Overview of Gas Sensors Focusing on Chemoresistive Ones for Cancer Detection

The necessity of detecting and recognizing gases is crucial in many research and application fields, boosting, in the last years, their continuously evolving technology. The basic detection principle of gas sensors relies on the conversion of gas concentration changes into a readable signal that can be analyzed to calibrate sensors to detect specific gases or mixtures. The large variety of gas sensor types is here examined in detail, along with an accurate description of their fundamental characteristics and functioning principles, classified based on their working mechanisms (electrochemical, resonant, optical, chemoresistive, capacitive, and catalytic). This review is particularly focused on chemoresistive sensors, whose electrical resistance changes because of chemical reactions between the gas and the sensor surface, and, in particular, we focus on the ones developed by us and their applications in the medical field as an example of the technological transfer of this technology to medicine. Nowadays, chemoresistive sensors are, in fact, strong candidates for the implementation of devices for the screening and monitoring of tumors (the second worldwide cause of death, with ~9 million deaths) and other pathologies, with promising future perspectives that are briefly discussed as well

Sensor Technology for Opening New Pathways in Diagnosis and Therapeutics of Breast, Lung, Colorectal and Prostate Cancer

This study analyzes the interaction between sensor research and technology and different types of cancer (breast, lung, colorectal, and prostate) with the goal of detecting new directions for improving diagnosis and therapeutics in medicine. This study develops an approach to computational scientometrics based on data from the Web of Science from the 1991 to 2021 period. The results of this analysis show the vital role of biosensors and electrochemical biosensors applied in breast cancer, lung cancer, and prostate cancer research. Instead, scientific research of optical sensors is developing main technological trajectories in breast, prostate, and colorectal cancer for improving diagnostics. Finally, oxygen sensor research has a main technological development in breast and lung cancer for new applications in breath analysis directed to treatment processes. Preliminary results presented here clearly illustrate the evolutionary paths of sensor research and technologies that have great potential for developing incremental and radical innovations in cancer diagnosis and therapies. These conclusions are, of course, tentative. There is a need for much more detailed research based on other aspects and factors for detecting stable technological trajectories that can foster the technology transfer of new sensor in cancer research for improving diagnosis and therapeutics, reducing, whenever possible, world-wide mortality of cancer in society.JEL Classification: I10, O30, O31, O32; O33. Doi: 10.28991/HIJ-2022-03-03-010 Full Text: PD

Clinical validation results of an innovative non-invasive device for colorectal cancer preventive screening through fecal exhalation analysis

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% (25–35% for FIT)

Chemoresistive Nanosensors Employed to Detect Blood Tumor Markers in Patients Affected by Colorectal Cancer in a One-Year Follow Up

Simple Summary Since colorectal cancer represents one of the most diffused pathologies worldwide, usually lacking specific symptoms, it is crucial to develop and validate innovative low-invasive techniques to detect it. Here, a device based on an array of nanostructured gas sensors has been employed to analyze and discriminate the exhalations of blood samples collected from colorectal cancer-affected patients at different stages of their pre- and post-surgery therapeutic path. The device was clearly able to distinguish between the pre-surgery samples, where the tumor was present, and the one-year post-surgery ones, following the tumor removal. These results raise high hopes for the device's clinical validation and its future use in clinical follow-up protocols, patient health status monitoring, and to detect possible post-treatment relapses. 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

Development of a compact, IoT-enabled electronic nose for breath analysis

In this paper, we report on an in-house developed electronic nose (E-nose) for use with breath analysis. The unit consists of an array of 10 micro-electro-mechanical systems (MEMS) metal oxide (MOX) gas sensors produced by seven manufacturers. Breath sampling of end-tidal breath is achieved using a heated sample tube, capable of monitoring sampling-related parameters, such as carbon dioxide (CO2), humidity, and temperature. A simple mobile app was developed to receive real-time data from the device, using Wi-Fi communication. The system has been tested using chemical standards and exhaled breath samples from healthy volunteers, before and after taking a peppermint capsule. Results from chemical testing indicate that we can separate chemical standards (acetone, isopropanol and 1-propanol) and different concentrations of isobutylene. The analysis of exhaled breath samples demonstrate that we can distinguish between pre- and post-consumption of peppermint capsules; area under the curve (AUC): 0.81, sensitivity: 0.83 (0.59–0.96), specificity: 0.72 (0.47–0.90), p-value: <0.001. The functionality of the developed device has been demonstrated with the testing of chemical standards and a simplified breath study using peppermint capsules. It is our intention to deploy this system in a UK hospital in an upcoming breath research study

Techniques and issues in breath and clinical sample headspace analysis for disease diagnosis

Analysis of volatile organic compounds (VOCs) from breath or clinical samples for disease diagnosis is an attractive proposition because it is noninvasive and rapid. There are numerous studies showing its potential, yet there are barriers to its development. Sampling and sample handling is difficult, and when coupled with a variety of analytical instrumentation, the same samples can give different results. Background air and the environment a person has been exposed to can greatly affect the VOCs emitted by the body; however, this is not an easy problem to solve. This review investigates the use of VOCs in disease diagnosis, the analytical techniques employed and the problems associated with sample handling and standardization. It then suggests the barriers to future development

