Chemoresistive Sensors Research Articles

Sensing Device for Colorectal Cancer Preventive Screening through Fecal Odor Analysis:Clinical Validation Outcomes

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

Chemoresistive Nanostructured Sensors for the Analysis of Human Tumor Tissue Exhalations

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.

Nanomechanical Gas Sensing with Laser Treated 2D Nanomaterials

Abstract2D nanomaterials such as graphene oxide (GO), molybdenum disulfide (MoS2), and tungsten disulfide (WS2) are viable candidates for use in chemical gas sensors due to their large specific surface area available for analyte adsorption. In this work, these 2D materials are treated with a femtosecond laser process to intentionally introduce defects, dopants, and functional groups to the material for improved gas adsorption properties. The materials are coated onto a nanomechanical membrane‐type surface stress sensor (MSS) to evaluate their sensing capability toward a select group of volatile organic compounds. By utilizing the MSS platform, the approach avoids the need for 2D materials with conductive properties typically required in chemoresistive sensors. The results show that a longer laser treatment time for graphene oxide increases the sensor response, which is attributed to an increase in defects and oxygen functional groups. Doping of graphene oxide with boron nitride improves sensor response, likely due to the introduction of pyrrolic nitrogen groups with high chemical activity. Additionally, the graphene oxides demonstrate partial selectivity toward the detection of toluene, attributable to π–π interactions. MoS2 and WS2 nanoflakes also show enhanced sensor response attributed to the formation of apical/bridging sulfur bonds with high catalytic activity.

LoRa Sensor Network Development for Air Quality Monitoring or Detecting Gas Leakage Events.

During the few last years, indoor and outdoor Air Quality Monitoring (AQM) has gained a lot of interest among the scientific community due to its direct relation with human health. The Internet of Things (IoT) and, especially, Wireless Sensor Networks (WSN) have given rise to the development of wireless AQM portable systems. This paper presents the development of a LoRa (short for long-range) based sensor network for AQM and gas leakage events detection. The combination of both a commercial gas sensor and a resistance measurement channel for graphene chemoresistive sensors allows both the calculation of an Air Quality Index based on the concentration of reducing species such as volatile organic compounds (VOCs) and CO, and it also makes possible the detection of NO2, which is an important air pollutant. The graphene sensor tested with the LoRa nodes developed allows the detection of NO2 pollution in just 5 min as well as enables monitoring sudden changes in the background level of this pollutant in the atmosphere. The capability of the system of detecting both reducing and oxidizing pollutant agents, alongside its low-cost, low-power, and real-time monitoring features, makes this a solution suitable to be used in wireless AQM and early warning systems.

MetaNChemo: A meta-heuristic neural-based framework for chemometric analysis

Gas sensors are present in almost every environmental monitoring application. They can be realized using different materials and production techniques while exploiting different physical/chemical processes to detect one or more target gas. Historically, their research and development are mainly driven by the materials science community. However, the seamless combination of artificial intelligence techniques with gas sensors in cyber–physical systems is recently attracting the interest of various computer science communities. In this paper, we propose MetaNChemo, a multidisciplinary end-to-end framework to build a chemometric system from the very production of chemoresistive sensors, through the data sampling and pre-processing phases necessary to calibrate such sensors, to the identification and the assessment of the most suitable artificial intelligence models able to supports the detection of the concentration of a target gas in the air. Without loss of generality, we focus our attention on carbon monoxide (CO) as our target gas. However, materials scientists may take full advantage of MetaNChemo, since its data-driven approach can accommodate very specific requirements of those environmental monitoring applications that have to properly detect one or more target gas. By resorting to state-of-the-art meta-heuristic techniques, we identify and train tiny neural networks (20-50 weights) able to achieve F1-scores greater than 0.95 over real environmental test conditions.

Surface Functionalization of Ti3C2Tx MXene with Highly Reliable Superhydrophobic Protection for Volatile Organic Compounds Sensing.

