A small-scale, rolled-membrane microfluidic artificial lung designed towards future large area manufacturing

Abstract

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the l/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10m tall artificial capillaries, and a 66 m thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O, atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.

An artificial placenta type microfluidic blood oxygenator with double-sided gas transfer microchannels and its integration as a neonatal lung assist device

“…In summary, the performance of dsSOUs was found to be superior to the ssSOU design. In order to compare its performance with other microfluidic blood oxygenators, 9,[16][17][18][19]22,23,[25][26][27][28][29][30] the reported oxygen transfer rate and blood flow rate could be normalized to the gas exchange surface area. So, the amount of oxygen uptake per 1 l of blood was calculated and defined as "oxygen transfer" to show the capacity of each device.…”

“…Most of other microfluidic blood oxygenators were designed to be operated with the assistance of an external pump, which can cause complications such as hemolysis, 20,21 or required additional actively perfused gas supply, such as pure oxygen or compressed air to enhance to gas exchange. 16,17,[22][23][24][25][26][27][28][29][30] One limitation of the previous pumpless, ambient gas exchange oxygenators 9,18,19 has been that only one side of the microfluidic network, through which the blood flows, is composed of the thin gas exchange membrane. This limitation can be overcome by incorporating thin gas exchange membrane on both sides albeit with additional fabrication complexity.…”

Steel reinforced composite silicone membranes and its integration to microfluidic oxygenators for high performance gas exchange

“…Table I shows the comparison among composite flat, composite sloping, and the LAD presented in this study with other microfluidic blood oxygenator devices which used air as ventilating gas. 2,16,17,29 In this comparison, oxygen transfer and blood flow rate are normalized to the effective gas exchange surface area to provide a better comparison among all devices. As shown in Table I, the LAD has better oxygen transfer at the same normalized blood flow rate compared to others except Potkay 16 2011 and Rieper 17 2015.…”

Understanding blood oxygenation in a microfluidic meander double side membrane contactor

“…Along the last years, a biomimetic microfluidic technology has been developed and reported by several authors [1][2][3][4][5][6] and recently reviewed by J. Potkay [7][8] for the application of lung assist device. In these microchips blood flows through vascular microchannels which are physically separated from an oxygen stream by a gas permeable membrane.…”

“…Recently, flat two-dimensional μALs stacked in parallel with a capillary height of 30 μm has been demonstrated as a trade-off to maximize oxygenation performance and reduce the number of layers that are needed for a clinically-relevant device [8]. The same group developed a new manufacturing approach for scaling up based on roll to roll polymer sheet processing [6]. In particular, a μAL with a four-layer structure (blood layer 10 µm height /membrane 66 µm thick/air layer/capping layer) was assembled by rolling a cylindrical substrate over the patterned PDMS substrate.…”