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Portable Electronic-Nose Devices for Noninvasive Early Disease Detection

A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 28682

Special Issue Editor

Head Research Pathologist, USDA Forest Service R&D, Southern Hardwoods Laboratory, Southern Research Station, Stoneville, MS 38776-0227, USA
Interests: electronic noses; biomedical applications; clinical diagnostics; chemical sensors; noninvasive early disease detection; disease biomarker identification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue focuses on recent developments in portable electronic-nose and related sensor devices developed for noninvasive early detection and diagnosis of diseases. Sensor technologies developed for early disease detection are moving into a new era of healthcare focused on precision medicine requiring utilization of methods and instruments that provide more rapid and accurate disease diagnoses that lead to more cost-effective and efficient treatments, improved prognoses, accelerated patient recovery, and reduced total healthcare costs. Early, more accurate diagnoses lead to more timely applications of targeted, prophylactic, and pretherapeutic treatments. Emphasis on early disease diagnostics aims to achieve disease detection far in advance of symptom development and to utilize smaller, more portable (easier to handle) disease detection devices that work equally well in remote field applications and clinical settings for initial point-of-care testing (POCT). A wide range of newer sensor technologies have been developed and applied to biomedical, veterinary, clinical, and diagnostic applications within the past five years. Some advantages include new capabilities ranging from detection of complex mixtures of volatile organic compounds (VOCs) to highly specific metabolites, e.g., disease biomarkers, uniquely associated with specific diseases. Some have capabilities to detect changes in host metabolic pathways (via identification of disease-associated metabolites) at relatively low cost, in real-time and with high sample throughput.

We will consider articles reporting original research or reviews on a wide range of sensor devices capable of achieving noninvasive early disease detection, with a focus on handheld and lightweight portable devices, but also considering larger devices with sensor technologies that could potentially be miniaturized through improvements and innovations in sensor technology. These include devices developed specifically for applications in field, laboratory, clinical, and point-of-care testing. We are particularly interested in receiving papers reporting on novel technologies with new approaches to early disease diagnostics that potentially improve on currently used, conventional diagnostic methods and procedures.

Dr. Alphus D. Wilson
Guest Editor

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Keywords

  • Clinical pathology
  • Chemical disease biomarkers
  • Disease diagnostics
  • Electronic-nose devices
  • Metabolomics
  • Noninvasive early disease detection
  • Point-of-care testing (POCT)
  • Portable disease-detection instruments
  • Volatile organic compounds
  • Telemedicine

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

10 pages, 217 KiB  
Editorial
Developments of Recent Applications for Early Diagnosis of Diseases Using Electronic-Nose and Other VOC-Detection Devices
by Alphus Dan Wilson
Sensors 2023, 23(18), 7885; https://doi.org/10.3390/s23187885 - 14 Sep 2023
Cited by 1 | Viewed by 979
Abstract
This Editorial provides summaries and an overview of research and review articles published in the Sensors journal, volumes 21 (2021), 22 (2022), and 23 (2023), within the biomedical Special Issue “Portable Electronic-Nose Devices for Noninvasive Early Disease Detection”, which focused on recent sensors, [...] Read more.
This Editorial provides summaries and an overview of research and review articles published in the Sensors journal, volumes 21 (2021), 22 (2022), and 23 (2023), within the biomedical Special Issue “Portable Electronic-Nose Devices for Noninvasive Early Disease Detection”, which focused on recent sensors, biosensors, and clinical instruments developed for noninvasive early detection and diagnosis of human and animal diseases. The ten articles published in this Special Issue provide new information associated with recent electronic-nose (e-nose) and related volatile organic compound (VOC)-detection technologies developed to improve the effectiveness and efficiency of diagnostic methodologies for early disease detection prior to symptom development. For review purposes, the summarized articles were placed into three broad groupings or topic areas, including veterinary-wildlife pathology, human clinical pathology, and the detection of dietary effects on VOC emissions. These specified categories were used to define sectional headings devoted to related research studies with a commonality based on a particular disease being investigated or type of analytical instrument used in analyses. Full article

