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Deformability-based microfluidic separation of pancreatic islets from exocrine acinar tissue for transplant applications
Lab on a Chip ( IF 6.1 ) Pub Date : 2017-09-21 00:00:00 , DOI: 10.1039/c7lc00890b Walter B. Varhue 1, 2, 3, 4 , Linda Langman 2, 3, 4, 5, 6 , Molly Kelly-Goss 2, 3, 4, 7 , Morgan Lataillade 2, 3, 4, 7 , Kenneth L. Brayman 2, 3, 4, 5, 6 , Shayn Peirce-Cottler 2, 3, 4, 7 , Nathan S. Swami 1, 2, 3, 4
Lab on a Chip ( IF 6.1 ) Pub Date : 2017-09-21 00:00:00 , DOI: 10.1039/c7lc00890b Walter B. Varhue 1, 2, 3, 4 , Linda Langman 2, 3, 4, 5, 6 , Molly Kelly-Goss 2, 3, 4, 7 , Morgan Lataillade 2, 3, 4, 7 , Kenneth L. Brayman 2, 3, 4, 5, 6 , Shayn Peirce-Cottler 2, 3, 4, 7 , Nathan S. Swami 1, 2, 3, 4
Affiliation
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The long-term management of type-1 diabetes (T1D) is currently achieved through lifelong exogenous insulin injections. Although there is no cure for T1D, transplantation of pancreatic islets of Langerhans has the potential to restore normal endocrine function versus the morbidity of hypoglycemic unawareness that is commonly associated with sudden death among fragile diabetics. However, since endocrine islet tissues form a small proportion of the pancreas, sufficient islet numbers can be reached only by combining islets from multiple organ donors and the transplant plug contains significantly high levels of exocrine acinar tissue, thereby exacerbating immune responses. Hence, lifelong administration of immunosuppressants is required after transplantation, which can stress islet cells. The density gradient method that is currently used to separate islets from acinar tissue causes islets to be sparsely distributed over the centrifuged bins, so that the transplant sample obtained by combining multiple bins also contains significant acinar tissue levels. We show that in comparison to the significant size and density overlaps between the islet and acinar tissue populations post-organ digestion, their deformability overlaps are minimal. This feature is utilized to design a microfluidic separation strategy, wherein tangential flows enable selective deformation of acinar populations towards the bifurcating waste stream and sequential switching of hydrodynamic resistance enables the collection of rigid islets. Using 25 bifurcating daughter channels, a throughput of ∼300 islets per hour per device is obtained for enabling islet enrichment from relatively dilute starting levels to purity levels that meet the transplant criteria, as well as to further enhance islet purity from samples following density gradient enrichment. Based on confirmation of viability and functionality of the microfluidic-isolated islets using insulin secretion analysis and an angiogenesis assay, we envision utilizing this strategy to generate small-volume transplant plugs with high islet purity and significantly reduced acinar levels for minimizing immune responses after transplantation.
中文翻译：
基于可变形性的胰腺胰岛与外分泌腺组织的微流分离，用于移植
目前，通过终身终生外源性胰岛素注射来实现1型糖尿病（T1D）的长期管理。虽然目前还没有治愈1型糖尿病中，朗格汉斯胰岛移植已恢复正常的内分泌功能的潜力与低血糖意识不足的发病率，通常与脆弱的糖尿病患者突然死亡相关。然而，由于内分泌胰岛组织占胰脏的一小部分，仅通过组合来自多个器官供体的胰岛就可以达到足够的胰岛数目，并且移植栓塞含有显着高水平的外分泌腺泡组织，从而加剧了免疫反应。因此，移植后需要终生给予免疫抑制剂，这会给胰岛细胞带来压力。当前用于从胰岛组织中分离胰岛的密度梯度法使胰岛稀疏地分布在离心桶上，因此，通过组合多个桶而获得的移植样品也含有显着的腺泡组织水平。我们显示，与胰脏和腺泡组织群体器官消化后的显着大小和密度重叠相比，它们的可变形性重叠很小。该特征用于设计微流体分离策略，其中切向流使腺泡群体朝着分叉的废物流选择性变形，而流体动力阻力的顺序切换使得能够收集刚性小岛。使用25个分叉子通道，每台设备每小时可获得约300个胰岛的通量，以实现从相对稀的起始水平到满足移植标准的纯度水平进行胰岛富集，并在密度梯度富集后进一步提高样品的胰岛纯度。
更新日期：2017-10-26
中文翻译：
基于可变形性的胰腺胰岛与外分泌腺组织的微流分离，用于移植
目前，通过终身终生外源性胰岛素注射来实现1型糖尿病（T1D）的长期管理。虽然目前还没有治愈1型糖尿病中，朗格汉斯胰岛移植已恢复正常的内分泌功能的潜力与低血糖意识不足的发病率，通常与脆弱的糖尿病患者突然死亡相关。然而，由于内分泌胰岛组织占胰脏的一小部分，仅通过组合来自多个器官供体的胰岛就可以达到足够的胰岛数目，并且移植栓塞含有显着高水平的外分泌腺泡组织，从而加剧了免疫反应。因此，移植后需要终生给予免疫抑制剂，这会给胰岛细胞带来压力。当前用于从胰岛组织中分离胰岛的密度梯度法使胰岛稀疏地分布在离心桶上，因此，通过组合多个桶而获得的移植样品也含有显着的腺泡组织水平。我们显示，与胰脏和腺泡组织群体器官消化后的显着大小和密度重叠相比，它们的可变形性重叠很小。该特征用于设计微流体分离策略，其中切向流使腺泡群体朝着分叉的废物流选择性变形，而流体动力阻力的顺序切换使得能够收集刚性小岛。使用25个分叉子通道，每台设备每小时可获得约300个胰岛的通量，以实现从相对稀的起始水平到满足移植标准的纯度水平进行胰岛富集，并在密度梯度富集后进一步提高样品的胰岛纯度。
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