Abstract
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 cm2, 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-1. 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-1.
Highlights
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 dimensions of our bifurcation structure designs are in the range for reasonable shear stress[12] and for fluidic resistance according to the generalized Murray's law.[23]
A compact and stackable PDMS microfluidic oxygenator was designed for highly efficient gas exchange, and the fabricated devices were tested by oxygenating and decarbonating swine venous blood
Summary
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. In 2019, Potkay's team[12] proposed an optimized design for one single-layer unit based on a closed-form mathematical model previously developed.[4] With a large exchange surface area of 0.31 m2, this optimized single-layer device exhibits an oxygen uptake of 0.4 ml O2 per min at a rated blood flow of 17 ml min−1 with a theoretical priming volume reduced to 0.40 ml and a capillary wall shear stress of 45 dyn cm−2 Despite this progress, there is room for further miniaturization of channel and membrane geometries for the optimization of gas exchange efficiency and oxygen uptake and carbon dioxide release. Simplification of the fabrication/assembly process is another remaining challenge for further scaling up
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