Research

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12 pages, 1178 KiB  
Article
Electronic Nose Sensor Drift Affects Diagnostic Reliability and Accuracy of Disease-Specific Algorithms
by Sofie Bosch, Renée X. de Menezes, Suzanne Pees, Dion J. Wintjens, Margien Seinen, Gerd Bouma, Johan Kuyvenhoven, Pieter C. F. Stokkers, Tim G. J. de Meij and Nanne K. H. de Boer
Sensors 2022, 22(23), 9246; https://doi.org/10.3390/s22239246 - 28 Nov 2022
Cited by 4 | Viewed by 1478
Abstract
Sensor drift is a well-known disadvantage of electronic nose (eNose) technology and may affect the accuracy of diagnostic algorithms. Correction for this phenomenon is not routinely performed. The aim of this study was to investigate the influence of eNose sensor drift on the [...] Read more.
Sensor drift is a well-known disadvantage of electronic nose (eNose) technology and may affect the accuracy of diagnostic algorithms. Correction for this phenomenon is not routinely performed. The aim of this study was to investigate the influence of eNose sensor drift on the development of a disease-specific algorithm in a real-life cohort of inflammatory bowel disease patients (IBD). In this multi-center cohort, patients undergoing colonoscopy collected a fecal sample prior to bowel lavage. Mucosal disease activity was assessed based on endoscopy. Controls underwent colonoscopy for various reasons and had no endoscopic abnormalities. Fecal eNose profiles were measured using Cyranose 320®. Fecal samples of 63 IBD patients and 63 controls were measured on four subsequent days. Sensor data displayed associations with date of measurement, which was reproducible across all samples irrespective of disease state, disease activity state, disease localization and diet of participants. Based on logistic regression, corrections for sensor drift improved accuracy to differentiate between IBD patients and controls based on the significant differences of six sensors (p = 0.004; p < 0.001; p = 0.001; p = 0.028; p < 0.001 and p = 0.005) with an accuracy of 0.68. In this clinical study, short-term sensor drift affected fecal eNose profiles more profoundly than clinical features. These outcomes emphasize the importance of sensor drift correction to improve reliability and repeatability, both within and across eNose studies. Full article
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26 pages, 3705 KiB  
Article
Piezoelectric Gas Sensors with Polycomposite Coatings in Biomedical Application
by Anastasiia Shuba, Tatiana Kuchmenko and Ruslan Umarkhanov
Sensors 2022, 22(21), 8529; https://doi.org/10.3390/s22218529 - 05 Nov 2022
Cited by 5 | Viewed by 1995
Abstract
When developing methods for diagnosing pathologies and diseases in humans and animals using electronic noses, one of the important trends is the miniaturization of devices, while maintaining significant information for diagnostic purposes. A combination of several sorbents that have unique sorption features of [...] Read more.
When developing methods for diagnosing pathologies and diseases in humans and animals using electronic noses, one of the important trends is the miniaturization of devices, while maintaining significant information for diagnostic purposes. A combination of several sorbents that have unique sorption features of volatile organic compounds (VOCs) on one transducer is a possible option for the miniaturization of sensors for gas analysis. This paper considers the principles of creating polycomposite coatings on the electrodes of piezoelectric quartz resonators, including the choice of sorbents for the formation of sensitive layers, determining the mass and geometry of the formation of sensitive layers in a polycomposite coating, as well as an algorithm for processing the output data of sensors to obtain maximum information about the qualitative and quantitative composition of the gas phase. A comparative analysis of the efficiency and kinetics of VOC vapor sorption by sensors with polycomposite coatings and a set of sensors with relevant single coatings has been carried out. Regression equations have been obtained to predict the molar-specific sensitivity of the microbalance of VOC vapors by a sensor with a polycomposite coating of three sorbents with an error of 5–15% based on the results of the microbalance of VOC vapors on single coatings. A method for creating “visual prints” of sensor signals with polycomposite coatings is shown, with results comparable to those from an array of sensors. The parameters Aij are proposed for obtaining information on the qualitative composition of the gas phase when processing the output data of sensors with polycomposite coatings. A biochemical study of exhaled breath condensate (EBC) samples, a microbiological investigation of calf tracheal washes, and a clinical examination were conducted to assess the presence of bovine respiratory disease (BRD). An analysis of the gas phase over EBC samples with an array of sensors with polycomposite coatings was also carried out. The “visual prints” of the responses of sensors with polycomposite coatings and the results of the identification of VOCs in the gas phase over EBC samples were compared to the results of bacteriological studies of tracheal washes of the studied calves. A connection was found between the parameters Aij of a group of sensors with polycomposite coatings and the biochemical parameters of biosamples. The adequacy of replacing an array of piezoelectric sensors with single coatings by the sensors with polycomposite coatings is shown. Full article
