS & INTERFACES 2025; 17:25083-25096. [PMID: 40244717 DOI: 10.1021/acsami.5c02988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
On-demand dental-floss-based point-of-care platform is developed for the noninvasive and real-time quantification of salivary cortisol utilizing redox-molecule embedded molecularly imprinted polymer structures and thread microfluidics. Herein, we explore the high-surface-area graphene-based electrode substrate for electrochemically synthesizing selective cortisol MIPs and integrate it with thread microfluidics to build a highly sensitive cortisol-sensing platform for stress monitoring. This platform uses flossing to collect and transport saliva to a flexible electrochemical sensor via capillary microfluidics, where cortisol, a stress biomarker, is measured. This strategy allowed us to detect cortisol as low as 0.048 pg mL-1 in real-time with a detection range of 0.10-10,000 pg mL-1 (R2 = 0.9916). The saliva-sensing dental floss provides results within 11-12 min. The thread-based microfluidic design minimizes interference and ensures consistent repeatability when testing both artificial and actual human saliva samples, yielding 98.64-102.4% recoveries with a relative standard deviation of 5.01%, demonstrating high accuracy and precision. For the human saliva sample (as part of the stress study), the platform showed a high correlation (r = 0.9910) against conventional ELISA assays. Combined with a wireless readout, this saliva floss offers a convenient way to monitor daily stress levels. It can be extended to detect other critical salivary biomarkers with high sensitivity and selectivity in complex environments.
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Affiliation(s)
- Atul Sharma
- Sonkusale Research Laboratories (SRLs), Advanced Technology Laboratory, Tufts University, Medford, Massachusetts 02155, United States
- Department of Electrical and Computer Engineering, Tufts University, Medford, Massachusetts 02155, United States
| | - Nafize Ishtiaque Hossain
- Sonkusale Research Laboratories (SRLs), Advanced Technology Laboratory, Tufts University, Medford, Massachusetts 02155, United States
- Department of Electrical and Computer Engineering, Tufts University, Medford, Massachusetts 02155, United States
| | - Ayanna Thomas
- Department of Psychology, Tufts University, Medford, Massachusetts 02155, United States
| | - Sameer Sonkusale
- Sonkusale Research Laboratories (SRLs), Advanced Technology Laboratory, Tufts University, Medford, Massachusetts 02155, United States
- Department of Electrical and Computer Engineering, Tufts University, Medford, Massachusetts 02155, United States
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Deshpande P, De D, Badhe Y, Tallur S, Paul D, Rai B. An in silico design method of a peptide bioreceptor for cortisol using molecular modelling techniques. Sci Rep 2024; 14:22325. [PMID: 39333310 PMCID: PMC11436820 DOI: 10.1038/s41598-024-73044-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 09/12/2024] [Indexed: 09/29/2024] Open
Abstract
Cortisol is established as a reliable biomarker for stress prompting intensified research in developing wearable sensors to detect it via eccrine sweat. Since cortisol is present in sweat in trace quantities, typically 8-140 ng/mL, developing such biosensors necessitates the design of bioreceptors with appropriate sensitivity and selectivity. In this work, we present a systematic biomimetic methodology and a semi-automated high-throughput screening tool which enables rapid selection of bioreceptors as compared to ab initio design of peptides via computational peptidology. Candidate proteins from databases are selected via molecular docking and ranked according to their binding affinities by conducting automated AutoDock Vina scoring simulations. These candidate proteins are then validated via full atomistic steered molecular dynamics computations including umbrella sampling to estimate the potential of mean force using GROMACS version 2022.6. These explicit molecular dynamic calculations are carried out in an eccrine sweat environment taking into consideration the protein dynamics and solvent effects. Subsequently, we present a candidate baseline peptide bioreceptor selected as a contiguous sequence of amino acids from the selected protein binding pocket favourably interacting with the target ligand (i.e., cortisol) from the active binding site of the proteins and maintaining its tertiary structure. A unique cysteine residue introduced at the N-terminus allows orientation-specific surface immobilization of the peptide onto the gold electrodes and to ensure exposure of the binding site. Comparative binding affinity simulations of this peptide with the target ligand along with commonly interfering species e.g., progesterone, testosterone and glucose are also presented to demonstrate the validity of this proposed peptide as a candidate baseline bioreceptor for future cortisol biosensor development.
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Affiliation(s)
- Parijat Deshpande
- TCS Research, Tata Research Development & Design Centre (TRDDC), Pune, 411028, India.
- Centre for Research in Nanotechnology & Science (CRNTS), IIT Bombay, Mumbai, 400076, India.
| | - Debankita De
- TCS Research, Tata Research Development & Design Centre (TRDDC), Pune, 411028, India
| | - Yogesh Badhe
- TCS Research, Tata Research Development & Design Centre (TRDDC), Pune, 411028, India
| | - Siddharth Tallur
- Department of Electrical Engineering, IIT Bombay, Mumbai, 400076, India
| | - Debjani Paul
- Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, 400076, India
| | - Beena Rai
- TCS Research, Tata Research Development & Design Centre (TRDDC), Pune, 411028, India
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4
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Yin X, Ji X, Liu W, Li X, Wang M, Xin Q, Zhang J, Yan Z, Song A. Electrolyte-gated amorphous IGZO transistors with extended gates for prostate-specific antigen detection. LAB ON A CHIP 2024; 24:3284-3293. [PMID: 38847194 DOI: 10.1039/d4lc00247d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
The prostate-specific antigen (PSA) test is considered an important way for preoperative diagnosis and accurate screening of prostate cancer. Current antigen detection methods, including radioimmunoassay, enzyme-linked immunosorbent assay and microfluidic electrochemical detection, feature expensive equipment, long testing time and poor stability. Here, we propose a portable biosensor composed of electrolyte-gated amorphous indium gallium zinc oxide (a-IGZO) transistors with an extended gate, which can achieve real-time, instant PSA detection at a low operating voltage (<2 V) owing to the liquid-free ionic conductive elastomer (ICE) serving as the gate dielectric. The electric double layer (EDL) capacitance in ICE enhances the accumulation of carriers in the IGZO channel, leading to strong gate modulation, which enables the IGZO transistor to have a small subthreshold swing (<0.5 V dec-1) and a high on-state current (∼4 × 10-4 A). The separate, biodegradable, and pluggable sensing pad, serving as an extended gate connected to the IGZO transistor, prevents contamination and depletion arising from direct contact with biomolecular buffers, enabling the IGZO transistor to maintain superior electronic performance for at least six months. The threshold voltage and channel current of the transistor exhibit excellent linear response to PSA molecule concentrations across five orders of magnitude ranging from 1 fg mL-1 to 10 pg mL-1, with a detection limit of 400 ag mL-1 and a detection time of ∼5.1 s. The fabricated biosensors offer a point-of-care system for antigen detection, attesting the feasibility of the electrolyte-gated transistors in clinical screening, healthcare diagnostics and biological management.
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Affiliation(s)
- Xuemei Yin
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Xingqi Ji
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Wenlong Liu
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Xiaoqian Li
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Mingyang Wang
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Qian Xin
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
- State Key Laboratory of Crystal Materials, Institute of Novel Semiconductors, Shandong University, Jinan 250100, China
| | - Jiawei Zhang
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Zhuocheng Yan
- School of Integrated Circuits, Shandong University, Jinan 250100, China.
| | - Aimin Song
- Institute of Nanoscience and Applications, College of Engineering, Southern University of Science and Technology, Shenzhen 518055, China
- School of Electrical and Electronic Engineering, University of Manchester, Manchester M13 9PL, UK.
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Weber CJ, Clay OM, Lycan RE, Anderson GK, Simoska O. Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol. Anal Bioanal Chem 2024; 416:87-106. [PMID: 37989847 DOI: 10.1007/s00216-023-05047-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/30/2023] [Accepted: 11/08/2023] [Indexed: 11/23/2023]
Abstract
The monitoring of stress levels in humans has become increasingly relevant, given the recent incline of stress-related mental health disorders, lifestyle impacts, and chronic physiological diseases. Long-term exposure to stress can induce anxiety and depression, heart disease, and risky behaviors, such as drug and alcohol abuse. Biomarker molecules can be quantified in biological fluids to study human stress. Cortisol, specifically, is a hormone biomarker produced in the adrenal glands with biofluid concentrations that directly correlate to stress levels in humans. The rapid, real-time detection of cortisol is necessary for stress management and predicting the onset of psychological and physical ailments. Current methods, including mass spectrometry and immunoassays, are effective for sensitive cortisol quantification. However, these techniques provide only single measurements which pose challenges in the continuous monitoring of stress levels. Additionally, these analytical methods often require trained personnel to operate expensive instrumentation. Alternatively, low-cost electrochemical biosensors enable the real-time detection and continuous monitoring of cortisol levels while also providing adequate analytical figures of merit (e.g., sensitivity, selectivity, sensor response times, detection limits, and reproducibility) in a simple design platform. This review discusses the recent developments in electrochemical biosensor design for the detection of cortisol in human biofluids. Special emphasis is given to biosensor recognition elements, including antibodies, molecularly imprinted polymers (MIPs), and aptamers, as critical components of electrochemical biosensors for cortisol detection. Furthermore, the advantages and limiting factors of various electrochemical techniques and sensing in complex biofluid matrices are overviewed. Remarks on the current challenges and future perspectives regarding electrochemical biosensors for stress monitoring are provided, including matrix effects (pH dependence and biological interferences), wearability, and large-scale production.
