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Colorectal cancer (CRC) represents 10% of the annual tumor diagnosis and deaths occurring worldwide. Given the lack of specific symptoms, which could determine a late diagnosis, the research for specific CRC biomarkers and for innovative low-invasive methods to detect them is crucial. Therefore, on the basis of previously published results, some volatile organic compounds (VOCs), detectable through gas sensors, resulted in particularly promising CRC biomarkers, making these sensors suitable candidates to be employed in CRC screening devices. A new device was employed here to analyze the exhalations of blood samples collected from CRC-affected patients at different stages of their pre- and post-surgery therapeutic path, in order to assess the sensor’s capability for discriminating among these samples. The stages considered were: the same day of the surgical treatment (T1); before the hospital discharge (T2); after one month and after 10–12 months from surgery (T3 and T4, respectively). This device, equipped with four different sensors based on different metal–oxide mixtures, enabled a distinction between T1 and T4 with a sensitivity and specificity of 93% and 82%, respectively, making it suitable for clinical follow-up protocols, patient health status monitoring and to detect possible post-treatment relapses.

Ethanol is an important chemical raw material widely used in chemical industry, medicine, cosmetics, paints, and biofuels [1]. It is volatile and flammable and a human exposure to its vapours could result in headache, drowsiness, irritation of eyes and difficulty in breathing. It derives that the precise quantitative detection of ethanol vapours is of interest for many applications. Different studies were focused on semiconducting metal oxides as sensing materials for the selective ethanol detection. It is well known that, despite their high stability over time and the low cost of production, these semiconductors suffer of low selectivity, which affects their effective use for real applications. Among the wide palette of the metal oxides, tungsten oxide (WO3) is an important intrinsic n-type wide gap semiconductor, which has attracted considerable attention to detect various hazardous gases. However, it is still challenging to significantly enhance the sensibility and selectivity of WO3 based gas sensors by tuning its crystal structures, morphology and adding dopants [2]. WO3 can be a promising candidate for alcohols detection for the presence of acidic sites that can promote the alcohol decomposition through dehydration [3]. In this work, the synthesis of WO3 nanoflakes (WO3-NF) was achieved via solvothermal route [4]. The peculiar morphology was characterized by SEM microscopy. XRD analysis reveals that the investigated sample is biphasic, composed by triclinic (s.g. P-1) and hexagonal (s.g. form with P63/mcm) WO3 with a phase fraction of about 97 and 3 wt.%, respectively. Sensing performance of the WO3-NF were studied and compared to those of WO3 nanoparticles synthetized by precipitation method. Tested sensors were realized by screen-printing of the functional material on alumina substrates with interdigitated electrodes. After a systematic investigation on the optimal working temperature, WO3 based sensors were tested at 250°C and 300°C for WO3-NF and WO3-NP, respectively. Gas measurements were performed testing the WO3-based sensors towards various gaseous molecules: H2S (10 ppm), H2 (50 ppm), CO (35 ppm), NO2 (1 ppm), NH3 (2 ppm) and different concentrations of methanol, ethanol and butanol (5-10, 25, 50 ppm). The sensing analysis indicates that the WO3-NF is sensitive towards alcohols, remarkably to ethanol, with negligible responses to other analytes. Fig. 1a, where the dynamic response to different concentration of ethanol for WO3-based sensors is shown, clearly highlights the enhanced sensing performance of the WO3-NF based sensor when compared to that of the WO3-NP. The influence of humidity on WO3-based sensors exposed to ethanol was also investigated (Fig. 1b). Even at low ethanol concentration (5 ppm), the influence of water vapour is limited, and after a partial drop up to 30 RH%, the WO3-based sensors performance seems to reach a stabilization, and no variations are observed up to 60 RH%. Noteworthy, the WO3-NF response to ethanol is always more than two times higher when compared to that of WO3-NP. The sensing response towards 50 ppm of methanol, ethanol and butanol are shown in Fig. 1c. While WO3-NP sensibility increases with the length of the alcohol chain, this trend is not observed for WO3-NF, which has higher response for ethanol. This peculiar behaviour will be the object of further investigation. References [1] S. Weiet al., Vacuum, 129, (2016) 13-19 [2] C. Dong et al., Journal of Alloys and Compounds, 820 (2020) [3] Arpan Kumar Nayak et al., Nanoscale, 7 (2015) 12460-12473 [4] C. A. Grimes et al., Nano Letters, 11, (2011) 203-208 Figure 1

User-friendly, low-cost equipment for preventive screening of severe or deadly pathologies are one of the most sought devices by the National Health Services, as they allow early disease detection and treatment, often avoiding its degeneration. In recent years more and more research groups are developing devices aimed at these goals employing gas sensors. Here, nanostructured chemoresistive metal oxide (MOX) sensors were employed in a patented prototype aimed to detect volatile organic compounds (VOCs), exhaled by blood samples collected from patients affected by colorectal cancer and from healthy subjects as a control. Four sensors, carefully selected after many years of laboratory tests on biological samples (cultured cells, human stools, human biopsies, etc.), were based here on various percentages of tin, tungsten, titanium, niobium, tantalum and vanadium oxides. Sensor voltage responses were statistically analyzed also with the receiver operating characteristic (ROC) curves, that allowed the identification of the cut-off discriminating between healthy and tumor affected subjects for each sensor, leading to an estimate of sensitivity and specificity parameters. ROC analysis demonstrated that sensors employing tin and titanium oxides decorated with gold nanoparticles gave sensitivities up to 80% yet with a specificity of 70%.

