A team of Penn doctors and engineers has been awarded a $100,000 grant to develop an unusual new way of diagnosing tuberculosis (TB): ringing the bacteria that cause the disease like a bell.  

By attaching to those bacteria biomarkers that respond to skin-penetrating infrared light, the researchers aim to create a system where the disease burden of a given patient can be more comprehensively studied using an ultrasound machine.  

The grant is part of the Grand Challenges Explorations initiative, a $100 million program funded by the Bill & Melinda Gates Foundation. The initiative seeks high-risk, high-reward proposals on how to solve a long list of global health problems.  

If the Penn team’s initial research shows promise, they will have the opportunity to receive a second grant of up to $1 million.

The team is led by Harvey Rubin, director of Penn’s Institute for Strategic Threat Analysis and Response, a professor at the Perelman School of Medicine, and a professor of computer and information science at the School of Engineering and Applied Science, and includes Andrew Tsourkas of the Department of Bioengineering, Takahiro Yano of Infectious Diseases, and Chandra Sehgal of Radiology. They are collaborating with researchers at the non-profit TB Alliance.   

“We currently test for TB by having patients cough up sputum or by biopsying tissue, but that doesn’t tell you how much TB you have in your whole body,” Rubin says. “That ‘total body burden’ is relevant, as bigger burdens are thought to be harder to cure, meaning those patients would spend more time being treated.”

A PET scan could reveal the total body burden of TB, but as that imaging technique uses a radioactive tracer and a massive, immovable scanner, new approaches are needed. Especially in the developing world, where TB is most prevalent and deadly, clinicians need an imaging technology that can be used repeatedly, monitoring the progression of the disease, but doesn’t require expensive, hard-to-maintain equipment.

Much work has already been done on targeting drugs to enzymes specific to the TB bacteria, as well as molecules for “photoacoustic imaging,” which respond to infrared light by producing ultrasound signals. The Penn researchers saw these two technologies as an ideal match for this challenge, and will tailor biomarkers that accomplish both tasks. 

“Sometimes a molecule absorbs a photon and then emits one; that’s fluorescence,” Rubin says. “Instead of emitting a photon, these molecules quickly expand, then retract. That produces an ultrasound wave, so you can literally listen to the tuberculosis.”  

The proposed biomarkers would stick to the bacteria without interacting with them or the rest of the body, so the technique could be used repeatedly to track the total body burden of the disease over time. If successful, next steps would include customizing portable ultrasound machines to do this kind of analysis.