Standardized Extraction Techniques for Meat Analysis with the Electronic Tongue: A Case Study of Poultry and Red Meat Adulteration.

The electronic tongue (e-tongue) is an advanced sensor-based device capable of detecting low concentration differences in solutions. It could have unparalleled advantages for meat quality control, but the challenges of standardized meat extraction methods represent a backdrop that has led to its scanty application in the meat industry. This study aimed to determine the optimal dilution level of meat extract for e-tongue evaluations and also to develop three standardized meat extraction methods. For practicality, the developed methods were applied to detect low levels of meat adulteration using beef and pork mixtures and turkey and chicken mixtures as case studies. Dilution factor of 1% w/v of liquid meat extract was determined to be the optimum for discriminating 1% w/w, 3% w/w, 5% w/w, 10% w/w, and 20% w/w chicken in turkey and pork in beef with linear discriminant analysis accuracies (LDA) of 78.13% (recognition) and 64.73% (validation). Even higher LDA accuracies of 89.62% (recognition) and 68.77% (validation) were achieved for discriminating 1% w/w, 3% w/w, 5% w/w, 10% w/w, and 20% w/w of pork in beef. Partial least square models could predict both sets of meat mixtures with good accuracies. Extraction by cooking was the best method for discriminating meat mixtures and can be applied for meat quality evaluations with the e-tongue.

Exhaled breath profiling by electronic nose enabled discrimination of allergic rhinitis and extrinsic asthma.

AIM: To assess whether an e-nose could discriminate between subjects affected by allergic rhinitis with and without concomitant extrinsic asthma, as well as from healthy controls, in terms of exhaled VOC-profile. METHODS: Fourteen patients with Extrinsic Asthma and Allergic Rhinitis (AAR), 14 patients with Allergic Rhinitis without asthma (AR) and 14 healthy controls (HC) participated in a cross-sectional study. Exhaled breath was collected by a standardized method and sampled by an e-nose (Cyranose 320). Raw data were reduced by Principal component analysis and analyzed by canonical discriminant analysis. Cross-validation accuracy (CVA) and Receiver Operating Characteristic(ROC)-curves were calculated. External validation in newly recruited patients (7 AAR, 7 AR and 7 HC) was tested using the previous training model. RESULTS: Breathprints of patients with AR clustered from those with AAR (CVA = 85.7%), as well as HC (CVA = 82.1%). Breathprints from AAR were also separated from those of HC (CVA = 75.0%). External validation confirmed the above findings. CONCLUSIONS: An e-nose can discriminate exhaled breath from subjects with allergic rhinitis with and without extrinsic asthma, which represent two different diseases with partly overlapping features. This supports the view of using breath profiling to diagnose asthma also in patients with allergic rhinitis.

The need for external validation in machine olfaction: emphasis on health-related applications.

Over the last two decades, electronic nose research has produced thousands of research works. Many of them were describing the ability of the e-nose technology to solve diverse applications in domains ranging from food technology to safety, security, or health. It is, in fact, in the biomedical field where e-nose technology is finding a research niche in the last years. Although few success stories exist, most described applications never found the road to industrial or clinical exploitation. Most described methodologies were not reliable and were plagued by numerous problems that prevented practical application beyond the lab. This work emphasizes the need of external validation in machine olfaction. I describe some statistical and methodological pitfalls of the e-nose practice and I give some best practice recommendations for researchers in the field.

In tube integrated electronic nose system on a flexible polymer substrate.

The fabrication of electronic devices, such as gas sensors on flexible polymer substrates, enables the use of electronics in applications where conventional devices on stiff substrates could not be used. We demonstrate the development of a new intra-tube electronic-nose (e-nose) gas sensor device with multiple sensors fabricated and integrated on a flexible substrate. For this purpose, we developed a new method of fabricating a sensor array of four gas sensors on a flexible polymer substrate. The method allowed the use of lithography techniques to pattern different polymers with a broad range of solubility parameters. Conductive polymer composites were used as a gas sensitive layer due to the high stretchability of the material. Each of the 30 e-nose devices on one substrate was designed to fit on a polymer strip with a width of 2 mm. A single e-nose strip was successfully integrated into the inlet tube of a gas-measurement apparatus with an inner-tube diameter of 3 mm. Using the e-nose, we were able to differentiate between four different volatile solvent vapors. The tube-integrated e-nose outperformed a chamber-integrated e-nose of the same type in terms of response time and flow-rate influences. The sensor array inside the tube showed a faster response time and detected short pulses of analyte exposure compared to the same sensor array outside of the tube. We measured gas flow rates from 1,000 to 30 sccm without significant changes in sensor performance using this intra-tube e-nose prototype. The tube could be bent to radii < 15 mm with a sensor performance similar to an unbent sensor.

