Approximately 20,317 patients globally received artificial pulmonary support via extra-corporeal membrane oxygenation (ECMO) in 2021. During ECMO, hollow fiber membrane (HFM) gas exchangers require a surface area of ~2 m2 to achieve therapeutic gas transfer; however, this large contact area with the blood activates the coagulation cascade that requires systemic anticoagulation for suppression, usually with heparin. Although heparin reduces the frequency of clotting, it does not effectively inhibit the surface deposition of platelets and proteins. The consumption of these critical clotting components, as well as continuous administration of systemic anticoagulant, results in an increased risk of bleeding during ECMO and increases the risk of complications and mortality. We propose that replacing the HFM gas exchanger with a liquid perfluorocarbon blood oxygenation system will lead to less clotting and require less anticoagulant use, reducing the incidence of both thrombosis and hemorrhage. Liquid perfluorocarbons such as perfluorodecalin (PFD) have several characteristics to make such a system viable: (1) They are completely immiscible with blood, allowing easy separation between the two liquids; (2) They have ~twice the density of blood, such that blood flows up through perfluorocarbons, making a flow system work through natural circulation; (3) They carry ~40% of their weight in oxygen and >160% of their weight in carbon dioxide, both at STP, enabling efficient gas transfer with blood; and (4) PFD is safe in the human body having been approved as a blood substitute in 1989. Boundless will create a device, a Perfluorocarbon Blood Oxygenation System (PBOS) that flows oxygenated PFD into a chamber in combination with blood using Venturi Blood Droplet generators, nozzles that create small droplets of blood with minimal shear, hemolysis, or platelet activation. The small blood droplets gain oxygen and release carbon dioxide into the PFD quickly before reagglomerating at the top of the PBOS. The newly oxygenated blood is returned to the body. The PFD moves into a chamber where it is re-oxygenated and carbon dioxide is removed. This proposal seeks to identify an optimal flow system that optimizes extracorporeal blood oxygenation (and carbon dioxide removal) while preventing blood activation, blood damage, or adding PFD to the body. In reducing blood shear in the PBOS, we will minimize hemolysis and blood activation. We will progress toward this objective through the following Specific Aims: Aim 1: Optimize VDG geometry and flow rates through a combination of in-silico modeling and prototypes. Aim 2: Quantify blood oxygenation and CO2 removal as a function of droplet sizes and PFD flow rates. Aim 3: Demonstrate a 2 L/min system with clinically useful oxygenation, CO2 removal, and hemolysis. Aim 4: Develop preliminary marketing and regulatory plans for the PBOS. Successful results will not only show the potential of PBOS but will provide the necessary design guidelines to drive the development of a clinically viable PBOS system.
Public Health Relevance Statement: PROJECT NARRATIVE Extra-corporeal membrane oxygenation (ECMO) circulates a patient's blood over a gas exchange membrane outside the body to provide artificial pulmonary support and is used when the patient's pulmonary and/or cardiac function is severely degraded due to disease or injury. However, ECMO also causes blood coagulation that must be treated with systemic anticoagulants, which themselves cause high incidences of both clotting and bleeding. We are developing a novel "Perfluorocarbon Blood Oxygenation System" (PBOS) that replaces current ECMO components for oxygen and carbon dioxide transfer that damage blood with ones that do not; this will improve the outcomes and survival of patients requiring ECMO by increasing safely, while also potentially making the device smaller and offering the potential for ambulatory ECMO.
Project Terms: Adsorption; Animals; Anticoagulant Agents; Anticoagulant Drugs; blood thinner; thrombopoiesis inhibitor; Anticoagulants; Anticoagulation; Asthma; Bronchial Asthma; Blood; Blood Reticuloendothelial System; Blood coagulation; Blood Clotting; Blood Platelets; Marrow platelet; Platelets; Thrombocytes; Blood Substitutes; Artificial Blood; Artificial Erythrocytes; Erythrocyte Substitutes; Red Cell Substitutes; Carbon Dioxide; CO2; Carbonic Anhydride; Complement Activation; complement pathway regulation; Disease; Disorder; Extracorporeal Membrane Oxygenation; Feedback; Fibrin; Fluorocarbons; Perfluorocarbons; Gases; Goals; Blood Tests; Hematologic Tests; Hematological Tests; Hematology Testing; Hemolysis; erythrolysis; Hemorrhage; Bleeding; blood loss; Heparin; Heparinic Acid; In Vitro; Incidence; Interview; Lung; Lung Respiratory System; pulmonary; Lung Transplantation; Lung Grafting; Pulmonary Graft; Pulmonary Transplant; Pulmonary Transplantation; lung transplant; Marketing; Medical Device; mortality; Oxygen; O element; O2 element; Oxygenators; Patients; Platelet Activation; Pneumonectomy; pressure; Proteins; Acute Respiratory Distress Syndrome; ARDS; Acute Respiratory Distress; Adult ARDS; Adult RDS; Adult Respiratory Distress Syndrome; Da Nang Lung; Shock Lung; Stiff lung; wet lung; Risk; Science; Family suidae; Pigs; Suidae; Swine; porcine; suid; Testing; Thrombosis; thrombotic disease; thrombotic disorder; Weight; weights; Work; Thrombus; Guidelines; injuries; Injury; density; Area; Surface; Acute; Clinical; Diffuse; Phase; Physiologic; Physiological; Fiber; pediatric; Childhood; lung function; pulmonary function; cardiac function; function of the heart; heart function; Blood flow; Orphan; Human Figure; Human body; inflammatory mediator; Inflammation Mediators; Therapeutic; fluid; liquid; Liquid substance; Deposition; Deposit; Venous; Hour; Frequencies; System; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; biomaterial compatibility; biocompatibility; experience; Membrane; membrane structure; Performance; Structure; novel; Devices; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Modeling; leukocyte activation; Airway failure; Respiratory Failure; preventing; prevent; Coagulation Process; Clotting; Coagulation; Alveolar; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Characteristics; Development; developmental; designing; design; Consumption; prototype; commercialization; good laboratory practice; Geometry; improved outcome; blood damage; COVID19; CV-19; CV19; corona virus disease 2019; coronavirus disease 2019; coronavirus disease-19; coronavirus infectious disease-19; COVID-19; in silico; Chronic Obstructive Pulmonary Disease; COPD; Chronic Obstruction Pulmonary Disease; Chronic Obstructive Lung Disease; graft dysfunction; Circulation; Diameter; lung failure; pulmonary failure
