Photonics West: Disease Detection Using Breath Analysis

Boris Mizaikoff of the University of Ulm in Germany held a presentation at SPIE Photonics West, on January 31, on how mid-infrared spectroscopy techniques and exhaled breath analysis can help detect diseases like gastric cancer (1).

There are various samples that can help detect disease in an individual, from blood to urine to saliva. These are usually conducted using different types of infrared spectroscopy. However, for this project, Mizaikoff and his team investigated creating a non-invasive diagnostic scenario, specifically using exhaled breath. This technique is based around various techniques, such as Fourier-transform infrared spectroscopy (FT-IR). FT-IR originated in the 1970s and has evolved significantly since. Today, FT-IR can be done with smaller and more compact analyzers, such as the Agilent 4300 Handheld FTIR Spectrometer, which weighs approximately 2 kg (2), which make this process ideal for breath analysis.

Each breath composition is personalized, Mizaikoff said, and “the molecules that we exhale are basically the summary of all metabolic processes that are going on in our bodies” (1). When one is sick, certain metabolites will start being created in their bodies, transitioning from blood cells to the cell layers inside their lungs. With exhaled breath analysis, these cells can theoretically be used to detect diseases. The problem is, the exhalome, which are the substances that are contained within exhaled breath, is very complex, with the average exhale containing more than 1000 molecules at a time. For this system to work, they had to figure out how to break down the exhalome.

Current breath analysis consists of collecting and preparing a breath sample, then putting it through a gas chromatography–mass spectrometry (GC–MS) system to analyze specific molecules. While effective, this practice can be very expensive and time-consuming, and cannot be used online. This sort of technology cannot be transported and used in point-of-care scenarios, which is what Mizaikoff’s team is trying to rectify.

Carbon dioxide is the major metabolite present in exhaled breath, with carbon-13 having a natural abundance of 1.1%. This led to the theory that if 13C-labeled molecules are administered in this process, metabolic turnover could be monitored by analyzing the 13CO2/12CO2 ratio in exhaled breath samples. The scientists tested this on mice, which have significantly less mass and breath volumes than humans. This led them to use what are known as waveguide structures.

Waveguides are structures that can be used as transmission lines for different types of molecules. Usually, they are made of multi-pass cells, but those are meant for cells with volumes between 500–1000 mL; for this experiment, the scientists opted for hollow waveguides serving as miniaturized gas cells, allowing them to efficiently track cells with volumes less than 1.5 mL. Additionally, new iHWG waveguide technology allowed for the analysis of many gases, such as carbon dioxide, carbon monoxide, and ozone. This system was tested on mice subjects, with the system allowing insight into respiratory ratios (RQs) and the patients’ metabolic statuses.

This sort of system can be useful in various medical scenarios. Gastrointestinal (GI) cancers make up 26% of global cancer cases and 35% of cancer-related death, with rapid screening tools being needed for early detection. With this system, detection can become more sensitive, non-invasive, and cost-effective. However, as is, this system can have limited selectivity, sensor drifts, and standardization issues; to rectify this, adding infrared spectroscopy to the system can lead to these issues being lessened, with infrared-attenuated total reflectance (IR-ATR) spectroscopy displaying >95% accuracy when detecting anal cancer in patients in one instance. There is still room for this system to grow, with Mizaikoff’s group hoping to “develop ultra-fast, low-power nanoscale optoelectronic devices for cost-effective and efficient sensing in diverse applications” (1).

References

(1) Mizaikoff, B. Mid-infrared optical biopsy: towards the detection of gastric cancer via exhaled breath analysis. In SPIE Photonics West, San Francisco, California, USA, January 30–31, 2024.

(2) Agilent. 4300 Handheld FTIR Spectrometer. Agilent Technologies Inc. 2024. https://www.agilent.com/en/product/molecular-spectroscopy/ftir-spectroscopy/ftir-compact-portable-systems/4300-handheld-ftir (accessed 2023-2-12)