Overcoming the slow recovery of MOX gas sensors through a system modeling approach.

Metal Oxide Semiconductor (MOX) gas transducers are one of the preferable technologies to build electronic noses because of their high sensitivity and low price. In this paper we present an approach to overcome to a certain extent one of their major disadvantages: their slow recovery time (tens of seconds), which limits their suitability to applications where the sensor is exposed to rapid changes of the gas concentration. Our proposal consists of exploiting a double first-order model of the MOX-based sensor from which a steady-state output is anticipated in real time given measurements of the transient state signal. This approach assumes that the nature of the volatile is known and requires a precalibration of the system time constants for each substance, an issue that is also described in the paper. The applicability of the proposed approach is validated with several experiments in real, uncontrolled scenarios with a mobile robot bearing an e-nose.

Assessment of the Portable C-320 Electronic Nose for Discrimination of Nine Insectivorous Bat Species: Implications for Monitoring White-Nose Syndrome.

The development of new C-320 electronic-nose (e-nose) methods for pre-symptomatic detection of White-Nose Syndrome (WNS) in bats has required efficacy studies of instrument capabilities to discriminate between major sources of volatile organic compounds (VOCs) derived from clinical samples. In this phase-2 study, we further tested this e-nose for capabilities to distinguish between bat species based on differences in whole-body VOC emissions. Live healthy individuals of nine bat species were temporarily captured outside of caves in Arkansas and Louisiana. VOC emissions from bats were collected using newly developed portable air collection and sampling-chamber devices in tandem. Sensor-array output responses to bat VOC emissions were compared to those of 22 pure VOC analytical standards from five chemical classes. Distinct smellprint signatures were produced from e-nose analyses of VOC metabolites derived from individual bat species. Smellprint patterns were analyzed using 2-dimensional and 3-dimensional Principal Component Analysis (PCA) to produce aroma map plots showing effective discrimination between bat species with high statistical significance. These results demonstrate potential instrument efficacy for distinguishing between species-specific, bat-derived VOC metabolite emissions as major components of clinical samples collected from bats in caves for disease detection prior to symptom development. This study provided additional information required to fully test the efficacy of a portable e-nose instrument for diagnostic applications in subsequent phase-3 testing of noninvasive, early WNS disease detection in intra-cave hibernating bats.

A review of breath analysis techniques in head and neck cancer.

Cancers of the head and neck region are a severely disabling group of diseases with no method for early detection. Analysis of exhaled breath volatile organic compounds shows promise as biomarkers for early detection and disease monitoring. This article reviews breath analysis in the setting of head and neck cancer, with a practical focus on breath sampling techniques, detection technologies and valid data analysis methods. Title and abstract keyword searches were conducted on PubMed and Embase databases to identify English language studies without a time-period limitation. The main inclusion criteria were human studies comparing head and neck cancer patients to healthy controls using exhaled breath analysis. Multiple breath collection techniques, three major detection technologies and multiple data analysis methods were identified. However, the variability in techniques and lack of methodological standardization does not allow for adequate study replication or data pooling. Twenty-two volatile organic compounds identified in five studies have been reported to discriminate head and neck cancer patients from healthy controls. Breath analysis for detection of head and neck cancer shows promise as a non-invasive detection tool. However, methodological standardization is paramount for future research study design to provide the potential for translating these techniques into routine clinical use.

Recognition of breathprints of lung cancer and chronic obstructive pulmonary disease using the Aeonose® electronic nose.