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Affiliation(s)
- Courtney J Weber
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Olivia M Clay
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Reese E Lycan
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Gracie K Anderson
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Olja Simoska
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA.
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Mishra A, Agrawal M, Ali A, Garg P. Uninterrupted real-time cerebral stress level monitoring using wearable biosensors: A review. Biotechnol Appl Biochem 2023; 70:1895-1914. [PMID: 37455443 DOI: 10.1002/bab.2491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 06/15/2023] [Indexed: 07/18/2023]
Abstract
Stress is the major unseen bug for the health of humans with the increasing workaholic era. Long periods of avoidance are the main precursor for chronic disorders that are quite tough to treat. As precaution is better than cure, stress detection and monitoring are vital. Although there are ways to measure stress clinically, there is still a constant need and demand for methods that measure stress personally and in an ex vitro manner for the convenience of the user. The concept of continuous stress monitoring has been introduced to tackle the issue of unseen stress accumulating in the body simultaneously with being user-friendly and reliable. Stress biosensors nowadays provide real-time, noninvasive, and continuous monitoring of stress. These biosensors are innovative anthropogenic creations that are a combination of biomarkers and indicators like heart rate variation, electrodermal activity, skin temperature, galvanic skin response, and electroencephalograph of stress in the body along with machine learning algorithms and techniques. The collaboration of biological markers, artificial intelligence techniques, and data science tools makes stress biosensors a hot topic for research. These attributes have made continuous stress detection a possibility with ease. The advancement in stress biosensing technologies has made a great impact on the lives of human beings so far. This article focuses on the comprehensive study of stress-indicating biomarkers and the techniques along with principles of the biosensors used for continuous stress detection. The precise overview of wearable stress monitoring systems is also sectioned to pave a pathway for possible future research studies.
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Affiliation(s)
- Anuja Mishra
- Department of Biotechnology, Institute of Applied Science & Humanities, GLA University, Mathura, Uttar Pradesh, India
| | - Mukti Agrawal
- Department of Biotechnology, Institute of Applied Science & Humanities, GLA University, Mathura, Uttar Pradesh, India
| | - Aaliya Ali
- School of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh, India
- Center for Omics and Biodiversity Research, Shoolini University, Solan, Himachal Pradesh, India
| | - Prakrati Garg
- School of Applied Sciences and Biotechnology, Shoolini University, Solan, Himachal Pradesh, India
- Center for Omics and Biodiversity Research, Shoolini University, Solan, Himachal Pradesh, India
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7
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Alqahtani A, Kokkinis A, Zizzi C, Dilek N, Fischbeck KH, Heatwole CR, Grunseich C. Patient-Reported Impact of Symptoms in Spinal and Bulbar Muscular Atrophy. Neurol Clin Pract 2023; 13:e200213. [PMID: 39140081 PMCID: PMC11318780 DOI: 10.1212/cpj.0000000000200213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 08/23/2023] [Indexed: 08/15/2024]
Abstract
Background and Objectives The aim of this study was to determine the frequency and relative importance of symptoms experienced by patients with spinal and bulbar muscular atrophy (SBMA). Methods We conducted a cross-sectional study of 232 participants with SBMA. Participants provided input regarding 18 themes and 208 symptoms that affect patients with SBMA. Participants were asked about the relative importance of each symptom, and analysis was conducted to determine how age, education, disease duration, CAG repeat length, and ambulation status relate to symptom prevalence. Results Hip, thigh, or knee weakness (96.5%), fatigue (96.5%), problems with hands and fingers (95.7%), and limitations with walking (95.7%) were the themes with the highest prevalence in the study population. Ambulatory status was associated with the prevalence of 9 of the 14 themes, and CAG repeat length and education were each associated with 4 of 14 themes. The prevalence of fatigue was reduced in those with a lower CAG repeat length and increased with a longer disease duration. Younger patients reported a higher prevalence of emotional issues. Discussion There are a diversity of themes that are important to patients with SBMA. These themes have a variable level of importance to the population with SBMA and represent clinically meaningful outcome measures for future therapeutic interventions.
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Affiliation(s)
- Abdullah Alqahtani
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
| | - Angela Kokkinis
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
| | - Christine Zizzi
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
| | - Nuran Dilek
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
| | - Kenneth H Fischbeck
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
| | - Chad R Heatwole
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
| | - Christopher Grunseich
- Neurogenetics Branch (AA, AK, KHF, CG), National Institute of Neurological Disorders and Stroke, Bethesda, MD; and Department of Neurology (CZ, ND, CRH), University of Rochester, NY
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8
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Hadad M, Hadad N, Zestos AG. Carbon Electrode Sensor for the Measurement of Cortisol with Fast-Scan Cyclic Voltammetry. BIOSENSORS 2023; 13:626. [PMID: 37366991 DOI: 10.3390/bios13060626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 05/29/2023] [Accepted: 06/03/2023] [Indexed: 06/28/2023]
Abstract
Cortisol is a vital steroid hormone that has been known as the "stress hormone", which is elevated during times of high stress and anxiety and has a significant impact on neurochemistry and brain health. The improved detection of cortisol is critically important as it will help further our understanding of stress during several physiological states. Several methods exist to detect cortisol; however, they suffer from low biocompatibility and spatiotemporal resolution, and they are relatively slow. In this study, we developed an assay to measure cortisol with carbon fiber microelectrodes (CFMEs) and fast-scan cyclic voltammetry (FSCV). FSCV is typically utilized to measure small molecule neurotransmitters by producing a readout cyclic voltammogram (CV) for the specific detection of biomolecules on a fast, subsecond timescale with biocompatible CFMEs. It has seen enhanced utility in measuring peptides and other larger compounds. We developed a waveform that scanned from -0.5 to -1.2 V at 400 V/s to electro-reduce cortisol at the surface of CFMEs. The sensitivity of cortisol was found to be 0.87 ± 0.055 nA/μM (n = 5) and was found to be adsorption controlled on the surface of CFMEs and stable over several hours. Cortisol was co-detected with several other biomolecules such as dopamine, and the waveform was fouling resistant to repeated injections of cortisol on the surface of the CFMEs. Furthermore, we also measured exogenously applied cortisol into simulated urine to demonstrate biocompatibility and potential use in vivo. The specific and biocompatible detection of cortisol with high spatiotemporal resolution will help further elucidate its biological significance and further understand its physiological importance and impact on brain health.
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Affiliation(s)
- Michelle Hadad
- Department of Chemistry, American University, Washington, DC 20016, USA
| | - Nadine Hadad
- Department of Chemistry, American University, Washington, DC 20016, USA
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9
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Iqbal T, Elahi A, Wijns W, Shahzad A. Cortisol detection methods for stress monitoring in connected health. HEALTH SCIENCES REVIEW 2023; 6:100079. [DOI: 10.1016/j.hsr.2023.100079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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10
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Li W, Peng YF. Advances in microfluidic chips based on islet hormone-sensing techniques. World J Diabetes 2023; 14:17-25. [PMID: 36684385 PMCID: PMC9850799 DOI: 10.4239/wjd.v14.i1.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 11/11/2022] [Accepted: 12/07/2022] [Indexed: 01/10/2023] Open
Abstract
Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance. The mechanisms of islet dysfunction are still under investigation. Islet hormone secretion is the main function of islets, and serves an important role in the homeostasis of blood glucose. Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes. Therefore, it is crucial to develop accurate, real-time, labor-saving, high-throughput, automated, and cost-effective techniques for the sensing of islet secretome. Microfluidic chips, an elegant platform that combines biology, engineering, computer science, and biomaterials, have attracted tremendous interest from scientists in the field of diabetes worldwide. These tiny devices are miniatures of traditional experimental systems with more advantages of time-saving, reagent-minimization, automation, high-throughput, and online detection. These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years. In this review, we present a brief introduction of microfluidic chips, and three microfluidic chips-based islet hormone sensing techniques. We focus mainly on the theory of these techniques, and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.