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19 pages, 2793 KiB  
Article
Noninvasive Detection of Bacterial Infection in Children Using Piezoelectric E-Nose
by Tatiana Kuchmenko, Daria Menzhulina and Anastasiia Shuba
Sensors 2022, 22(21), 8496; https://doi.org/10.3390/s22218496 - 04 Nov 2022
Cited by 8 | Viewed by 1575
Abstract
Currently, antibiotics are often prescribed to children without reason due to the inability to quickly establish the presence of a bacterial etiology of the disease. One way to obtain additional diagnostic information quickly is to study the volatile metabolome of biosamples using arrays [...] Read more.
Currently, antibiotics are often prescribed to children without reason due to the inability to quickly establish the presence of a bacterial etiology of the disease. One way to obtain additional diagnostic information quickly is to study the volatile metabolome of biosamples using arrays of sensors. The goal of this work was to assess the possibility of using an array of chemical sensors with various sensitive coatings to determine the presence of a bacterial infection in children by analyzing the equilibrium gas phase (EGP) of urine samples. The EGP of 90 urine samples from children with and without a bacterial infection (urinary tract infection, soft tissue infection) was studied on the “MAG-8” device with seven piezoelectric sensors in a hospital. General urine analysis with sediment microscopy was performed using a Uriscan Pro analyzer and using an Olympus CX31 microscope. After surgical removal of the source of inflammation, the microbiological studies of the biomaterial were performed to determine the presence and type of the pathogen. The most informative output data of an array of sensors have been established for diagnosing bacterial pathology. Regression models were built to predict the presence of a bacterial infection in children with an error of no more than 15%. An indicator of infection is proposed to predict the presence of a bacterial infection in children with a high sensitivity of 96%. Full article
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8 pages, 1850 KiB  
Communication
The Role of a Polymer-Based E-Nose in the Detection of Head and Neck Cancer from Exhaled Breath
by Roberta Anzivino, Pasqua Irene Sciancalepore, Silvano Dragonieri, Vitaliano Nicola Quaranta, Paolo Petrone, Domenico Petrone, Nicola Quaranta and Giovanna Elisiana Carpagnano
Sensors 2022, 22(17), 6485; https://doi.org/10.3390/s22176485 - 29 Aug 2022
Cited by 13 | Viewed by 2064
Abstract
The aim of our study was to assess whether a polymer-based e-nose can distinguish head and neck cancer subjects from healthy controls, as well as from patients with allergic rhinitis. A total number of 45 subjects participated in this study. The first group [...] Read more.
The aim of our study was to assess whether a polymer-based e-nose can distinguish head and neck cancer subjects from healthy controls, as well as from patients with allergic rhinitis. A total number of 45 subjects participated in this study. The first group was composed of 15 patients with histology confirmed diagnosis of head and neck cancer. The second group was made up of 15 patients with diagnoses of allergic rhinitis. The control group consisted of 15 subjects with a negative history of upper airways and/or chest symptoms. Exhaled breath was collected from all participants and sampled by a polymer-based e-nose (Cyranose 320, Sensigent, Pasadena, CA, USA). In the Principal Component Analysis plot, patients with head and neck cancer clustered distinctly from the controls as well as from patients with allergic rhinitis. Using canonical discriminant analysis, the three groups were discriminated, with a cross validated accuracy% of 75.1, p < 0.01. The area under the curve of the receiver operating characteristic curve for the discrimination between head and neck cancer patients and the other groups was 0.87. To conclude, e-nose technology has the potential for application in the diagnosis of head and neck cancer, being an easy, quick, non-invasive and cost-effective tool. Full article
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10 pages, 948 KiB  
Article
Prediction of Inflammatory Bowel Disease Course Based on Fecal Scent
by Sofie Bosch, Dion S. J. Wintjens, Alfian Wicaksono, Marieke Pierik, James A. Covington, Tim G. J. de Meij and Nanne K. H. de Boer
Sensors 2022, 22(6), 2316; https://doi.org/10.3390/s22062316 - 17 Mar 2022
Cited by 5 | Viewed by 2436
Abstract
The early prediction of changes in disease state allows timely treatment of patients with inflammatory bowel disease (IBD) to be performed, which improves disease outcome. The aim of this pilot study is to explore the potential of fecal volatile organic compound (VOC) profiles [...] Read more.
