A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology.

INTRODUCTION: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer. METHODS: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models. RESULTS: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001). CONCLUSIONS: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.

Use of Sensor Array Analysis to Detect Ovarian Cancer through Breath, Urine, and Blood: A Case-Control Study.

Ovarian cancer (OC) is the eighth most common cancer in women. Since screening programs do not exist, it is often diagnosed in advanced stages. Today, the detection of OC is based on clinical examination, transvaginal ultrasound (US), and serum biomarker (Carbohydrate Antigen 125 (CA 125) and Human Epididymis Protein 4 (HE4)) dosage, with a sensitivity of 88% and 95%, respectively, and a specificity of 84% for US and 76% for biomarkers. These methods are clearly not enough, and OC in its early stages is often missed. Many scientists have recently focused their attention on volatile organic compounds (VOCs). These are gaseous molecules, found in the breath, that could provide interesting information on several diseases, including solid tumors. To detect VOCs, an electronic nose was invented by a group of researchers. A similar device, the e-tongue, was later created to detect specific molecules in liquids. For the first time in the literature, we investigated the potential use of the electronic nose and the electronic tongue to detect ovarian cancer not just from breath but also from urine, blood, and plasma samples.

Integration of voltammetric analysis, protein electrophoresis and pH measurement for diagnosis of pleural effusions: a non-conventional diagnostic approach.

Pleural effusion is very common, but an etiologic diagnosis is often difficult. We used three unconventional diagnostic techniques (voltammetric analysis, protein electrophoresis and pH measurement) performed on pleural effusion to do a preliminary distinction between a neoplastic and a non-neoplastic origin. Pleural fluid samples were collected through thoracentesis, thoracoscopy, or post-surgery pleural drainage of 116 patients admitted to acute care wards. Samples were analyzed with the three unconventional techniques: voltammetric analysis using the BIONOTE system, capillary electrophoresis and pH measurement using a potentiometric method. The BIONOTE system is an innovative system that performs a cyclic voltammetric analysis of a biological liquid sample. The final output of the electrochemical analysis is an electrical pattern that represents a fingerprint of the analyzed sample and each sample has a different fingerprint. Data from the three unconventional diagnostic techniques were analyzed using partial least squares discriminant analysis to discriminate neoplastic from non-neoplastic effusions; we also evaluated sensitivity, specificity and percentage of correct classification. The mean age was 68 years (SD: 12); 78 (67.24%) participants were men. Results obtained from all the unconventional techniques employed showed that neoplastic and non-neoplastic pleural effusions were correctly classified in 80.2% of cases, with a sensitivity of 77% and specificity of 83%. The combined use of voltammetric analysis, protein electrophoresis and pH measurement of pleural fluid can easily and quickly distinguish a neoplastic from a non-neoplastic pleural effusion with reliable accuracy and represents an innovative diagnostic approach. In fact, this protocol can be executed in just few minutes directly in the patient's bed and it holds great promise to improve the prognosis and therapeutic chances.

Voltammetric analysis for distinguishing portal hypertension-related from malignancy-related ascites: A proof of concept study.

BACKGROUND: Serum-ascites albumin gradient (SAAG) remains the most sensitive and specific marker for the differentiation of ascites due to portal hypertension from ascites due to other causes. SAAG has some limitations and may fail in selected conditions. Voltammetric analysis (VA) has been used for the detection of electroactive species of biological significance and has proven effective for detection infections in biological fluids. AIMS: In this study, we compared the accuracy of voltammetric analysis (VA) with that of SAAG to differentiate ascites due to portal hypertension from that having a different origin. METHODS: 80 ascites samples were obtained from patients undergoing paracentesis at the Campus Bio-Medico Hospital of Rome. VA was performed using the BIONOTE device. The ability of VA to discriminate ascitic fluid etiology and biochemical parameters was evaluated using Partial Least Square Discriminant Analysis (PLS-DA), with ten-fold cross-validations. RESULTS: Mean age was 68.6 years (SD 12.5), 58% were male. Ascites was secondary to only portal hypertension in 72.5% of cases (58 subjects) and it was secondary to a baseline neoplastic disease in 27.5% of cases (22 subjects). Compared to SAAG≥1.1, e-tongue predicted ascites from portal hypertension with a better accuracy (92.5% Vs 87.5%); sensitivity (98.3% Vs 94.8%); specificity (77.3% Vs 68.2%); predictive values (PPV 91.9% Vs 88.7% and NPV 94.4% Vs 83.3%). VA correctly classified ascites etiology in 57/58 (98.2%) of cases with portal hypertension and in 17/22 (77.2%) of cases with malignancy. Instead, VA showed poor predictive capacities towards total white blood count and polymorphonuclear cell count. CONCLUSIONS: According to this proof of concept study, VA qualifies as a promising low-cost and easy method to discriminate between ascites secondary to portal hypertension and ascites due to malignancy.