Screening is recommended to reduce both incidence and mortality of colorectal cancer. Currently, many countries employ fecal occult blood test (FOBT). In Emilia-Romagna (Italy), since 2005, FOBT immunochemical version (FIT) is performed every two years on people aged between 50 and 69 years. A colonoscopy is then carried out on those who are FIT positive. However, FIT shows approximately 65% false positives (non-tumoral bleedings), leading to many negative colonoscopies. The use of an economic and easy-to-use method to check FOBT-positives will improve screening effectiveness, reducing costs to the national health service. This work illustrates the results of a three-year clinical validation protocol (started in 2016) of a patented device composed of a core of nanostructured gas sensors. This device was designed to identify CRC presence by fecal volatile compounds, with a non-invasive, in vitro and low-cost analysis. Feces are, in fact, affected by tumor-volatile biomarkers, produced by cellular peroxidation and metabolic alterations. The protocol consisted in the analysis of fecal samples of FIT-positive subjects, using colonoscopy as a gold standard. A total of 398 samples were analyzed with machine learning techniques, leading to a sensitivity and specificity of 84.1% and 82.4%, respectively, and a positive predictive value of 72% (25&ndash, 35% for FIT).

Despite the great progress in screening techniques and medical treatments, colorectal cancer remains one of the most widespread cancers in both sexes, with a high death rate. In this work, the volatile compounds released from human colon cancer tissues were detected by a set of four different chemoresistive sensors, made with a nanostructured powder of metal-oxide materials, inserted into an innovative patented device. The sensor responses to the exhalation of a primary cancer sample and of a healthy sample (both of the same weight, collected during colorectal surgery from the intestine of the same patient) were statistically analyzed. The sensors gave reversible, reproducible, and fast responses for at least one year of continuous use, making them quite superior in respect to the existing diagnostic methods. Preliminary results obtained using principal component analysis of the sensor responses to samples removed from 13 patients indicate that the nanostructured sensors employed in this study were able to distinguish between healthy and tumor tissue samples with coherent responses (the discrimination power of the most sensitive sensor was about 17%), highlighting a strong potential for clinical practice.

Silicon carbide is a well-known material with high thermal, mechanical and chemical stability. These properties have allowed, over time, its wide use as an inert material to be employed as a substrate or support in different applications. In this work, we demonstrate that, under proper conditions, it is possible to activate the chemical reactivity of nanostructured SiC, which can be employed for chemoresistive purposes. With this aim, a commercial powder of SiC has been characterized from a morphological, structural and thermal point of view. Then, screen–printed thick films were obtained from SiC powder and thus tested as a functional material for chemoresistive gas sensors, in thermo-activation mode. The samples were exposed to 13 gases with important chemical differences. Analyses showed that SiC is an extremely selective functional material for the detection of sulphur dioxide (SO2) in concentrations within the ppm range. This interesting result was found at high working temperatures (600−800 °C), useful for harsh environments, and the measurements proved to be completely free from humidity negative interference. Thermo-gravimetric and X-ray photoelectron spectroscopy characterizations highlighted that the high selectivity of the SiC layer is promoted by the thermal formation of a SiC/SiOC core-shell, tunable by controlling temperature and humidity parameters. An interpretation of the gas sensing mechanism occurring between SO2 molecules and SiC/SiOC core-shell has been proposed. The unexpected chemical activity, identified for nanostructured SiC, can be exploited for the specific detection of SO2, since this gaseous compound plays an important role in air pollution, industrial processes and winemaking.

International audience; In this paper two kind of sensors based on WO3 sputtered by magnetron sputtering and annealed at 600 °C have been studied. The first kind was processed by two-dimensional direct laser interfering patterning (DLIP) and the second one without any additional treatment. Morphological and structural characterization have shown a hole structure in a periodic line-pattern for the DLIP-processed sensors and a flat surface for the only-annealed sensors, both with a tetragonal WO3 phase. TOF-SIMS analysis has revealed that the first WO3 layers are reduced for both samples, which could improve sensing performance. Promising response enhancement of DLIP-processed sensors has been observed for low concentrations of NO2 (from 0.5 ppm to 5 ppm) at 200 °C, lowering the limit of detection (LOD) to 10 ppb, half of the LOD of the only-annealed sensors (20 ppb). Cross sensitivity to CO and HCHO have been investigated and the sensing mechanisms discussed.

Nowadays, the demand for devices capable of efficiently identifying the presence of various biomarkers in human body, connected to a wide variety of pathologies, is progressively increasing. Chemoresistive semiconductor sensors, capable of changing their conductance depending on the chemical reactions between their surface and gaseous analytes, could be a suitable choice for medical devices implementation. In this work, a prototype based on an array of nanostructured sensors was tested, in order to detect the presence of airborne tumor markers in blood samples. These chemicals were conveyed to sensors with an air-flow circuit, equipped with antibacterial filters to maintain the sterility of the system. Resulting signals were acquired, processed and plotted thanks to a custom-made software, realized in Labview®. Statistics on these signals was performed by means of Principal Component Analysis. Both male and female subjects, ranging between 21 to 91 years of age, have accepted to participate in this study, donating their blood samples. Donors were patients affected by colorectal and stomach cancers, at different stages of evolution, and/or having differently localized metastasis, and a healthy control group. The results have shown that the processed sensor responses, well discriminate healthy and tumor affected subjects. Obtained results can be also employed to assess the level of tumor growth and vascularization.

One of the greatest goals in medicine is early-stage detection of tumors, to allow physicians and surgeons to apply the available therapies, which are usually successful on small volume cancers only. [...]

The demand for reliable devices to detect tumor biomarkers in human body is constantlyincreasing [...]

Direct Laser Interference Patterning (DLIP) technique has been used to generate a line pattern on the surface of WO3 thin films, due to the interference of two coherent laser beams, modifying its surface morphology and physical properties. Gas sensing devices based on WO3 thin films annealed at 600 °C and nanostructured by DLIP have been fabricated and compared to samples simply annealed at the same temperature. The sensors processed by DLIP present a great enhancement on the response in NO2 atmospheres indicating possible modifications on the composition, aside from the morphological one.

Colorectal cancer (CRC) preventive screening is fundamental to identify tumors before their possible degeneration. [...]