OBJECTIVES: There is a high unmet need in a non-invasive screening of lung cancer (LC). We conducted this single-center trial to evaluate the effectiveness of the electronic nose Aeonose ® in LC recognition. MATERIALS AND METHODS: Exhaled volatile organic compound (VOC) signatures were collected by Aeonose ® in 42 incident and 78 prevalent LC patients, of them 29 LC patients in complete remission (LC CR), 33 healthy controls (HC) and 23 COPD patients. By dichotomous comparison of VOC's between incident LC and HC, a discriminating algorithm was established and also applied to LC CR and COPD subjects. Area under Curve (AUC), sensitivity, specificity and Matthews's correlation coefficient (MC) were used to interpret the data. RESULTS: The established algorithm of Aeonose ® signature allowed safe separation of LC and HC, showing an AUC of 0.92, sensitivity of 0.84 and a specificity of 0.97. When tested in a blinded fashion, the device recognized 19 out of 29 LC CR patients (=65.5%) as LC-positive, of which only five developed recurrent LC later on (after 18.6 months [Formula: see text]; mean value [Formula: see text]). Unfortunately, the algorithm also recognized 11 of 24 COPD patients as being LC positive (with only one of the 24 COPD patients developing LC 56 months after the measurement). CONCLUSION: The Aeonose ® revealed some potential in distinguishing LC from HC, however, with low specificity when applying the algorithm in a blinded fashion to other disease cohorts. We conclude that relevant VOC signals originating from comorbidities in LC such as COPD may have erroneously led to the separation between LC and controls. CLINICAL TRIAL REGISTRATION: (NCT02951416).

Volatile organic compounds in breath can serve as a non-invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer diagnosis in the Western world. AIM: To evaluate exhaled volatile organic compounds (VOCs) as a non-invasive biomarker for the detection of CRC and precursor lesions using an electronic nose. METHODS: In this multicentre study adult colonoscopy patients, without inflammatory bowel disease or (previous) malignancy, were invited for breath analysis. Two-thirds of the breath tests were randomly assigned to develop training models which were used to predict the diagnosis of the remaining patients (external validation). In the end, all data were used to develop final-disease models to further improve the discriminatory power of the algorithms. RESULTS: Five hundred and eleven breath samples were collected. Sixty-four patients were excluded due to an inadequate breath test (n = 51), incomplete colonoscopy (n = 8) or colitis (n = 5). Classification was based on the most advanced lesion found; CRC (n = 70), advanced adenomas (AAs) (n = 117), non-advanced adenoma (n = 117), hyperplastic polyp (n = 15), normal colonoscopy (n = 125). Training models for CRC and AAs had an area under the curve (AUC) of 0.76 and 0.71 and blind validation resulted in an AUC of 0.74 and 0.61 respectively. Final models for CRC and AAs yielded an AUC of 0.84 (sensitivity 95% and specificity 64%) and 0.73 (sensitivity and specificity 79% and 59%) respectively. CONCLUSIONS: This study suggests that exhaled VOCs could potentially serve as a non-invasive biomarker for the detection of CRC and AAs. Future studies including more patients could further improve the discriminatory potential of VOC analysis for the detection of (pre-)malignant colorectal lesions. (https://clinicaltrials.gov Identifier NCT03488537).

Diagnosing complex regional pain syndrome using an electronic nose, a pilot study.

OBJECTIVE: Complex regional pain syndrome (CRPS) is a complication after surgery or trauma and is characterized by a continuing regional pain in a distal extremity. The pain is disproportionate in severity and duration in relation to the preceding trauma. Currently, the diagnosis is based on the patients' signs and symptoms. There is no objective clinically applicable test available to confirm the diagnosis of CRPS, however this could contribute to a more reliable and valid diagnosis. Since the treatment of CRPS differs from that of other types of pain this could thereby lead to earlier and (more) appropriate treatment and possibly to lower medical costs. The Aeonose™ is a diagnostic test device which detects volatile organic profiles in exhaled air. Exhaled breath analysis using an electronic nose has been successfully applied to differentiate between sick and healthy persons for various indications. This study was a feasibility study in which we investigated whether the Aeonose™ is able to measure a difference in the volatome of CRPS patients compared to the volatome of healthy controls. DESIGN: Prospective observational study. SETTING: University Center for Pain Medicine. SUBJECTS: Adult patients diagnosed with CRPS according to the latest IASP criteria (n = 36) and matched healthy controls (n = 36). METHODS: Breath profiles were sampled by breathing in and out through the Aeonose™. Data were compressed using a Tucker3-like solution and subsequently used for training an artificial neural network together with the classification 'CRPS: Yes' or 'CRPS: No'. Cross-validation was applied using the leave-10%-out method. RESULTS: Data of the 72 participants were analyzed, resulting in a sensitivity of 83% (95% CI 67%-93%), specificity of 78% (95% CI 60%-89%), and an overall accuracy of 81%. CONCLUSIONS: This study suggests that the Aeonose™ can possibly distinguish patients with CRPS from healthy controls based on analysis of their volatome (MEC-2014-149).

