Approximately 16,000 patients received artificial pulmonary support via extra-corporeal membrane oxygenation(ECMO) in 2019. During ECMO, hollow fiber membrane (HFM) gas exchangers require a surface area of ~2m2 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 ofcomplications and mortality.We propose that reducing the surface area of the HFM gas exchanger will lead to less clotting and require less anticoagulant use, reducing the incidence of both thrombosis and hemorrhage. To achieve this, BoundlessScience is developing a novel blood oxygenation system that uses ultrasound to dramatically enhance gas transfer efficiency, and thereby reduce the required gas exchanger area. A smaller gas exchanger will induce less clotting and require less anticoagulation and associated bleeding risks. An additional benefit is that a smaller surface area will allow us to develop a dramatically smaller ECMO system, offering the potential for ambulatory ECMO. Our initial results with ultrasound-enhanced ECMO (US-ECMO) show that ultrasound (US) enhances the rate of oxygen transport across a planar nano-porous polypropylene membrane by 4-6.4-fold.We hypothesize that US enhances transport through two mechanisms. First, the absorption of US travelling through the blood induces a bulk force, which in turn generates flow known as bulk streaming. Second, US oscillates gas/blood menisci at the membrane surface, rapidly mixing the blood near the membrane in a process known as microstreaming. Blood mixing from these mechanisms disrupts the boundary layer at theblood-membrane interface, steepening the oxygen gradient and driving faster diffusion.This proposal seeks to identify the US and membrane configurations that maximize gas exchange withinclinically relevant HFM. We will constrain US parameters to avoid blood damage. We will progress toward thisobjective through the following specific aims. Aim 1) Determine the specific ultrasound parameters (amplitude,frequency, duty cycle, pulse duration, and transducer geometry) that separately optimize bulk streaming andmicrostreaming, while avoiding hemolysis, inertial cavitation, excessive heating, and bubble generation. Aim 2)Determine the maximal fiber bundle thickness over which acoustic streaming and microstreaming are effective.Aim 3) Fabricate and evaluate a custom ultrasound delivery system that safely enhances oxygen transport byat least seven-fold. Successful results will not only show the potential of US-ECMO but will provide thenecessary design guidelines to drive the development of a clinically viable US-ECMO 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 blood oxygenation system that uses ultrasound to dramatically improve the efficiency of ECMO such that less anticoagulation is required, reducing the incidence of both thrombosis and hemorrhage and thereby improving safety and patient outcomes, as well as making the device smaller and offering the potential for ambulatory ECMO.
Project Terms: absorption ; Acoustics ; Acoustic ; Adult ; 21+ years old ; Adult Human ; adulthood ; Animals ; Anticoagulants ; Anticoagulant Agents ; Anticoagulant Drugs ; blood thinner ; thrombopoiesis inhibitor ; Anticoagulation ; Automobile Driving ; driving ; Biocompatible Materials ; Biomaterials ; biological material ; Blood ; Blood Reticuloendothelial System ; Blood coagulation ; Blood Clotting ; Blood Platelets ; Marrow platelet ; Platelets ; Thrombocytes ; Capital ; Diffusion ; Disease ; Disorder ; Extracorporeal Membrane Oxygenation ; Gases ; Heating ; Hemolysis ; erythrolysis ; Hemorrhage ; Bleeding ; blood loss ; Heparin ; Heparinic Acid ; Recording of previous events ; History ; Incidence ; Lung ; Lung Respiratory System ; pulmonary ; mortality ; Oxygen ; O element ; O2 element ; Oxygenators ; Patients ; PF4 Gene ; Antiheparin Factor ; Blood Platelet Factor IV ; Blood platelet factor 4 ; Chemokine (C-X-C motif) Ligand 4 ; Factor 4 ; Heparin Neutralizing Protein ; Platelet Factor 4 ; Recombinant Platelet Factor 4 ; SCYB4 ; Small Inducible Cytokine B4 ; Small Inducible Cytokine Subfamily B, Member 4 ; gamma-Thromboglobulin ; platelet factor IV ; Polypropylenes ; Propene Polymers ; Propylene Polymers ; Proteins ; Pulmonary Embolism ; Quality of life ; QOL ; Registries ; Risk ; Safety ; Science ; Sonication ; Thrombosis ; thrombotic disease ; thrombotic disorder ; Transducers ; Travel ; Ultrasonography ; Echography ; Echotomography ; Medical Ultrasound ; Ultrasonic Imaging ; Ultrasonogram ; Ultrasound Diagnosis ; Ultrasound Medical Imaging ; Ultrasound Test ; diagnostic ultrasound ; sonogram ; sonography ; sound measurement ; ultrasound ; ultrasound imaging ; ultrasound scanning ; Venous Thrombosis ; Phlebothrombosis ; Work ; Generations ; Entrepreneurship ; Entrepreneurial Skill ; Deep Vein Thrombosis ; Deep-Venous Thrombosis ; Blood gas ; Intracranial Hemorrhages ; Custom ; Guidelines ; Injury ; injuries ; improved ; Area ; Surface ; Clinical ; Phase ; Medical ; Meniscus structure of joint ; Meniscus ; Fiber ; Childhood ; pediatric ; pulmonary function ; lung function ; heart function ; cardiac function ; function of the heart ; Funding ; Therapeutic ; Deposit ; Deposition ; Pulse ; Physiologic pulse ; Frequencies ; Stream ; System ; membrane structure ; Membrane ; oxygen transport ; success ; novel ; Devices ; Reporting ; Position ; Positioning Attribute ; Thickness ; Thick ; Clotting ; Coagulation ; Coagulation Process ; Artificial Heart Ventricle ; Artificial Ventricles ; Ventricle-Assist Device ; ventricular assist device ; International ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Process ; Development ; developmental ; neonate ; Advanced Development ; design ; designing ; Consumption ; clinically relevant ; clinical relevance ; Geometry ; Nanoporous ; blood damage ; safety outcomes ;