Reproducibility of the sensor response is one of the fundamental themes for obtaining marketable devices with a high degree of reliability. This parameter becomes decisive especially if the sensor signals are used to identify compound mixtures by means of recognition algorithms. In fact, to apply the same algorithm to different devices, sensors must be identical within a minimum error margin. This point became crucial for medical diagnostic tools, e.g., for cancer screening and monitoring. A set of three thermo-activated thick-film Zinc Oxide (ZnO) sensors, obtained from the same screen-printing deposition, have been tested in laboratory with diverse gases and two biological fecal samples. Fecal samples have been employed in the clinical validation protocol of a device for non-invasive colorectal cancer pre-screening, as emitters of oncologic volatile biomarkers. Sensors showed a good reproducibility degree, with an error lower than 10% of response value for all compounds, reaching 1%–2% for some gases.

Colorectal cancer (CRC) is a worldwide diffused pathology for both men and women and it is the third most common cancer for both genders, in the United States[1] However, if promptly diagnosed, CRC is also one of the most curable tumor types (90% curability rate at stage I), therefore prevention is fundamental to avoid degeneration. Here the clinical validation outcomes of a preventive screening method based on a patented device, SCENT A1, composed by a core of nanostructured MOX sensors [2]. SCENT A1 is capable of detecting the presence of CRC from fecal odor with an in-vitro, inexpensive and non-invasive methodology. Fecal odor can be affected by the presence of CRC-biomarkers produced by membrane peroxidation and metabolic alterations [3,4]. The screening analysis adopted by NHS of Italy and of other countries is fecal occult blood test (FOBT). In Italy, FOBT is performed every two years on subjects from 50 to 69 years old and shows a huge percentage of false positives (about 65% according to data). FOBT-positives are then invited to undergo colonoscopy. SCENT A1 is capable of reducing FOBT false positives and so the total number of non-operative colonoscopies with related risks (e.g. bowel perforation). The device, presently undergoing instrumental certification, is composed by a core of two chemoresistive MOX sensors, chosen and calibrated for this specific aim [5-11]. Sensors (Figure 1) have been synthesized at Sensor Laboratory of the University of Ferrara and are composed by a nanostructured semiconductor film screen-printed onto an alumina substrate and a platinum heater to modulate operating temperature. The first sensor is composed by Iron and Samarium oxides while the second one by Tin and Titanium oxides. The data collection and analysis software employs support vector machine (SVM) [9]. The clinical validation protocol of this device started in May 2016 and ended in July 2019, in collaboration with Hospital St. Anna of Ferrara and Department of Public Health of Ferrara. A total of 398 fecal samples of FOBT-positive subjects have been analyzed by SCENT A1 system with the k-fold cross validation method. Samples have been grouped into two macro categories, depending on the gold-standard (colonoscopy) outcomes: 260 healthy subjects (negative to colonoscopy); 138 colorectal adenomas and carcinomas (positive to colonoscopy), 54 low-risk adenomas and 84 high-risk adenomas and carcinomas. The system has been capable of distinguishing among these two categories with a sensitivity (TPR: true positive rate) and specificity (TNR: true negative rate) respectively of 84,1% and 82,4%, defined as follows: TPR=TP/P=TP/(FN+TP); TN/N=TN/(FP+TN); where TP, TN, FP and FN are the abbreviations that indicate respectively true positives, true negatives, false positives and false negatives. The choice to group carcinomas, high- and low-risk adenomas into a single class and not into two diverse classes as before [10], has simplified the test and ensured greater doctor protection, despite a small loss in specificity. Low-risk adenomas are, in fact, often similar to healthy tissues and have a risk of evolving into cancer comparable to the risk of colonoscopy complications. As already emerging from a previous study [10-11], in fact, the major error of classification (only 57%) concerned just low-risk tumors that emit gases halfway between healthy and tumoral samples. What emerges is that, if SCENT A1 test is carried out on FOBT-positives subjects as a second check, it would guarantee a reduction of about two thirds of the colonoscopies performed on healthy patients. A new collaboration, involving private clinic Quisisana, started in 2020 with some laboratory tests on sensors reproducibility [12] will continue in January 2021 with tests on patients directly inside the clinic, in order to test the new shape of the device under certification. Moreover, if employed by the NHS of countries without screening system, this method will significantly reduce CRC-mortality rate. [1] [https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html [2] Italian #: RM2014A000595, European #: 3210013 (Germany, UK); [3] B. Szachowicz-Petelska et al., NMR in Biomedicine V5,226–233, 1992; [4] T. G. de Meij et al., International Journal of Cancer (2014), 134, 1132–1138; [5] C. Malagù et al., Sensors, 14, 18982-18992, 2014; [6] G. Zonta et al., Sensors and Actuators B, 218, 289-295, 2015; [7] N. Landini et al., Scholars' Press, ISBN-13: 978-3-639-76538-0; [8] G. Zonta et al., Sensors and Actuators B, 238, 1098–110, 2016; [9] G. Zonta et al., Sensors and Actuators B 262 (2018) 884–891; [10] G. Zonta et al., Sensors and Actuators B: Chemical, Volume 301, 12 December 2019, 127062; [11] G. Zonta et al., Cancers 2020, 12(6), 1471; [12] G. Zonta et al., Ceramics International Volume 46, Issue 5, 1 April 2020, Pages 6847-6855. Figure 1: a) external view of the patented prototype SCENT A1, composed by flowmeters, a flow diverter and a sample box; b) one of the chemoresistive sensors composing the core of the instrument; c) magnificated scheme of the sensor. Figure 1

