Clinical Microfluidic Assessment of Red Blood Cell Adhesion, Deformability, Cellular Hemoglobin Distribution, Cellular Density, and Blood Rheology for Curative Therapies in Sickle Cell Disease

镰状细胞病治疗中红细胞粘附、变形能力、细胞血红蛋白分布、细胞密度和血液流变学的临床微流体评估

• 批准号: 10329080
• 负责人: Umut A. Gurkan
• 金额: $ 2.97万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10329080
• 关键词: Acute Pain; Address; Adult; Area; Award; Biological Assay; Biological Markers; Biomechanics; Cell Adhesion; Cells; Clinical; Erythrocytes; Flow Cytometry; Gamunex; Hemoglobin; Image; Individual; Intravenous; Leukocytes; Measures; Microfluidics; Monitor; National Heart, Lung, and Blood Institute; Phenotype; Publishing; Research Activity; Rheology; Sickle Cell; Sickle Cell Anemia; Sickle Hemoglobin; Standardization; Technology; Validation; Whole Blood; advanced analytics; assay development; blood rheology; candidate marker; clinical care; curative treatments; density; fetal; improved; novel; phase II trial; response; sickling

PROJECT SUMMARY In this proposal we build on our relevant published work1-14, and ongoing research activities supported by an active NHLBI R01 (R01HL133574, PI: Gurkan, Little), titled: “Standardized Monitoring of Cellular Adhesion to Improve Clinical Care in Sickle Cell Disease”, an active FDA R01 (R01FD005341, PI: Manwani), titled: “Phase 2 Trial of Gamunex (Intravenous Gammaglobulin) for Sickle Cell Acute Pain”, and an active NSF Award (1552782, PI Gurkan): “CAREER: Biomechanics of Red Blood Cell Adhesion and Deformability”. We have developed red blood cell (RBC) and white blood cell (WBC) biomarker assays for more robust phenotypic analyses in sickle cell disease (SCD)1-14, supported by an NHLBI R01 (R01HL133574) and an FDA R01 (R01FD005341) award, as described above. In this project we build on our expertise in novel SCD biomarker assay development to uniquely address the following high priority areas identified in OTA- 19-007 for Cure Sickle Cell Initiative: (1) Develop and validate assays to quantitatively determine cellular distribution and semi-quantitative cellular expression of fetal, adult and/or sickle hemoglobin. (2) Develop and validate assays to assess red blood cell rheology, including microfluidics and imaging flow cytometry sickling assays. In this project we propose advanced analytical and clinical validation of integrated clinical microfluidic assays to assess RBC adhesion, deformability, cellular hemoglobin distribution, cellular density (as mass to volume ratio for each individual cell), and whole blood rheology as candidate biomarkers to assess response to curative therapies in SCD.

项目总结 在本提案中，我们建立在已发表的相关工作1-14的基础上，以及由 一个活动的NHLBI R01(R01HL133574，PI：Gurkan，Little)，标题为 黏附改善镰状细胞疾病的临床护理“，活性FDA R01(R01FD005341，PI： Manwani)，标题为“Gamunex(静脉丙种球蛋白)治疗镰状细胞急性疼痛的第二阶段试验”， 和一个活跃的国家科学基金会奖(1552782，皮古尔坎)：“职业生涯：红细胞黏附的生物力学 和变形性“。 我们已经开发了红细胞(RBC)和白细胞(WBC)生物标记物分析，以实现更可靠的检测 由NHLBI R01(R01HL133574)和AN支持的镰状细胞病(SCD)1-14的表型分析 FDA R01(R01FD005341)奖，如上所述。在这个项目中，我们以我们在小说方面的专业知识为基础 SCD生物标志物分析开发，以独特地解决以下在OTA中确定的高度优先领域- 19-007治愈镰状细胞倡议： (1)开发和验证定量确定细胞分布和半定量的分析方法 胎儿、成人和/或镰状血红蛋白的细胞表达。 (2)开发和验证评估红细胞流变学的分析方法，包括微流体和成像 流式细胞仪镰刀试验。 在这个项目中，我们提出了集成临床微流控技术的高级分析和临床验证 测定红细胞粘附性、变形性、细胞血红蛋白分布、细胞密度(AS 每个单个细胞的质量体积比)和全血流变学作为候选生物标志物 评估SCD患者对治疗的反应。