Optogenetic and biosensing technologies for a bioartificial pancreas system

生物人工胰腺系统的光遗传学和生物传感技术

• 批准号: 1951104
• 负责人: Emmanouhl Tzanakakis
• 金额: $ 55.39万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1951104&HistoricalAwards=false
• 关键词: Optogenetic; biosensing; technologies; bioartificial; pancreas

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.

几乎百分之十的美国人患有糖尿病。这种疾病的相关医疗费用是主要疾病中最高的。 本研究的目的是设计一种新型的生物人工胰腺（BAP）装置。BAP器械无需患者干预。它将包含人类胰腺β细胞，这些细胞的胰岛素分泌被蓝光增强，没有明显的副作用。BAP设备还将持续监测血糖水平并对其做出响应。相对于每日胰岛素注射疗法，该特征应改善血糖调节。一个成功开发的BAP设备将减少许多长期的健康并发症所造成的大血糖波动与日常注射治疗。 该项目的计划外展活动包括为高中生、本科生和研究生提供STEM领域的跨学科培训和研究机会。该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）将控制蓝光应用。光将影响光敏腺苷酸环化酶的变化。将BAP耦合到经皮植入的基于螺纹的无线葡萄糖传感器将允许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）设计用于递送光敏腺苷酸环化酶表达人类β细胞的混合LED/水凝胶装置，（iii）实现柔性葡萄糖传感线和无线电路，以及（4）将它们与混合LED/水凝胶集成。该项目需要解决将葡萄糖传感器、电子器件和LED与活体组件功能连接以实现体内最佳操作的重大基本挑战。这一进展将为植入式器械的制造提供广泛适用的见解。所产生的光敏腺苷酸环化酶表达人类β细胞将是筛选糖尿病候选药物和增加对胰腺细胞功能的理解的宝贵资源。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

Non‐xenogeneic expansion and definitive endoderm differentiation of human pluripotent stem cells in an automated bioreactor

自动化生物反应器中人多能干细胞的非异种扩增和定形内胚层分化

• DOI: 10.1002/bit.27629
• 发表时间: 2020
• 期刊: Biotechnology and Bioengineering
• 影响因子: 3.8
• 作者: Jacobson, Elena F.;Chen, Zijing;Stoukides, Demetrios M.;Nair, Gopika G.;Hebrok, Matthias;Tzanakakis, Emmanuel S.
• 通讯作者: Tzanakakis, Emmanuel S.

Rapid cleanroom-free fabrication of thread based transistors using three-dimensional stencil-based patterning

• DOI: 10.1088/2058-8585/abe459
• 发表时间: 2021-02
• 期刊: Flexible and Printed Electronics
• 影响因子: 3.1
• 作者: T. Kumar;Rachel Owyeung;S. Sonkusale

Light-Mediated Enhancement of Glucose-Stimulated Insulin Release of Optogenetically Engineered Human Pancreatic Beta-Cells

• DOI: 10.1021/acssynbio.3c00653
• 发表时间: 2024-02-20
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Chen，Zijing;Stoukides，Demetrios M.;Tzanakakis，Emmanuel S.
• 通讯作者: Tzanakakis，Emmanuel S.