Early-stage tumor detection is one of the most coveted goals for the world research community. An effective prevention, associated to reliable screening protocols, is crucial to favor a early diagnosis, allowing doctors and surgeons to intervene with high probabilities of success on tumor affected patients. The main purpose of this study is cancer detection, exploiting the volatile organic compounds (VOCs) produced by cancer cells as tumor biomarkers [1][2], by investigating tumor tissue and blood samples. Tumor biomarkers exhalation is attributed to two main cell involving biological mechanisms: altered metabolism and cellular membrane peroxidation [3]. This experimental work was carried on using an innovative, fast-responding and reliable patented device, named SCENT B1 [4], entirely designed and assembled in the Sensor Laboratory of the University of Ferrara. It hosts an array of four specific metal-oxide (MOX) sensors able to detect gases in low concentration (up to 10 ppm) with high stability and repeatability, chosen after many tests on different types of biological samples (feces, blood, cell cultures, etc.) [5,6]; the chosen sensors are based on different mixtures of tin, titanium, tungsten, niobium, tantalum and vanadium oxides (ST25Au, W11, STN, TiTaV). Moreover, SCENT B1 is gifted of a power supply and sensor signal transduction electronic boards, a pneumatic air system (necessary to direct the VOCs contaminated air from the sample chamber to the sensors) and an ad hoc management and data acquisition software (LSS4) [6]. The sensor output signal is a voltage directly proportional to the sensor conductance, depending on the chemical redox reactions taking place on the surface of the sensor sensing material. The sensor response is: R=Vgas/Vair , where Vgas and Vair are the sensor voltage in gas presence and in dry air after the steady state achievement respectively [6].Sensor responses were further elaborated, using different statistical approaches as principal component analysis and receiver operating characteristics methods. Measurements have been performed on colorectal cancer and healthy tissues surgically removed from the same operatory piece (directly and far enough from tumor mass respectively) (Figure 1a), and on blood samples collected from tumor affected subjects and healthy ones as controls (Figure 1b). with the future aim of extending the study to other tumor types. All four sensors gave larger responses (although with different amplitudes) to the tumor tissue with respect to the healthy one. Smaller and reproducible responses were given by the breeding ground (DMEM) only, confirming that it does not alter the measurements. The results are consistent with the stronger and altered metabolism of tumor cells, leading them to emit a larger amount of volatile biomarkers with respect to the healthy ones;. All the four sensors hosted by SCENT B1 proved to be capable of distinguishing between healthy and tumor tissue and blood samples, although with different discrimination power. The encouraging results of this feasibility study are the basis of a new in-depth study, which includes also a follow-up protocol based on post surgery blood monitoring of patients. Our future aims foresee the extension of this study to other tumor types and the obtainment of the SCENT B1 clinical validation as oncologic screening device. Figure 1

Humidity is always present in real applications of semiconductor gas sensors, e.g. in the environmental monitoring or medical applications, therefore it is important to study the effects that water vapor has on sensors conduction. This work is a study of the humidity role in the conduction mechanisms of two sensor materials: tin oxide (SnO2) and a mixture of tin, titanium and niobium oxide (STN), showing the property of the second of being less affected by humidity, therefore useful in medical and environmental applications. Laboratory and on-field tests have been performed with water vapor and CO, at different concentration, initial conditions and partial pressures, both singularly and in combination. A novel concept of sensitivity is introduced in this work, called two-dimensional sensitivity, which not only quantifies the dependence of sensors response on the concentration of the analyte, but also on the variation of humidity and their non-linear combination. By taking the partial derivative of the fitting function with respect to CO concentration, it is possible to gather not only information about the dependence of the signal variation on the gas concentration, but also how it is influenced by water vapour, even when the water vapor partial pressure is kept constant, and vice versa.

Zinc Oxide has been widely investigated for its photocatalytic properties, which enhance the bulk/surface charge transfer at room temperature. At the same time, the doping of semiconductor materials with metals allows the modification of their physical and chemical properties, and hence their performance as gas sensors. The aim of this work was to investigate the difference between thin-film sensors based on pure ZnO nanoparticles and on gold-cluster decorated ZnO in photo-activation mode. The nanopowders were synthesized through simple sol-gel methods and chemically, morphologically and structurally characterized. Thin films were deposited by spin coating onto alumina substrates. The sensing layers were tested with several gases in photo-activation mode, illuminated with radiation wavelengths of 525, 468, 400 and 385 nm. Gold-decorated ZnO thin film showed some interesting features, such as better chemoresistive properties than pure ZnO under photo-activation mode, when illuminated with a wavelength of 385 nm. A selective response of the sensing film to NO 2 under green light irradiation was observed, in particular in dry air condition. Furthermore, the humidity effect on the sensing responses was investigated, highlighting a possible application of Au/ZnO for the detection of few ppm of SO 2 with a high percentage of relative humidity.

Nanosized tin disulfide (SnS 2 ) powder was synthesized through a simple and inexpensive process, then characterized via thermal, chemical, structural and morphological analyses. Conductometric gas sensors based on thick films of synthesized SnS 2 were fabricated by means of screen-printing technology and their sensing properties tested vs. aldehydes, ketones and other gaseous compounds. We found that, at working temperature of 300 °C, the SnS 2 films showed a strong selectivity vs. the carbonyl group of aldehydes and ketones, proving that they can efficiently be detected even in complex mixtures with interferers. In comparison with its oxide counterpart, SnS 2 proved to be more stable, in term of the long-term drift of the signal. On the base of the obtained results, practical applications of such a sensor have been addressed.

Commercially available nanosized powder of silicon carbide (named SiC), was thermally, morphologically and structurally characterized. After that, it was screen-printed onto alumina substrates in order to obtain thick films to be tested as functional material for conductometric gas sensors. Samples were exposed to SO2 and H2S, gases with high importance in many application fields, with the aim of verifying its capability of distinguishing between them. The characterization highlighted that this semiconductor type is selective for sulphur dioxide (SO2), in concentrations within the ppm range. This interesting result was found at high temperatures (600-800°C), useful for harsh environmental, and the measurements proved to be completely free from humidity interference. Applications of such a sensor could span many fields, since SO2 plays an important role in air pollution, industrial processes and wine making monitoring.

