CAREER: Secure Miniaturized Bio-Electronic Sensors for Real-Time In-Body Monitoring

Real-time in-body monitoring can provide essential health information for achieving early diagnosis and intervention of complex disorders, such as inflammatory bowel disease. Effective tracking of these inflammatory processes in real time is challenging because the chemical environment in the gastrointestinal (GI) tract is difficult to access and sample.

Moreover, many key mediators of inflammatory diseases are extremely short-lived in the body. Profiling these short-lived biomolecules that mediate disease and response to medicine would enhance our ability to diagnose, monitor, treat, and prevent GI disorders. The current gold standard for monitoring the GI tract relies on invasive endoscopic biospies or non-real-time stool analysis.

Commercial diagnostic pills such as the video capsule endoscopy provide a non-invasive real-time alternative as a powerful technology. However, electronic-only systems are functionally limited since they cannot directly monitor the gut chemical environment. This project aims to develop inexpensive and non-invasive miniaturized ingestible sensors that tap into the biochemical in-body domain to surpass the limited accuracy of existing methods.

The proposed secure hybrid bio-electronic sensors will enable real-time and accurate tracking of disease progression in a home setting while protecting confidential medical information. Beyond healthcare, this platform technology has transformative potential for addressing broader societal challenges. It can provide an unprecedented tool for gaining insights into internal bodily events, facilitating early detection of water contamination crises, and supporting sustainable manufacturing practices.

Furthermore, the program integrates education into its core mission. Students from K-12 to graduate levels will be exposed and trained to develop semiconductor-enabled platforms that interface with other diverse fields, such as Biomedical Engineering. By transcending traditional Electrical Engineering disciplines and fostering interdisciplinary learning, the program aims to cultivate a diverse and globally competitive semiconductor workforce.

This project will create the first-of-its-kind secure hybrid bio-electronic sensors, thereby establishing the field of Cyber-Secure Biological Systems (CSBS), for accurate, reliable, and safe real-time in-body monitoring. CSBS platforms will use genetically engineered biological systems augmented with secure integrated circuits for biochemical sensing, providing reliable data generation and communication abilities.

Engineered living systems of CSBS, such as bacterial cells made to sense different analytes, achieve high specificity and sensitivity in harsh environments, e.g., human gut. The core intellectual contributions of this program are to: 1) create a novel secure miniaturized ingestible capsule that measures extremely short-lived disease biomarkers in the GI tract, 2) design effective information transfer mechanisms to couple bacterial-cell sensors with integrated electronics under tight constraints of power and size, 3) develop an ultra-low-power multi-modal sensor integrated circuit for cross-validation of biomarker detection to achieve high accuracy, 4) self-power these hybrid bio-electronic sensors by harvesting energy in the GI environment, and 5) develop a physical-layer security design and evaluation framework for the resource-constrained sensors, including the first open-source library of analog/radio-frequency (RF) security primitives and a dynamically-adaptive security protocol to minimize the security overhead.

The new field of CSBS, tightly coupling semiconductor-enabled platforms with synthetic biology for accurate real-time monitoring and control, has the potential for significantly transforming research in medicine and environmental science.

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.