The proposed microfluidic oxygenator project is aimed at developing a safer and more effective treatment for respiratory failure for Warfighters in both combat casualty care and in military Veterans suffering from chronic lung diseases. The technology is also applicable to civilian populations suffering from either acute or chronic lung conditions that are currently very difficult to treat. In military settings, Service members suffering from severe pulmonary infections or respiratory failure following a combat injury are often treated using mechanical ventilation, where oxygen is pumped into their lungs by a breathing machine to enable them to survive while their lungs heal. Mechanical ventilators are often ineffective because the lungs are too compromised to function properly, requiring high pressure oxygenation that can cause further injury or hospital-acquired infections. A method known as ECMO (ExtraCorporeal Membrane Oxygenation) has been developed over the past several decades to provide an alternative to mechanical ventilation, in which the patient’s blood is pumped through a circuit external to the body at very high rates approaching one cycle of the entire blood volume per minute. In the ECMO circuit, blood is oxygenated by passing it by a gas transfer membrane, where carbon dioxide is also removed to maintain stable levels of these gases in the patient’s blood. The main challenge with ECMO is the high level of complexity of the blood circuit and the tendency for the circuit to form clots, and therefore patients on ECMO receive high doses of anti-clotting agents. In particular, for critically ill or injured patients or military Service members, these high doses of anti-clotting agents cause a serious risk of bleeding and other complications that threaten patient survival.

This proposal aims to demonstrate the ability of an innovative new technology, termed microfluidics, to improve the safety and efficacy of ECMO, enabling the treatment to be applied to situations such as prolonged battlefield care and acute care in military hospitals, as well as in civilian populations suffering from acute and chronic lung diseases. Draper is a pioneer in the field of microfluidics and microsystems technologies and has been applying these capabilities toward a range of applications for the Department of Defense over the past 20 years. Microfluidics technologies enable the fabrication of high-precision devices that can mimic the geometry of the human lung, in comparison with current ECMO therapy that relies upon decades-old bundles of hollow fibers that do not resemble or function like blood vessels in the body in any way. Problems with clotting of hollow fiber-based ECMO devices arise from the ways that blood flow through the devices and the very large surface area of the fibers contacting the patient’s blood. Blood flow follows highly disturbed patterns with areas of stagnation and other areas of rapid and almost turbulent flow, which causes blood to form clots as it would in the body. Another trigger for clotting is the contact between large surface areas of hollow fiber membranes and the blood. Our microfluidics technology addresses both of these critical issues by permitting the construction of devices with arrays of small channels that look very much like a capillary bed or branching blood vessel network in the body. The microfluidics design is so efficient that we can reduce the contact area between the gas exchange membrane and the blood very significantly, further reducing the likelihood of clotting.

In Draper’s project, we will design a set of microfluidic devices that mimic the manner in which blood flows in the body, as well as the way in which the lungs exchange oxygen and carbon dioxide with the atmosphere. These highly efficient designs will be tested in the laboratory to determine how well gases are exchanged, and then how well blood flows through the devices without clotting. In the first phase of the project, we will conduct smaller-scale prototype evaluation in the laboratory. Once these initial prototypes are tested, we will select the highest performing devices and build larger-scale systems that can be compared directly with current hollow fiber-based ECMO cartridges. Two stages of larger prototype devices will be built and tested, first a mid-scale design comparable to a neonatal oxygenator and then an adult-scale device that can be compared with standard hollow-fiber oxygenators. These will be pre-screened in the laboratory and then tested at our collaborator institution at The Geneva Foundation and the U.S. Army Institute of Surgical Research, where there is extensive expertise in evaluating new technologies for military medicine. Our work will be guided by critical care and respiratory experts from the Uniformed Services University and Harvard Medical School. The near-term goal of this project is to establish a safer and more effective way to treat respiratory failure in combat casualty care, and ultimately to extend this advancement toward wider use in chronic lung disease applications in military Veterans and in civilian populations suffering from Chronic Obstructive Pulmonary Disease and other diseases.