Two-dimensional (2D) transition-metal carbides (Ti3C2Tx MXene) have received a great deal of attention for potential use in gas sensing showing the highest sensitivity among 2D materials and good gas selectivity. However, one of the long-standing challenges of the MXenes is their poor stability against hydration and oxidation in a humid environment, limiting their long-term storage and applications. Integration of an effective protection layer with MXenes shows promise for overcoming this major drawback. Herein, we demonstrate a surface functionalization strategy for Ti3C2Tx with fluoroalkylsilane (FOTS) molecules through surface treatment, providing not only a superhydrophobic surface, mechanical/environmental stability but also enhanced sensing performance. The experimental results show that high sensitivity, good repeatability, long-term stability, and selectivity and faster response/recovery property were achieved by the FOTS-functionalized when Ti3C2Tx was integrated into chemoresistive sensors sensitive to oxygen-containing volatile organic compounds (ethanol, acetone). FOTS functionalization provided protection to sensing response when the dynamic response of the Ti3C2Tx-F sensor to 30 ppm of ethanol was measured over in the 5 to 80% relative humidity range. Density functional theory simulations suggested that the strong adsorption energy of ethanol on Ti3C2Tx-F and the local structure deformation induced by ethanol adsorption, contributing to the gas-sensing enhancement. This study offers a facile and practical solution for developing highly reliable MXene based gas-sensing devices with response that is stable in air and in the presence of water.

Superior Acetone Selectivity in Gas Mixtures by Catalyst-Filtered Chemoresistive Sensors.

Acetone is a toxic air pollutant and a key breath marker for non‐invasively monitoring fat metabolism. Its routine detection in realistic gas mixtures (i.e., human breath and indoor air), however, is challenging, as low‐cost acetone sensors suffer from insufficient selectivity. Here, a compact detector for acetone sensing is introduced, having unprecedented selectivity (>250) over the most challenging interferants (e.g., alcohols, aldehydes, aromatics, isoprene, ammonia, H2, and CO). That way, acetone is quantified with fast response (<1 min) down to, at least, 50 parts per billion (ppb) in gas mixtures with such interferants having up to two orders of magnitude higher concentration than acetone at realistic relative humidities (RH = 30–90%). The detector consists of a catalytic packed bed (30 mg) of flame‐made Al2O3 nanoparticles (120 m2 g−1) decorated with Pt nanoclusters (average size 9 nm) and a highly sensitive chemo‐resistive sensor made by flame aerosol deposition and in situ annealing of nanostructured Si‐doped ε‐WO3 (Si/WO3). Most importantly, the catalytic packed bed converts interferants continuously enabling highly selective acetone sensing even in the exhaled breath of a volunteer. The detector exhibits stable performance over, at least, 145 days at 90% RH, as validated by mass spectrometry.

Impact of heterostructures on hydrogen sulfide sensing: Example of core-shell CuO/CuFe2O4 nanostructures

Toxic and corrosive H2S gas is detected using chemoresistive sensors based on CuO/CuFe2O4 core-shell heterostructures, which are characterized by DC resistance measurements, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Exposure to various test gases (CO, H2, NO2, VOCs) reveals low responses. However, unique reactivity towards H2S at low operating temperatures leads to accumulation of CuS clusters on the surface, which can connect to create a percolation path of high electric conductance. The core-shell heterostructures differ in their response to H2S, as the materials’ shell (CuFe2O4) partly converts incoming H2S to its combustion products, effectively reducing the amount of H2S reaching the core structures. This behavior was observed for both pulsed and continuous exposure to H2S, making it an inherent property of the examined core-shell heterostructures. SEM images and EDX spectra reveal that the phase transition with subsequent regeneration have a strong impact on the morphology of the functional layer.

