Microfluidic Technology for Concurrent Assessment of Red Blood Cell Adhesion and Deformability

用于同时评估红细胞粘附和变形能力的微流控技术

• 批准号: 10811328
• 负责人: Chiara Federici
• 金额: $ 86.54万
• 依托单位: BIOCHIP LABS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10811328
• 关键词: Microfluidic; Technology; Concurrent; Assessment; Red

PROJECT SUMMARY Deformability and non-adherence are the most intrinsic biorheological properties of red blood cells (RBCs), as they play a critical role in modulating RBC perfusion through the microvasculature. In acquired or inherited blood disorders, such as sickle cell disease (SCD), these two interrelated properties are pathologically altered. SCD is an autosomal recessive disorder associated with considerable morbidity and mortality in its afflicted populations. In SCD, RBCs undergo radical morphological and structural transformations leading to decreased deformability and increased adhesiveness, which further trigger vascular complications and a number of co-morbidities including painful crises, stroke, acute chest syndrome, and organ failure. OcclusionChip is a novel standardized in vitro microfluidic assay to measure microvascular occlusion mediated by RBCs in a wide range of clinical conditions. The unique design embodies the two key features of the capillary bed: a gradient of microcapillary networks and side passageways mimicking the arteriovenous anastomoses. Occlusion Index, measured by the OcclusionChip assay, may serve as a new standard parameter to evaluate the clinical efficacy of treatments improving red blood cell adhesion and deformability, such as hemoglobin modifying drugs, anti-sickling agents, and emerging genetic therapies. The objective of this STTR Phase I/II Fast-Track project is to translate and commercialize novel OcclusionChip microfluidic technology as a standardized and validated companion diagnostic assay for SCD. In Phase I, we propose to streamline the manufacturing process with a third-party manufacturer and establish quality control strategy. In Phase II, we propose to contract manufacture a large number of devices (1000), establish analytical validation and clinical validation relative to conventional, targeted, or curative therapies in SCD. Our goal is to establish the manufacturability, analytical validation, and clinical utility of the OcclusionChip in providing comprehensive functional characterization of red cell biorheological properties and assessment of patient-specific response to emerging targeted and curative therapies in SCD.

项目摘要 可变形性和不遵守性是红细胞（RBC）的最内在的生物学特性，如 它们在通过微脉管系统调节RBC灌注方面起着关键作用。在获得或遗传的血液中 疾病，例如镰状细胞疾病（SCD），这两个相互关联的特性在病理上改变了。 SCD是 与其患病人群中相当大的发病率和死亡率相关的常染色体隐性疾病。 在SCD中，RBC经历了根本的形态和结构变换，导致可变形性降低 并提高了粘附性，这进一步引发了血管并发症和多种合并症 包括痛苦的危机，中风，急性胸部综合征和器官衰竭。 Occlusechip是一种新颖的标准化 体外微流体分析，以测量由RBC在广泛的临床条件下介导的微血管闭塞。 独特的设计体现了毛细管床的两个关键特征：微毛细管网络的梯度和侧面 通道模仿动静脉吻合。闭塞指数，通过咬合法测定法测量， 可以用作评估改善红细胞治疗的临床疗效的新标准参数 粘附和可变形性，例如修饰药物，抗溶剂和新兴遗传 疗法。这个STTR I/II阶段快速轨道项目的目的是翻译和商业化小说 Occlusionchip微流体技术作为SCD的标准化和经过验证的伴侣诊断测定。 在第一阶段，我们建议与第三方制造商简化制造过程并建立 质量控制策略。 在第二阶段，我们建议合同制造大量设备（1000），建立分析验证 相对于SCD中的常规，靶向或治疗疗法的临床验证。 我们的目标是建立闭塞性的制造性，分析验证和临床实用性 提供红细胞生物学特性的全面功能表征和评估 SCD中对新兴靶向和治疗疗法的患者特定反应。