In this work two devices are presented, named SCENT A1 (A1) and SCENT B1 (B1), composed of chemoresistive sensors. Such devices are capable of discriminating the different compositions of gas mixtures emitted by stools, for colorectal cancer screening (A1), and by blood, for tumors monitoring (B1), according to defined sampling protocols. Results have been acquired by a LabView® software and statistically treated (e.g. quadratic discriminant analysis, QDA) and show to be encouraging with an error of 5% for SCENT A1. Preliminary results of SCENT B1 proved to be promising. Further studies will be carried out for clinically validating the two devices.

One of the greatest goals in medicine is early-stage tumor detection. An effective prevention is crucial to allow physicians and surgeons to intervene on tumor affected patients with the available therapies and surgical techniques with a high probability of success. The purpose of this research relies on the identification of cancer presence by detecting the volatile organic biomarkers directly produced by cancer cells. Cancer cells produce different biomarkers with respect to healthy cells, mainly due to the altered metabolism and cellular membrane peroxidation. This difference can be recognized by using an innovative device manufactured in the Sensor Laboratory of the University of Ferrara, hosting a specific sensor array chosen for biological sample investigation. The sensor array is composed by four chemoresistive metal-oxide nanostructured sensors, able to detect gases in low concentration (up to 1 ppm) with excellent stability and repeatability. In this study, a fast-responding, reliable and reproducible sensing device, named SCENT B1[1], showed to be capable of discriminating cancerous cells from healthy ones, proving to be an efficient and low-invasive screening system. The device combines a specific electronic and pneumatic system to a specifically selected sensor array. The sample is inserted inside a sample box through a support composed by Petri dishes, while a stabilized ambient airflow conveys the exhalations to sensors. Sensor responses are then statistically analyzed by principal component analysis (PCA). Measurements have been performed on cancer and healthy tissues, extracted during surgery from human colon and rectum, with the future aim of extending the study to the other tumor types. Sensors chosen are the following: a mixture of tin and titanium oxides with addition of gold (ST25Au), tungsten oxide (W11), a mixture of tin, titanium and niobium oxides (STN) and a solid solution of titanium oxide, tantalum and vanadium (TiTaV). Sensors have been selected after a feasibility study performed on immortalized cells of diverse types, where sensors responses have been correlated with cell type and cell initial plating concentration of the samples; the measures have been performed after 24, 48, 72 hours of incubation. The sensor output signal is a voltage directly proportional to the sensor conductance; it depends on the chemical redox reactions taking place on sensor surface [2,3]. In Figure (a) the response R=ÄG/G for each sensor is reported, where ÄG is the difference between the sensor conductance with and without the metabolites expelled by the cells of a tissue. All four sensors gave larger responses (although with different amplitudes) to the tumor tissue with respect to the healthy one. Smaller and reproducible responses were given by the breeding ground (DMEM) only, confirming that it does not alter the measurement. The results are consistent with the stronger metabolism of tumor cells with respect to the healthy ones, because the former emits larger amounts of volatile biomarkers [4,5]. Other tests proved also that different initial plating concentrations (250k, 500k and 1M) of cell give increasing responses, as shown in Figure (b). From this study what emerges is that the device is capable of distinguishing different cell samples basing on their health status and concentrations. The encouraging results of this study are the basis of a deepen study for the clinical validation of the device as a oncologic screening device. References [1] SCENT B1, Italian Patent Number: 102015000057717; [2] Zonta, G. Anania, B. Fabbri, A. Gaiardo, S. Gherardi, A. Giberti, V. Guidi, N. Landini, C. Malagù; “Detection of colorectal cancer biomarkers in the presence of interfering gases”; Sensors and Actuators B 218 (2015), 289–295; [3] Zonta, G. Anania, B. Fabbri, A. Gaiardo, S. Gherardi, A. Giberti, N. Landini, C. Malagù, L. Scagliarini, V. Guidi, Preventive screening of colorectal cancer with a device based on chemoresistive sensors. Sensors and Actuators B, 238, 1098–110, 2016. [4] F. Altomare, M. Di Lena, F. Porcelli, L. Trizio, E. Travaglio, M. Tutino, S. Dragonieri, V. Memeo, G. de Gennaro; “Exhaled volatile organic compounds identify patients with colorectal cancer”; British Journal of Surgery 100 (2013), 144-150; [5] Chan, E.C.Y., Koh, P.K., Mal, M., Cheah, P.Y., Eu, K.W., Backshall, A., Cavill, R., Nicholson, J.K., Keun, H.C., 2009. “Metabolic Profiling of Human Colorectal Cancer Using High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy and Gas Chromatography Mass Spectrometry (GC/MS)”, Journal of Proteome Research 8(1), 352–361; Figure 1