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Affiliation(s)
- Wei Li
- Department of Endocrinology, Suzhou Hospital of Anhui Medical University, Suzhou 234000, Anhui Province, China
| | - You-Fan Peng
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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11
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Zhang X, Zhang Z, Diao W, Zhou C, Song Y, Wang R, Luo X, Liu G. Early-diagnosis of major depressive disorder: From biomarkers to point-of-care testing. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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12
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Panahi Z, Ren T, Halpern JM. Nanostructured Cyclodextrin-Mediated Surface for Capacitive Determination of Cortisol in Multiple Biofluids. ACS APPLIED MATERIALS & INTERFACES 2022; 14:42374-42387. [PMID: 35918826 PMCID: PMC9504479 DOI: 10.1021/acsami.2c07701] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
The aim of this work is to develop a reusable polypropylene glycol (PPG):β-cyclodextrin (βCD) biosensor for cortisol detection. To achieve the most stable support for βCD, we developed two PPG surfaces. The first surface is based on a gold surface modified with SAM of 3-mercaptopropionic acid (3MPA), and the second surface is based on a glassy carbon surface grafted with 4-carboxyphenyl diazonium salt. We characterized both surfaces by EIS, XPS, and ATR-FTIR and evaluated the stability and reusability of each surface. We found the GC-carboxyphenyl-PPG:βCD is stable for at least 1 month. We have also demonstrated the reusability of the surface up to 10 times. In detecting cortisol, we used a nonfaradaic electrochemical impedance capacitive model to interpret the surface confirmation changes. We achieved sensitive detection of cortisol in PBS buffer, urine, and saliva with limit of detection of 2.13, 1.29, and 1.33 nM, respectively.
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Affiliation(s)
- Zahra Panahi
- Department
of Chemical Engineering and Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, United States
| | - Tianyu Ren
- Department
of Chemical Engineering and Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, United States
| | - Jeffrey Mark Halpern
- Department
of Chemical Engineering and Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, United States
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An ultrasensitive electrochemical immunosensor based on in-situ growth of CuWO4 nanoparticles on MoS2 and chitosan-gold nanoparticles for cortisol detection. Microchem J 2022. [DOI: 10.1016/j.microc.2022.107434] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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14
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Nunes MJ, Moura JJG, Noronha JP, Branco LC, Samhan-Arias A, Sousa JP, Rouco C, Cordas CM. Evaluation of Sweat-Sampling Procedures for Human Stress-Biomarker Detection. ANALYTICA 2022; 3:178-194. [DOI: 10.3390/analytica3020013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/14/2024] Open
Abstract
Sweat is a potential biological fluid for the non-invasive analytical assessment of diverse molecules, including biomarkers. Notwithstanding, the sampling methodology is critical, and it must be assessed prior to using sweat for clinical diagnosis. In the current work, the analytical methodology was further developed taking into account the sampling step, in view of the identification and level variations of sweat components that have potential to be stress biomarkers using separation by liquid chromatography and detection by tandem mass spectrometry, in order to attain a screening profile of 26 molecules in just one stage. As such, the molecule identification was used as a test for the evaluation of the sampling procedures, including the location on the body, using patches for long-term sampling and vials for direct sampling, through a qualitative approach. From this evaluation it was possible to conclude that the sampling may be performed on the chest or back skin. Additionally, possible interference was evaluated. The long-term sampling with patches can be used under both rest and exercise conditions with variation of the detected molecule’s levels. The direct sampling, using vials, has the advantage of not having interferences but the disadvantage of only being effective after exercise in order to have enough sample for sweat analysis.
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Affiliation(s)
- Maria João Nunes
- LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
| | - José J. G. Moura
- LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
| | - João Paulo Noronha
- LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
| | - Luís Cobra Branco
- LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
| | - Alejandro Samhan-Arias
- LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
- Departamento de Bioquímica, Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), Universidad Autónoma de Madrid, C/Arturo Duperier 4, 28029 Madrid, Spain
| | - João P. Sousa
- CINAMIL, Academia Militar, Rua Gomes Freire, 1150-244 Lisboa, Portugal
| | - Carlos Rouco
- CINAMIL, Academia Militar, Rua Gomes Freire, 1150-244 Lisboa, Portugal
| | - Cristina M. Cordas
- LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
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15
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Naik AR, Zhou Y, Dey AA, Arellano DLG, Okoroanyanwu U, Secor EB, Hersam MC, Morse J, Rothstein JP, Carter KR, Watkins JJ. Printed microfluidic sweat sensing platform for cortisol and glucose detection. LAB ON A CHIP 2021; 22:156-169. [PMID: 34881383 DOI: 10.1039/d1lc00633a] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Wearable sweat biosensors offer compelling opportunities for improved personal health monitoring and non-invasive measurements of key biomarkers. Inexpensive device fabrication methods are necessary for scalable manufacturing of portable, disposable, and flexible sweat sensors. Furthermore, real-time sweat assessment must be analyzed to validate measurement reliability at various sweating rates. Here, we demonstrate a "smart bandage" microfluidic platform for cortisol detection and continuous glucose monitoring integrated with a synthetic skin. The low-cost, laser-cut microfluidic device is composed of an adhesive-based microchannel and solution-processed electrochemical sensors fabricated from inkjet-printed graphene and silver solutions. An antibody-derived cortisol sensor achieved a limit of detection of 10 pM and included a low-voltage electrowetting valve, validating the microfluidic sensor design under typical physiological conditions. To understand effects of perspiration rate on sensor performance, a synthetic skin was developed using soft lithography to mimic human sweat pores and sweating rates. The enzymatic glucose sensor exhibited a range of 0.2 to 1.0 mM, a limit of detection of 10 μM, and reproducible response curves at flow rates of 2.0 μL min-1 and higher when integrated with the synthetic skin, validating its relevance for human health monitoring. These results demonstrate the potential of using printed microfluidic sweat sensors as a low-cost, real-time, multi-diagnostic device for human health monitoring.
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Affiliation(s)
- Aditi R Naik
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
| | - Yiliang Zhou
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
| | - Anita A Dey
- Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | | | - Uzodinma Okoroanyanwu
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
| | - Ethan B Secor
- Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA
| | - Mark C Hersam
- Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA
- Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA
| | - Jeffrey Morse
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
| | - Jonathan P Rothstein
- Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Kenneth R Carter
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
| | - James J Watkins
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
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16
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Brunyé TT, Yau K, Okano K, Elliott G, Olenich S, Giles GE, Navarro E, Elkin-Frankston S, Young AL, Miller EL. Toward Predicting Human Performance Outcomes From Wearable Technologies: A Computational Modeling Approach. Front Physiol 2021; 12:738973. [PMID: 34566701 PMCID: PMC8458818 DOI: 10.3389/fphys.2021.738973] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 08/18/2021] [Indexed: 12/16/2022] Open
Abstract
Wearable technologies for measuring digital and chemical physiology are pervading the consumer market and hold potential to reliably classify states of relevance to human performance including stress, sleep deprivation, and physical exertion. The ability to efficiently and accurately classify physiological states based on wearable devices is improving. However, the inherent variability of human behavior within and across individuals makes it challenging to predict how identified states influence human performance outcomes of relevance to military operations and other high-stakes domains. We describe a computational modeling approach to address this challenge, seeking to translate user states obtained from a variety of sources including wearable devices into relevant and actionable insights across the cognitive and physical domains. Three status predictors were considered: stress level, sleep status, and extent of physical exertion; these independent variables were used to predict three human performance outcomes: reaction time, executive function, and perceptuo-motor control. The approach provides a complete, conditional probabilistic model of the performance variables given the status predictors. Construction of the model leverages diverse raw data sources to estimate marginal probability density functions for each of six independent and dependent variables of interest using parametric modeling and maximum likelihood estimation. The joint distributions among variables were optimized using an adaptive LASSO approach based on the strength and directionality of conditional relationships (effect sizes) derived from meta-analyses of extant research. The model optimization process converged on solutions that maintain the integrity of the original marginal distributions and the directionality and robustness of conditional relationships. The modeling framework described provides a flexible and extensible solution for human performance prediction, affording efficient expansion with additional independent and dependent variables of interest, ingestion of new raw data, and extension to two- and three-way interactions among independent variables. Continuing work includes model expansion to multiple independent and dependent variables, real-time model stimulation by wearable devices, individualized and small-group prediction, and laboratory and field validation.
