Modular monitoring of hormone release from human islets

该提案的目的是将新技术与正在开发的微流体系统相结合 人类胰岛仿生学联盟（Consortium on Human Islet Biomimetics，CHIB）这些技术将连接到CHIB 该设备采用模块化格式，并将允许近实时监测胰岛素分泌。的理由 执行这项工作的目的是，利用这些技术，CHIB和人类胰岛研究的目标 网络（HIRN）将更快地完成。本提案的目标将通过以下方式实现： 追求三个具体目标，建立在增加敏感性和模块化的顺序：1）利用一个 用于监测胰岛素分泌的荧光各向异性免疫测定方法; 2）采用 用于高灵敏度胰岛素测量的电泳免疫测定装置; 3）开发并整合 电化学传感器，用于在微流体系统上原位监测胰岛素释放。根据第一项 目标是，用于测量胰岛素释放的全光学分析将被纳入CHIB的输出中 设备.该测定将提供监测胰岛胰岛素释放的快速途径。在第二 本发明的目的是提供一种将CHIB装置的输出耦合到高灵敏度测定以测量 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， 电化学适体传感器将被开发用于胰岛素。该方法将有助于现场测量 而在未来导致与这种生物传感器的集成系统。拟议研究 目标是创新的，因为它们将为CHIB和HIRN内的团队提供第一种手段， 实时监测胰岛分泌的激素据我们所知，没有一个团队 在CHIB或HIRN中有这些能力。不同实验室之间的新合作 在这个提议中，工程和分析化学的结合将提供独特的 未来调查的机会。这些结果将大大提高HIRN的能力， 履行其总体使命，以“支持创新和合作的翻译研究，重点是 了解人类β细胞在1型糖尿病中是如何丢失的，并找到创新的策略来保护 并取代人体中的功能性β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.”