The early prediction of changes in disease state allows timely treatment of patients with inflammatory bowel disease (IBD) to be performed, which improves disease outcome. The aim of this pilot study is to explore the potential of fecal volatile organic compound (VOC) profiles to predict disease course. In this prospective cohort, IBD patients were asked to collect two fecal samples and fill in a questionnaire at set intervals. Biochemically, active disease was defined by FCP ≥ 250 mg/g and remission was defined by FCP < 100 mg/g. Clinically, active disease was defined by a Harvey Bradshaw Index (HBI) ≥ 5 for Crohn’s disease or by a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3 for ulcerative colitis. Clinical remission was defined by an HBI < 4 or SCCAI ≤ 2. Fecal VOC profiles were measured using gas chromatography-ion mobility spectrometry (GC-IMS). The fecal samples collected first were included for VOC analysis to predict disease state at the following collection. A total of 182 subsequently collected samples met the disease-state criteria. The fecal VOC profiles of samples displaying low FCP levels at the first measurements differed between patients preceding exacerbation versus those who remained in remission (AUC 0.75; p < 0.01). Samples with FCP levels at the first time point displayed different VOC profiles in patients preceding remission compared with those whose disease remained active (AUC 0.86; p < 0.01). Based on disease activity scores, there were no significant differences in any of the comparisons. Alterations in fecal VOC profiles preceding changes in FCP levels may be useful to detect disease-course alterations at an early stage. This could lead to earlier treatment, decreased numbers of complications, surgery and hospital admission. Full article
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12 pages, 819 KiB  
Article
Minimal Gluten Exposure Alters Urinary Volatile Organic Compounds in Stable Coeliac Disease
by Michael McFarlane, Ramesh P. Arasaradnam, Beryl Reed, Emma Daulton, Alfian Wicaksono, Heena Tyagi, James A. Covington and Chuka Nwokolo
Sensors 2022, 22(3), 1290; https://doi.org/10.3390/s22031290 - 08 Feb 2022
Cited by 3 | Viewed by 1910
Abstract
Coeliac disease (CD) patients are distinguishable from healthy individuals via urinary volatile organic compounds (VOCs) analysis. We exposed 20 stable CD patients on gluten-free diet (GFDs) to a 14-day, 3 g/day gluten challenge (GCh), and assessed urinary VOC changes. A control cohort of [...] Read more.
Coeliac disease (CD) patients are distinguishable from healthy individuals via urinary volatile organic compounds (VOCs) analysis. We exposed 20 stable CD patients on gluten-free diet (GFDs) to a 14-day, 3 g/day gluten challenge (GCh), and assessed urinary VOC changes. A control cohort of 20 patients continued on GFD. Urine samples from Days 0, 7, 14, 28 and 56 were analysed using Lonestar FAIMS and Markes Gas Chromatography–Time of Flight–Mass Spectrometer (GC-TOF-MS). VOC signatures on D (day) 7–56 were compared with D0. Statistical analysis was performed using R. In GCh patients, FAIMS revealed significant VOC differences for all time points compared to D0. GC-TOF-MS revealed significant changes at D7 and D14 only. In control samples, FAIMS revealed significant differences at D7 only. GC-TOF-MS detected no significant differences. Chemical analysis via GC-MS-TOF revealed 12 chemicals with significantly altered intensities at D7 vs. D0 for GCh patients. The alterations persisted for six chemicals at D14 and one (N-methyltaurine) remained altered after D14. This low-dose, short-duration challenge was well tolerated. FAIMS and GC-TOF-MS detected VOC signature changes in CD patients when undergoing a minimal GCh. These findings suggest urinary VOCs could have a role in monitoring dietary compliance in CD patients. Full article
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27 pages, 3816 KiB  
Article
Biomarker Metabolites Discriminate between Physiological States of Field, Cave and White-nose Syndrome Diseased Bats
by Anna C. Doty, A. Dan Wilson, Lisa B. Forse and Thomas S. Risch
Sensors 2022, 22(3), 1031; https://doi.org/10.3390/s22031031 - 28 Jan 2022
Cited by 2 | Viewed by 2357
Abstract
Analysis of volatile organic compound (VOC) emissions using electronic-nose (e-nose) devices has shown promise for early detection of white-nose syndrome (WNS) in bats. Tricolored bats, Perimyotis subflavus, from three separate sampling groups defined by environmental conditions, levels of physical activity, and WNS-disease [...] Read more.