Enhancement of 2-butanone sensing properties of SiO2@CoO core-shell structures

Volatile organic compounds (VOCs) can be associated with some diseases when found in human exhaled breath as a result of alterations in metabolic pathways. Therefore, the development of highly selective sensors to a particular VOC is required. In this paper, we used silica (SiO2) nanospheres as support for the growth of cobalt (II) oxide (CoO) nanosheets, resulting in the SiO2@CoO core-shell structure with a high specific surface area. This structure was applied as a chemoresistive VOCs sensor. The SiO2@CoO material exhibited increased sensitivity to 2-butanone in comparison with acetone, methanol, ethanol, isopropanol, acetaldehyde, benzene, toluene, and m-xylene. The response to 100 ppm of 2-butanone was ~44.7, with a response time of 27 s. The enhanced performance might be attributed to the high surface area provided by the unique core-shell structure with 2D CoO nanosheets.

Selective formaldehyde detection at ppb in indoor air with a portable sensor

Formaldehyde is a carcinogenic indoor air pollutant emitted from wood-based furniture, building materials, paints and textiles. Yet, no low-cost sensor exists for on-site monitoring to fulfill stringent current and upcoming (e.g., 8 parts-per-billion by volume, ppb, in France by 2023) exposure guidelines. Here, we present an inexpensive and handheld formaldehyde detector with proven performance in real indoor air. Selectivity is achieved by a compact packed bed column of nanoporous polymer sorbent that separates formaldehyde from interferants present in ambient air. Downstream, a highly sensitive nanoparticle-based chemoresistive Pd-doped SnO2 sensor detects formaldehyde in the relevant concentration range down to 5 ppb within 2 min. As a proof-of-concept, we measured formaldehyde in indoor air and from different wood product emissions, in excellent agreement (R2 > 0.98) with high-resolution proton-transfer-reaction time-of-flight mass spectrometry. This detector is simple-in-use and readily applicable for on-site formaldehyde exposure monitoring at home or work. It is promising for internet-of-things (IOT) sensing networks or even wearables for personal exposure assessment.

Chemoresistive Nanostructured Sensors for the Analysis of Tumor Tissues Exhalations

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

Selective Breath Sensors for Metabolic Monitoring

Introduction Despite a growing diagnostic toolset and a plethora of preventative and therapeutic interventions, a major challenge remains the control of epidemic diseases like obesity, diabetes or cancer. Great promise bears the current transformation of healthcare from disease-reactive to predictive, preventive, personalized and participatory - the so-called “4P” medicine [1]. Breath analysis could play a key role in this by providing on-demand critical health data. For daily breath analysis in wide-spread populations, simple-in-use and portable breath detectors are required. For this purpose, chemoresistive sensors are quite attractive due to their compact design, low cost and low power consumption being ideal for integration into handheld devices [2]. Here, I will describe recent progress on the development of selective/single-molecule breath sensors. In particular, I will showcase our recent in-vivo tests of Si-doped WO3 breath acetone sensors in a clinical environment during ketogenic dieting (KD) [3]. Finally, I will update on our newest development on orthogonal sensor arrays and present their application to sniff breath- and skin-emitted tracers (including acetone, isoprene and ammonia) for search & rescue applications [4]. Methods The sensor is based on a Si-doped WO3 nanoparticle films prepared by flame spray pyrolysis (FSP). Obtained nanoparticles were deposited directly by thermophoresis onto interdigitated Pt electrodes. End-tidal breath was extracted in a monitored and reproducible fashion with a tailor-made and modular sampler described in detail elsewhere [5]. The acetone sensor was mounted on a Macor holder, installed inside a Teflon chamber and fed with 130 mL min-1 from the sampler with a pump (SP 135 FZ, Schwarzer Precision). An additional line was connected just before the acetone sensor chamber to extract samples for the QMS (QMS 422, ThermoStarTM, Pfeiffer Vacuum). Healthy non-smokers free from respiratory or cardiovascular disease were included in this study. Each volunteer was informed about the experimental protocol prior to the test, gave written consent and could interrupt the test or withdraw consent anytime. The participants followed a fat:(carbohydrate+protein) 4:1 KD based on the Johns Hopkins protocol for 36 h including overnight fasting periods. Results and Conclusions Eleven volunteers (five female and six male) with a median age (± SD) of 22.7 (± 2.0) years participated in this study. Their body mass index was 22.4 (± 3.3) kg/m2. All volunteers had office jobs and were rather inactive. With the compact and inexpensive sensor, the individual breath acetone dynamics were monitored accurately up to concentrations of 66 ppm, in good agreement with mass spectrometry. The breath acetone dynamic reflected well the status of ketosis, as indicated by blood BOHB. Most interestingly, strong differences in individual breath and blood profiles were identified between the volunteers despite identical KD conditions. These were correctly recognized by the breath acetone sensor including patterns possibly associated to low tolerance to the KD protocol.As a result, this breath sensor is promising as a portable ketosis monitor. It has broad application as ketogenic diet is a proven medical treatment of refractory epilepsy (i.e. drug-resistant) [6] occurring in ~30% of the approx. 50 million epileptics worldwide. Also, it is an effective therapy for weight loss with growing interest to treat obesity-associated metabolic disorders [7] (e.g. diabetes or fatty liver disease), acts anti-inflammatory [8] and is even beneficial for athletes to improve their endurance performance by altering fuel preference [9].

