I-Corps: A point-of-care diagnostic sensor for tuberculosis

The broader impact/commercial potential of this I-Corps project is the development of point-of-care diagnostic sensor to support health agencies globally in overcoming tuberculosis (TB). Current laminar-flow diagnostic tests do not target the pathogen directly, but instead detect macromolecules produced by the bacteria, mainly lipoarabinomannan (LAM) in urine. However, not all TB patients excrete this molecule into the urine, and LAM concentrations can be affected significantly by the infection sites. This may explain the low sensitivity (~50%) of such assays. TB is the world’s second leading cause of death from a single infectious agent. In 2020, 10 million people were infected, and 1.8 million died. It is recognized that the high mortality is attributed to lack of TB testing affecting 3-6 million people per year, as well as misdiagnoses, late diagnoses, co-infection with HIV and malaria, and lack of adherence to treatment strategy. The proposed technology may overcome the limitations of current tests, especially for developing areas where medical resources are limited. This I-Corps project is based on the development of a point-of-care sensor for bacteria detection in biological fluids. The proposed sensor is built on the interactions of silver (Ag+) and bacteria. It is established that Ag+ can enter various bacterial species through outer membrane proteins, particularly the OmpF—a 39 kD transmembrane protein with a trimeric β-barrel structure, and binds to cytoplasm components, including proteins and nucleic acid. The proposed method is based on detecting the loss of free [Ag+] added to a sample with bacteria, and determining the bacteria number. The detection limit may be as low as 80 bacteria per milliliter sample. Moreover, an open-source potentiometer provides a low-cost and customizable opportunity for such sensor development and translation, especially in under-developed areas with limited budgets. The sensor also allows for wireless data transfer and storage in smartphones, which may allow for large-scale screening and remote healthcare. For TB detection, antibodies that are specific to m. tuberculosis will be integrated in the sensor for selective diagnosis of the presence of the bacteria. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.