RAPID: Hierarchical Carbon Adsorbent for Cytokines Removal from Blood of the Ebola Virus Disease Patients

RAPID：用于去除埃博拉病毒病患者血液中细胞因子的分级碳吸附剂

• 批准号: 1518999
• 负责人: Vadym Mochalin
• 金额: $ 10万
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1518999&HistoricalAwards=false
• 关键词: RAPID; Hierarchical; Carbon; Adsorbent; Cytokines

PI: Mochalin, VadymProposal Number: 1518999The devastating effects of the Ebola virus in humans are largely related to overproduction of pro-inflammatory proteins, called cytokines, which are responsible for fatal clinical symptoms of the Ebola disease: inflammation, fever, massive internal hemorrhage, and catastrophic thrombosis around the body. Quick removal of pro-inflammatory cytokines from blood by adsorption is essential to mitigate these severe clinical symptoms while the immune system prepares to eliminate the virus. The adsorption of cytokines is complicated by their large variations in molecular size and shape, some being small and elongated, others large and more globular, so when a mix of these molecules is present, larger molecules quickly stick to the outer surface of the adsorbent blocking access to the smaller pores for smaller molecules, significantly reducing available surface. The solution is to create adsorbents with hierarchical pore structure, containing large and small pores which fit all possible sizes and shapes of cytokines. These hierarchical carbon adsorbents will be synthesized from polymer precursors and optimized for specific, quick, and complete removal of cytokines from blood of the Ebola virus disease patients. The proposed research will allow the development of a range of carbon materials featuring precisely controlled pore size, pore volume, pore shape, surface area, and surface chemistry. The developed materials will find broader applications in biotechnology, bioengineering, medicine, water purification, and cosmetics. Medical applications of selective protein adsorption, including removal of wastes or toxins from blood of patients with kidney disease or liver failure, may particularly benefit from this research. This award is being made jointly by two Programs: (1) Chemical and Biological Separations, (2) Biomedical Engineering, both in the Chemical, Bioengineering, Environmental and Transport Systems Division in the Engineering Directorate.The proposed research is focused on investigation of the effects of pore size, shape, and surface termination in hierarchical mesoporous carbons on adsorption and intraporous diffusion of cytokines. Based on this knowledge, hierarchical porous carbon adsorbents will be synthesized and tailored for quick removal of a mix of cytokines specific for the Ebola virus disease. The performance of the developed hierarchical carbon adsorbents will be demonstrated on blood plasma samples spiked with cytokine cocktails in compositions and concentrations typical for those in patients with the Ebola virus disease. The adsorbents will be synthesized from silicon containing polymer-derived ceramics with subsequent removal of silicon by high temperature chlorination. This process allows for full control of pore size and shape through variations of precursor composition, chlorination temperature and time, and has been demonstrated to produce hierarchical porosity with subnanometer control of the pore size. Adsorption of cytokines from blood plasma will then be measured by the enzyme-linked immunosorbent assay. To increase their affinity to cytokines, surface chemistry of the synthesized adsorbents will be modified by oxidation in air or carbon dioxide, reduction in hydrogen, and treatment in ammonia gas. At the end of the experimental program, mesoporous carbon adsorbents with a hierarchical pore structure and large particle size will be developed for quick and complete removal of cytokines from blood of the Ebola virus disease patients by extracorporeal perfusion. The proposed treatments will reduce mortality, accelerate recovery and, when used in conjunction with emerging methods and supporting care, will minimize long-term damage to the patient.

PI: Mochalin, VadymProposal Number: 1518999The devastating effects of the Ebola virus in humans are largely related to overproduction of pro-inflammatory proteins, called cytokines, which are responsible for fatal clinical symptoms of the Ebola disease: inflammation, fever, massive internal hemorrhage, and catastrophic thrombosis around the body.通过吸附从血液中快速去除促炎性细胞因子对于减轻这些严重的临床症状至关重要，而免疫系统准备消除病毒。细胞因子在分子大小和形状方面的较大变化使细胞因子的吸附变得复杂，有些变化很小且细长，有些较大，更球形，因此，当存在这些分子的混合物时，较大的分子很快就会迅速粘贴在较小的孔中，可用于较小的分子的较小孔的外表面，显着可用的表面。解决方案是创建具有分层孔结构的吸附剂，其中包含适合所有可能的细胞因子大小和形状的大孔。这些分层碳吸附剂将从聚合物前体合成，并优化，以特异性，快速和完全清除埃博拉病毒疾病患者血液中细胞因子的去除。拟议的研究将允许开发一系列具有精确控制的孔径，孔体积，孔形，表面积和表面化学的碳材料。开发的材料将在生物技术，生物工程，医学，水纯化和化妆品中找到更广泛的应用。选择性蛋白吸附的医学应用，包括从肾脏疾病或肝衰竭患者血液中清除废物或毒素，可能会从这项研究中受益。 This award is being made jointly by two Programs: (1) Chemical and Biological Separations, (2) Biomedical Engineering, both in the Chemical, Bioengineering, Environmental and Transport Systems Division in the Engineering Directorate.The proposed research is focused on investigation of the effects of pore size, shape, and surface termination in hierarchical mesoporous carbons on adsorption and intraporous diffusion of cytokines.基于这些知识，将合成和量身定制分层多孔碳吸附剂，以快速去除特定于埃博拉病毒疾病的细胞因子混合物。发达的分层碳吸附剂的性能将在血浆样品上呈现在埃博拉病毒疾病患者中的成分和浓度中的细胞因子鸡尾酒和浓度。这些吸附剂将从含有聚合物衍生的陶瓷的硅中合成，随后通过高温氯化去除硅。该过程可以通过前体组成，氯化温度和时间的变化来完全控制孔径和形状，并已证明可以产生分层孔隙率，并控制孔径的次纳米。然后，将通过酶联免疫吸附测定法测量血浆中细胞因子的吸附。为了增加其对细胞因子的亲和力，合成吸附剂的表面化学将通过空气或二氧化碳的氧化，氢的减少以及氨气的处理来改变。在实验计划结束时，将开发具有分层孔结构和较大粒径的介孔碳吸附剂，以通过体外灌注从埃博拉病毒疾病患者的血液中快速并完全清除细胞因子。拟议的治疗方法将降低死亡率，加速恢复，并结合新兴方法并支持护理时，将最大程度地减少对患者的长期损害。