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Application of Microfluidics in the Field of Diabetes and Islets.

機譯：微流控技術(shù)在糖尿病和胰島領域的應用。

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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.
機譯：I型糖尿病（TIDM）是一種自身免疫性疾病，涉及β細胞的破壞，導致胰島素缺乏和血糖水平升高。人胰島的微囊化是無需免疫抑制劑即可治療TIDM的有前途的療法。然而，與微囊化有關(guān)的一個缺點是由于防止了血運重建和增加了氧的擴散距離，可能導致胰島缺氧。為了研究缺氧對包封的胰島的影響，開發(fā)了一種微流控陣列并將其與氧合控制相集成，以提供和模擬各種低氧條件。我們能夠證明缺氧會在單個胰島水平上損害微囊化胰島的功能，顯示出細胞內(nèi)鈣信號傳導，線粒體能量和氧化還原活性所反映的異質(zhì)性模式。我們的方法證明了相對于常規(guī)缺氧室的改進。這項工作證明了基于陣列的細胞分析的可行性，并為進行微囊化胰島的信息分析和基于細胞的篩選開辟了新的模式。目前研究胰島和糖尿病的體內(nèi)工具的主要挑戰(zhàn)之一是數(shù)量有限可以在單個設備中評估的胰島數(shù)量。另一個挑戰(zhàn)是無法令人滿意地評估單個胰島的異質(zhì)性，尤其是在同時測試大量胰島時。與基于平均的種群方法相比，在單個胰島水平上檢查異質(zhì)性通?？梢蕴峁└敿毜纳砘虿±砩硇畔?。例如，如果可以單獨評估許多單個胰島而不是平均總體反應，那么它將能夠從合理的樣本量中更好地了解人類胰島功能，并為胰島移植結(jié)果提供更好的預測價值。在本報告中，目的是基于流體動力學捕集原理，開發(fā)一種新穎的微流胰島陣列，以研究較大胰島群體中單個胰島的生理或病理生理行為的復雜性。此外，我們旨在探索基于陣列的細胞分析的可行性，以提供有關(guān)胰島的更多信息數(shù)據(jù)，并充當評估抗糖尿病藥物的平臺。;我們與麻省理工學院的實驗室合作確定，材料的纖維化在很大程度上取決于大小和形狀。業(yè)已證明，在1.5毫米藻酸鹽膠囊中制備的胰島能夠恢復長達180天的血糖控制，是傳統(tǒng)尺寸的0.5毫米藻酸鹽膠囊化胰島的五倍以上。這些新發(fā)現(xiàn)表明，只需調(diào)整其球形尺寸，即可顯著增強生物醫(yī)學設備的體內(nèi)生物相容性。在第三個項目中，已經(jīng)設計，驗證并成功測試了一個新平臺，該平臺可以成功地用于研究和研究1.5 mm大膠囊的特性，并評估這些微膠囊內(nèi)部的胰島功能。該設備能夠固定大膠囊，用于短期和長期的動態(tài)和靜態(tài)刺激以及活細胞成像。使用這個新平臺，我們正在繼續(xù)進行大膠囊研究，以研究免疫隔離物質(zhì)的大小/體積如何影響胰島功能。最后，為了實現(xiàn)胰島素獨立性，每公斤患者體重至少需要5000 IEq。胰島細胞移植需要的。當前，在移植前對胰島的定量是手動進行的，這可能導致總計數(shù)的可變性增加并且很耗時。為了克服這一挑戰(zhàn)，已經(jīng)提出了與智能手機集成的基于微流體的胰島定量平臺，以進行準確，具有成本效益的快速胰島細胞計數(shù)和定量。在這四個項目中，我們能夠展示微流體技術(shù)在裸露和封裝的胰島細胞研究中的一系列應用，這些研究有助于更好地了解糖尿病。

著錄項

  • 作者單位

    University of Illinois at Chicago.;

  • 授予單位 University of Illinois at Chicago.;
  • 學科 Biomedical engineering.
  • 學位 Ph.D.
  • 年度 2015
  • 頁碼 144 p.
  • 總頁數(shù) 144
  • 原文格式 PDF
  • 正文語種 eng
  • 中圖分類 遙感技術(shù);
  • 關(guān)鍵詞

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