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

基本信息

批准号：
10384175
负责人：
Chiara Federici
金额：
$ 25.96万
依托单位：
BIOCHIP LABS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10384175
关键词：
Abnormal Red Blood Cell Adhesiveness Adhesives Antisickling Agents Biological Assay Blood Cell Count Blood Tests Blood Vessels Blood specimen Cell Adhesion Clinical Contracts Devices Disease Drug Screening Erythrocytes Food Functional disorder Goals Guidelines Hematological Disease Hemoglobin In Vitro Individual Industrialization Inherited Legal patent Manufacturer Name Measures Mediating Medical Care Costs Methods Microfluidic Microchips Microfluidics Morbidity - disease rate Morphology Optics Organ Organ failure Pain Pathologic Perfusion Pharmaceutical Preparations Pharmacologic Substance Phase Physiologic arteriovenous anastomosis Play Population Procedures Property Publishing Quality Control Role Sickle Cell Anemia Side Small Business Technology Transfer Research Standardization Stroke Surface Testing Translating Treatment Efficacy Validation acute chest syndrome base capillary bed clinical efficacy comorbidity companion diagnostics conventional therapy cost estimate curative treatments design diagnostic assay digital drug candidate gene therapy human subject improved indexing manufacturability manufacturing process microdevice microfluidic technology mortality novel patient response photonics success targeted agent targeted treatment treatment response

项目摘要

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.

项目概要可变形性和非粘附性是红细胞 (RBC) 最本质的生物流变特性，如它们在通过微血管调节红细胞灌注方面发挥着关键作用。在获得性或遗传性血液中疾病，例如镰状细胞病（SCD），这两种相互关联的特性发生了病理改变。 SCD 是一种常染色体隐性遗传病，其患病人群的发病率和死亡率很高。在 SCD 中，红细胞经历彻底的形态和结构转变，导致变形能力下降粘着性增加，进一步引发血管并发症和许多并发症包括痛苦危机、中风、急性胸部综合症和器官衰竭。 OcclusionChip 是一种新颖的标准化体外微流体测定，用于测量各种临床条件下红细胞介导的微血管闭塞。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 OcclusionChip 测定测量，可以作为新的标准参数来评估改善红细胞治疗的临床疗效粘附和变形，例如血红蛋白修饰药物、抗镰状化药物和新兴的遗传药物疗法。 STTR 第一/二期快速通道项目的目标是翻译小说并将其商业化 OcclusionChip 微流控技术作为 SCD 的标准化且经过验证的伴随诊断测定。在第一阶段，我们建议与第三方制造商一起简化制造流程，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），建立分析验证以及相对于 SCD 的常规、靶向或治疗疗法的临床验证。我们的目标是建立 OcclusionChip 的可制造性、分析验证和临床实用性提供红细胞生物流变特性的全面功能表征和评估患者对 SCD 新兴靶向治疗的特异性反应。