Rapid Profiling of Soybean Aromatic Compounds Using Electronic Nose.

Soybean (Glycine max (L.)) is the world's most important seed legume, which contributes to 25% of global edible oil, and about two-thirds of the world's protein concentrate for livestock feeding. One of the factors that limit soybean's utilization as a major source of protein for humans is its characteristic soy flavor. This off-flavor can be attributed to the presence of various chemicals such as phenols, aldehydes, ketones, furans, alcohols, and amines. In addition, these flavor compounds interact with protein and cause the formation of new off-flavors. Hence, studying the chemical profile of soybean seeds is an important step in understanding how different chemical classes interact and contribute to the overall flavor profile of the crop. In our study, we utilized the HERCALES Fast Gas Chromatography (GC) electronic nose for identification and characterization of different volatile compounds in five high-yielding soybean varieties, and studied their association with off-flavors. With aroma profiling and chemical characterization, we aim to determine the quantity and quality of volatile compounds in these soybean varieties and understand their effect on the flavor profiles. The study could help to understand soybean flavor characteristics, which in turn could increase soybean use and enhance profitability.

Response Standardization for Drift Correction and Multivariate Calibration Transfer in "Electronic Tongue" Studies.

The procedures for response standardization in "electronic tongue" (ET) studies are described. The construction of reliable multivariate calibration for "electronic tongue" requires the analysis of a large number of representative samples both with ET and reference techniques. This is a laborious and expensive process. Long-term sensor array operation leads to the changes in sensor response characteristics and thus invalidates the multivariate predictive models. Moreover, due to the individual parameters of each sensor in different sensor arrays, it is not possible to use the calibration model for one system together with the data acquired by another system, even if they have the same sensors. Both of these issues lead to the necessity of frequent sensor array calibration which would be ideal to avoid. Instead of recalibration, these two problems can be handled using mathematical methods intended for sensor response standardization. This chapter describes two popular methods of standardization which can be used for both drift correction and calibration transfer. Thus, significant efforts on measuring representative sample sets for sensor array recalibration can be avoided.

Breath Analysis Using eNose and Ion Mobility Technology to Diagnose Inflammatory Bowel Disease-A Pilot Study.

Early diagnosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), remains a clinical challenge with current tests being invasive and costly. The analysis of volatile organic compounds (VOCs) in exhaled breath and biomarkers in stool (faecal calprotectin (FCP)) show increasing potential as non-invasive diagnostic tools. The aim of this pilot study is to evaluate the efficacy of breath analysis and determine if FCP can be used as an additional non-invasive parameter to supplement breath results, for the diagnosis of IBD. Thirty-nine subjects were recruited (14 CD, 16 UC, 9 controls). Breath samples were analysed using an in-house built electronic nose (Wolf eNose) and commercial gas chromatograph-ion mobility spectrometer (G.A.S. BreathSpec GC-IMS). Both technologies could consistently separate IBD and controls [AUC ± 95%, sensitivity, specificity], eNose: [0.81, 0.67, 0.89]; GC-IMS: [0.93, 0.87, 0.89]. Furthermore, we could separate CD from UC, eNose: [0.88, 0.71, 0.88]; GC-IMS: [0.71, 0.86, 0.62]. Including FCP did not improve distinction between CD vs UC; eNose: [0.74, 1.00, 0.56], but rather, improved separation of CD vs controls and UC vs controls; eNose: [0.77, 0.55, 1.00] and [0.72, 0.89, 0.67] without FCP, [0.81, 0.73, 0.78] and [0.90, 1.00, 0.78] with FCP, respectively. These results confirm the utility of breath analysis to distinguish between IBD-related diagnostic groups. FCP does not add significant diagnostic value to breath analysis within this study.

