Modular monitoring of hormone release from human islets

这项提议的目标是将新技术与正在开发的微流控系统相结合。 在人类胰岛仿生学联盟(CHIB)。这些技术将连接到CHIB 设备采用模块化格式，并将允许近乎实时地监测胰岛素分泌。其基本原理是 进行这项工作的是，有了这些技术，CHIB和人类小岛研究的目标 网络(Hirn)将更快完成。这项提议的目标将通过以下方式实现 追求三个具体目标，按增加敏感性和模块化的顺序构建：1)利用 荧光各向异性免疫分析方法监测胰岛素分泌；2)采用 用于高灵敏度胰岛素测定的免疫电泳仪；3)开发和整合 一种用于在线监测微流控系统中胰岛素释放的电化学传感器。在第一个下 AIM，一种用于测量胰岛素释放的全光学方法将被整合到CHIB的输出中 设备。这项检测将提供一种快速监测胰岛胰岛素释放的途径。在第二个 目的：提出一种将CHIB装置的输出与高灵敏度的血药浓度测定方法相结合的方法。 给出了胰岛素分泌动力学。与第一种方法相比，这种方法的优点是 更高的灵敏度，不仅可以识别胰岛素水平，还可以识别它们的模式。在第三个目标中， 将开发用于胰岛素的电化学适配传感器。这种方法将有助于现场测量 胰岛素，同时在未来导致一个与这种生物传感器集成的系统。拟议的研究 AIMS是创新的，因为它们将为Chib和Hirn内部的团队提供第一个手段 近乎实时地监测胰岛的荷尔蒙释放。据我们所知，没有团队 在具有这些能力的Chib或Hirn中。各实验室之间的新合作 在这项建议中，结合了工程和分析化学，这将提供独特的 未来调查的机会。这一结果将显著提高Hirn的能力 履行其总体使命，支持专注于以下领域的创新和协作翻译研究 了解人类β细胞是如何在1型糖尿病中丢失的并找到创新的策略来保护 并取代人类的功能性贝塔细胞群。

The objective of this proposal is to couple novel technologies to the microfluidic systems being developed in the Consortium on Human Islet Biomimetics (CHIB). These technologies will be connected to the CHIB devices in a modular format and will allow near real-time monitoring of insulin secretion. The rationale for performing this work is that with these technologies, the goals of CHIB and the Human Islet Research Network (HIRN) will be accomplished more quickly. The objective of this proposal will be accomplished by pursuing three specific aims that build in order of increasing sensitivity and modularity: 1) Utilize a fluorescence anisotropy immunoassay method for monitoring insulin secretion; 2) Employ an electrophoretic immunoassay device for high sensitivity insulin measurements; 3) Develop and incorporate an electrochemical sensor for monitoring insulin release in situ on the microfluidic systems. Under the first aim, an all-optical assay for measurement of insulin release will be incorporated into the output of the CHIB device. This assay will provide an expedited path to monitoring insulin release from islets. In the second aim, a method to couple the output of the CHIB device to a high sensitivity assay for measurement of insulin secretion dynamics is presented. The advantage of this method compared to that from the first is higher sensitivity, allowing not only insulin levels but also their patterns to be discerned. In the third aim, an electrochemical aptasensor will be developed for insulin. This method will facilitate in situ measurement of the insulin while in the future leading to an integrated system with this biosensor. The proposed research aims are innovative because they will provide the first means for the teams within CHIB and HIRN to monitor hormone release from islets in near real-time. To the best of our knowledge, there are no teams within CHIB or HIRN that have these capabilities. The new collaboration between the various laboratories within this proposal is a combination of engineering and analytical chemistry which will provide unique opportunities for future investigations. The results will provide a significant improvement in HIRN’s ability to fulfill its overall mission to “support innovative and collaborative translational research focused on understanding how human beta cells are lost in Type 1 diabetes and finding innovative strategies to protect and replace functional beta cell mass in humans.”