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

职业：用于实时体内监测的安全微型生物电子传感器

• 批准号: 2338792
• 负责人: Rabia Yazicigil Kirby
• 金额: $ 57.49万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2029-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338792&HistoricalAwards=false
• 关键词: CAREER; Secure; Miniaturized; Bio; Electronic

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.

实时体内监测可以提供必要的健康信息，以实现复杂疾病的早期诊断和干预，如炎症性肠病。在真实的时间内有效跟踪这些炎症过程是具有挑战性的，因为胃肠道（GI）中的化学环境难以接近和采样。此外，炎症性疾病的许多关键介质在体内的寿命非常短。分析这些介导疾病和药物反应的短寿命生物分子将提高我们诊断，监测，治疗和预防胃肠道疾病的能力。目前监测胃肠道的金标准依赖于侵入性内窥镜活检或非实时粪便分析。商业诊断药丸，如视频胶囊内窥镜提供了一个非侵入性的实时替代作为一个强大的技术。然而，纯电子系统在功能上受到限制，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且非侵入性的小型化可摄取传感器，这些传感器可以进入体内生物化学领域，以超越现有方法的有限精度。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准确地跟踪疾病进展，同时保护机密的医疗信息。除了医疗保健，该平台技术还具有解决更广泛社会挑战的变革潜力。它可以提供一个前所未有的工具，用于深入了解内部身体事件，促进水污染危机的早期检测，并支持可持续的制造实践。此外，该方案将教育纳入其核心使命。从K-12到研究生级别的学生将接受培训，以开发与生物医学工程等其他不同领域对接的半导体平台。通过超越传统的电气工程学科和促进跨学科学习，该计划旨在培养多元化和具有全球竞争力的半导体劳动力。该项目将创建首个安全的混合生物电子传感器，从而建立网络安全生物系统（CSBS）领域，以实现准确，可靠和安全的实时体内监测。CSBS平台将使用基因工程生物系统，并通过安全的集成电路进行生化传感，提供可靠的数据生成和通信能力。CSBS的工程化活系统，例如用于感测不同分析物的细菌细胞，在恶劣环境中实现了高特异性和灵敏度，例如，人类的内脏该计划的核心智力贡献是：1）创造一种新颖的安全的小型化可摄取胶囊，其测量胃肠道中极短寿命的疾病生物标志物，2）设计有效的信息传递机制，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器件耦合，3）开发用于生物标志物检测交叉验证的超低功耗多模态传感器集成电路，以实现高精度，4）通过在GI环境中收集能量来为这些混合生物电子传感器自供电，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，包括模拟/射频（RF）安全原语的第一开源库和动态自适应安全协议以最小化安全开销。CSBS这一新领域将生物传感器平台与合成生物学紧密结合，实现精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知识价值和更广泛的影响审查标准进行评估，被认为值得支持。