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

实时体内监测可以为实现炎症性肠病等复杂疾病的早期诊断和干预提供必要的健康信息。实时有效地跟踪这些炎症过程是具有挑战性的，因为胃肠道(GI)中的化学环境很难获取和采样。此外，许多炎症性疾病的关键介质在体内都是极其短暂的。分析这些调节疾病和药物反应的短暂生物分子将增强我们诊断、监测、治疗和预防胃肠道疾病的能力。目前监测胃肠道的黄金标准依赖于侵入性内窥镜生物显微镜或非实时粪便分析。商业诊断药丸，如视频胶囊内窥镜，作为一项强大的技术提供了一种非侵入性的实时替代方案。然而，纯电子系统在功能上是有限的，因为它们不能直接监测肠道化学环境。该项目旨在开发廉价、非侵入性的微型可摄取传感器，利用体内生化领域来超越现有方法有限的准确性。拟议的安全混合生物电子传感器将能够在家庭环境中实时和准确地跟踪疾病进展，同时保护机密医疗信息。除了医疗保健，这种平台技术在应对更广泛的社会挑战方面具有变革性的潜力。它可以提供一种前所未有的工具，以深入了解内部身体事件，促进及早发现水污染危机，并支持可持续的生产实践。此外，该计划将教育纳入其核心使命。从K-12到研究生水平的学生将接触到并接受培训，以开发与其他不同领域对接的半导体平台，如生物医学工程。通过超越传统的电气工程学科，促进跨学科学习，该项目旨在培养一支多元化的、具有全球竞争力的半导体劳动力队伍。该项目将创造首个此类安全混合式生物电子传感器，从而建立网络安全生物系统(CSBS)领域，用于准确、可靠和安全的实时体内监测。CSB平台将使用基因工程生物系统，并增加安全集成电路用于生化传感，提供可靠的数据生成和通信能力。CSBS的工程生命系统，如用于检测不同分析物的细菌细胞，在恶劣环境(如人类肠道)中实现了高特异性和敏感性。该计划的核心智力贡献是：1)创建一种新型的安全的微型可食用胶囊，其测量胃肠道中极其短暂的疾病生物标记物；2)设计有效的信息传输机制，以在功率和尺寸的严格限制下将细菌细胞传感器与集成电子设备耦合；3)开发用于生物标记物检测的交叉验证的超低功耗多模传感器集成电路，以实现高精度；4)通过在GI环境中获取能量来为这些混合生物电子传感器供电；以及5)为资源受限的传感器开发物理层安全设计和评估框架，包括第一个开放源代码库的模拟/射频(RF)安全原语和动态自适应安全协议，以最大限度地减少安全开销。CSBS这一新领域将半导体驱动的平台与合成生物学紧密结合，以实现准确的实时监测和控制，具有显著改变医学和环境科学研究的潜力。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.