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Affiliation(s)
- Tad T Brunyé
- Cognitive Science Team, US Army DEVCOM Soldier Center, Natick, MA, United States.,Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Kenny Yau
- Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Kana Okano
- Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Grace Elliott
- Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Sara Olenich
- Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Grace E Giles
- Cognitive Science Team, US Army DEVCOM Soldier Center, Natick, MA, United States.,Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Ester Navarro
- Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Seth Elkin-Frankston
- Cognitive Science Team, US Army DEVCOM Soldier Center, Natick, MA, United States.,Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States
| | - Alexander L Young
- Department of Statistics, Harvard University, Cambridge, MA, United States
| | - Eric L Miller
- Center for Applied Brain and Cognitive Sciences, Tufts University, Medford, MA, United States.,Department of Electrical and Computer Engineering, Tufts University, Medford, MA, United States
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17
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Perkins H, Higgins M, Marcato M, Galvin P, Teixeira SR. Immunosensor for Assessing the Welfare of Trainee Guide Dogs. BIOSENSORS 2021; 11:bios11090327. [PMID: 34562917 PMCID: PMC8465025 DOI: 10.3390/bios11090327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/04/2021] [Accepted: 09/06/2021] [Indexed: 11/16/2022]
Abstract
Cortisol is a well established biomarker hormone that regulates many processes in the body and is widely referred to as the stress hormone. Cortisol can be used as a stress marker to allow for detection of stress levels in dogs during the training process. This test will indicate if they will handle the stress under the training or if they might be more suitable as an assistant or companion dog. An immunosensor for detection of cortisol was developed using electrochemical impedance spectroscopy (EIS). The sensor was characterized using chemical and topographical techniques. The sensor was calibrated and its sensitivity determined using a cortisol concentration range of 0.0005 to 50 μg/mL. The theoretical limit of detection was found to be 3.57 fg/mL. When the immunosensor was tested on canine saliva samples, cortisol was detected and measured within the relevant physiological ranges in dogs.
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Affiliation(s)
- Hannah Perkins
- Tyndall National Institute, University College Cork, T12 R5CP Cork, Ireland; (H.P.); (M.H.); (M.M.); (P.G.)
- School of Chemistry, University College Cork, T12 YN60 Cork, Ireland
| | - Michelle Higgins
- Tyndall National Institute, University College Cork, T12 R5CP Cork, Ireland; (H.P.); (M.H.); (M.M.); (P.G.)
- School of Chemistry, University College Cork, T12 YN60 Cork, Ireland
| | - Marinara Marcato
- Tyndall National Institute, University College Cork, T12 R5CP Cork, Ireland; (H.P.); (M.H.); (M.M.); (P.G.)
| | - Paul Galvin
- Tyndall National Institute, University College Cork, T12 R5CP Cork, Ireland; (H.P.); (M.H.); (M.M.); (P.G.)
| | - Sofia Rodrigues Teixeira
- Tyndall National Institute, University College Cork, T12 R5CP Cork, Ireland; (H.P.); (M.H.); (M.M.); (P.G.)
- Correspondence: ; Tel.: +353-8-3155-4592
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18
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Mahmoodi SR, Xie P, Zachs DP, Peterson EJ, Graham RS, Kaiser CRW, Lim HH, Allen MG, Javanmard M. Single-step label-free nanowell immunoassay accurately quantifies serum stress hormones within minutes. SCIENCE ADVANCES 2021; 7:eabf4401. [PMID: 34193414 PMCID: PMC8245048 DOI: 10.1126/sciadv.abf4401] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 05/18/2021] [Indexed: 05/14/2023]
Abstract
A non-faradaic label-free cortisol sensing platform is presented using a nanowell array design, in which the two probe electrodes are integrated within the nanowell structure. Rapid and low volume (≤5 μl) sensing was realized through functionalizing nanoscale volume wells with antibodies and monitoring the real-time binding events. A 28-well plate biochip was built on a glass substrate by sequential deposition, patterning, and etching steps to create a stack nanowell array sensor with an electrode gap of 40 nm. Sensor response for cortisol concentrations between 1 and 15 μg/dl in buffer solution was recorded, and a limit of detection of 0.5 μg/dl was achieved. Last, 65 human serum samples were collected to compare the response from human serum samples with results from the standard enzyme-linked immunosorbent assay (ELISA). These results confirm that nanowell array sensors could be a promising platform for point-of-care testing, where real-time, laboratory-quality diagnostic results are essential.
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Affiliation(s)
| | - Pengfei Xie
- Rutgers University, Piscataway, NJ 08854, USA
| | | | | | | | | | - Hubert H Lim
- University of Minnesota, Minneapolis, MN 55455, USA
| | - Mark G Allen
- University of Pennsylvania, Philadelphia, PA 19104, USA
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19
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Sheibani S, Capua L, Kamaei S, Akbari SSA, Zhang J, Guerin H, Ionescu AM. Extended gate field-effect-transistor for sensing cortisol stress hormone. COMMUNICATIONS MATERIALS 2021; 2:10. [PMID: 33506228 PMCID: PMC7815575 DOI: 10.1038/s43246-020-00114-x] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 12/08/2020] [Indexed: 05/14/2023]
Abstract
Cortisol is a hormone released in response to stress and is a major glucocorticoid produced by adrenal glands. Here, we report a wearable sensory electronic chip using label-free detection, based on a platinum/graphene aptamer extended gate field effect transistor (EG-FET) for the recognition of cortisol in biological buffers within the Debye screening length. The device shows promising experimental features for real-time monitoring of the circadian rhythm of cortisol in human sweat. We report a hysteresis-free EG-FET with a voltage sensitivity of the order of 14 mV/decade and current sensitivity up to 80% over the four decades of cortisol concentration. The detection limit is 0.2 nM over a wide range, between 1 nM and 10 µM, of cortisol concentrations in physiological fluid, with negligible drift over time and high selectivity. The dynamic range fully covers those in human sweat. We propose a comprehensive analysis and a unified, predictive analytical mapping of current sensitivity in all regimes of operation.
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Affiliation(s)
- Shokoofeh Sheibani
- Nanolab, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
- Center of Excellence in Electrochemistry, School of Chemistry, University of Tehran, Tehran, Iran
| | - Luca Capua
- Nanolab, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Sadegh Kamaei
- Nanolab, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | | | | | | | - Adrian M. Ionescu
- Nanolab, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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20
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Urizar GG, Hernandez HS, Rayo J, Bhansali S. Validation of an Electrochemical Sensor to Detect Cortisol Responses to the Trier Social Stress Test. Neurobiol Stress 2020; 13:100263. [PMID: 33344716 PMCID: PMC7739168 DOI: 10.1016/j.ynstr.2020.100263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/28/2020] [Accepted: 10/15/2020] [Indexed: 11/24/2022] Open
Abstract
Recent advances in sensor technology allow for the detection of salivary cortisol levels in real-time, yet studies are needed to test their reliability in clinically at-risk populations. This study examined whether a new electrochemical sensor reliably detected cortisol patterns, compared to a conventional immunoassay test (i.e., ELISA), among women and men with low and high depressive symptoms who participated in the Trier Social Stress Test (TSST; a laboratory-based stressor). Results demonstrated that women and those with high depressive symptoms showed lower cortisol levels throughout the TSST overall compared to men and those with low depressive symptoms. The cortisol sensor was highly reliable when compared to the ELISA immunoassay in detecting cortisol responses to the TSST for both women and men and for participants with low and high depressive symptoms. These results suggest that the sensor is a promising tool for assessing real-time cortisol responses to laboratory stressors in at-risk populations.
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Affiliation(s)
- Guido G Urizar
- Department of Psychology, California State University, Long Beach, 1250 Bellflower Blvd, Long Beach, CA, 90840-0901, USA
| | - Hugo Sanchez Hernandez
- Department of Psychology, California State University, Long Beach, 1250 Bellflower Blvd, Long Beach, CA, 90840-0901, USA
| | - Jessica Rayo
- Department of Psychology, California State University, Long Beach, 1250 Bellflower Blvd, Long Beach, CA, 90840-0901, USA
| | - Shekhar Bhansali
- Department of Electrical & Computer Engineering, Florida International University, 10555 West Flagler St. EC 3900, Miami, FL, 33174, USA
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21
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Lee MA, Wang S, Jin X, Bakh NA, Nguyen FT, Dong J, Silmore KS, Gong X, Pham C, Jones KK, Muthupalani S, Bisker G, Son M, Strano MS. Implantable Nanosensors for Human Steroid Hormone Sensing In Vivo Using a Self-Templating Corona Phase Molecular Recognition. Adv Healthc Mater 2020; 9:e2000429. [PMID: 32940022 DOI: 10.1002/adhm.202000429] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 08/13/2020] [Indexed: 12/19/2022]
Abstract
Dynamic measurements of steroid hormones in vivo are critical, but steroid sensing is currently limited by the availability of specific molecular recognition elements due to the chemical similarity of these hormones. In this work, a new, self-templating synthetic approach is applied using corona phase molecular recognition (CoPhMoRe) targeting the steroid family of molecules to produce near infrared fluorescent, implantable sensors. A key limitation of CoPhMoRe has been its reliance on library generation for sensor screening. This problem is addressed with a self-templating strategy of polymer design, using the examples of progesterone and cortisol sensing based on a styrene and acrylic acid copolymer library augmented with an acrylated steroid. The pendant steroid attached to the corona backbone is shown to self-template the phase, providing a unique CoPhMoRE design strategy with high efficacy. The resulting sensors exhibit excellent stability and reversibility upon repeated analyte cycling. It is shown that molecular recognition using such constructs is viable even in vivo after sensor implantation into a murine model by employing a poly (ethylene glycol) diacrylate (PEGDA) hydrogel and porous cellulose interface to limit nonspecific absorption. The results demonstrate that CoPhMoRe templating is sufficiently robust to enable a new class of continuous, in vivo biosensors.