Development of a Molecularly Imprinted Sensing Material for Antibiotics Detection

Introduction Antibiotic detection has become a major issue in many fields such as water analysis, food control, health, etc. Besides the immediate dangers, the spread of antibiotics everywhere provokes the phenomenon of bacterial resistance which, on the long run, will cause health issues. Indeed, the excessive use of antibiotics allows the bacteria to mutate and thus develop resistance, requiring the development of new compounds. This work aims to develop and characterize a sensing material to detect multiple antibiotics in liquid phase using various methods. The idea is to conceive low power sensors or even disposable sensors. Therefore, sensors should be low cost and compatible for mass production. The most interesting sensitive materials seem to be molecularly imprinted polymers (also called MIP) using conductive polymers [1],[2]. Synthesis of the MIP Polypyrrole (PPy) is chosen as conductive polymer to be molecularly imprinted. Pyrrole (Py) is used as the cross-linker and pyrrole-3-carboxylic acid as the functional monomer, to obtain chemical interactions between polymer and the target molecule (also called “template”). The synthesis is performed in-situ (also called bulk polymerization) in aqueous media by mixing the target molecule, the functional monomer and the cross-linker with the oxidizer, ammonium persulfate (APS), while pH value is set to around 2.2, well below the template’s pKa to allow better interactions between monomers and the template. While oxidative polymerization takes place, temperature is kept at 30 °C, for 2 hours. The polymer is deposited everywhere in the reactor, and also on the substrates used to get the sensor.The next step, so-called extraction, consists in removing the template from the polymer. It is performed by using a solution of methanol and HCl (9:1) wherein substrates are immersed for 2 hours [3]. Then, substrates are stored in PBS (phosphate buffered saline) solution before being tested. Non-Imprinted Polymers (NIP) are also synthetized following the same steps, except that the template is not present during the synthesis. Measurement methods Polymerization has been performed on various substrates allowing to use multiple sensing methods to explore as much path as possible. Up to now, sensors had been performed and tested on chemoresistive plastic IDE sensors to perform impedimetric measurements, on quartz crystal microbalance substrates to perform mass variation measurements and on glass slide to perform UV/VIS/NIR absorbance measurements (the ultimate goal is to use the sensing material on optical fibers), as shown on Fig.1. Results and Conclusions Sensors are tested in PBS 0.5x solution (half the usual concentration). After the extraction step carried out on the various substrates, detection is performed by adding the target antibiotic into the PBS solution. Fig. 2 shows impedance measurements and this parameter grows nearly linearly as soon as we add a dozen ppb of the antibiotic. Fig.3 shows that for the same measurement method, the NIP nearly doesn’t react when we add the template, which means that the imprinting is functional and significantly increases the performance of the sensor. Fig. 4 and Fig. 5 show the evolution of the NIR spectrum of the sensing layers after contact with the antibiotic, for the MIP ad NIP, respectively. This method exhibits some limitation with a saturation above 50 ppb. Fig.6 shows the mass evolution on a quartz microbalance of the sensitive layer in contact with the target antibiotic and an interferent with the same concentrations to show the sensor specificity. The response shown to the interferent is quite weak in comparison with the one corresponding to the target molecule. In conclusion, the sensors were found to be able to detect concentrations of approximately 15 ppb and are close to the detection limits of conventional methods (10 ppb). In addition, they have proven their specificity to the target molecule by showing no reaction when exposed to the usual interferents. We showed that the MIP is suitable for both impedimetric sensors as well as for optical sensors (optical fibers or dipsticks for instance).

