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

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.PROJECT NARRATIVE 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. OcclusionChip is a novel standardized in vitro microfluidic assay to measure microvascular occlusion mediated by red blood cells in a wide range of clinical conditions. The goal of this project 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 sickle cell disease.