Collaborative Research: SCH: A wireless optoelectronic implant for closed-loop control of bi-hormone secretion from genetically modified islet organoid grafts

1型糖尿病（T1 D）是一种慢性自身免疫性疾病，影响150万美国人和全球2000万至4000万人。虽然在过去的几十年里，人们对T1 D有了广泛的了解，但T1 D的治疗方法仍然不可用。密歇根州立大学和德克萨斯大学奥斯汀分校的研究人员正在合作开发一种新的框架，用于使用微型无线光电植入物连续，精确和闭环控制双激素（胰岛素或胰高血糖素）分泌。这项研究是第一次尝试使用光遗传学工具，使用一系列高效，可植入，无线（无束缚和无电池）光电植入物（WOEI），其足迹可忽略不计，侵入性最小，以控制胰岛类器官的双激素分泌。这种方法应该为开发T1 D的新技术疗法铺平道路。对全球数百万受影响的个体的直接益处包括提高生活质量和降低相关医疗护理的成本。该项目的总体目标是开发一个闭环框架，用于快速，选择性和精确控制转基因胰岛类器官移植物的双激素分泌，使用高效，可植入的WOEI。WOEI将在一个超小、重量轻的封装中单片集成一个双色光学刺激器和一个光学葡萄糖传感器以及一个无线片上系统。这种WOEI的分布式阵列可以同时控制许多胰岛类器官，以获得大的体积覆盖率和更好的均匀性。由动物穿戴的无线背包将携带高效的无线电子设备，用于从无线电力笼到WOEI的安全电力传输，以及与WOEI和最终用户的宽带数据通信。托管在个人设备上的交互式用户界面（即，个人计算机、智能手机等）将实时接收和分析葡萄糖传感数据，并以闭环方式控制光遗传学调节。该项目是多学科的，将对生物医学设备、干细胞生物学和无线微电子学的研究和技术发展产生重大影响。此外，该项目预计将对工程/健康相关的STEM教育产生广泛的影响，通过研究与不同的教育和推广活动，如项目演示/实地图尔斯，研究生和本科生研究，教师培训，K-12课程，新的课程组成部分，社交媒体和YouTube节目的整合。这些努力将通过为T1 D管理提供有效的个性化治疗，吸引大量服务不足的人群，促进个性化医疗的生物医学研究，以及培训美国STEM劳动力，共同造福更广泛的社会。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。

Type 1 diabetes (T1D) is a chronic autoimmune disease that affects 1.5 million Americans and 20–40 million people worldwide. While a broad understanding of T1D has been gained over the past few decades, a cure for T1D is still not available. Researchers at Michigan State University and the University of Texas at Austin are collaborating to develop a novel framework for continuous, precise, and closed-loop control of bi-hormone (insulin or glucagon) secretion, using tiny wireless optoelectronic implants. This research is the first attempt to use optogenetic tools, using an array of highly efficient, implantable, Wireless (untethered and battery-free) OptoElectronic Implants (WOEIs) with a negligible footprint and minimal invasiveness to control bi-hormone secretion from islet organoids. This approach should pave the way for developing a new technological therapy for T1D. The direct benefits to millions of affected individuals worldwide include improved quality of life and reduced cost of associated medical care.The overarching goal of this project is to develop a closed-loop framework for rapid, selective, and precise control of bi-hormone secretion from genetically modified islet organoid grafts, using highly efficient, implantable WOEIs. The WOEI will monolithically integrate a dual-color optical stimulator and an optical glucose sensor with a wireless system-on-chip in an ultra-small and lightweight package. A distributed array of such WOEIs can simultaneously control many islet organoids for large volumetric coverage and better uniformity. A wireless backpack worn by the animal will carry highly efficient wireless electronics for safe power transfer from a wireless power cage to the WOEIs, and wideband data communication with the WOEIs and with the end-user. An interactive user interface hosted on a personal device (i.e., personal computer, smartphone, etc.) will receive and analyze glucose-sensing data in real-time and control optogenetic modulation in a closed-loop manner. This project is multidisciplinary and will significantly impact research and technological development in biomedical devices, stem cell biology, and wireless microelectronics. Furthermore, this project is expected to have a broad impact on engineering-/health-related STEM education through the integration of research with diverse educational and outreach activities, such as project demos/field tours, graduate and undergraduate research, teacher training, K-12 curricula, new course components, social media, and YouTube programs. These efforts will collectively benefit the broader society by providing effective personalized therapies for T1D management, engaging significant underserved populations, promoting biomedical research for personalized medicine, and training the US STEM workforce.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.