ACOUSTOPHORETIC TRANSFUSION TO REDUCE EMBOLIZATION IN CARDIOPULMONARY BYPASS

描述（由申请人提供）：在心肺转流术期间回输患者流出的血液是有吸引力的，因为它减少了对同种异体输血的需求，最大限度地降低了成本，并降低了输血相关的发病率。异体输血与心脏手术后长期死亡率增加有关。然而，心脏手术后的脑损伤伴失血回输是发病的重要原因，包括术后、短期和长期认知功能障碍和死亡率。与卒中有显著相关性的术前和术后因素包括糖尿病、高血压和近期心肌梗死。有充分证据表明，这些因素在少数群体中更为普遍。有证据表明，与流出血回输相关的脂质微栓塞是神经认知障碍的主要原因。从流出的血液中去除脂质的传统技术包括细胞处理器的筛选和离心，这两种技术都是几十年前的技术，具有显著的缺点。过滤器堵塞，效率低下，并受到吞吐量限制。冷冻也不能有效地去除脂质，去除有益的血液成分，如血小板和凝血因子，并且仅将浓缩的红细胞（RBC）循环到患者体内。清除也是耗时的，可引起RBC的碎片化，并可能导致凝血和其他炎症级联反应的激活。需要一种新的技术，可以更有效地去除脂质，浓缩RBC而不溶血，并连续运行。FloDesign Sonics正在开发一种新型的声泳过滤系统，该系统具有提供这些所需特性的潜力。与其他声泳分离系统不同，新的超声技术在宏观尺度上工作，因此能够处理比典型的微机电（MEMS）尺度声泳分离装置更大的流速。第一个原型研究的结果表明成功分离了RBC和脂质颗粒。该技术有可能去除几乎所有的脂质，提供健康的红细胞，并以大幅降低的设备成本连续运行。[Our所提出的装置将在所有心脏手术病例中取代细胞回收器，以保存全血元素，同时去除心脏手术期间积聚在胸腔内的危险颗粒物质和脂质颗粒 血液体积几乎没有稀释。我们的设备具有额外的成本优势，它不需要专门的技术人员来运行设备。FloDesign Sonics Inc.，来自西新英格兰大学的Rust博士和Kennedy博士、马萨诸塞州斯普林菲尔德的Bay State Medical Center的心脏外科医生Engelman博士、以及波士顿的哈佛医学院和Beth Israel Deaconess Medical Center的Zwicker博士建议设计并测试一种用于从血流中去除微脂质的声泳系统，其流速为2 L/hr，脂质去除超过80%，红细胞的回收率和浓缩率为80%。第二阶段的重点是系统优化，生物相容性，并在围手术期设置与动物模型的声泳装置的测试。对相关生理参数（如术后脑栓塞）进行测量，以量化新型系统提供的改善的手术结局。

DESCRIPTION (provided by applicant): Retransfusion of a patient's shed blood during cardiopulmonary bypass is attractive since it reduces the need for allogeneic transfusion, minimizes cost, and decreases transfusion related morbidity. Heterologous transfusions are linked to increased long term mortality after cardiac surgery. However, brain damage after cardiac surgery with retransfusion of shed blood is a significant cause of morbidity, including post-operative, short-term and long-term cognitive dysfunction, and mortality. Among the preoperative and postoperative factors that have a significant correlation with stroke are diabetes, hypertension, and recent myocardial infarction. It is well-documented that these factors are more prevalent in minorities. Evidence suggests that lipid microembolisms associated with the retransfusion of the shed blood are the predominant causes of the neurocognitive disorders. Traditional techniques to remove the lipids from the shed blood include screens and centrifugation by cell processors, both of which are decades old technologies with significant drawbacks. Filters clog, are inefficient, and suffer from throughput constraints. Centrifugation is also not efficient at removal of the lipids, removes beneficial bloo components such as platelets and clotting factors, and circulates only the concentrated red blood cells (RBCs) to the patient. Centrifugation is also time-consuming, can cause fragmentation of RBCs, and may lead to activation of clotting and other inflammatory cascades. A new technology is needed that is more efficient at removal of the lipids, concentrates the RBCs without hemolysis, and operates continuously. FloDesign Sonics is developing a novel acoustophoretic filtration system with the potential to deliver these desired characteristics. Unlike other acoustophoretic separation systems, the novel ultrasound technology works at the macroscale, and is therefore able to process larger flow rates than typical microelectromechanical (MEMS) scale acoustophoretic separation devices. Results from a first prototype study indicate successful separation of RBCs and lipid particles. The technology has the potential to remove nearly all of the lipids, provide healthy RBCs, and operate continuously at a substantially reduced device cost. [Our proposed device would replace the cell saver in all cardiac surgical cases to preserve the whole blood elements while removing the dangerous particulate matter and lipid particles that accumulate within the chest cavity during heart surgery with little to no dilution of blood volume. Our device has the additional cost benefit that it woul not require a dedicated technician to run the device.] FloDesign Sonics Inc., Dr. Rust and Dr. Kennedy from Western New England University, Dr. Engelman, MD, Cardiac Surgeon at Bay State Medical Center in Springfield, Massachusetts, and Dr. Zwicker, MD, Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, propose to design and test an acoustophoretic system for removal of micro-lipids from a blood stream with a flow rate of 2 L/hr, lipid removal in excess of 80%, and recovery and concentration of 80% of RBCs. Phase II focuses on system optimization, biocompatibility, and testing of the acoustophoretic device in a perioperative setting with an animal model. Measurements of relevant physiological parameters such as cerebral embolization post-surgery are performed to quantify the improved surgical outcomes provided by the novel system.