Advances in the Electronics for Cyclic Voltammetry: the Case of Gas Detection by Using Microfabricated Electrodes.

This paper presents an advanced voltammetric system to be used as electronic tongue for liquid and gas analysis. It has been designed to be more flexible and accurate with respect to other existing and similar systems. It features improved electronics and additional operative conditions. Among others these include the possibility to optically excite the solution and to treat the output signal by a differentiation process in order to better evidence the existence of small details in the response curve. Finally by the same type of tongue preliminary results are shown dealing with O2 and CO2 concentration measurements in appropriate solutions.

Environmental conditions influence the biochemical properties of the fruiting bodies of Tuber magnatum Pico.

The influences of various factors, including the symbiosis established with the roots of specific tree species, on the production of volatiles in the fruiting bodies of Tuber magnatum have not been investigated yet. Volatiles in T. magnatum fruiting bodies were quantitatively and qualitatively determined by both PTR-MS and GC-MS in order to compare the accuracy of the two methods. An electronic nose was also used to characterize truffle samples. The influence of environmental changes on the antioxidant capabilities of fruiting bodies was also determined. Statistically significant differences were found between fruiting bodies with different origins. The relationship between the quality of white truffle fruiting bodies and their specific host plant is described along with an analysis of metabolites other than VOCs that have ecological roles. Our results indicate that the geographical origin (Italy and Istria) of the fruiting bodies is correlated with the quantity and quality of volatiles and various antioxidant metabolites. This is the first report characterizing antioxidant compounds other than VOCs in white truffles. The correlation between geographical origin and antioxidant contents suggests that these compounds may be useful for certifying the geographical origin of truffles.

Breathprinting and Early Diagnosis of Lung Cancer.

The electronic nose (e-nose) is a promising technology as a useful addition to the currently available modalities to achieve lung cancer diagnosis. The e-nose can assess the volatile organic compounds detected in the breath and derived from the cellular metabolism. Volatile organic compounds can be analyzed to identify the individual chemical elements as well as their pattern of expression to reproduce a sensorial combination similar to a fingerprint (breathprint). The e-nose can be used alone, mimicking the combinatorial selectivity of the human olfactory system, or as part of a multisensorial platform. This review analyzes the progress made by investigators interested in this technology as well as the perspectives for its future utilization.

Screening of Obstructive Sleep Apnea Syndrome by Electronic-Nose Analysis of Volatile Organic Compounds.

Obstructive Sleep Apnea Syndrome (OSAS) carries important social and economic implications. Once the suspicion of OSAS has arisen, Polysomnography (PSG) represents the diagnostic gold standard. However, about 45% of people who have undergone PSG are free from OSAS. Thus, efforts should be made to improve the selection of subjects. We verified whether the pattern of Volatile Organic Compounds (VOCs) helps to select patients amenable to PSG. We studied 136 subjects (20 obese non-OSAS, 20 hypoxic OSAS, 20 non-hypoxic OSAS, and 20 non-hypoxic Chronic Obstructive Pulmonary Disease (COPD) vs 56 healthy controls) without any criteria of exclusion for comorbidity to deal with a real-life population. VOCs patterns were analyzed using electronic-nose (e-nose) technology. A Discriminant Analysis (Partial Least Square-Discriminant Analysis) was performed to predict respiratory functions and PSG parameters. E-nose distinguished controls (100% correct classification) from others and identified 60% of hypoxic, and 35% of non-hypoxic OSAS patients. Similarly, it identified 60% of COPD patients. One-by-one group comparison yielded optimal discrimination of OSAS vs controls and of COPD vs controls (100% correct classification). In conclusion, e-nose technology applied to breath-analysis can discriminate non-respiratory from respiratory diseased populations in real-life multimorbid populations and exclude OSAS. If confirmed, this evidence may become pivotal for screening purposes.

