Optogenetic and biosensing technologies for a bioartificial pancreas system

近10%的美国人患有糖尿病。该病的相关医疗费用在主要疾病中是最高的。本研究项目的目标是设计一种新型生物人工胰腺（BAP）装置。BAP装置不需要患者干预。它将含有人类胰腺β细胞，这种细胞的胰岛素分泌在蓝光下增强，没有明显的副作用。BAP装置还将持续监测并对血糖水平作出反应。相对于日常胰岛素注射治疗，这一特点应能改善血糖调节。成功开发的BAP设备将减少许多长期健康并发症，这些并发症是由每日注射治疗相关的血糖波动引起的。该项目计划的外展活动为STEM领域的高中生、本科生和研究生提供跨学科培训和研究机会。本研究项目的目标是建立一个自主的闭环BAP平台。葡萄糖刺激的胰岛素分泌将由蓝光调节，无线调节的嵌入式发光二极管（led）将控制蓝光的应用。光会影响光敏腺苷酸环化酶的变化。将BAP与透皮植入的基于线程的无线葡萄糖传感器相结合，可以实现设备的自主闭环操作。具体的项目任务将包括：(i)产生具有光敏葡萄糖刺激胰岛素分泌的人类β细胞，（ii）设计一种混合LED/水凝胶装置，用于递送表达光敏腺苷酸环化酶的人类β细胞，（iii）实现灵活的葡萄糖传感线程和无线电路，以及(4)将它们与混合LED/水凝胶集成。该项目需要解决葡萄糖传感器、电子设备和led与活体组件功能的接口方面的重大基础挑战，以实现最佳的活体操作。这一进展将为植入式设备的制造提供广泛适用的见解。生成的光敏腺苷酸环化酶表达人β细胞将成为筛选糖尿病候选药物和增加对胰腺细胞功能了解的宝贵资源。该奖项反映了美国国家科学基金会的法定使命，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。

Almost ten percent of the U.S. population suffers from diabetes. The associated healthcare costs for this disease are the highest amongst major maladies. The goal of this research project is to engineer a novel bioartificial pancreas (BAP) device. The BAP device will require no patient intervention. It will contain human pancreatic beta-cells, which are cells whose insulin secretion is enhanced by blue light that is free of significant side effects. The BAP device also will continuously monitor and respond to blood glucose level. This feature should improve the regulation of blood glucose relative to daily insulin injection therapies. A successfully developed BAP device would reduce many of the long-term health complications resulting from large blood glucose swings associated with daily injection therapies. The planned outreach activities for this project feature inter-disciplinary training and research opportunities for high school, undergraduate and graduate students in STEM fields.The goal of this research project is to build an autonomous, closed-loop BAP platform. Glucose-stimulated insulin secretion will be regulated by blue light, and embedded light-emitting diodes (LEDs) regulated wirelessly will control the blue light application. The light will effect a change in a photo-sensitive adenylyl cyclase. Coupling the BAP to a transdermally-implanted, thread-based wireless glucose sensor will allow for autonomous, closed-loop operation of the device. Specific project tasks will include: (i) generating human beta-cells with photosensitive glucose-stimulated insulin secretion, (ii) designing a hybrid LED/hydrogel device for delivery of the photo-sensitive adenylyl cyclase-expressing human beta-cells, (iii) realizing flexible glucose-sensing threads and wireless circuitry and (4) integrating them with the hybrid LED/hydrogel. The project entails addressing significant fundamental challenges in interfacing glucose sensors, electronics, and LEDs with the function of living components for optimal operation in vivo. This advance will offer broadly applicable insights for the manufacturing of implantable devices. The generated photo-sensitive adenylyl cyclase-expressing human beta-cells will be a valuable resource for screening diabetes drug candidates and for increasing understanding of pancreatic cell function.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.