Colorectal cancer (CRC) is a worldwide diffused pathology for both men and women and it is the third most common cancer for both genders, in the United States[1] However, if promptly diagnosed, CRC is also one of the most curable tumor types (90% curability rate at stage I), therefore prevention is fundamental to avoid degeneration. Here the clinical validation outcomes of a preventive screening method based on a patented device, SCENT A1, composed by a core of nanostructured MOX sensors[2]. SCENT A1 is capable of detecting the presence of CRC from fecal odor with an in-vitro, inexpensive and non-invasive methodology. Fecal odor can be affected by the presence of CRC-biomarkers produced by membrane peroxidation and metabolic alterations[3,4]. The screening analysis adopted by NHS of Italy and of other countries is fecal occult blood test (FOBT). In Italy, FOBT is performed every two years on subjects from 50 to 69 years old and shows a huge percentage of false positives (about 65% according to data). Positives are then invited to undergo colonoscopy. SCENT A1 is capable of reducing FOBT false positives and so the total number of non-operative colonoscopies with related risks (e.g. bowel perforation). The device is composed by a core of five chemoresistive MOX sensors, chosen and calibrated for this specific aim [5-10]. Sensors (Figure 1) have been synthesized at Sensor Laboratory of the University of Ferrara and are composed by a nanostructured semiconductor film screen-printed onto an alumina substrate and a platinum heater to modulate operating temperature. In the ending protocol phase, the chosen sensors have been limited to two, one composed by Iron and Samarium oxides and the other by Tin and Titanium oxides, to simplify the device, facilitating a future large scale reproduction, without any information loss. The data collection and analysis software employs support vector machine (SVM) [9]. The clinical validation protocol of this device started in May 2016, in collaboration with Hospital St. Anna of Ferrara, Delta Hospital of Lagosanto and Department of Public Health of Ferrara. A total of 398 fecal samples of FOBT-positive subjects have been analyzed by SCENT A1 system with the k-fold cross validation method. Samples have been grouped into two macrocategories, depending on the gold-standard (colonoscopy) outcomes: 260 healthy subjects (negative to colonoscopy); 138 colorectal adenomas and carcinomas (positive to colonoscopy), 54 low-risk adenomas and 84 high-risk adenomas and carcinomas. The system has been capable of distinguishing among these two cathegories with a sensitivity (TPR: true positive rate) and specificity (TNR: true negative rate) respectively of of 84,1% and 82,4%, defined as follows: TPR=TP/P=TP/(FN+TP); TN/N=TN/(FP+TN); where TP, TN, FP and FN are the abbreviations that indicate respectively true positives, true negatives, false positives and false negatives. The choice to group carcinomas, high- and low-risk adenomas into a single class and not into two diverse classes as before [10], has been done in order to simplify the test and to ensure greater doctor protection, despite a small loss in specificity. Low-risk adenomas are, in fact, often similar to healthy tissues and they have a risk of evolving into cancer comparable to the risk of colonoscopy complications. As already emerging from a previous study [10], in fact, the major error of classification (only 57%) concerned just low-risk tumors that emit gases halfway between healthy and tumoral samples. What emerges is that, if SCENT A1 test is carried out on FOBT-positives subjects as a second check, it would guarantee a reduction of about two thirds of the colonoscopies performed on healthy patients. A new multicenter protocol, involving also Ospedale Maggiore of Bologna (Italy) and the private clinic Quisisana will start at the end of 2020, in order to test diverse devices of the same type also to FOBT and colonoscopy negatives, in to identify interval cancers. Moreover, if employed by the NHS of countries without screening system, this method will significantly reduce CRC-mortality rate. [1] [https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html [2] Italian #: RM2014A000595, European #: 3210013 (Germany, UK); [3] B. Szachowicz-Petelska et al., NMR in Biomedicine V5,226–233, 1992; [4] T. G. de Meij et al., International Journal of Cancer (2014), 134, 1132–1138; [5] C. Malagù et al., Sensors, 14, 18982-18992, 2014; [6] G. Zonta et al., Sensors and Actuators B, 218, 289-295, 2015; [7] N. Landini et al., Scholars' Press, ISBN-13: 978-3-639-76538-0; [8] G. Zonta et al., Sensors and Actuators B, 238, 1098–110, 2016; [9] G. Zonta et al., Sensors and Actuators B 262 (2018) 884–891; [10] G. Zonta et al., Sensors and Actuators B: Chemical, Volume 301, 12 December 2019, 127062; [11] B. Scholkopf, A.J. Smola, 2001 (ISBN: 9780262253437); Figure 1

Among the various chemoresistive gas sensing properties studied so far, the sensing response reproducibility, i.e., the capability to reproduce a device with the same sensing performance, has been poorly investigated. However, the reproducibility of the gas sensing performance is of fundamental importance for the employment of these devices in on-field applications, and to demonstrate the reliability of the process development. This sensor property became crucial for the preparation of medical diagnostic tools, in which the use of specific chemoresistive gas sensors along with a dedicated algorithm can be used for screening diseases. In this work, the reproducibility of SmFeO3 perovskite-based gas sensors has been investigated. A set of four SmFeO3 devices, obtained from the same screen-printing deposition, have been tested in laboratory with both controlled concentrations of CO and biological fecal samples. The fecal samples tested were employed in the clinical validation protocol of a prototype for non-invasive colorectal cancer prescreening. Sensors showed a high reproducibility degree, with an error lower than 2% of the response value for the test with CO and lower than 6% for fecal samples. Finally, the reproducibility of the SmFeO3 sensor response and recovery times for fecal samples was also evaluated.