Electronic Nose Technology in Respiratory Diseases.

Electronic noses (e-noses) are based on arrays of different sensor types that respond to specific features of an odorant molecule, mostly volatile organic compounds (VOCs). Differently from gas chromatography and mass spectrometry, e-noses can distinguish VOCs spectrum by pattern recognition. E-nose technology has successfully been used in commercial applications, including military, environmental, and food industry. Human-exhaled breath contains a mixture of over 3000 VOCs, which offers the postulate that e-nose technology can have medical applications. Based on the above hypothesis, an increasing number of studies have shown that breath profiling by e-nose could play a role in the diagnosis and/or screening of various respiratory and systemic diseases. The aim of the present study was to review the principal literature on the application of e-nose technology in respiratory diseases.

Volatile signature for the early diagnosis of lung cancer.

Exhaled breath contains hundreds of volatile organic compounds (VOCs). Several independent researchers point out that the breath of lung cancer patients shows a characteristic VOC-profile which can be considered as lung cancer signature and, thus, used for diagnosis. In this regard, the analysis of exhaled breath with gas sensor arrays is a potential non-invasive, relatively low-cost and easy technique for the early detection of lung cancer. This clinical study evaluated the gas sensor array response for the identification of the exhaled breath of lung cancer patients. This study involved 146 individuals: 70 with lung cancer confirmed by computerized tomography (CT) or positron emission tomography-(PET) imaging techniques and histology (biopsy) or with clinical suspect of lung cancer and 76 healthy controls. Their exhaled breath was measured with a gas sensor array composed of a matrix of eight quartz microbalances (QMBs), each functionalized with a different metalloporphyrin. The instrument produces, for each analyzed sample, a vector of signals encoding the breath (breathprint). Breathprints were analyzed with multivariate analysis in order to correlate the sensor signals to the disease. Breathprints of the lung cancer patients were differentiated from those of the healthy controls with a sensitivity of 81% and specificity of 91%. Similar values were obtained in patients with and without metabolic comorbidities, such as diabetes, obesity and dyslipidemia (sensitivity 85%, specificity 88% and sensitivity 76%, specificity 94%, respectively). The device showed a large sensitivity to lung cancer at stage I with respect to stage II/III/IV (92% and 58% respectively). The sensitivity for stage I did not change for patients with or without metabolic comorbidities (90%, 94%, respectively). Results show that this electronic nose can discriminate the exhaled breath of the lung cancer patients from those of the healthy controls. Moreover, the largest sensitivity is observed for the subgroup of patients with a lung cancer at stage I.

BIONOTE e-nose technology may reduce false positives in lung cancer screening programmes†.

OBJECTIVES: Breath composition may be suggestive of different conditions. E-nose technology has been used to profile volatile organic compounds (VOCs) pattern in the breath of patients compared with that of healthy individuals. BIOsensor-based multisensorial system for mimicking NOse, Tongue and Eyes (BIONOTE) technology differs from Cyranose® based on a set of separate transduction features. On the basis of our previously published experience, we investigated the discriminating ability of BIONOTE in a high-risk population enrolled in a lung cancer screening programme. METHODS: One hundred individuals were selected for BIONOTE based on the attribution to the high-risk category (i.e. age, smoking status, chronic obstructive pulmonary disease status) of the University Campus Bio-Medico lung screening programme. We used a measure chain consisting of (i) a device named Pneumopipe (EU patent: EP2641537 (A1):2013-09-25) able to catch exhaled breath by an individual normally breathing into it and collect the exhalate onto an adsorbing cartridge; (ii) an apparatus for thermal desorption of the cartridge into the sensors chamber and (iii) a gas sensor array which is part of a sensorial platform named BIONOTE for the VOCs mixture analysis. Partial least square (PLS) has been used to build up the model, with Leave-One-Out cross-validation criterion. Each breath fingerprint analysis costs €10. RESULTS: The overall sensitivity and specificity were 86 and 95%, respectively, delineating a substantial difference between patients and healthy individuals. CONCLUSIONS: Our preliminary data show that BIONOTE technology may be used to reduce false-positive rates resulting from lung cancer screening with low-dose computed tomography in a cost-effective fashion. The model will be tested on a larger number of patients to confirm the reliability of these results.

