Coagulation management is the leading challenge during extracorporeal life support (ECLS) due to shear stress and foreign-surface–induced coagulation disturbance during circulation. A nonadhesive, liquid-infused coating called tethered liquid perfluorocarbon (TLP) was developed to prevent adhesion of blood on medical materials. We investigated the novel application of TLP to commercial ECLS circuits compared with standard heparin-coated circuits in vivo in anesthetized swine for 6 hours veno-venous ECLS (1 L/min blood flow) without systemic anticoagulation (n = 3/group). We hypothesized that TLP coating permits heparin-free circulation without untoward effects while reducing thrombus deposition compared with controls. Vital signs, respiration, gas transfer, coagulation, and histology were assessed. Scanning electron microscopy (SEM), elemental mapping, and digital imaging were used to assess thrombus deposition after circulation. There were no group differences in vitals, gas exchange, coagulation, and histology. In both groups, ECLS enabled a decrease in minute volume and end-tidal CO2, with concomitant increase in pH (p < 0.05). Scanning electron microscopy and digital imaging revealed significant thrombus on heparin-coated membranes, which was reduced or absent on TLP-coated materials. Tethered liquid perfluorocarbon permitted heparin-free ECLS without altering device performance and prevented thrombus deposition versus immobilized heparin. Pending multiday in vivo testing, TLP is a promising biomaterial solution to eliminate anticoagulation requirements during ECLS.

Supplemental Digital Content is available in the text.

The recent emergence of microfluidic extracorporeal lung support technologies presents an opportunity to achieve high gas transfer efficiency and improved hemocompatibility relative to the current standard of care in extracorporeal membrane oxygenation (ECMO). However, a critical challenge in the field is the ability to scale these devices to clinically relevant blood flow rates, in part because the typically very low blood flow in a single layer of a microfluidic oxygenator device requires stacking of a logistically challenging number of layers. We have developed biomimetic microfluidic oxygenators for the past decade and report here on the development of a high-flow (30 mL/min) single-layer prototype, scalable to larger structures via stacking and assembly with blood distribution manifolds. Microfluidic oxygenators were designed with biomimetic in-layer blood distribution manifolds and arrays of parallel transfer channels, and were fabricated using high precision machined durable metal master molds and microreplication with silicone films, resulting in large area gas transfer devices. Oxygen transfer was evaluated by flowing 100% O2 at 100 mL/min and blood at 0–30 mL/min while monitoring increases in O2 partial pressures in the blood. This design resulted in an oxygen saturation increase from 65% to 95% at 20 mL/min and operation up to 30 mL/min in multiple devices, the highest value yet recorded in a single layer microfluidic device. In addition to evaluation of the device for blood oxygenation, a 6-h in vitro hemocompatibility test was conducted on devices (n = 5) at a 25 mL/min blood flow rate with heparinized swine donor blood against control circuits (n = 3). Initial hemocompatibility results indicate that this technology has the potential to benefit future applications in extracorporeal lung support technologies for acute lung injury.

Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as barriers to further expansion of the technology. Recent advances in microfluidic fabrication techniques, devices, and systems present an opportunity to develop new solutions stemming from the ability to precisely maintain critical dimensions such as gas transfer membrane thickness and blood channel geometries, and to control levels of fluid shear within narrow ranges throughout the cartridge. Here, we present a physiologically inspired multilayer microfluidic oxygenator device that mimics physiologic blood flow patterns not only within individual layers but throughout a stacked device. Multiple layers of this microchannel device are integrated with a three-dimensional physiologically inspired distribution manifold that ensures smooth flow throughout the entire stacked device, including the critical entry and exit regions. We then demonstrate blood flows up to 200 ml/min in a multilayer device, with oxygen transfer rates capable of saturating venous blood, the highest of any microfluidic oxygenator, and a maximum blood flow rate of 480 ml/min in an eight-layer device, higher than any yet reported in a microfluidic device. Hemocompatibility and large animal studies utilizing these prototype devices are planned. Supplemental Visual Abstract, http://links.lww.com/ASAIO/A769 .