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Affiliation(s)
- Michael A. Lee
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Song Wang
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Xiaojia Jin
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Naveed Ali Bakh
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Freddy T. Nguyen
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Juyao Dong
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Kevin S. Silmore
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Xun Gong
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Crystal Pham
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Kelvin K. Jones
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Sureshkumar Muthupalani
- Division of Comparative Medicine Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Gili Bisker
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
- Department of Biomedical Engineering Tel‐Aviv University Tel Aviv 6997801 Israel
| | - Manki Son
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
| | - Michael S. Strano
- Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA
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22
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Zea M, Bellagambi FG, Ben Halima H, Zine N, Jaffrezic-Renault N, Villa R, Gabriel G, Errachid A. Electrochemical sensors for cortisol detections: Almost there. Trends Analyt Chem 2020. [DOI: 10.1016/j.trac.2020.116058] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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23
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Ku M, Kim J, Won JE, Kang W, Park YG, Park J, Lee JH, Cheon J, Lee HH, Park JU. Smart, soft contact lens for wireless immunosensing of cortisol. SCIENCE ADVANCES 2020; 6:eabb2891. [PMID: 32923592 PMCID: PMC7455488 DOI: 10.1126/sciadv.abb2891] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/26/2020] [Indexed: 05/04/2023]
Abstract
Despite various approaches to immunoassay and chromatography for monitoring cortisol concentrations, conventional methods require bulky external equipment, which limits their use as mobile health care systems. Here, we describe a human pilot trial of a soft, smart contact lens for real-time detection of the cortisol concentration in tears using a smartphone. A cortisol sensor formed using a graphene field-effect transistor can measure cortisol concentration with a detection limit of 10 pg/ml, which is low enough to detect the cortisol concentration in human tears. In addition, this soft contact lens only requires the integration of this cortisol sensor with transparent antennas and wireless communication circuits to make a smartphone the only device needed to operate the lens remotely without obstructing the wearer's view. Furthermore, in vivo tests using live rabbits and the human pilot experiment confirmed the good biocompatibility and reliability of this lens as a noninvasive, mobile health care solution.
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Affiliation(s)
- Minjae Ku
- Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
| | - Joohee Kim
- Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
| | - Jong-Eun Won
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
| | - Wonkyu Kang
- Department of Chemical Engineering, Myongji University, Yongin 17058, Republic of Korea
| | - Young-Geun Park
- Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
- School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
| | - Jihun Park
- Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
- School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
| | - Jae-Hyun Lee
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
- Advanced Science Institute, Yonsei University, Seoul 03722, Republic of Korea
| | - Jinwoo Cheon
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
- Advanced Science Institute, Yonsei University, Seoul 03722, Republic of Korea
- Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
| | - Hyun Ho Lee
- Department of Chemical Engineering, Myongji University, Yongin 17058, Republic of Korea
| | - Jang-Ung Park
- Nano Science Technology Institute, Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea
- Center for Nanomedicine, Institute for Basic Science (IBS), Seoul 03722, Republic of Korea
- Advanced Science Institute, Yonsei University, Seoul 03722, Republic of Korea
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24
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Zamkah A, Hui T, Andrews S, Dey N, Shi F, Sherratt RS. Identification of Suitable Biomarkers for Stress and Emotion Detection for Future Personal Affective Wearable Sensors. BIOSENSORS-BASEL 2020; 10:bios10040040. [PMID: 32316280 PMCID: PMC7235866 DOI: 10.3390/bios10040040] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 04/10/2020] [Accepted: 04/13/2020] [Indexed: 02/07/2023]
Abstract
Skin conductivity (i.e., sweat) forms the basis of many physiology-based emotion and stress detection systems. However, such systems typically do not detect the biomarkers present in sweat, and thus do not take advantage of the biological information in the sweat. Likewise, such systems do not detect the volatile organic components (VOC’s) created under stressful conditions. This work presents a review into the current status of human emotional stress biomarkers and proposes the major potential biomarkers for future wearable sensors in affective systems. Emotional stress has been classified as a major contributor in several social problems, related to crime, health, the economy, and indeed quality of life. While blood cortisol tests, electroencephalography and physiological parameter methods are the gold standards for measuring stress; however, they are typically invasive or inconvenient and not suitable for wearable real-time stress monitoring. Alternatively, cortisol in biofluids and VOCs emitted from the skin appear to be practical and useful markers for sensors to detect emotional stress events. This work has identified antistress hormones and cortisol metabolites as the primary stress biomarkers that can be used in future sensors for wearable affective systems.
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Affiliation(s)
- Abdulaziz Zamkah
- Biomedical Sciences and Biomedical Engineering, The University of Reading, Reading RG6 6AY, UK; (A.Z.); (T.H.); (S.A.)
| | - Terence Hui
- Biomedical Sciences and Biomedical Engineering, The University of Reading, Reading RG6 6AY, UK; (A.Z.); (T.H.); (S.A.)
| | - Simon Andrews
- Biomedical Sciences and Biomedical Engineering, The University of Reading, Reading RG6 6AY, UK; (A.Z.); (T.H.); (S.A.)
| | - Nilanjan Dey
- Department of Information Technology, Techno India College of Technology, West Bengal 700156, India;
| | - Fuqian Shi
- Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA;
| | - R. Simon Sherratt
- Biomedical Sciences and Biomedical Engineering, The University of Reading, Reading RG6 6AY, UK; (A.Z.); (T.H.); (S.A.)
- Correspondence: ; Tel.: +44-118-378-8588
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25
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Tu E, Pearlmutter P, Tiangco M, Derose G, Begdache L, Koh A. Comparison of Colorimetric Analyses to Determine Cortisol in Human Sweat. ACS OMEGA 2020; 5:8211-8218. [PMID: 32309731 PMCID: PMC7161047 DOI: 10.1021/acsomega.0c00498] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 03/19/2020] [Indexed: 05/14/2023]
Abstract
Colorimetric analysis, which relies on a chemical reaction to facilitate a change in visible color, is a great strategy for detecting cortisol, which is necessary to diagnose and manage the wide variety of diseases related to the hormone, because it is simple in design, inexpensive, and reliable as a standard cortisol analysis technique. In this study, four different colorimetric cortisol analyses that use various chromogens, which include sulfuric acid, Porter-Silber reagent, Prussian blue, and blue tetrazolium, are studied. Modifications to the classic Porter-Silber method are made by increasing the carbon content of the alcohol and adding gold nanoparticles, which result in a twofold increase in reaction rate and a slight decrease in the limit of detection (LoD). After a comparison of the reaction rate, LoD, dynamic range, characteristic peaks, and color stability of all methods, blue tetrazolium demonstrates a low LoD (97 ng/mL), broad dynamic range (0.05-2 μg/mL), and quick reaction rate (color development as fast as 10 min), which are well within the requirements for human biofluids. Cortisol in artificial saliva and sweat and in human sweat was determined while confirming that no excipients or other biomarkers interfered with the reactions. Twenty-one human sweat samples were tested using blue tetrazolium and revealed a significant difference between male and female apocrine cortisol concentrations and showed a highly significant difference between apocrine and eccrine cortisol concentrations. Colorimetric methods of cortisol can compete with existing electrochemical sensors because of their similar accuracy and detection range in certain wearable biosensor applications. The simplicity of colorimetric methods advances potential applications in skin-interfaced bio-electronics and point-of-care devices.
