Point of Care Screening of Tuberculosis from Breath Using Functionalized TiO2 Nanotube Array Sensing Platform

Improving screening and diagnosis of tuberculosis (TB) is critical to reducing its burden around the world. Some of the key challenges include that up to 1/3^rd of adults and most young children with TB do not produce sputum and, even among those who do, bacillary burden in sputum is often low. Due this these reasons, the World Health-Organization has ranked rapid non-sputum based biomarker based tests has the highest priority for diagnostics and screening of TB. One approach is to evaluate volatile organic compounds (VOCs) in exhaled breath, which is easily collected from patients of all ages. Recent research has identified at least two VOCs – methyl nicotinate and methyl p-anisate – that are a by-product of Mycobacterium tuberculosis metabolism and should therefore be present in anyone with active TB, regardless of age. These VOCs do not appear to be emitted by other bacteria of the respiratory tract; do not appear to be found at high concentrations in the ambient environment; and have been identified at high concentrations in the breath of TB patients but not healthy controls. However, the lack of a technology to easily measure specific VOCs at the point-of-care has been a key barrier to further validation and use of these VOCs as a biomarker for TB diagnosis.

This work will describe a low-cost, handheld device for identifying target VOCs in exhaled breath. The device is a solid-state sensor based on metal-functionalized 3D titanium dioxide (TiO2) nanotube arrays that bind specific VOCs when a specific voltage gradient is applied. Binding results in a change in current that is proportional to the concentration of target VOCs present in the breath. The sensor has been customized to specifically bind methyl-nicotinate and methyl p-anisate and has a limit-of-detection that is several orders of magnitude below levels of the two VOCs observed to date in TB patients. Furthermore, the detection is fast (on the order of minutes), reagent-free, and requires no sample preparation. The concept of the point-of-care breath sensor device is shown in Figure 1a. Device is portable, operated using a smartphone, and can be taken directly to the patient’s home which is important for individuals that live far from medical facilities as is often the case in high TB burden countries.

Results of the sensor showed the TiO2 sensor gave a positive response to breath taken from TB positive patients and no response to breath taken from health individual controls.

Initial results of the TiO2 nanotube sensor shows a correlation between a high sensor response and TB positive patient. Site studies are currently underway in Uganda and India to establish the feasibility of using the technology in the field as a point of care screening/diagnostic device. A summary of these results will be presented.