Université Paris-Saclay, CNRS, Centre de Nanosciences et Nanotechnologies C2N, UMR9001, Palaiseau 91120, France.
Université Paris-Saclay, INSERM, UMR-S-MD 1197, Hôpital Paul Brousse, Villejuif, France.
Lab Chip. 2021 Dec 7;21(24):4791-4804. doi: 10.1039/d1lc00356a.
We have developed and tested a novel microfluidic device for blood oxygenation, which exhibits a large surface area of gas exchange and can support long-term sustainable endothelialization of blood microcapillaries, enhancing its hemocompatibility for clinical applications. The architecture of the parallel stacking of the trilayers is based on a central injection for blood and a lateral injection/output for gas which allows significant reduction in shear stress, promoting sustainable endothelialization since cells can be maintained viable for up to 2 weeks after initial seeding in the blood microchannel network. The circular design of curved blood capillaries allows covering a maximal surface area at 4 inch wafer scale, producing high oxygen uptake and carbon dioxide release in each single unit. Since the conventional bonding process based on oxygen plasma cannot be used for surface areas larger than several cm, a new "wet bonding" process based on soft microprinting has been developed and patented. Using this new protocol, each 4 inch trilayer unit can be sealed without a collapsed membrane even at reduced 15 μm thickness and can support a high blood flow rate. The height of the blood channels has been optimized to reduce pressure drop and enhance gas exchange at a high volumetric blood flow rate up to 15 ml min. The simplicity of connecting different units in the stacked architecture is demonstrated for 3- or 5-unit stacked devices that exhibit remarkable performance with low primary volume, high oxygen uptake and carbon dioxide release and high flow rate of up to 80 ml min.
我们开发并测试了一种新颖的血液氧合微流控装置,该装置具有较大的气体交换表面积,并能支持血液微血管的长期可持续内皮化,从而提高其血液相容性,适用于临床应用。该装置的三层平行堆叠结构基于血液中央注射和气体侧向注射/输出,可显著降低切应力,促进可持续内皮化,因为细胞在最初接种到血液微通道网络后最多可维持 2 周的活力。弯曲血液毛细血管的圆形设计允许在 4 英寸晶圆规模上覆盖最大表面积,从而在每个单个单元中实现高氧气摄取和二氧化碳释放。由于基于氧等离子体的传统键合工艺不能用于大于几平方厘米的表面积,因此开发并获得专利的一种新的“湿键合”工艺基于软微印刷。使用这种新方案,即使在厚度减小到 15 μm 的情况下,每个 4 英寸的三层单元也可以在不发生膜塌陷的情况下进行密封,并且可以支持高血流速率。优化了血液通道的高度,以降低压降并增强在高体积血流速率下的气体交换,最高可达 15 ml min。堆叠结构中不同单元的连接简单性已通过 3 或 5 个单元堆叠装置得到证明,这些装置具有低初始体积、高氧气摄取和二氧化碳释放以及高达 80 ml min 的高流速的显著性能。