Advances in Electronic-Nose Technologies Developed for Biomedical Applications

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry

Diagnosis of pathological conditions through electronic nose analysis of urine samples: a systematic review and meta-analysis

Currently available urinalysis methods are often applied for screening and monitoring of several pathologies. However, traditionally analyzed biomarkers in urinalysis still lack sensitivity and specificity to accurately diagnose some diseases. Several studies have proposed the use of electronic noses (eNoses) for the analysis of volatile organic compounds in urine samples that may, directly or indirectly, correlate with certain pathologies. Hence, the aim of this study was to perform a systematic review and meta-analysis of studies concerning the use of portable electronic noses for diagnosis or monitoring of pathologies through analysis of urine samples. A systematic review of the literature was held according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-four articles met the inclusion criteria and were included in the analysis. The results of the revised studies showed that there are various volatile organic compound profiles, identified through eNose analysis, that may be applied for diagnosis or monitoring of several diseases, such as diabetes, urinary tract infection, inflammatory bowel disease, and kidney disease. A meta-analysis was conducted taking into consideration the data of 10 of the initial 24 articles. The pooled sensitivity, specificity, and diagnostic odds ratio were 84% (95% CI, 0.72–0.92), 85% (95% CI, 0.75–0.91), and 24.17 (95% CI: 7.85–74.41), respectively. The area under the receiver operating characteristic curve was 0.897. These results suggest that eNose technology has adequate diagnostic accuracy for several pathologies and could be a promising screening tool for clinical settings. However, more studies are needed to reduce heterogeneity between results.João Cavaleiro Rufo was funded by Fundação para a Ciência e Tecnologia through the Stimulus for Scientific Employment Individual Support (2020.01350.CEECIND). Mariana Farraia was funded by Fundação para a Ciência e Tecnologia through the PhD Grant Number SFRH/BD/145168/2019. This study was funded by FEDER through the Operational Program Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology, and Higher Education) under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2019)

Application and uses of electronic noses for clinical diagnosis on urine samples: A review

The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents

Sniffing out urinary tract infection—diagnosis based on volatile organic compounds and smell profile

Current available methods for the clinical diagnosis of urinary tract infection (UTI) rely on a urine dipstick test or culturing of pathogens. The dipstick test is rapid (available in 1–2 min), but has a low positive predictive value, while culturing is time-consuming and delays diagnosis (24–72 h between sample collection and pathogen identification). Due to this delay, broad-spectrum antibiotics are often prescribed immediately. The over-prescription of antibiotics should be limited, in order to prevent the development of antimicrobial resistance. As a result, there is a growing need for alternative diagnostic tools. This paper reviews applications of chemical-analysis instruments, such as gas chromatography–mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS), ion mobility spectrometry (IMS), field asymmetric ion mobility spectrometry (FAIMS) and electronic noses (eNoses) used for the diagnosis of UTI. These methods analyse volatile organic compounds (VOCs) that emanate from the headspace of collected urine samples to identify the bacterial pathogen and even determine the causative agent’s resistance to different antibiotics. There is great potential for these technologies to gain wide-spread and routine use in clinical settings, since the analysis can be automated, and test results can be available within minutes after sample collection. This could significantly reduce the necessity to prescribe broad-spectrum antibiotics and allow the faster and more effective use of narrow-spectrum antibiotics

Electronic nose implementation for biomedical applications

The growing rate of diabetes and undiagnosed diabetes related diseases is becoming a worldwide major health concern. The motivation of this thesis was to make use of a technology called the ‘electronic nose’ (eNose) for diagnosing diseases. It presents a comprehensive study on metabolic and gastro-intestinal disorders, choosing diabetes as a target disease. Using eNose technology with urinary volatile organic compounds (VOCs) is attractive as it allows non-invasive monitoring of various molecular constituents in urine. Trace gases in urine are linked to metabolic reactions and diseases. Therefore, urinary volatile compounds were used for diagnosis purposes in this thesis. The literature on existing eNose technologies, their pros and cons and applications in biomedical field was thoroughly reviewed, especially in detecting headspace of urine. Since the thesis investigates urinary VOCs, it is important to discover the stability of urine samples and their VOCs in time. It was discovered that urine samples lose their stability and VOCs emission after 9 months. A comprehensive study with 137 diabetic and healthy control urine samples was done to access the capability of commercially available eNose instruments for discrimination between these two groups. Metal oxide gas sensor based commercial eNose (Fox 4000, AlphaMOS Ltd) and field asymmetric ion mobility spectrometer (Lonestar, Owlstone Ltd) were used to analyse volatiles in urinary headspace. Both technologies were able to distinguish both groups with sensitivity and specificity of more than 90%. Then the project moved onto developing a Non-dispersive infrared (NDIR) sensor system that is non-invasive, low-cost, precise, rapid, simple and patient friendly, and can be used at both hospitals and homes. NDIR gas sensing is one of the most widely used optical gas detection techniques. NDIR system was used for diagnosing diabetes and gastro related diseases from patient’s wastes. To the best of the authors’ knowledge, this is the first and only developed tuneable NDIR eNose system. The developed optical eNose is able to scan the whole infrared range between 3.1μm and 10.5 μm with step size of 20 nm. To simulate the effect of background humidity and temperature on the sensor response, a gas test rig system that includes gas mixture, VOC generator, humidity generator and gas analyser was designed to enable the user to have control of gas flow, humidity and temperature. This also helps to find out system’s sensitivity and selectivity. Finally, after evaluating the sensitivity and selectivity of optical eNose, it was tested on simple and complex odours. The results were promising in discriminating the odours. Due to insufficient sample batches received from the hospital, synthetic urine samples were purchased, and diabetic samples were artificially made. The optical eNose was able to successfully separate artificial diabetic samples from non-diabetic ones