Analysis of volatile organic compound (VOC) emissions using electronic-nose (e-nose) devices has shown promise for early detection of white-nose syndrome (WNS) in bats. Tricolored bats, Perimyotis subflavus, from three separate sampling groups defined by environmental conditions, levels of physical activity, and WNS-disease status were captured temporarily for collection of VOC emissions to determine relationships between these combinations of factors and physiological states, Pseudogymnoascus destructans (Pd)-infection status, and metabolic conditions. Physiologically active (non-torpid) healthy individuals were captured outside of caves in Arkansas and Louisiana. In addition, healthy and WNS-diseased torpid bats were sampled within caves in Arkansas. Whole-body VOC emissions from bats were collected using portable air-collection and sampling-chamber devices in tandem. Electronic aroma-detection data using three-dimensional Principal Component Analysis provided strong evidence that the three groups of bats had significantly different e-nose aroma signatures, indicative of different VOC profiles. This was confirmed by differences in peak numbers, peak areas, and tentative chemical identities indicated by chromatograms from dual-column GC-analyses. The numbers and quantities of VOCs present in whole-body emissions from physiologically active healthy field bats were significantly greater than those of torpid healthy and diseased cave bats. Specific VOCs were identified as chemical biomarkers of healthy and diseased states, environmental conditions (outside and inside of caves), and levels of physiological activity. These results suggest that GC/E-nose dual-technologies based on VOC-detection and analyses of physiological states, provide noninvasive alternative means for early assessments of Pd-infection, WNS-disease status, and other physiological states. Full article
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14 pages, 1358 KiB  
Article
Quantitative GC–TCD Measurements of Major Flatus Components: A Preliminary Analysis of the Diet Effect
by Rafael Freire, Marianela Mego, Luciana Fontes Oliveira, Silvia Mas, Fernando Azpiroz, Santiago Marco and Antonio Pardo
Sensors 2022, 22(3), 838; https://doi.org/10.3390/s22030838 - 22 Jan 2022
Cited by 6 | Viewed by 5535
Abstract
The impact of diet and digestive disorders in flatus composition remains largely unexplored. This is partially due to the lack of standardized sampling collection methods, and the easy atmospheric contamination. This paper describes a method to quantitatively determine the major gases in flatus [...] Read more.
The impact of diet and digestive disorders in flatus composition remains largely unexplored. This is partially due to the lack of standardized sampling collection methods, and the easy atmospheric contamination. This paper describes a method to quantitatively determine the major gases in flatus and their application in a nutritional intervention. We describe how to direct sample flatus into Tedlar bags, and simultaneous analysis by gas chromatography–thermal conductivity detection (GC–TCD). Results are analyzed by univariate hypothesis testing and by multilevel principal component analysis. The reported methodology allows simultaneous determination of the five major gases with root mean measurement errors of 0.8% for oxygen (O2), 0.9% for nitrogen (N2), 0.14% for carbon dioxide (CO2), 0.11% for methane (CH4), and 0.26% for hydrogen (H2). The atmospheric contamination was limited to 0.86 (95% CI: [0.7–1.0])% for oxygen and 3.4 (95% CI: [1.4–5.3])% for nitrogen. As an illustration, the method has been successfully applied to measure the response to a nutritional intervention in a reduced crossover study in healthy subjects. Full article
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17 pages, 2786 KiB  
Article
Non-Invasive Detection and Staging of Colorectal Cancer Using a Portable Electronic Nose
by Heena Tyagi, Emma Daulton, Ayman S. Bannaga, Ramesh P. Arasaradnam and James A. Covington
Sensors 2021, 21(16), 5440; https://doi.org/10.3390/s21165440 - 12 Aug 2021
Cited by 21 | Viewed by 4133
Abstract
Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy–to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). [...] Read more.
Electronic noses (e-nose) offer potential for the detection of cancer in its early stages. The ability to analyse samples in real time, at a low cost, applying easy–to-use and portable equipment, gives e-noses advantages over other technologies, such as Gas Chromatography-Mass Spectrometry (GC-MS). For diseases such as cancer with a high mortality, a technology that can provide fast results for use in routine clinical applications is important. Colorectal cancer (CRC) is among the highest occurring cancers and has high mortality rates, if diagnosed late. In our study, we investigated the use of portable electronic nose (PEN3), with further analysis using GC-TOF-MS, for the analysis of gases and volatile organic compounds (VOCs) to profile the urinary metabolome of colorectal cancer. We also compared the different cancer stages with non-cancers using the PEN3 and GC-TOF-MS. Results obtained from PEN3, and GC-TOF-MS demonstrated high accuracy for the separation of CRC and non-cancer. PEN3 separated CRC from non-cancerous group with 0.81 AUC (Area Under the Curve). We used data from GC-TOF-MS to obtain a VOC profile for CRC, which identified 23 potential biomarker VOCs for CRC. Thus, the PEN3 and GC-TOF-MS were found to successfully separate the cancer group from the non-cancer group. Full article
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Review