The lung cancer breath signature: a comparative analysis of exhaled breath and air sampled from inside the lungs.

Results collected in more than 20 years of studies suggest a relationship between the volatile organic compounds exhaled in breath and lung cancer. However, the origin of these compounds is still not completely elucidated. In spite of the simplistic vision that cancerous tissues in lungs directly emit the volatile metabolites into the airways, some papers point out that metabolites are collected by the blood and then exchanged at the air-blood interface in the lung. To shed light on this subject we performed an experiment collecting both the breath and the air inside both the lungs with a modified bronchoscopic probe. The samples were measured with a gas chromatography-mass spectrometer (GC-MS) and an electronic nose. We found that the diagnostic capability of the electronic nose does not depend on the presence of cancer in the sampled lung, reaching in both cases an above 90% correct classification rate between cancer and non-cancer samples. On the other hand, multivariate analysis of GC-MS achieved a correct classification rate between the two lungs of only 76%. GC-MS analysis of breath and air sampled from the lungs demonstrates a substantial preservation of the VOCs pattern from inside the lung to the exhaled breath.

Unmasking of Olive Oil Adulteration Via a Multi-Sensor Platform.

Methods for the chemical and sensorial evaluation of olive oil are frequently changed and tuned to oppose the increasingly sophisticated frauds. Although a plethora of promising alternatives has been developed, chromatographic techniques remain the more reliable yet, even at the expense of their related execution time and costs. In perspective of a continuous increment in the number of the analyses as a result of the global market, more rapid and effective methods to guarantee the safety of the olive oil trade are required. In this study, a novel artificial sensorial system, based on gas and liquid analysis, has been employed to deal with olive oil genuineness and authenticity issues. Despite these sensors having been widely used in the field of food science, the innovative electronic interface of the device is able to provide a higher reproducibility and sensitivity of the analysis. The multi-parametric platform demonstrated the capability to evaluate the organoleptic properties of extra-virgin olive oils as well as to highlight the presence of adulterants at blending concentrations usually not detectable through other methods.

Exhaled breath analysis by electronic nose in respiratory diseases.

Breath analysis via electronic nose is a technique oriented around volatile organic compound (VOC) profiling in exhaled breath for diagnostic and prognostic purposes. This approach, when supported by methodologies for VOC identification, has been often referred to as metabolomics or breathomics. Although breath analysis may have a substantial impact on clinical practice, as it may allow early diagnosis and large-scale screening strategies while being noninvasive and inexpensive, some technical and methodological limitations must be solved, together with crucial interpretative issues. By integrating a review of the currently available literature with more speculative arguments about the potential interpretation and application of VOC analysis, the authors aim to provide an overview of the main relevant aspects of this promising field of research.

Detection and identification of cancers by the electronic nose.

INTRODUCTION: The early determination of serious pathologies has so far been an important issue in both the medical and social fields. The search for an instrument able to detect cancers has led to the consideration of the usage of chemicals of the human body, which carry, through its volatile compounds, information coming from or related to defined pathologies. AREAS COVERED: The electronic nose (EN) seems to represent a good solution for the detection of cancers of different types. Recent results showed the utility of an EN to smell chemicals related to lung, melanoma, prostatic, breast and pancreatic cancers. The results obtainable from ENs are chemical images and, as it will be shown in this paper, the probability of cancer recognition is rather high. Main results obtained at international level and by the authors of this paper will be commented upon. EXPERT OPINION: A personal opinion is given trying to foresee future developments of the olfaction strategy. To this purpose, two main aspects are considered: looking for better overall stability of the EN and for a new use of ENs in detecting alterations between blood and pathology components.

An investigation on electronic nose diagnosis of lung cancer.