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Affiliation(s)
- Ethan Tu
- Department
of Biomedical Engineering, Binghamton University—State
University of New York, Binghamton, New York 13902, United States
- Department
of Biomedical Engineering, Michigan State
University, East Lansing, Michigan 48824, United States
| | - Paul Pearlmutter
- Department
of Biomedical Engineering, Binghamton University—State
University of New York, Binghamton, New York 13902, United States
| | - Michelle Tiangco
- Department
of Biomedical Engineering, Binghamton University—State
University of New York, Binghamton, New York 13902, United States
| | - Gia Derose
- Health
and Wellness Studies Department, Binghamton
University—State University of New York, Binghamton, New York 13902, United States
| | - Lina Begdache
- Health
and Wellness Studies Department, Binghamton
University—State University of New York, Binghamton, New York 13902, United States
| | - Ahyeon Koh
- Department
of Biomedical Engineering, Binghamton University—State
University of New York, Binghamton, New York 13902, United States
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26
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Jung YH, Kim JU, Lee JS, Shin JH, Jung W, Ok J, Kim TI. Injectable Biomedical Devices for Sensing and Stimulating Internal Body Organs. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2020; 32:e1907478. [PMID: 32104960 DOI: 10.1002/adma.201907478] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 01/15/2020] [Indexed: 06/10/2023]
Abstract
The rapid pace of progress in implantable electronics driven by novel technology has created devices with unconventional designs and features to reduce invasiveness and establish new sensing and stimulating techniques. Among the designs, injectable forms of biomedical electronics are explored for accurate and safe targeting of deep-seated body organs. Here, the classes of biomedical electronics and tools that have high aspect ratio structures designed to be injected or inserted into internal organs for minimally invasive monitoring and therapy are reviewed. Compared with devices in bulky or planar formats, the long shaft-like forms of implantable devices are easily placed in the organs with minimized outward protrusions via injection or insertion processes. Adding flexibility to the devices also enables effortless insertions through complex biological cavities, such as the cochlea, and enhances chronic reliability by complying with natural body movements, such as the heartbeat. Diverse types of such injectable implants developed for different organs are reviewed and the electronic, optoelectronic, piezoelectric, and microfluidic devices that enable stimulations and measurements of site-specific regions in the body are discussed. Noninvasive penetration strategies to deliver the miniscule devices are also considered. Finally, the challenges and future directions associated with deep body biomedical electronics are explained.
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Affiliation(s)
- Yei Hwan Jung
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
| | - Jong Uk Kim
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
| | - Ju Seung Lee
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
| | - Joo Hwan Shin
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
| | - Woojin Jung
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
| | - Jehyung Ok
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
| | - Tae-Il Kim
- School of Chemical Engineering, Department of Biomedical Engineering, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
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Electrochemical immunoassay for the detection of stress biomarkers. Heliyon 2020; 6:e03558. [PMID: 32211542 PMCID: PMC7082534 DOI: 10.1016/j.heliyon.2020.e03558] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 01/09/2020] [Accepted: 03/04/2020] [Indexed: 01/11/2023] Open
Abstract
A rapid electrochemical immunoassay method was developed to detect and measure stress biomarkers (cortisol and cortisone) in two biological samples (Zebrafish whole-body and artificial saliva). This methodology utilizes an immunoassay approach taking advantage of the lock and key mechanism that is related to the antibody-antigen interaction depending on the reliable immobilization of the antibody labelled with ferrocene tags (Ab-Fc) on a modified tin-doped indium oxide (ITO) electrode using electrochemical instrumentation to build a POC platform. The limit of detection (LOD) obtained for this biosensor was 1.03 pg ml−1 for cortisol and 0.68 pg ml−1 for cortisone, respectively. The correlation coefficient was 0.9852 and 0.9841 for cortisol and cortisone, respectively with a linear concentration from (0-50 ng ml−1) which covers the standard levels of stress hormones in both selected biological samples. The incubation time was investigated and 30 min was found to be the optimum incubation time. This time would be acceptable for the POC system as total process time can be determined within 35 min.
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28
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Su J, Du Y, Bevers K, Xiao P, Licciardone J, Brotto M, Gatchel RJ. Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain. J Transl Med 2019; 17:306. [PMID: 31492167 PMCID: PMC6729046 DOI: 10.1186/s12967-019-2030-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 08/18/2019] [Indexed: 11/24/2022] Open
Abstract
Background Identifying how pain transitions from acute to chronic is critical in designing effective prevention and management techniques for patients’ well-being, physically, psychosocially, and financially. There is an increasingly pressing need for a quantitative and predictive method to evaluate how low back pain trajectories are classified and, subsequently, how we can more effectively intervene during these progression stages. Methods In order to better understand pain mechanisms, we investigated, using computational modeling, how best to describe pain trajectories by developing a platform by which we studied the transition of acute chronic pain. Results The present study uses a computational neuroscience-based method to conduct such trajectory research, motivated by the use of hypothalamic–pituitary–adrenal (HPA) axis activity-history over a time-period as a way to mimic pain trajectories. A numerical simulation study is presented as a “proof of concept” for this modeling approach. Conclusions This model and its simulation results have highlighted the feasibility and the potential of developing such a broader model for patient evaluations.
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Affiliation(s)
- Jianzhong Su
- Department of Mathematics, University of Texas at Arlington, Arlington, USA
| | - Ying Du
- Department of Mathematics, East China University of Science and Technology, Shanghai, China
| | - Kelley Bevers
- Department of Psychology, University of Texas at Arlington, Arlington, USA
| | - Pengcheng Xiao
- Department of Mathematics, Kennesaw State University, 1100 South Marietta Pkwy, Marietta, GA, 30060, USA
| | - John Licciardone
- Department of Family Medicine, UNT Health Science Center, Fort Worth, USA
| | - Marco Brotto
- College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, USA
| | - Robert J Gatchel
- Department of Psychology, University of Texas at Arlington, Arlington, USA.
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29
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Liu X, Hsu SPC, Liu WC, Wang YM, Liu X, Lo CS, Lin YC, Nabilla SC, Li Z, Hong Y, Lin C, Li Y, Zhao G, Chung RJ. Salivary Electrochemical Cortisol Biosensor Based on Tin Disulfide Nanoflakes. NANOSCALE RESEARCH LETTERS 2019; 14:189. [PMID: 31165287 PMCID: PMC6548787 DOI: 10.1186/s11671-019-3012-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 05/13/2019] [Indexed: 05/06/2023]
Abstract
Cortisol, a steroid hormone, is secreted by the hypothalamic-pituitary-adrenal system. It is a well-known biomarker of psychological stress and is hence known as the "stress hormone." If cortisol overexpression is prolonged and repeated, dysfunction in the regulation of cortisol eventually occurs. Therefore, a rapid point-of-care assay to detect cortisol is needed. Salivary cortisol electrochemical analysis is a non-invasive method that is potentially useful in enabling rapid measurement of cortisol levels. In this study, multilayer films containing two-dimensional tin disulfide nanoflakes, cortisol antibody (C-Mab), and bovine serum albumin (BSA) were prepared on glassy carbon electrodes (GCE) as BSA/C-Mab/SnS2/GCE, and characterized using electrochemical impedance spectroscopy and cyclic voltammetry. Electrochemical responses of the biosensor as a function of cortisol concentrations were determined using cyclic voltammetry and differential pulse voltammetry. This cortisol biosensor exhibited a detection range from 100 pM to 100 μM, a detection limit of 100 pM, and a sensitivity of 0.0103 mA/Mcm2 (R2 = 0.9979). Finally, cortisol concentrations in authentic saliva samples obtained using the developed electrochemical system correlated well with results obtained using enzyme-linked immunosorbent assays. This biosensor was successfully prepared and used for the electrochemical detection of salivary cortisol over physiological ranges, based on the specificity of antibody-antigen interactions.
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Affiliation(s)
- Xinke Liu
- College of Materials Science and Engineering, Shenzhen University, No. 3688, Nanhai Ave, Shenzhen, 518060 China
| | - Sanford P. C. Hsu
- Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, 11217 Taiwan
- School of Medicine, National Yang Ming University, Taipei, 11221 Taiwan
| | - Wai-Ching Liu
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd, Taipei, 10608 Taiwan
| | - Yi-Min Wang
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd, Taipei, 10608 Taiwan
| | - Xinrui Liu
- Department of Neurosurgical Oncology, First Hospital, Jilin University, Changchun, 130021 China
| | - Ching-Shu Lo
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd, Taipei, 10608 Taiwan
| | - Yu-Chien Lin
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd, Taipei, 10608 Taiwan
| | - Sasza Chyntara Nabilla
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd, Taipei, 10608 Taiwan
| | - Zhiwen Li
- College of Materials Science and Engineering, Shenzhen University, No. 3688, Nanhai Ave, Shenzhen, 518060 China
| | - Yuehua Hong
- College of Materials Science and Engineering, Shenzhen University, No. 3688, Nanhai Ave, Shenzhen, 518060 China
| | - Chingpo Lin
- Department of Neurosurgical Oncology, First Hospital, Jilin University, Changchun, 130021 China
| | - Yunqian Li
- Department of Neurosurgical Oncology, First Hospital, Jilin University, Changchun, 130021 China
| | - Gang Zhao
- Department of Neurosurgical Oncology, First Hospital, Jilin University, Changchun, 130021 China
| | - Ren-Jei Chung
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No. 1, Sec. 3, Zhongxiao E. Rd, Taipei, 10608 Taiwan
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Khan MS, Dighe K, Wang Z, Srivastava I, Schwartz-Duval AS, Misra SK, Pan D. Electrochemical-digital immunosensor with enhanced sensitivity for detecting human salivary glucocorticoid hormone. Analyst 2019; 144:1448-1457. [PMID: 30608068 DOI: 10.1039/c8an02085j] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In this work, an ultra-sensitive electrochemical-digital sensor chip is devised for potential use as a digital stress analyzer for point-of-care testing (POCT) and preventive on-site recording of the hormone 'cortisol', a glucocorticoid class of steroid hormone present in the human saliva. The sensor was interfaced and re-configured with a high precision impedance converter system (AD5933) and used for electrochemical impedance spectroscopy (EIS) to evaluate the cortisol levels in seven saliva samples. To obtain enhanced biological (cortisol) recognition and achieve a lower limit of detection 0.87 ± 0.12 pg mL-1 (2.4 ± 0.38 pmol mL-1) with a wide range from 1 pg mL-1 to 10 ng mL-1 (2.75 pmol mL-1 to 27.58 pmol mL-1; R2 = 0.9831), bovine serum albumin (1% BSA) was utilized as an effective sensitivity enhancer in addition to optimizing the other two parameters: (i) anti-cortisol antibody (anti-CAb) covalently attached to micro-Au electrodes and (ii) saliva sample incubation time on the sensor chip. The results obtained in this work were corroborated with the gold standard ELISA test with an accuracy of 96.3% and other previously reported biosensors. We envisage that the conceivable standpoint of this study can be a practice towards new development in cortisol biosensing, which will be pertinent to POCT targeted for in vitro psychobiological study on patient cortisol in saliva, and finally an implantable sensor chip in the future.
