Non-invasive TB Triage and Patient Mapping Platform Using Breath Via Low-Cost Titanium Dioxide Nanotube Sensor

TB is an infectious disease caused by various strains of mycobacteria. It typically infects the lungs and is spread through the air when an infected patient sneezes, coughs, or spits. When this occurs, the TB bacilli are propelled into the air in droplets that can remain suspended for long periods of time. An individual simply needs to inhale a small amount of bacilli to become infected.

Conventional methods for TB detection and diagnosis are traditionally performed in laboratories or hospitals. For example, the most common method for diagnosis of TB is the acid fast staining of a sputum sample which is then followed by a sputum smear microscopy test. However a disadvantage with the sputum smear test is its poor sensitivity, which is estimated to be at 70%. Additionally, the sensitivity of sputum smear spectroscopy in field settings has been shown to be much lower (35%), especially in populations that have high rates of TB and HIV coinfection. Culturing of mycobacterium from sputum samples is a more sensitive technique. Sputum samples are collected and cultured in either solid media or liquid media looking for the presence of the mycobacterium. However this methodology takes time to conduct (3-4 weeks for solid cultures, and 10-14 days for liquid cultures), which makes it difficult to employ in low resource settings that are typically far from testing facilities.

Recently, other technologies have been developed including fluorescence microscopy for smear tests (10% more sensitive than light microscopy), LED fluorescent microscopy for inexpensive imaging equipment that can be used in the field without the need for a darkroom, and rapid culturing techniques to reduce incubation time. Despite all the improvements that have been made in TB diagnosis, no simple inexpensive POC test is currently available. The techniques mentioned above either focus on variations of microscopy or culture technique. In either case, these methods require lab facilities and highly trained personnel that typically are not available in many rural or low resource areas.

Recent research has shown that various strains of the mycobacteria produce distinct gaseous volatile biomarkers that can be used as a methodology for detecting and identifying the mycobacterium. Specifically, Syhre and Chambers found that Mycobacterium tuberculosis and Mycobacterium bovis cultures give off four specific volatile organic biomarkers (VOBs): methyl phenylacetate, methyl p-anisate, methyl nicotinate, and o-phenylanisole. These compounds were detectable before the visual appearance of colonies, which could have implications in detection of latent TB infection. Syhre et al. were able to detect statistically significant differences of methyl nicotinate in the breath of smear positive TB patients when compared to healthy (smear negative) subjects. Analyses in these studies were done using gas chromatography/mass spectroscopy analysis tools. While they are effective in identifying and quantifying complex gas samples, they are expensive, bulky, and not appropriate for point of care (POC) diagnostics.

These challenges associated with the diagnosis of TB are significant as TB is the second leading cause of death due to a single infectious organism and is responsible for 1.3 million deaths annually (over 3,500 every day), according to the WHO. Overall, an estimated 2 billion people are currently infected worldwide with 8.6 million new active infections occurring each year.[8] Each of these individuals can transmit the disease to 10 to 15 people per year and face a mortality rate of 50% if untreated. The economic burden of TB is staggering as the World Bank estimates that high burden countries can lose up to 7% of GDP due to productivity losses from TB patients and their caretakers. It is so critical that the World Bank committed $100 million to testing for and treating TB in India in 2014 alone.