A NOVEL ULTRAFAST LASER TECHNIQUE FOR PATHOGEN INACTIVATION

描述(申请人提供)：病原体减少(PR)是确保血液供应安全的理想先发制人措施。然而，目前可用的PR技术存在临床副作用的担忧，限制了它们在美国的使用。理想的PR技术应该能够在不引入化学或生物制剂的情况下有效地杀灭各种病原体，同时保留血液产品的功能。在这一点上，超快激光代表了一种很有前途的无化学物质的新型PR技术。建议研究的目的是建立一种超快激光PR技术，用于治疗 并确定超快激光杀死病原体的物理和分子机制。拟议研究的长期目标是开发一种适用于血浆、血小板和红细胞的超快激光PR系统，以便在全球范围内提供安全的输血。该项目的具体目标是：(1)演示超快激光灭活 西尼罗河病毒(WNV)，一种模型输血传播病原体；(2)确定超快激光诱导病原体灭活的物理和分子基础；(3)在输血小鼠模型中确定西尼罗河病毒灭活的效果。该项目完成后，我们预计将在开发一种新的超快激光等离子体PR技术方面取得重大进展，该技术可用于临床环境。我们预计在未来的研究中，这项技术将很快转化为血小板、红细胞和全血的PR。这项技术还将特别有益于军事用途，例如用于现场紧急输血，以及世界各地筛查和检测尚未建立良好基础的低资源地区。据我们所知，这是超快激光在输血医学领域的首次应用，代表了激光在医学上的新应用。对这种激光PR技术的继续探索预计将产生更多的应用，包括药品、医疗设备、手术伤口和手术器械的消毒，以及打击生物恐怖威胁。

DESCRIPTION (provided by applicant): Pathogen reduction (PR) represents the ideal preemptive measure to ensure the safety of the blood supply. However, currently available PR technologies have concerns of clinical side effects, limiting their use in the United States. The ideal PR technology should be able to effectively kill a wide variety of pathogens without introducing chemical or biological agents, while retaining the function of the blood products. In this regard, ultrafast lasers represent a promising new chemical-free PR technology. The objective of the proposed studies is to establish an ultrafast laser PR technology for treatment of human plasma, and to determine the physical and molecular mechanisms by which ultrafast lasers kill pathogens. The long-term goal of the proposed studies is to develop an ultrafast laser PR system applicable to plasma, platelets and red blood cells to provide safe transfusion worldwide. The specific aims of the project are: (1) To demonstrate ultrafast laser inactivation of West Nile virus (WNV), a model transfusion-transmitted pathogen; (2) To determine the physical and molecular basis of ultrafast laser-induced inactivation of pathogens; and (3) To determine efficacy of WNV inactivation in a mouse model of plasma transfusion. At the completion of the project, we expect to have made significant progress in the development of a new ultrafast laser technology for PR of plasma, amenable to use in a clinical setting. We anticipate translation of this technology soon to PR of platelets, RBCs, and whole blood in future studies. This technology will also be especially beneficial in military use, such as for emergency transfusions in the field, and low resource areas worldwide where screening and testing are not well established. To our knowledge, this is the first use of ultrafast lasers in the field of transfusio medicine and represents a new medical application for lasers. Continued exploration of this laser PR technology is expected to generate additional applications including sterilization of pharmaceuticals, medical devices, surgical wounds, and surgical instruments, and combating bioterror threats.