Vishal A. Manickam

BioE PhD Defense Presentation

Date: Wednesday, November 11th, 2026

Time: 2:00 PM

Location: EBB CHOA Seminar Room

Virtual Meeting Link: https://gatech.zoom.us/j/91747576515

Committee Members:

Leslie Chan, PhD (Advisor); M.G. Finn, PhD; Andrés García, PhD; Rheinallt Jones, PhD; Gabe Kwong, PhD

Engineering ingestible probes for breath-based detection of gastrointestinal diseases

Gastrointestinal (GI) diseases are a significant healthcare burden and affect 70 million people in the United States. Endoscopic imaging plays a crucial role in the diagnosis and clinical management of many GI diseases, including GI cancers, gastroesophageal reflux disease, and inflammatory bowel disease (IBD). However, its invasive nature deters individuals from recommended testing and hinders its routine use as a monitoring tool. Non-invasive tests for detection of blood and fecal biomarkers are used in the clinic, but either have poor sensitivity for early detection or poor disease specificity. For these reasons, there remains a critical unmet need for non-invasive tests for GI disease. 

Breath tests are a highly attractive alternative to endoscopy because breath can be sampled non-invasively and analyzed for disease-indicating volatile organic compounds (VOCs) (i.e., breath biomarkers). However, few breath biomarkers have been successfully identified due to technical and statical limitations of conventional -omic approaches. In this work, we have developed an approach to induce exhalation of breath biomarkers to diagnose and monitor GI diseases. Our strategy uses new ingestible molecular probes, which release volatile reporters upon activation by disease activity in the GI tract. Once released, reporters are rapidly cleared from the body in breath and measured via mass spectrometry. Thus, probe ingestion induces exhalation of pre-specified volatile reporters of known mass to indicate disease activity (i.e., synthetic breath biomarkers), obviating the need for biomarker discovery.

Our approach leverages dysregulated glycosidase activities, which play a central role in the pathogenesis of diverse GI diseases. The GI tract houses hundreds of distinct glycosidases from the host and microbiome that regulate gut barrier function, mucosal immunity, host-microbe interactions, and the metabolism of drugs and dietary sugars. In Aim 1, I establish design principles for the ingestible probes and develop a probe to monitor the activity of a microbial glycosidase that causes drug-induced GI toxicity. In Aim 2, I use the established platform to develop a probe for a human intestinal glycosidase which, when deficient, leads to a sugar malabsorption disorder. I further demonstrate how induced breath signals can be detected via novel carbon nanotube detection arrays, a low-cost alternative to mass spectrometry. Lastly, in Aim 3, I demonstrate the multiplexing capabilities of our platform and assemble a volatile-barcoded probe array to induce breath biomarker signatures of mucosal injury and healing in the context of IBD.