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Affiliation(s)
- Muhammad S Khan
- Bioengineering Department, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
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31
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Chronic and acute stress monitoring by electrophysiological signals from adrenal gland. Proc Natl Acad Sci U S A 2019; 116:1146-1151. [PMID: 30617062 DOI: 10.1073/pnas.1806392115] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We present electrophysiological (EP) signals correlated with cellular cell activities in the adrenal cortex and medulla using an adrenal gland implantable flexible EP probe. With such a probe, we could observe the EP signals from the adrenal cortex and medulla in response to various stress stimuli, such as enhanced hormone activity with adrenocorticotropic hormone, a biomarker for chronic stress response, and an actual stress environment, like a forced swimming test. This technique could be useful to continuously monitor the elevation of cortisol level, a useful indicator of chronic stress that potentially causes various diseases.
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32
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Nandhakumar P, Haque AMJ, Lee NS, Yoon YH, Yang H. Washing-Free Displacement Immunosensor for Cortisol in Human Serum Containing Numerous Interfering Species. Anal Chem 2018; 90:10982-10989. [DOI: 10.1021/acs.analchem.8b02590] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Ponnusamy Nandhakumar
- Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea
| | - Al-Monsur Jiaul Haque
- Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea
| | | | | | - Haesik Yang
- Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea
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33
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Combining ecological momentary assessment with objective, ambulatory measures of behavior and physiology in substance-use research. Addict Behav 2018; 83:5-17. [PMID: 29174666 DOI: 10.1016/j.addbeh.2017.11.027] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 11/02/2017] [Accepted: 11/02/2017] [Indexed: 02/06/2023]
Abstract
Whereas substance-use researchers have long combined self-report with objective measures of behavior and physiology inside the laboratory, developments in mobile/wearable electronic technology are increasingly allowing for the collection of both subjective and objective information in participants' daily lives. For self-report, ecological momentary assessment (EMA), as implemented on contemporary smartphones or personal digital assistants, can provide researchers with near-real-time information on participants' behavior and mood in their natural environments. Data from portable/wearable electronic sensors measuring participants' internal and external environments can be combined with EMA (e.g., by timestamps recorded on questionnaires) to provide objective information useful in determining the momentary context of behavior and mood and/or validating participants' self-reports. Here, we review three objective ambulatory monitoring techniques that have been combined with EMA, with a focus on detecting drug use and/or measuring the behavioral or physiological correlates of mental events (i.e., emotions, cognitions): (1) collection and processing of biological samples in the field to measure drug use or participants' physiological activity (e.g., hypothalamic-pituitary-adrenal axis activity); (2) global positioning system (GPS) location information to link environmental characteristics (disorder/disadvantage, retail drug outlets) to drug use and affect; (3) ambulatory electronic physiological monitoring (e.g., electrocardiography) to detect drug use and mental events, as advances in machine learning algorithms make it possible to distinguish target changes from confounds (e.g., physical activity). Finally, we consider several other mobile/wearable technologies that hold promise to be combined with EMA, as well as potential challenges faced by researchers working with multiple mobile/wearable technologies simultaneously in the field.
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34
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Impact of Electrical Stimulation on Cortisol Secretion in Rat Adrenal Gland. BIOCHIP JOURNAL 2018. [DOI: 10.1007/s13206-017-2303-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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35
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Jang HJ, Lee T, Song J, Russell L, Li H, Dailey J, Searson PC, Katz HE. Electronic Cortisol Detection Using an Antibody-Embedded Polymer Coupled to a Field-Effect Transistor. ACS APPLIED MATERIALS & INTERFACES 2018; 10:16233-16237. [PMID: 29701946 PMCID: PMC6026499 DOI: 10.1021/acsami.7b18855] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
A field-effect transistor-based cortisol sensor was demonstrated in physiological conditions. An antibody-embedded polymer on the remote gate was proposed to overcome the Debye length issue (λD). The sensing membrane was made by linking poly(styrene- co-methacrylic acid) (PSMA) with anticortisol before coating the modified polymer on the remote gate. The embedded receptor in the polymer showed sensitivity from 10 fg/mL to 10 ng/mL for cortisol and a limit of detection (LOD) of 1 pg/mL in 1× PBS where λD is 0.2 nm. A LOD of 1 ng/mL was shown in lightly buffered artificial sweat. Finally, a sandwich ELISA confirmed the antibody binding activity of antibody-embedded PSMA.
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Affiliation(s)
- Hyun-June Jang
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Taein Lee
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Jian Song
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Luisa Russell
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Hui Li
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Jennifer Dailey
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Peter C. Searson
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
| | - Howard E. Katz
- Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2608, United States
- Corresponding Author: (H.E.K.)
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36
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Sankhala D, Muthukumar S, Prasad S. A Four-Channel Electrical Impedance Spectroscopy Module for Cortisol Biosensing in Sweat-Based Wearable Applications. SLAS Technol 2018; 23:529-539. [PMID: 29447045 DOI: 10.1177/2472630318759257] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
A four-channel electrochemical impedance spectroscopy (EIS) analyzer module has been demonstrated on flexible chemi-impedance sensors fabricated with gold electrodes for wearable applications. The module can perform time division multiplexed (TDM) impedance measurements on four sensors at 1 kHz. In this work, we characterize the system for the detection of cortisol in an ultralow volume (1-3 µL) of perspired human sweat, sensor performance, and effects during continuous cortisol dosing and with pH and temperature variations expected on the surface of the skin that would be representative of use conditions as seen by a wearable device. Detection of cortisol was shown for concentrations of 1 pg/mL to 200 ng/mL in both synthetic and perspired human sweat, and output response reported as a change in impedance with varying cortisol concentrations. Continuous dose testing was performed to demonstrate the stability of the sensors over prolonged periods of operation for cortisol concentrations within the physiologically relevant range of 10-200 ng/mL reported in human sweat. Temperature and pH effects testing was performed for pH range 4-8 and in a temperature chamber for the clinical range reported on the surface of human skin: 25-40 °C. The cortisol sensor demonstrated stability of operation with 7.58% variability under these conditions.
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Affiliation(s)
- Devangsingh Sankhala
- 1 Department of Electrical Engineering, The University of Texas at Dallas, Richardson, TX, USA
| | | | - Shalini Prasad
- 3 Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA
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37
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Chen LS, Singh RJ. Niche point-of-care endocrine testing - Reviews of intraoperative parathyroid hormone and cortisol monitoring. Crit Rev Clin Lab Sci 2018; 55:115-128. [PMID: 29357735 DOI: 10.1080/10408363.2018.1425975] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Point-of-care (POC) testing, which provides quick test results in near-patient settings with easy-to-use devices, has grown continually in recent decades. Among near-patient and on-site tests, rapid intraoperative and intra-procedural assays are used to quickly deliver critical information and thereby improve patient outcomes. Rapid intraoperative parathyroid hormone (ioPTH) monitoring measures postoperative reduction of parathyroid hormone (PTH) to predict surgical outcome in patients with primary hyperparathyroidism, and therefore contributes to the change of parathyroidectomy to a minimally invasive procedure. In this review, recent progress in applying ioPTH monitoring to patients with secondary and tertiary hyperparathyroidism and other testing areas is discussed. In-suite cortisol monitoring facilitates the use of adrenal vein sampling (AVS) for the differential diagnosis of primary aldosteronism and adrenocorticotropic hormone (ACTH)-independent Cushing syndrome. In clinical and psychological research settings, POC testing is also useful for rapidly assessing cortisol in plasma and saliva samples as a biomarker of stress. Careful resource utilization and coordination among stakeholders help to determine the best approach for implementing cost-effective POC testing. Technical advances in integrating appropriate biosensors with microfluidics-based devices hold promise for future real-time POC cortisol monitoring.
