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Application of Microfluidics in the Field of Diabetes and Islets.

机译：微流控技术在糖尿病和胰岛领域的应用。

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摘要

Type I Diabetes Mellitus (TIDM) is an autoimmune disease, which involves the destruction of beta-cells leading to insulin deficiency and an increase in blood glucose levels. Microencapsulation of human islets is a promising therapy for treatment of TIDM without the need for immunosuppressants. However, one disadvantage associated with microencapsulation is the possible induction of islet hypoxia due to the prevention of revascularization and an increase in the oxygen diffusion distance. In order to investigate the effects of hypoxia on encapsulated islets, a microfluidic array was developed and integrated with oxygenation control to provide and mimic various hypoxic conditions. We were able to demonstrate that hypoxia impairs the function of microencapsulated islets at the single islet level, showing a heterogeneous pattern reflected in intracellular calcium signaling, mitochondrial energetic, and redox activity. Our approach demonstrated an improvement over conventional hypoxia chambers. This work demonstrates the feasibility of array-based cellular analysis and opens up new modality to conduct informative analysis and cell-based screening for microencapsulated pancreatic islets.;One of the major challenges of current in vivo tools to study islets and diabetes is the limited number of islets that can be assessed in a single device. Another challenge is the inability to satisfactorily assess the heterogeneous property of individual islets, especially when testing a large quantity of islets simultaneously. Examination of heterogeneous properties at the individual islet level often provides more detailed physiological or pathophysiological information than averaging-based population methodologies. For example, it will enable better understanding of human islet functionality from a reasonable sample size and will provide a better predictive value for islet transplant outcomes if many individual islets can be individually assessed instead of averaging a bulk response. In this report, the aim is to develop a novel microfluidic islet array, based on the hydrodynamic trapping principle, for investigating the complexity of physiological or pathophysiological behavior of individual pancreatic islets in a larger islet population. Furthermore, we aim to explore the feasibility of array-based cellular analysis to provide more informative data on pancreatic islets and to act as a platform to evaluate antidiabetic drugs.;Our Lab collaboration with MIT determined that fibrosis of materials is largely dependent on the size and shape. It has been proven that islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for conventionally sized 0.5-mm alginate encapsulated islet. These new findings propose that the in vivo biocompatibility of biomedical devices can be significantly enhanced simply by tuning their spherical dimensions. In third project, a new platform has been designed, verified and successfully tested that can be successfully applied to investigate and study the properties of 1.5 mm macrocapsules and also to evaluate the functionality of islets inside these microcapsules. The device is capable of immobilizing macrocapsules for short-term and long-term dynamic and static stimulation and live cell imaging. Using this new platform, we are continuing the study on macrocapsules to investigate how the size/volume of the immune-isolation material affects islet functionality.;Lastly, in order to achieve insulin independence, a minimum of 5000 IEq/ kilogram patient body weight is needed per islet cell transplantation. Currently, islet quantification prior to transplantation is conducted manually, which can result in increased variability in total counts as well as being time-consuming. To overcome this challenge a microfluidic based islet quantification platform integrated with a smartphone has been proposed for accurate, cost-effective and rapid islet cell counting and quantification. In these four projects, we were able to demonstrate an array of applications for microfluidic technology in the study of both naked and encapsulated islet cells that can help to better understand diabetes.
机译：I型糖尿病（TIDM）是一种自身免疫性疾病，涉及β细胞的破坏，导致胰岛素缺乏和血糖水平升高。人胰岛的微囊化是无需免疫抑制剂即可治疗TIDM的有前途的疗法。然而，与微囊化有关的一个缺点是由于防止了血运重建和增加了氧的扩散距离，可能导致胰岛缺氧。为了研究缺氧对包封的胰岛的影响，开发了一种微流控阵列并将其与氧合控制相集成，以提供和模拟各种低氧条件。我们能够证明缺氧会在单个胰岛水平上损害微囊化胰岛的功能，显示出细胞内钙信号传导，线粒体能量和氧化还原活性所反映的异质性模式。我们的方法证明了相对于常规缺氧室的改进。这项工作证明了基于阵列的细胞分析的可行性，并为进行微囊化胰岛的信息分析和基于细胞的筛选开辟了新的模式。目前研究胰岛和糖尿病的体内工具的主要挑战之一是数量有限可以在单个设备中评估的胰岛数量。另一个挑战是无法令人满意地评估单个胰岛的异质性，尤其是在同时测试大量胰岛时。与基于平均的种群方法相比，在单个胰岛水平上检查异质性通常可以提供更详细的生理或病理生理信息。例如，如果可以单独评估许多单个胰岛而不是平均总体反应，那么它将能够从合理的样本量中更好地了解人类胰岛功能，并为胰岛移植结果提供更好的预测价值。在本报告中，目的是基于流体动力学捕集原理，开发一种新颖的微流胰岛阵列，以研究较大胰岛群体中单个胰岛的生理或病理生理行为的复杂性。此外，我们旨在探索基于阵列的细胞分析的可行性，以提供有关胰岛的更多信息数据，并充当评估抗糖尿病药物的平台。;我们与麻省理工学院的实验室合作确定，材料的纤维化在很大程度上取决于大小和形状。业已证明，在1.5毫米藻酸盐胶囊中制备的胰岛能够恢复长达180天的血糖控制，是传统尺寸的0.5毫米藻酸盐胶囊化胰岛的五倍以上。这些新发现表明，只需调整其球形尺寸，即可显着增强生物医学设备的体内生物相容性。在第三个项目中，已经设计，验证并成功测试了一个新平台，该平台可以成功地用于研究和研究1.5 mm大胶囊的特性，并评估这些微胶囊内部的胰岛功能。该设备能够固定大胶囊，用于短期和长期的动态和静态刺激以及活细胞成像。使用这个新平台，我们正在继续进行大胶囊研究，以研究免疫隔离物质的大小/体积如何影响胰岛功能。最后，为了实现胰岛素独立性，每公斤患者体重至少需要5000 IEq。胰岛细胞移植需要的。当前，在移植前对胰岛的定量是手动进行的，这可能导致总计数的可变性增加并且很耗时。为了克服这一挑战，已经提出了与智能手机集成的基于微流体的胰岛定量平台，以进行准确，具有成本效益的快速胰岛细胞计数和定量。在这四个项目中，我们能够展示微流体技术在裸露和封装的胰岛细胞研究中的一系列应用，这些研究有助于更好地了解糖尿病。

著录项

  • 作者

    Nourmohammadzadeh, Mohammad.;

  • 作者单位

    University of Illinois at Chicago.;

  • 授予单位 University of Illinois at Chicago.;
  • 学科 Biomedical engineering.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 144 p.
  • 总页数 144
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遥感技术;
  • 关键词

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