Light-Activated Chemoresistive and Plasmonic-Resonant Optical Sensors for NO2 and H2 Sensing Based on ZnO Doped Nanoparticles

Light-Activated Chemoresistive and Plasmonic-Resonant Optical Sensors for NO2 and H2 Sensing Based on ZnO Doped Nanoparticles

Sensing Device for Colorectal Cancer Preventive Screening through Fecal Odor Analysis: Clinical Validation Outcomes

Sensing Device for Colorectal Cancer Preventive Screening through Fecal Odor Analysis: Clinical Validation Outcomes

In Situ Resistance Monitoring during Flame-Aerosol Deposition of Metal Oxide Gas Sensing Layers

Introduction Chemo-resistive sensors are highly promising for the detection of trace-level compounds in medical diagnostics[1] or indoor air monitoring[2]. In particular, gas sensors made by direct flame-aerosol synthesis are attractive due to their highly porous and crack-free sensing films[3]. They are composed of high-surface area nanoparticles with diverse composition tuned for ppb-level sensitivity and high selectivity towards key analytes such as Si-doped WO3 for acetone[1] or Ti-doped ZnO for isoprene[4]. Fabrication development has also led to the ability to process flame-made sensors by techniques compatible with standard silicon-wafer micromachining[5]. This enables the preparation of low power sensors that are attractive for portable handheld devices. So far, the development of such sensors has been focused mostly on material composition and, to a lesser extent, on film morphology and design. However, optimizing the latter could improve the sensor sensitivity as well as response and recovery times. Measuring the resistance during flame-deposition of nanostructured films in situ offers fabrication control by providing immediate feedback when an interconnected film is created[6]. This ultimately allows the fabrication of sensing films of minimal thickness and optimal resistance in a reproducible and economical manner. In situ resistance monitoring This work focuses on in situ monitoring the resistance of nanostructured films fabricated by direct deposition of flame-made Sb-doped SnO2 nanoparticles[6]. The sensing film morphology was tuned by a substrate-impinging particle flame, fed by a precursor solution containing varying metal ion concentrations. In situ resistance monitoring enabled control over final film resistance as well as direct insight into network formation and nanoparticle growth, necking and coalescence. The performance of these films as ethanol vapor sensors was assessed and related to their in situ resistance and nanoparticle film characteristics. Method Gas sensing nanoparticle films were prepared by direct deposition of flame-made Sb-doped (12 at%) SnO2 onto alumina substrates with interdigitated platinum electrodes. Deposition was carried-out for up to 6 min. Substrate preheating, film deposition and cooling to room temperature was closely monitored by the in situ resistance (Ri) between the interdigitated electrodes with a multimeter (Tektronix DMM4050). Nanoparticle sensing films were imaged by scanning electron microscopy (Hitachi S-4800 FE-SEM) after particle deposition for 2 min. Results and Conclusions Figure 1a shows the formation of Sb-doped SnO2 nanoparticles in a flame, followed by direct deposition onto the sensor substrate and in situ film resistance (Ri) read out. Figure 1b shows the in situ film resistance as a function of deposition duration using 1 (red squares), 10 (blue circles) or 100 (green triangles) mM FSP precursor solution concentrations (PSC). At low PSC (1 mM), the Ri remains at first (up to ca. 1 min) rather indifferent to nanoparticle deposition as it takes some time to build the interconnected particle bridges. But as deposition is prolonged (t >1.5 min), the Ri starts to drop. This clearly indicates the formation of an interconnected network of nanoparticles. Also quite notable is the strong oscillation of Ri by more than an order of magnitude during network formation. This stems from the constant formation (by deposition) and break-up of necked nanoparticles (by coalescence) on the substrate (i.e., repeatedly from lace-like to cauliflower-like structures) during flame-deposition. Increasing the PSC from 1 to 10 mM or 100 mM leads naturally to a higher generation rate of nanoparticles and, therefore, faster drop in resistance. This is confirmed by SEM imaging after 2 minute deposition time for 1, 10 and 100 mM (Figure 2 a-c). As expected, nanoparticles are assembled more densely at higher PSC. As a result, the film formation and morphology of Sb-doped SnO2 can be monitored during direct flame-deposition. This monitored Ri is correlated to its evolving particle size and necking, enabling the ability to optimize material quantity, fabrication time and the final film resistance. This leads to the ability to rapidly synthesize thin flame-made gas sensors with improved sensitivity and reduced response/recovery times.

