Chemoresistive Nanostructured Sensors for the Analysis of Tumor Tissues Exhalations

Abstract

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