The use of gas sensor arrays as medical diagnosis instruments has been proposed several years ago. Since then, the idea has been proven for a limited number of diseases. The case of lung cancer is particularly interesting because it is supported by studies that have shown the correlation between the composition of breath and the disease. However, it is known that many other diseases can alter the breath composition, so for lung cancer diagnosis it is necessary not only to detect generic alterations but those specifically consequent to cancer. In this paper an experiment, performed in the bronchoscopy unit of a large hospital, aimed at discriminating between lung cancer, diverse lung diseases and reference controls is illustrated. Results show not only a satisfactory identification rate of lung cancer subjects but also a non-negligible sensitivity to breath modification induced by other affections. Furthermore, the effects of some compounds frequently found in the breath of lung cancer subjects have also been studied. Results indicate that breath samples of control individuals drift towards the lung cancer group when added with either single or mixtures of these alleged cancer-related compounds.

Application of a quartz microbalance based gas sensor array for the study of halitosis.

Research into the monitoring and control of oral malodor has nowadays received new stimulus from the importance gained by this phenomenon as a medical and social problem. In this paper the performance of an electronic nose to detect this manifestation has been investigated in order to explore the possibility of using this instrument as a complement to those already existing for the assessment of oral malodor. In particular, a breath sampling procedure has been optimized to maximize the transfer to the sensors of those molecules that are known to be associated with the malodor. The sensitivity of electronic nose sensors to hydrogen sulfide, butyric acid and valeric acid-three compounds known to play a major role in halitosis-has been measured and the results indicate that the threshold limits are compatible with halitosis detection. An experiment with real and artificial samples indicates the possibility of identifying halitosis-affected individuals and of discriminating them according to breath composition.

Fish freshness detection by a computer screen photoassisted based gas sensor array.

In the last years a large number of different measurement methodologies were applied to measure the freshness of fishes. Among them the connection between freshness and headspace composition has been considered by gas chromatographic analysis and from the last two decades by a number of sensors and biosensors aimed at measuring some characteristic indicators (usually amines). More recently also the so-called artificial olfaction systems gathering together many non-specific sensors have shown a certain capability to transduce the global composition of the fish headspace capturing the differences between fresh and spoiled products. One of the main objectives related to the introduction of sensor systems with respect to the analytical methods is the claimed possibility to distribute the freshness control since sensors are expected to be "portable" and "simple". In spite of these objectives, until now sensor systems did not result in any tool that may be broadly distributed. In this paper, we present a chemical sensor array where the optical features of layers of chemicals, sensitive to volatile compounds typical of spoilage processes in fish, are interrogated by a very simple platform based on a computer screen and a web cam. An array of metalloporphyrins is here used to classify fillets of thawed fishes according to their storage days and to monitor the spoilage in filleted anchovies for a time of 8 h. Results indicate a complete identification of the storage days of thawed fillets and a determination of the storage time of anchovies held at room temperature with a root mean square error of validation of about 30 min. The optical system produces a sort of spectral fingerprint containing information about both the absorbance and the emission of the sensitive layer. The system here illustrated, based on computer peripherals, can be easily scaled to any device endowed with a programmable screen and a camera such as cellular phones offering for the first time the possibility to fulfil the sensor expectation of diffused and efficient analytical capabilities.

Identification of schizophrenic patients by examination of body odor using gas chromatography-mass spectrometry and a cross-selective gas sensor array.

BACKGROUND: Previous findings have shown that the body odor of patients affected by schizophrenia contains some specific compounds. Chemical sensor technology has proved to be able to classify different odours. We investigated the possibility of using a chemical sensor array to detect body odor alteration in schizophrenic patients. MATERIAL/METHODS: The sweat of subjects was sampled and analysed by Gas Chromatography-Mass Spectrometry (GC-MS) and by an array of cross-selective gas sensors. A total of 27 individuals were involved in the experiment: 9 schizophrenics, 9 with other mental disorders, and 9 controls. RESULTS: GC-MS analysis showed a richer composition for the sweat of schizophrenic patients. Nevertheless, the individuation of specific markers was unsuccessful. On the other hand, statistical analysis of cross-selective gas sensor data provided a complete classification of schizophrenic patients with respect to the other three groups. CONCLUSIONS: The alteration of body odor in schizophrenic patients was confirmed by GC-MS and chemical sensor array. Results show that the alteration is complex and cannot be limited to a single compound, but rather to a global variation of the body odor.