Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ

• Published in: Nature (London) 2023-08, Vol.620 (7973), p.386-392
• Main Authors: Inda-Webb, M. E., Jimenez, M., Liu, Q., Phan, N. V., Ahn, J., Steiger, C., Wentworth, A., Riaz, A., Zirtiloglu, T., Wong, K., Ishida, K., Fabian, N., Jenkins, J., Kuosmanen, J., Madani, W., McNally, R., Lai, Y., Hayward, A., Mimee, M., Nadeau, P., Chandrakasan, A. P., Traverso, G., Yazicigil, R. T., Lu, T. K.
• Format: Article
• Language: English
• Subjects: 59; 631/92/552; 64; 64/60; 692/700/139; 82; 96/10; Animal models; Bacteria; Biomarkers; Biosensors; Form factors; Gastrointestinal system; Gastrointestinal tract; Genetic code; Genetic engineering; Humanities and Social Sciences; Hydrogen sulfide; Inflammatory bowel disease; Inflammatory bowel diseases; Ingestion; multidisciplinary; Nitric oxide; Probiotics; Science; Science (multidisciplinary); Sensors; Wireless communications
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-023-06369-x

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors 1 , we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits 2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm 3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care. A biosensor comprising bacteria engineered to respond to transient inflammatory signals has been packaged with electronic readout and transmission circuits in a small device that could be swallowed to monitor gastrointestinal health.