Advancing Engineered Microbes for IBD Diagnostics and Treatments
Principal Investigator: Timothy Lu, MIT
Cells can be engineered by synthetic biology to sense environmental signals, for example, toxic molecules or biomarkers indicative of particular disease states. We have designed and built an ingestible micro-bio-electronic device (IMBED) consisting of engineered probiotic sensor bacteria combined with ultra–low-power microelectronics. IMBEDs leverage the advantages of biological systems and electrical devices to enable the detection of markers of gastrointestinal disease. In the IMBED, biosensor probiotics adjacent to readout electronics are separated from the outside environment by a semipermeable membrane that keeps cells inside the device but allows the diffusion of small molecules. Sensing of target biomarkers causes the bacteria to generate light, which is detected by the embedded photodetectors. The electrical signals are processed by an integrated bioluminescence detection circuit and transmitted wirelessly to an external radio or cellular phone, enabling sustained and convenient in situ biomolecular detection. As proof-of-concept, we engineered heme-sensitive probiotic biosensors and demonstrated accurate diagnosis of upper gastrointestinal bleeding in swine. We also built alternative biosensors to show the modularity and extensibility of the detection platform. Moving forward, we are developing additional biosensors that can interface with the IMBED to detect early signs of inflammatory bowel disease.