Electronic nose responses and acute phase proteins correlate in blood using a bovine respiratory infection

This study aimed (i) to assess the ability of electronic nose (e-nose) technology to differentiate between blood samples of experimentally infected and non-infected subjects, and (ii) to evaluate e-nose responses given by volatile organic compounds in relation to the acute phase reaction generated in the host. In an animal model of gram-negative bacterial infection (20 calves; intratracheal inoculation of Mannheimia haemolytica A1), the concentrations of the acute phase proteins (APPs; i.e. lipopolysaccharide binding protein and haptoglobin) were measured in serum samples before and after challenge, and headspaces of pre- and post-inoculation serum samples were analysed using a conducting polymer based e-nose. Significant changes of certain e-nose sensor responses allowed discrimination between samples before and after challenge. The maximal changes in responses of sensitive e-nose sensors corresponded to the peak of clinical signs. Significant correlations linked decreasing responses of multiple e-nose sensors to increasing concentrations of APPs in the peripheral blood

Development of a Portable Electronic Nose System for the Detection and Classification of Fruity Odors

In this study, we have developed a prototype of a portable electronic nose (E-Nose) comprising a sensor array of eight commercially available sensors, a data acquisition interface PCB, and a microprocessor. Verification software was developed to verify system functions. Experimental results indicate that the proposed system prototype is able to identify the fragrance of three fruits, namely lemon, banana, and litchi

Medical applications of artificial olfactometry

The present invention provides methods for detecting the presence of an analyte indicative of various medical conditions, including halitosis, periodontal disease and other diseases are also disclosed

Trace level detection of analytes using artificial olfactometry

The present invention provides a device for detecting the presence of an analyte, wherein said analyte is a microorganism marker gas. The device comprises a sample chamber having a fluid inlet port for the influx of the microorganism marker gas; a fluid concentrator in flow communication with the sample chamber, wherein the fluid concentrator has an absorbent material capable of absorbing the microorganism marker gas and thereafter releasing a concentrated microorganism marker gas; and an array of sensors in fluid communication with the concentrated microorganism marker gas. The sensor array detects and identifies the marker gas upon its release from fluid concentrate

The influence of smoking status on exhaled breath profiles in asthma and COPD patients

Breath analysis using eNose technology can be used to discriminate between asthma and COPD patients, but it remains unclear whether results are influenced by smoking status. We aim to study whether eNose can discriminate between ever- vs. never-smokers and smoking <24 vs. >24 h before the exhaled breath, and if smoking can be considered a confounder that influences eNose results. We performed a cross-sectional analysis in adults with asthma or chronic obstructive pulmonary disease (COPD), and healthy controls. Ever-smokers were defined as patients with current or past smoking habits. eNose measurements were performed by using the SpiroNose. The principal component (PC) described the eNose signals, and linear discriminant analysis determined if PCs classified ever-smokers vs. never-smokers and smoking <24 vs. >24 h. The area under the receiver-operator characteristic curve (AUC) assessed the accuracy of the models. We selected 593 ever-smokers (167 smoked <24 h before measurement) and 303 never-smokers and measured the exhaled breath profiles of discriminated ever- and never-smokers (AUC: 0.74; 95% CI: 0.66-0.81), and no cigarette consumption <24h (AUC 0.54, 95% CI: 0.43-0.65). In healthy controls, the eNose did not discriminate between ever or never-smokers (AUC 0.54; 95% CI: 0.49-0.60) and recent cigarette consumption (AUC 0.60; 95% CI: 0.50-0.69). The eNose could distinguish between ever and neversmokers in asthma and COPD patients, but not recent smokers. Recent smoking is not a confounding factor of eNose breath profiles