טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentShuster Gregory
SubjectSensor Based on Monolayer-Capped Nanoparticles:
Towards Diagnosis of Breast Cancer from Exhaled
Breath
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisor Professor Hossam Haick
Full Thesis textFull thesis text - English Version


Abstract

An emerging approach for diagnosis of breast cancer (BC) relies on volatile organic compounds (VOCs) that are emitted due to the biological metabolism. These VOCs can be detected directly from the headspace of the cancer cells or via the exhaled breath. The principle of the latter is that cancer-related changes in blood chemistry are reflected in measurable changes in the breath through exchange via the lung.

The current thesis aims to fabricate and characterize a cross-reactive sensor array of monolayer-capped metal nanoparticles (MCMNP) (5-20 nm in diameter) that can be utilized for detecting BC VOCs from exhaled breath. As a first step towards achieving this goal, we have investigated the utility of resistance and capacitance responses, as derived from impedance spectroscopy, in well-controlled and real-world applications of MCMNP sensors. Exposure of the MCMNP films to well-controlled analytes showed stable sensing responses and low baseline drift of the pertinent capacitance signals, as compared to equivalent resistance signals. In contrast, exposure of the MCMNP films to real-world multi-component mixtures, showed low baseline drift, but, the signals were rather scattered, as compared to equivalent resistance response. We ascribe these discrepancies to the level and fluctuating concentration of water molecules in real-world samples. With these findings in mind, we have investigated the effect of morphology variations within a continuous MCMNP film on the sensing of VOCs and water molecules. The results showed that continuous MCMNP film morphology and perforated morphology exhibit similar responses upon exposure to VOCs but completely different responses upon exposure to water. The difference is explained by ionization of water molecules and/or the SiO2 sites in the nanoparticle-free domains of the perforated film. For the purposes of the current thesis, these results provide a new avenue to deliberately control and diversify the sensing properties of these chemiresistor for the detection of BC VOCs.

To check the validity of the developed devices in real confounding factors, a clinical study was carried out. Breath samples were collected from 36 volunteers and were analyzed using a tailor-made cross reactive sensor array.  The results showed that the sensor array could distinguish between women with negative mammography, women with benign breast conditions and women with malignant lesions, using two independent approaches for the statistical data analysis.

These results show that breath testing with cross-reactive sensor array based on MCMNP holds future potential as a cost-effective, fast and reliable diagnostic test for BC risk factors and precursors.