Jump to: Editorial, Research

42 pages, 517 KiB  
Review
Potential for Early Noninvasive COVID-19 Detection Using Electronic-Nose Technologies and Disease-Specific VOC Metabolic Biomarkers
by Alphus Dan Wilson and Lisa Beth Forse
Sensors 2023, 23(6), 2887; https://doi.org/10.3390/s23062887 - 07 Mar 2023
Cited by 7 | Viewed by 2517
Abstract
The established efficacy of electronic volatile organic compound (VOC) detection technologies as diagnostic tools for noninvasive early detection of COVID-19 and related coronaviruses has been demonstrated from multiple studies using a variety of experimental and commercial electronic devices capable of detecting precise mixtures [...] Read more.
The established efficacy of electronic volatile organic compound (VOC) detection technologies as diagnostic tools for noninvasive early detection of COVID-19 and related coronaviruses has been demonstrated from multiple studies using a variety of experimental and commercial electronic devices capable of detecting precise mixtures of VOC emissions in human breath. The activities of numerous global research teams, developing novel electronic-nose (e-nose) devices and diagnostic methods, have generated empirical laboratory and clinical trial test results based on the detection of different types of host VOC-biomarker metabolites from specific chemical classes. COVID-19-specific volatile biomarkers are derived from disease-induced changes in host metabolic pathways by SARS-CoV-2 viral pathogenesis. The unique mechanisms proposed from recent researchers to explain how COVID-19 causes damage to multiple organ systems throughout the body are associated with unique symptom combinations, cytokine storms and physiological cascades that disrupt normal biochemical processes through gene dysregulation to generate disease-specific VOC metabolites targeted for e-nose detection. This paper reviewed recent methods and applications of e-nose and related VOC-detection devices for early, noninvasive diagnosis of SARS-CoV-2 infections. In addition, metabolomic (quantitative) COVID-19 disease-specific chemical biomarkers, consisting of host-derived VOCs identified from exhaled breath of patients, were summarized as possible sources of volatile metabolic biomarkers useful for confirming and supporting e-nose diagnoses. Full article
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