Highly Selective Chemical Sensors Enabled By Ethanol Filters

Introduction Compact and low-cost gas sensors are urgently sought in emerging applications including indoor air monitoring[1], search and rescue[2], and medical diagnostics[3]. While chemo-resistive sensors feature remarkable sensitivities to detect even parts-per-billion (ppb) concentrations, a key limitation is selectivity, impeding commercial use[4]. An important interfering molecule is ethanol due to its omnipresence in the environment at high concentrations. In specific, ethanol concentrations may reach high parts-per-million (ppm) levels released from disinfectants and cleaning agents[5], thus exceeding trace level concentrations of target analytes such as acetone in breath analysis (500 ppb in healthy humans[6]) or carcinogenic benzene in indoor air (8 h exposure limit of 50 ppb in the EU[7]) by orders of magnitudes. This is particularly problematic, as most sensors (e.g. carbon-based or metal-oxide sensors) are sensitive to ethanol. Thus, ethanol interference is a major concern even for sensors with rather high selectivity to ethanol. A simple approach to mitigate ethanol interference is through interface design, i.e., by combining sensors with a modular filter. Thereby, the filter is placed before the sensor to pre-select complex gas mixtures. Particularly suitable are catalytic filters[8], as they allow continuous conversion of active species into inactive species, while target analytes remain unscathed. State-of-the-art catalytic filters, however, do not allow to distinguish between volatile organic compounds such as ethanol and acetone. Here, we explore the use of a highly selective flame-made nano-catalyst as packed bed filter for the removal of ethanol in gas mixtures at high relative humidity (RH). Method Nano-catalyst filters were installed before flame-made Si-doped WO3[3] sensors. The performance of the filter-sensor system was characterized with a gas mixing setup at high RH (90%) and calibrated gas standards. Finally, the filter was tested as proof of concept with the breath of an alcohol-intoxicated volunteer. Therefore, a single volunteer consumed 150 mL of red wine prior to experiments. Thereafter, ethanol concentrations were investigated in three consecutive breath pulses both with and without the activated nano-catalyst with a proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS). Results and Conclusions The sensor response to breath-relevant 0-1 parts per million (ppm) acetone in presence of 0-20 ppm ethanol at 90 % RH is shown in Figure 1. Without the activated filter, the sensor clearly detects even low acetone concentrations (0.25 ppm) in absence of ethanol with high response (4) and signal to noise ratio > 100 (Figure 1a, squares). However, when testing gas mixtures with additional 5 (triangles), 10 (diamonds) or 20 (stars) ppm of ethanol, the sensor response is shifted upwards, resulting in an overestimation of acetone concentration. In contrast, with the activated filter, the interference of ethanol is reduced significantly, for example by 88% in case of 20 ppm ethanol only (stars) (Figure 1b). The residual error (e.g., 25% at 0.5 ppm acetone with 20 ppm ethanol) can be attributed to the formation of H2 during ethanol oxidation.Figure 2 shows the ethanol concentration profile for three consecutive exhalations of an alcohol-intoxicated volunteer without (0 ≤ t ≤ 3 min) and with (t > 3 min) the nano-catalyst filter. Without filter, ethanol concentrations reach 185 ppm as measured by PTR-ToF-MS. Most importantly, with filter, such high ethanol concentrations are removed completely even in the complex gas mixture of breath (> 800 compounds[9]). As a result, this filter presents a simple and inexpensive solution to the long-standing challenge of interference of chemical sensors by high concentrations of ethanol. Due to its compact and modular design, it can be flexibly combined with any type of gas sensor and integrated into portable devices for wide applicability.