Evolution of Electronic Noses from Research Objects to Engineered Environmental Odour Monitoring Systems: A Review of Standardization Approaches.

Since electronic noses are used more and more for air quality monitoring purposes, and in some countries are starting to have a legal value, there is a need for standardization and programs for the quality verification of instruments. Such quality programs have the aim to guarantee the main characteristics of the instrument for both the final user and local authorities, let the user establish a suitable maintenance procedure and give information on measurement uncertainty. One critical aspect when dealing with electronic noses for environmental odour monitoring is that environmental odours are complex mixtures that are not repeatable nor reproducible, giving that they are not suitable for quality verifications. This paper aims to review and discuss the different approaches that can be adopted in order to perform quality checks on electronic noses (e-noses) used for environmental odour monitoring, thereby referring to existing technical standards, such as the Dutch NTA 9055:2012, the new German VDI 3518-3:2018, and the Italian UNI 1605848 project, which directly refer to electronic noses. Moreover, also the European technical standards that are prescriptive for automatic measuring systems (AMSs) are taken into consideration (i.e., EN 14181:2014 and EN 15267:2009), and their possible applicability to electronic noses is investigated. Finally, the pros and cons of the different approaches are presented and discussed in the conclusions section.

Use of Electronic Noses in Seawater Quality Monitoring: A Systematic Review.

Electronic nose (eNose) systems are particularly appreciated for their portability, usability, relative low cost, and real-time or near real-time response. Their application finds space in several domains, including environmental monitoring. Within this field, marine monitoring is of particular scientific relevance due to the fragility of this specific environment, daily threatened by human activities that can potentially bring to catastrophic and irreversible consequences on marine wildlife. Under such considerations, a systematic review, complying with the PRISMA guidelines, was conducted covering the period up to 15 October 2018, in PubMed, ScienceDirect, and Google Scholar. Despite the relatively low number of articles published on this specific topic and the heterogeneity of the technological approaches employed, the results obtained by the various groups highlight the positive contribution eNose has given and can provide in near future for the monitoring and safeguarding of this delicate environment.

The Smell of Hypoxia: using an electronic nose at altitude and proof of concept of its role in the prediction and diagnosis of acute mountain sickness.

Electronic nose (e-nose) devices may be used to identify volatile organic compounds (VOCs) in exhaled breath. VOCs generated via metabolic processes are candidate biomarkers of (patho)physiological pathways. We explored the feasibility of using an e-nose to generate human "breathprints" at high altitude. Furthermore, we explored the hypothesis that pathophysiological processes involved in the development of acute mountain sickness (AMS) would manifest as altered VOC profiles. Breath analysis was performed on Sherpa and lowlander trekkers at high altitude (3500 m). The Lake Louise Scoring (LLS) system was used to diagnose AMS. Raw data were reduced by principal component (PC) analysis (PCA). Cross validated linear discriminant analysis (CV-LDA) and receiver-operating characteristic area under curve (ROC-AUC) assessed discriminative function. Breathprints suitable for analysis were obtained from 58% (37/64) of samples. PCA showed significant differences between breathprints from participants with, and without, AMS; CV-LDA showed correct classification of 83.8%, ROC-AUC 0.86; PC 1 correlated with AMS severity. There were significant differences between breathprints of participants who remained AMS negative and those whom later developed AMS (CV-LDA 68.8%, ROC-AUC 0.76). PCA demonstrated discrimination between Sherpas and lowlanders (CV-LDA 89.2%, ROC-AUC 0.936). This study demonstrated the feasibility of breath analysis for VOCs using an e-nose at high altitude. Furthermore, it provided proof-of-concept data supporting e-nose utility as an objective tool in the prediction and diagnosis of AMS. E-nose technology may have substantial utility both in altitude medicine and under other circumstances where (mal)adaptation to hypoxia may be important (e.g., critically ill patients).