A high gas transfer efficiency microfluidic oxygenator for extracorporeal respiratory assist applications in critical care medicine
A high gas transfer efficiency microfluidic oxygenator for extracorporeal respiratory assist applications in critical care medicine
复制标题
DOI：
10.1111/aor.13935
复制
发表时间：
2021-04-04
影响因子：
2.4
通讯作者：
Borenstein, Jeffrey T.
中科院分区：
文献类型：
--
作者：
Gimbel, Alla A.;Hsiao, James C.;Borenstein, Jeffrey T.
微流控技术的进步刺激了新一代微流控呼吸辅助设备的发展，该设备采用微制造技术构建，能够产生与人类毛细血管和气体传输膜中发现的类似的微通道尺寸，其厚度范围与肺泡膜相同。这些设备已经在实验室环境中进行了测试，在某些情况下还进行了体外动物实验，但没有一种设备进入人类临床研究。微流控氧合器开发中的一个主要挑战是难以将技术扩展到支持成人人体所需的高血流量；这种扩展努力往往受到制造过程的复杂性和血液在微通道三维网络中的分布方式的限制。从概念上讲，与现有的基于中空纤维膜的结构相比，微流控氧合器的一个主要优势是具有更浅的通道和更薄的气体传输膜的潜力，这些特性可以缩短氧气扩散距离，从而产生更高的气体传输效率，其定义为每单位时间传输到血液中的氧气体积与气体传输膜的有效表面积之比。如果这一比率没有显著高于中空纤维膜氧合器(HFMO)的报告值，那么微流控方法的预期优势就不会在实践中实现，这可能是因为在将微流控设计扩展到更高的流速时，血液分配策略遇到了挑战。在这里，我们报告了一种微流控氧合器的设计，从4毫升/分钟的血流到92毫升/分钟的血流，在新生儿应用所需的流量的数量级内。这种规模化的设备被证明具有比文献中任何其他报道的系统更高的气体传输效率，包括其他微流控原型和商业HFMO弹盒。虽然高的氧气传输效率是微流控体系临床规模的一个有希望的进步，但它伴随着电路中过度的血压下降，这是由于浅层气体传输通道和同样浅的分配歧管的组合引起的。因此，下一代微流控氧合器将需要新颖的设计和制造策略，以最大限度地降低压降，同时保持非常高的氧气转移效率。
Advances in microfluidics technologies have spurred the development of a new generation of microfluidic respiratory assist devices, constructed using microfabrication techniques capable of producing microchannel dimensions similar to those found in human capillaries and gas transfer films in the same thickness range as the alveolar membrane. These devices have been tested in laboratory settings and in some cases in extracorporeal animal experiments, yet none have been advanced to human clinical studies. A major challenge in the development of microfluidic oxygenators is the difficulty in scaling the technology toward high blood flows necessary to support adult humans; such scaling efforts are often limited by the complexity of the fabrication process and the manner in which blood is distributed in a three-dimensional network of microchannels. Conceptually, a central advantage of microfluidic oxygenators over existing hollow-fiber membrane-based configurations is the potential for shallower channels and thinner gas transfer membranes, features that reduce oxygen diffusion distances, to result in a higher gas transfer efficiency defined as the ratio of the volume of oxygen transferred to the blood per unit time to the active surface area of the gas transfer membrane. If this ratio is not significantly higher than values reported for hollow fiber membrane oxygenators (HFMO), then the expected advantage of the microfluidic approach would not be realized in practice, potentially due to challenges encountered in blood distribution strategies when scaling microfluidic designs to higher flow rates. Here, we report on scaling of a microfluidic oxygenator design from 4 to 92 mL/min blood flow, within an order of magnitude of the flow rate required for neonatal applications. This scaled device is shown to have a gas transfer efficiency higher than any other reported system in the literature, including other microfluidic prototypes and commercial HFMO cartridges. While the high oxygen transfer efficiency is a promising advance toward clinical scaling of a microfluidic architecture, it is accompanied by an excessive blood pressure drop in the circuit, arising from a combination of shallow gas transfer channels and equally shallow distribution manifolds. Therefore, next-generation microfluidic oxygenators will require novel design and fabrication strategies to minimize pressure drops while maintaining very high oxygen transfer efficiencies.