Colorectal cancer (CRC) is a worldwide diffused pathology for both men and women. It showed to be the third most common cancer for both genders, in the United States. [1] On the other hand, if promptly diagnosed, CRC is also one of the most curable tumor types (curability rate of about 90% at stage I), therefore prevention is fundamental to avoid its degeneration. This work shows the clinical validation outcomes of a preventive screening method based on a portable device composed by a core of nanostructured MOX sensors. This patented device, named SCENT A1 [2], is capable of detecting the presence of colorectal adenomas and carcinomas from fecal odor with an in-vitro, inexpensive and non-invasive methodology. Fecal odor can be affected by the presence of CRC-biomarkers produced by cancer cells through mechanisms of membrane peroxidation and metabolic alterations [3,4]. The analysis currently adopted by National Health Service (NHS) of Italy and of other countries as mass population screening is fecal occult blood test (FOBT). In Italy, this test is performed every two years on subjects from 50 to 69 years old and shows a huge percentage of false positives (about 65% according to the analyzed data). FOBT positives are then invited to undergo colonoscopy. SCENT A1 is capable of reducing FOBT-false positives, also diminishing the total number of non-operative colonoscopies, preventing healthy patients, often elderly, from undergoing the related risks (e.g. bowel perforation). The device presented here is composed by a core of five chemoresistive MOX sensors, chosen and calibrated for this specific aim through a study started in 2013 that lead to encouraging results [5-10]. Sensors have been synthesized at Sensor Laboratory on the University of Ferrara and are composed by a nanostructured semiconductor film screen-printed onto an alumina substrate and a platinum heater to modulate the operating temperature. In Figure 1 both the device and a sensor schematization are shown. In the ending phase of the protocol, the chosen sensors have been limited to two, one composed by Iron and Samarium oxides and the other by Tin and Titanium oxides. This choice has been done in order to simplify the device and to facilitate a future large scale reproduction, without any loss in the information carried by the system. The data collection and analysis software has been realized by employing machine learning techniques like support vector machine (SVM) [9] method. The clinical validation protocol of this device started in May 2016, in collaboration with Hospital St. Anna of Ferrara, Delta Hospital of Lagosanto and Department of Public Health of Ferrara. A total of 398 fecal samples of FOBT-positive subjects have been analyzed by SCENT A1 system with the k-fold cross validation method. Samples have been grouped into two macro-categories, depending on the gold-standard (colonoscopy) outcomes: healthy subjects (negative to colonoscopy), in total 260; all types of colorectal adenomas and carcinomas (positive to colonoscopy), in total 138 (54 low-risk adenomas and 84 high-risk adenomas and carcinomas). The system has been capable of distinguishing among these two cathegories with a sensitivity (TPR: true positive rate) and specificity (TNR: true negative rate) respectively of of 84,1% and 82,4%, defined as follows: TPR=TP/P=TP/(FN+TP); TN/N=TN/(FP+TN); where TP, TN, FP and FN are the abbreviations that indicate respectively true positives, true negatives, false positives and false negatives. The choice to group carcinomas, high- and low-risk adenomas into a single class and not into two diverse classes as before [10], has been done in order to simplify the test and to ensure greater doctor protection, despite a small loss in specificity. This is due to the fact that low-risk adenomas are often similar to healthy tissues and they have a risk of evolving into cancer comparable to the risk of colonoscopy complications. As already emerging from a previous study [10], in fact, the major error of classification (only 57%) concerned just low-risk tumors that emit gases halfway between healthy and tumoral samples. By observing these results, what emerges is that, if SCENT A1 test is carried out on FOBT-positives subjects as a second check, it would guarantee a reduction of about two thirds of the colonoscopies performed on healthy patients. A new multicenter protocol, involving also Ospedale Maggiore of Bologna (Italy) and the private clinic Quisisana will start in 2020, in order to test diverse devices of the same type also to subjects resulted negative to FOBT and colonoscopy. This double comparison will be useful to evaluate the possible capability of this method of identifying interval cancers. Moreover, if employed by the NHS of countries where screening systems are not currently carried out on population, this method will significantly reduce the mortality rate related to CRC. [1] [https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html [2] C. Malagu', G. Zonta, S. Gherardi, A. Giberti, N. Landini, A. Gaiardo (2014), Italian #: RM2014A000595, European #: 3210013 (Germany, UK); [3] B. Szachowicz-Petelska et al., NMR in Biomedicine V5, Issue 5, 226–233, September/October 1992; [4] T. G. de Meij et al., International Journal of Cancer (2014), 134, 1132–1138; [5] C. Malagù et al., Sensors, 14, 18982-18992, 2014; [6] G. Zonta et al., Sensors and Actuators B, 218, 289-295, 2015; [7] N. Landini et al., Scholars' Press, ISBN-13: 978-3-639-76538-0; [8] G. Zonta et al., Sensors and Actuators B, 238, 1098–110, 2016; [9] G. Zonta et al., Sensors and Actuators B 262 (2018) 884–891; [10] G. Zonta et al., Sensors and Actuators B: Chemical, Volume 301, 12 December 2019, 127062; [11] B. Scholkopf, A.J. Smola, 2001 (ISBN: 9780262253437); Figure 1