Nanotechnology for Early Cancer Detection

Vast numbers of studies and developments in the nanotechnology area have been conducted and many nanomaterials have been utilized to detect cancers at early stages. Nanomaterials have unique physical, optical and electrical properties that have proven to be very useful in sensing. Quantum dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, gold nanowires and many other materials have been developed over the years, alongside the discovery of a wide range of biomarkers to lower the detection limit of cancer biomarkers. Proteins, antibody fragments, DNA fragments, and RNA fragments are the base of cancer biomarkers and have been used as targets in cancer detection and monitoring. It is highly anticipated that in the near future, we might be able to detect cancer at a very early stage, providing a much higher chance of treatment

Electronic Noses for Biomedical Applications and Environmental Monitoring

This book, titled “Electronic Noses for Biomedical Applications and Environmental Monitoring”, includes original research works and reviews concerning the use of electronic nose technology in two of the more useful and interesting fields related to chemical compounds detection of gases. Authors have explained their latest research work, including different gas sensors and materials based on nanotechnology and novel applications of electronic noses for the detection of diverse diseases. Some reviews related to disease detection through breath analysis, odor monitoring systems standardization, and seawater quality monitoring are also included

Electronic nose for analysis of volatile organic compounds in air and exhaled breath.

Exhaled breath is a complex mixture containing numerous volatile organic compounds (VOCs) at trace levels (ppb to ppt) including hydrocarbons, alcohols, ketones, aldehydes, esters and other non-volatile compounds. Different patterns of VOCs have been correlated with various diseases. The concentration levels of VOCs in exhaled breath depend on an individual subject’s health status. Therefore, breath analysis has great potential for clinical diagnostics, monitoring therapeutic progress and drug metabolic products. Even though up to 3000 compounds may be detected in breath, the matrix of exhaled breath is less complex than that of blood or other body fluids. Breath analysis can be performed on people irrespective of age, gender, lifestyle, or other confounding factors. Breath gas concentration can be related to VOC concentrations in blood via mathematical modeling; for example, as in blood alcohol testing. Since exhaled breath samples are easy to collect and online instruments are commercially available, VOC analysis in exhaled breath appears to be a promising tool for noninvasive detection and monitoring of diseases. Breath analysis has been very successful in identifying cancer, diabetes and other diseases by using a chemiresistor sensor array to detect biomarkers. The objective of this research project is to develop sensor arrays ― or so-called electronic nose ― for analysis of VOCs in air and exhaled breath. In this dissertation, we have investigated both commercial and synthesized thiol functionalized gold nanoparticles (AuNPs) as sensing materials for analysis of VOCs in air and exhaled breath. The advantages of these sensors include very high sensitivity, selectivity for detection of target analytes and operation at ambient temperature. The synthesis and material characterization of new thiols and AuNPs for increasing sensitivity and selectivity have been studied. Selected commercial thiols and in-house synthesized new functional thiols have been used to modify AuNP-based sensors for detection of VOCs in air and exhaled breath. The interdigitated electrodes (IDE) used for the sensors were fabricated by microelectromechanical systems (MEMS) microfabrication technologies. The sensor arrays were characterized by measuring the resistance difference from vacuum and different spiked analyte concentrations in air and breath samples. Air samples and breath samples were collected using Tedlar bags, and analyzed using the thiol functionalized AuNP sensors. The analysis of air samples provides a reference for analysis of exhaled breath samples. The sensors have demonstrated a low detection limit of 0.1 ppbv of acetone and ethanol in dry air and exhaled breath. The concentrations of acetone in air and exhaled breath were determined by a silicon microreactor approach. The measurements of acetone by the microreactor approach were correlated with the sensor signals. The intellectual thrust of this research is the rational design of an electronic nose for analysis of VOCs in exhaled breath, which offers a new frontier in medical diagnostics because of its non-invasive and inexpensive characteristics

Breath analysis using electronic nose and gas chromatography-mass spectrometry: A pilot study on bronchial infections in bronchiectasis

Background and aims: In this work, breath samples from clinically stable bronchiectasis patients with and without bronchial infections by Pseudomonas Aeruginosa- PA) were collected and chemically analysed to determine if they have clinical value in the monitoring of these patients. Materials and methods: A cohort was recruited inviting bronchiectasis patients (25) and controls (9). Among the former group, 12 members were suffering PA infection. Breath samples were collected in Tedlar bags and analyzed by e-nose and Gas Chromatography-Mass Spectrometry (GC-MS). The obtained data were analyzed by chemometric methods to determine their discriminant power in regards to their health condition. Results were evaluated with blind samples. Results: Breath analysis by electronic nose successfully separated the three groups with an overall classification rate of 84% for the three-class classification problem. The best discrimination was obtained between control and bronchiectasis with PA infection samples 100% (CI95%: 84-100%) on external validation and the results were confirmed by permutation tests. The discrimination analysis by GC-MS provided good results but did not reach proper statistical significance after a permutation test. Conclusions: Breath sample analysis by electronic nose followed by proper predictive models successfully differentiated between control, Bronchiectasis and Bronchiectasis PA samples