Low-Temperature Carbon Dioxide Gas Sensor Based on Yolk–Shell Ceria Nanospheres

Monitoring carbon dioxide (CO2) levels is extremely important in a wide range of applications. Although metal oxide-based chemoresistive sensors have emerged as a promising approach for CO2 detection, the development of efficient CO2 sensors at low temperature remains a challenge. Herein, we report a low-temperature hollow nanostructured CeO2-based sensor for CO2 detection. We monitor the changes in the electrical resistance after CO2 pulses in a relative humidity of 70% and show the high performance of the sensor at 100 °C. The yolk-shell nanospheres have not only 2 times higher sensitivity but also significantly increased stability and reversibility, faster response times, and greater CO2 adsorption capacity than commercial ceria nanoparticles. The improvements in the CO2 sensing performance are attributed to hollow and porous structure of the yolk-shell nanoparticles, allowing for enhanced gas diffusion and high specific surface area. We present an easy strategy to enhance the electrical and sensing properties of metal oxides at a low operating temperature that is desirable for practical applications of CO2 sensors.

Colorectal Cancer Study with Nanostructured Sensors: Tumor Marker Screening of Patient Biopsies.

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.

Hydrogen Gas Sensing Performances of p-Type Mn3O4 Nanosystems: The Role of Built-in Mn3O4/Ag and Mn3O4/SnO2 Junctions.

Among oxide semiconductors, p-type Mn3O4 systems have been exploited in chemo-resistive sensors for various analytes, but their use in the detection of H2, an important, though flammable, energy vector, has been scarcely investigated. Herein, we report for the first time on the plasma assisted-chemical vapor deposition (PA-CVD) of Mn3O4 nanomaterials, and on their on-top functionalization with Ag and SnO2 by radio frequency (RF)-sputtering, followed by air annealing. The obtained Mn3O4-Ag and Mn3O4-SnO2 nanocomposites were characterized by the occurrence of phase-pure tetragonal α-Mn3O4 (hausmannite) and a controlled Ag and SnO2 dispersion. The system functional properties were tested towards H2 sensing, yielding detection limits of 18 and 11 ppm for Mn3O4-Ag and Mn3O4-SnO2 specimens, three orders of magnitude lower than the H2 explosion threshold. These performances were accompanied by responses up to 25% to 500 ppm H2 at 200 °C, superior to bare Mn3O4, and good selectivity against CH4 and CO2 as potential interferents. A rationale for the observed behavior, based upon the concurrence of built-in Schottky (Mn3O4/Ag) and p-n junctions (Mn3O4/SnO2), and of a direct chemical interplay between the system components, is proposed to discuss the observed activity enhancement, which paves the way to the development of gas monitoring equipments for safety end-uses.