<p> Volatile organic compounds (VOCs) are byproducts of metabolic processes that can be uniquely dysregulated by various medical conditions and are expressed in biological samples. Therefore, VOCs expressed in breath, urine and other sample types may be utilized for noninvasive, rapid, and accurate diagnostics in a point-of-care setting. Currently, the most common methods for VOC detection include gas chromatography-mass spectrometry (GC-MS) and electronic noses (E-noses) that integrate nanosensors. Both methods present important advantages and challenges that allow their implementation for different applications. While GC-MS can be used to directly identify VOCs in complex matrices, it is a non-portable and high-cost instrument. On the other hand, E-noses are portable and user-friendly VOC detectors, but they do not allow for direct VOC identification or quantification. Among different VOC rich sample types, breath offers the advantage of being a virtually limitless source of endogenous biomarkers that can be implemented for noninvasive VOC detection.</p>
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<p>The presented thesis focuses on the optimization of the operating parameters (heater and sensor voltages) of a metal oxide (MOX) sensor and breath sampling techniques (sensor casing, breath fractionation, and exhalation volume) for their implementation in exhaled VOC analysis. In parallel, an in-house feature extraction algorithm was developed and implemented for the optimization of a MOX sensor composed of a tin oxide (SnO2) sensing layer. The optimized sensor parameters (heater voltage equal to 2 V and sensor voltage equal to 0.8 V) and breath sampling protocol (24 L of whole breath analyzed using the in-house sensor casing design) were tested with exhaled breath samples from distinct volunteers which could be successfully separated with 100% accuracy. The sensor response also showed a high degree of intrasubject reproducibility (RSD < 6%). Additionally, the sensor performance was further validated under ambient conditions, and sensor degradation was studied over the course of 3 months. Finally, sensor response to synthetic VOC profiles and individual VOC standards was explored. Optimized SnO2 sensors distinguished between VOC mixtures regardless of variations in relative humidity (RH) levels. Furthermore, the characteristic sensor response to VOC standards indicates that the sensors are most sensitive toward isopropanol by a factor of 1.15 in 45% RH and a factor of 3.58 in 85% RH relative to isoprene. </p>
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<p>To translate the potential of MOX sensors to point-of-care biomedical applications, there first exists the need to establish a reference of sensor baseline signals corresponding to exhaled breath samples from healthy individuals. SnO2 sensors and breath sampling methods were implemented for the collection of individual samples from 109 relatively healthy volunteers. 10 of these volunteers provided 9 additional samples over the course of six months. In parallel, exhaled breath samples were also analyzed by GC-MS to comprehensively profile VOCs present in the samples. The results from these experiments not only aid in the identification of the healthy breath signal baseline but also allow the exploration of VOC reproducibility over time. High variation between samples from distinct volunteers was observed, but samples longitudinally collected across volunteers could not be distinguished, alluding to the existence of a universal range of sensor signals that could describe the composition of exhaled breath from healthy subjects. Finally, results were compared with relevant confounding variables to better understand how VOCs are impacted by an array of factors that are not directly correlated to disease diagnosis. Sensor signals were significantly elevated in breath samples from male volunteers compared to samples from female subjects (p-value = 0.044). Interestingly, isoprene signals resulting from the GC-MS analysis were also higher in male subjects relative to females. No other relationships were identified between sensor signals and the confounding variables of interest. </p>
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<p>Future work would require a deeper understanding of sensor degradation and life cycle, along with sensor testing using a broader range of individual VOC standards and more complex VOC profiles. Additionally, further comparison between sensor signal and GC-MS signal of relevant VOC biomarkers present in breath would be beneficial. Nonetheless, the presented be leveraged in future investigations aiming to identify biomarkers for different medical conditions. Finally, the findings disclosed in the deposited thesis suggest the ability of a SnO2 nanosensor array to be implemented for breath analysis, providing a noninvasive, easy to use, and reliable diagnostic device in a point-of-care setting. </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/23523582 |
| Date | 30 August 2023 |
| Creators | Mariana Maciel (16374078) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/OPTIMIZATION_AND_CHARACTERIZATION_OF_METAL_OXIDE_NANOSENSORS_FOR_THE_ANALYSIS_OF_VOLATILE_ORGANIC_COMPOUND_PROFILES_IN_BREATH_SAMPLES/23523582 |
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