Chemoresistive Nanostructured Sensors for the Analysis of Human Tumor Tissue Exhalations
Authors: Astolfi Michele , Zonta Giulia , Landini Nicolò , Gherardi Sandro , Rispoli Giorgio , Anania Gabriele , Benedusi Mascia , Guidi Vincenzo , Palmonari Caterina , Valt Matteo , Malagù Cesare 
Published: December 2020

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