A Clinical‐Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks

Abstract

Recent global events such as COVID‐19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs). Here the development and demonstration of the first microfluidic respiratory assist device at a clinical scale is reported, demonstrating efficient oxygen transfer at blood flow rates of 750 mL min⁻1, the highest ever reported for a microfluidic device. The central innovation of this technology is a fully 3D branching network of blood channels mimicking key features of the physiological microcirculation by avoiding anomalous blood flows that lead to thrombus formation and blood damage in conventional oxygenators. Low, stable blood pressure drop, low hemolysis, and consistent oxygen transfer, in 24‐hour pilot large animal experiments are demonstrated – a key step toward translation of this technology to the clinic for treatment of a range of lung diseases.

First 24-Hour-Long Intensive Care Unit Testing of a Clinical-Scale Microfluidic Oxygenator in Swine: A Safety and Feasibility Study

“…In the intervention group (BLOx), the MiniLung membrane oxygenator was removed from the circuit and replaced with the multilayer microfluidic oxygenator device (Figure 1 and Figure S1 http://links.lww.com/ASAIO/B184), fabrication and assembly described previously. 23 The BLOx devices did not receive an antithrombogenic coating, as is present on the MiniLung oxygenators (see Supplemental Methods, Supplemental Digital Content 1, http://links.lww.com/ASAIO/B184).…”

“…20 Draper (Cambridge, MA) has been developing microfluidic oxygenator technology for the past decade, producing genera-in collaboration with the Autonomous Reanimation and Evacuation (AREVA) Research Program (San Antonio, TX). [21][22][23] Devices are designed to support clinically relevant blood flow rates and lung support after an architecture consisting of layers of branching networks of microchannels that recapitulate key aspects of the natural branching in lung vasculature and that overcome the aforementioned limitations in blood flow patterning. 23 Each layer is designed to support a blood flow of 100 ml/min.…”

“…[21][22][23] Devices are designed to support clinically relevant blood flow rates and lung support after an architecture consisting of layers of branching networks of microchannels that recapitulate key aspects of the natural branching in lung vasculature and that overcome the aforementioned limitations in blood flow patterning. 23 Each layer is designed to support a blood flow of 100 ml/min. The device was observed to mimic physiologic blood flow patterns, leveraging design principles such as Murray's Law 24 and computational approaches that provide uniform flow, pressure drop, and wall shear stress across the blood channel network, not only within individual layers but throughout the stacked device.…”

“…21,22 As reported before, gas exchange targets can be reached or modulated with this design while reducing contact surface area and optimizing the blood flow to minimize nonphysiologic conditions. [21][22][23] From these promising results, Draper designed an eight-layer version of this microfluidic blood oxygenator design, called "BLOx," capable of supporting a 750-800 ml/min blood flow rate-equivalent to a neonatal oxygenator or extracorporeal carbon dioxide removal devices. 25 This article describes the first in vivo evaluation of the upscaled BLOx device in a veno-venous ECLS configuration at clinically relevant blood flows compared to a reference HFMO.…”

Toward 3D printed microfluidic artificial lungs for respiratory support

“…20 To achieve clinically relevant blood flows, these geometrically constrained μALs must be scaled-up by stacking or combining tens to thousands of devices with tubing and connections, increasing blood priming volumes (filling volume), and potentially decreasing hemocompatibilty. 10,16,21,22 Maintaining low pressure drops is a also a challenge which restricts the size of these planar, 2D μALs and requires many devices to be assembled together to increase flow rate. 10…”