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Affiliation(s)
- Li-Sheng Chen
- a Bureau of Laboratories , Michigan Department of Health and Human Services , Lansing , MI , USA
| | - Ravinder J Singh
- b Laboratory Medicine and Pathology , Mayo Clinic , Rochester , MN , USA
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38
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Fernandez RE, Umasankar Y, Manickam P, Nickel JC, Iwasaki LR, Kawamoto BK, Todoki KC, Scott JM, Bhansali S. Disposable aptamer-sensor aided by magnetic nanoparticle enrichment for detection of salivary cortisol variations in obstructive sleep apnea patients. Sci Rep 2017; 7:17992. [PMID: 29269831 PMCID: PMC5740141 DOI: 10.1038/s41598-017-17835-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 11/26/2017] [Indexed: 11/09/2022] Open
Abstract
We report a disposable point-of-care sensing platform specific to salivary cortisol detection. The sensor is inkjet printed on a paper substrate with a metalloporphyrin based macrocyclic catalyst ink that can electrochemically reduce cortisol, captured by aptamer functionalized magnetic nanoparticles. The sensor consists of a thin magnet disc, aligned at the back of the electrode, in order to populate the magnetic nanoparticle bound cortisol at the sensing electrode area. Proof of concept studies were performed to detect salivary cortisol levels in human subjects with high and low risks for obstructive sleep apnea (OSA). High selectivity was observed to salivary cortisol against a background of closely related steroids.
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Affiliation(s)
- Renny Edwin Fernandez
- Bio-MEMS and Microsystems Laboratory, Department of Electrical and Computer Engineering, Florida International University, Miami, Florida, USA
| | - Yogeswaran Umasankar
- Biomolecular Sciences Institute, Florida International University, Miami, Florida, USA
| | - Pandiaraj Manickam
- Bio-MEMS and Microsystems Laboratory, Department of Electrical and Computer Engineering, Florida International University, Miami, Florida, USA
| | - Jeffrey C Nickel
- School of Dentistry, Departments of Orthodontics and Dentofacial Orthopedics and Oral and Craniofacial Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Laura R Iwasaki
- School of Dentistry, Departments of Orthodontics and Dentofacial Orthopedics and Oral and Craniofacial Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Burt K Kawamoto
- School of Dentistry, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Kristen C Todoki
- School of Dentistry, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - JoAnna M Scott
- School of Dentistry, Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Shekhar Bhansali
- Bio-MEMS and Microsystems Laboratory, Department of Electrical and Computer Engineering, Florida International University, Miami, Florida, USA.
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Aro K, Wei F, Wong DT, Tu M. Saliva Liquid Biopsy for Point-of-Care Applications. Front Public Health 2017; 5:77. [PMID: 28443278 PMCID: PMC5387045 DOI: 10.3389/fpubh.2017.00077] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 03/28/2017] [Indexed: 01/05/2023] Open
Abstract
Saliva is a non-invasive biofluid, which is easy to collect, transport, and store. Because of its accessibility and connection to systemic diseases, saliva is one of the best candidates for the advancement of point-of-care medicine, where individuals are able to easily monitor their health status by using portable convenient tools such as smartphones. There are a variety of scenarios with which saliva can be used: studies have been conducted on using saliva to measure stress hormones, enzyme levels, developmental disease biomarkers, and even cancer mutations. If validated biomarkers were combined with high-quality detection tools, saliva would open up a new frontier in high-quality healthcare, allowing physicians and patients to work together for real-time health monitoring and high-impact personalized preventative medicine. One of the most exciting emerging frontiers of saliva is liquid biopsy, which is a non-invasive means to assess the presence and characteristics of cancer in a patient. This article will review current basic knowledge of biomarkers, review their relation to different diseases and conditions, and explore liquid biopsy for point-of-care applications.
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Affiliation(s)
- Katri Aro
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Fang Wei
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - David T Wong
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Michael Tu
- School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
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40
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Khan MS, Misra SK, Wang Z, Daza E, Schwartz-Duval AS, Kus JM, Pan D, Pan D. Paper-Based Analytical Biosensor Chip Designed from Graphene-Nanoplatelet-Amphiphilic-diblock-co-Polymer Composite for Cortisol Detection in Human Saliva. Anal Chem 2017; 89:2107-2115. [DOI: 10.1021/acs.analchem.6b04769] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Muhammad S. Khan
- Biomedical
Research Center, Carle Foundation Hospital, Urbana, Illinois United States
| | - Santosh K. Misra
- Biomedical
Research Center, Carle Foundation Hospital, Urbana, Illinois United States
| | - Zhen Wang
- Biomedical
Research Center, Carle Foundation Hospital, Urbana, Illinois United States
| | - Enrique Daza
- Biomedical
Research Center, Carle Foundation Hospital, Urbana, Illinois United States
| | | | - Joseph M. Kus
- Biomedical
Research Center, Carle Foundation Hospital, Urbana, Illinois United States
| | | | - Dipanjan Pan
- Biomedical
Research Center, Carle Foundation Hospital, Urbana, Illinois United States
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41
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Usha SP, Shrivastav AM, Gupta BD. A contemporary approach for design and characterization of fiber-optic-cortisol sensor tailoring LMR and ZnO/PPY molecularly imprinted film. Biosens Bioelectron 2017; 87:178-186. [DOI: 10.1016/j.bios.2016.08.040] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Revised: 08/03/2016] [Accepted: 08/13/2016] [Indexed: 01/20/2023]
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RoyChoudhury S, Rawat V, Jalal AH, Kale S, Bhansali S. Recent advances in metamaterial split-ring-resonator circuits as biosensors and therapeutic agents. Biosens Bioelectron 2016; 86:595-608. [DOI: 10.1016/j.bios.2016.07.020] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 07/06/2016] [Accepted: 07/07/2016] [Indexed: 11/26/2022]
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Kaushik A, Yndart A, Jayant RD, Sagar V, Atluri V, Bhansali S, Nair M. Electrochemical sensing method for point-of-care cortisol detection in human immunodeficiency virus-infected patients. Int J Nanomedicine 2015; 10:677-85. [PMID: 25632229 PMCID: PMC4304596 DOI: 10.2147/ijn.s75514] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
A novel electrochemical sensing method was devised for the first time to detect plasma cortisol, a potential psychological stress biomarker, in human immunodeficiency virus (HIV)-positive subjects. A miniaturized potentiostat (reconfigured LMP91000 chip) interfaced with a microfluidic manifold containing a cortisol immunosensor was employed to demonstrate electrochemical cortisol sensing. This fully integrated and optimized electrochemical sensing device exhibited a wide cortisol-detection range from 10 pg/mL to 500 ng/mL, a low detection limit of 10 pg/mL, and sensitivity of 5.8 μA (pg mL)−1, with a regression coefficient of 0.995. This cortisol-selective sensing system was employed to estimate plasma cortisol in ten samples from HIV patients. The electrochemical cortisol-sensing performance was validated using an enzyme-linked immunosorbent assay technique. The results obtained using both methodologies were comparable within 2%–5% variation. The information related to psychological stress of HIV patients can be correlated with disease-progression parameters to optimize diagnosis, therapeutic, and personalized health monitoring.
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Affiliation(s)
- Ajeet Kaushik
- Center of Personalized Nanomedicine, Institute of Neuroimmune Pharmacology, Department of Immun ology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Adriana Yndart
- Center of Personalized Nanomedicine, Institute of Neuroimmune Pharmacology, Department of Immun ology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Rahul Dev Jayant
- Center of Personalized Nanomedicine, Institute of Neuroimmune Pharmacology, Department of Immun ology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Vidya Sagar
- Center of Personalized Nanomedicine, Institute of Neuroimmune Pharmacology, Department of Immun ology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Venkata Atluri
- Center of Personalized Nanomedicine, Institute of Neuroimmune Pharmacology, Department of Immun ology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Shekhar Bhansali
- BioMEMS Microsystems Laboratory, Department of Electrical and Computer Engineering, Florida International University, Miami, FL, USA
| | - Madhavan Nair
- Center of Personalized Nanomedicine, Institute of Neuroimmune Pharmacology, Department of Immun ology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
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