One of the greatest goals in medicine is early-stage tumor detection. An effective prevention is crucial to allow physicians and surgeons to intervene on patients with the available therapies, usually successful on small volume cancers only. The purpose of this research relies on the identification of cancer presence by detecting the volatile organic biomarkers directly produced by cancer cells. Cancer cell biomarkers are different by the ones exhaled by healthy cells and this difference can be recognized by means of a specific chemoresistive sensor array. In this study, a fast-responding, reliable and reproducible sensing technique proved to discriminate cancerous from healthy cells, making it an efficient low invasive screening system. The device employed, named SCENT B1 [1] combines a specific electronic and pneumatic system to a sensor core made of four nanostructured chemoresistive metal-oxide sensors (nanograins with average size of 40-50 nm) manufactured in the Sensor Laboratory of the University of Ferrara. The sample is inserted inside a specific sample box in a specific support composed by Petri dishes, while an ambient airflow, humidity stabilized, conveys the exhalations to sensors. Sensors responses are then analyzed by principal component analysis (PCA). Measurements have been performed on cancer and healthy tissues extracted during surgery from human colon and rectum, with the future aim of extending the study to the other type of tumors. Neoplastic tissues exhibit altered metabolic processes with respect to the metabolism of healthy cells, therefore the chemicals (metabolites) expelled during cellular respiration depend upon the cell health status. Sensors chosen to compose the array have been selected after a feasibility study performed on immortalized cells of diverse types, correlating also sensors responses with cell concentration inside the Petri dish (after 24, 48, 72 hours of incubation). Sensors chosen are: a mixture of tin and titanium oxides with addition of gold (ST25Au), tungsten oxide (W11), a mixture of tin, titanium and niobium oxides (STN) and a solid solution of titanium oxide, tantalum and vanadium (TiTaV). The voltage output of each sensor is directly proportional to its conductance, that depends on the chemical reactions happening on sensor surface [2,3]. In Figure (a) the response R=DG/G for each sensor is reported, where DG is the difference between the sensor conductance with and without the metabolites expelled by the cells of a tissue. All four sensors gave larger responses (although with different amplitudes) to the tumor tissue with respect to the healthy one. Smaller responses were given by the breeding ground (DMEM) only, confirming that it does not alter the measurement. Results are consistent with the stronger metabolism of tumor cells with respect to the healthy ones, because the former emits larger amounts of volatile biomarkers [4,5]. Other tests proved also that different initial plating concentrations (250k, 500k and 1M) of cell give increasing responses, as shown in Figure (b). From this study what emerges is that the the device is capable of distinguishing different cell samples basing on their health status and concentrations, laying the foundation for a deepen study for the clinical validation of the device as a oncologic screening device. References SCENT B1, Italian Patent Number: 102015000057717; Zonta, G. Anania, B. Fabbri, A. Gaiardo, S. Gherardi, A. Giberti, V. Guidi, N. Landini, C. Malagù; “Detection of colorectal cancer biomarkers in the presence of interfering gases”; Sensors and Actuators B 218 (2015), 289–295; Zonta, G. Anania, B. Fabbri, A. Gaiardo, S. Gherardi, A. Giberti, N. Landini, C. Malagù, L. Scagliarini, V. Guidi, Preventive screening of colorectal cancer with a device based on chemoresistive sensors. Sensors and Actuators B, 238, 1098–110, 2016. F. Altomare, M. Di Lena, F. Porcelli, L. Trizio, E. Travaglio, M. Tutino, S. Dragonieri, V. Memeo, G. de Gennaro; “Exhaled volatile organic compounds identify patients with colorectal cancer”; British Journal of Surgery 100 (2013), 144-150; Chan, E.C.Y., Koh, P.K., Mal, M., Cheah, P.Y., Eu, K.W., Backshall, A., Cavill, R., Nicholson, J.K., Keun, H.C., 2009. “Metabolic Profiling of Human Colorectal Cancer Using High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy and Gas Chromatography Mass Spectrometry (GC/MS)”, Journal of Proteome Research 8(1), 352–361; Figure 1

Preventive screening does not only allow to preemptively intervene on pathologies before they can harm the host, but also to reduce the costs of the intervention itself, boosting the efficiency of the NHS (National Health System) by saving resources for other purposes. To improve technology advancements in this field, user-friendly yet low-cost devices are required, and various applications for gas sensors have been tested and proved reliable in past studies. In this work, cell cultures and blood samples have been studied, using nanostructured chemoresistive sensors, to both verify if this technology can reliably detect tumor markers, and if correlations between responses from tumor line metabolites and the screening outcomes on human specimens could be observed. The results showed how sensors responded differently to the emanations from healthy and mutant (for cells) or tumor affected (for blood) samples, and how those results were consistent between them, since the tumoral specimens had higher responses compared to the ones of their healthy counterparts. Even though the patterns in the responses require a bigger population to be defined properly, it appeared that the different macro-groups between the same kind of samples are distinguishable from some of the sensors chosen in the study, giving promising outcomes for further research.

Among the major challenges of medicine today there are screening and early detection of tumors (since the adenoma stage) in order to prevent their degeneration into malignant cancer and/or metastases. In particular, the colorectal cancer shows a high curability rate, up to 90%, if identified when in its benign stage. The Protocol discussed here is proposed to implement the clinical validation of a device consisting of an array of chemoresistive gas sensors made of semiconductor materials, able of identifying the difference between fecal exhalation of healthy subjects and of subjects suffering from high-risk colorectal polyps or tumors. The tests are compared to the results of fecal occult blood test and colonoscopy as a gold standard.

During the last decade, due to its excellent electrical, mechanical and thermal properties of chemically modified graphene has been extensively studied for many applications, such as polymer composites, energy-related materials, biomedical applications and sensors. The aim of this work is to evaluate the gas sensing performance of niobium oxide (Nb2O5) nanoclusters deposited onto few-layers graphene powder by magneton sputtering. Two different samples were prepared by changing electrical power of deposition. The materials were deeply morphologically, structurally and chemically characterized. Finally, they were deposited onto alumina substrates and their sensing properties were investigated vs. different gases, showing good sensing performance vs. ppm concentrations of NO2 at room temperature.

Medical studies have shown that tumor growth is accompanied by protein changes that may lead to the peroxidation of the cell membrane, with consequent emission of volatile organic compounds (VOCs). VOCs can be detected through breath or intestinal gases and are biomarkers for colorectal cancer (CRC). The analysis of VOCs represents a non-invasive and potentially inexpensive pre-screening technique. An array of chemoresistive gas sensors, based on screen-printed Metal OXide (MOX) semiconducting films, has been selected to identify gaseous compounds of oncological interest, i.e. benzene, 1-iodo-nonane and decanal, from the main interferers that can be found in the intestine. MOX sensors are able to detect concentrations down to about 10th ppb, as experimentally proven in previous works, so they can identify very slight differences in concentration among gas mixtures. In this work it has been proven that the array used is able to identify tumor markers singularly and in combination with other gases both in wet and dry conditions. Moreover, the sensors chosen can discriminate target VOCs from interferers even at low concentrations.

In the recent years, metal sulfide nanostructured materials have become established in different research fields thanks to their excellent properties. Among the potential applications, metal sulfides may have a high standing role for gas sensing, in which, despite the wide assortment of sensing materials, still metal-oxides maintain a leading role because of their high sensitivity, low cost, small dimensions and simple integration. Experimentation carried out in this work with CdS and SnS2 thick film sensors has showed an unexpected improvements of the chemoresistive properties with respect to their oxides counterparts, in particular toward selectivity to specific compounds, stability and the possibility to operate at room temperature. This opens towards the study of a novel class of sensing materials, which may solve the constant drift of the signal suffered by metal-oxides and ascribed to the in/out diffusion of oxygen vacancies, which alters the doping level.