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.
Public Health Relevance Statement: 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.
Project Terms: Adhesiveness; Adhesives; Sickle Cell Anemia; Hb SS disease; HbSS disease; Hemoglobin S Disease; Hemoglobin sickle cell disease; Hemoglobin sickle cell disorder; sickle cell disease; sickle cell disorder; sickle disease; sicklemia; Antisickling Agents; Antisickling Drugs; Physiologic arteriovenous anastomosis; Arteriovenous Anastomosis; Arteriovenous Shunt; physiologic anastomosis; Biological Assay; Assay; Bioassay; Biologic Assays; Blood Cell Count; Blood Cell Number; Blood Vessels; vascular; Cell Adhesion; Cellular Adhesion; comorbidity; co-morbid; co-morbidity; Disease; Disorder; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Erythrocytes; Blood erythrocyte; Erythrocytic; Marrow erythrocyte; Red Blood Cells; Red Cell; blood corpuscles; Abnormal Red Blood Cell; Abnormal Erythrocytes; Food; Food or Food Product; gene therapy; DNA Therapy; Gene Transfer Clinical; Genetic Intervention; gene repair therapy; gene-based therapy; genetic therapy; genomic therapy; Goals; Hematological Disease; Blood Diseases; Hematologic Diseases; Hematological Disorder; blood disorder; Blood Tests; Hematologic Tests; Hematological Tests; Hematology Testing; Hemoglobin; In Vitro; indexing; Industrialization; Methods; Morbidity - disease rate; Morbidity; mortality; optical; Optics; Painful; Pain; Patents; Legal patent; Perfusion; Play; Publishing; Quality Control; social role; Role; Standardization; Apoplexy; Brain Vascular Accident; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Stroke; brain attack; cerebral vascular accident; cerebrovascular accident; Stroke; Testing; Translating; Measures; Mediating; Medical Care Costs; medical costs; Guidelines; base; human subject; Organ; Blood specimen; Blood Sample; improved; Procedures; Surface; Clinical; Phase; Individual; Dysfunction; Physiopathology; pathophysiology; Functional disorder; Morphology; Contracting Opportunities; Contracts; Hereditary; Inherited; Side; capillary bed; success; novel; Devices; acute chest syndrome; Property; Manufacturer Name; Manufacturer; Organ failure; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; µfluidic; Microfluidics; photonics; Microfluidic Device; Microfluidic Lab-On-A-Chip; microfluidic chip; Microfluidic Microchips; Small Business Technology Transfer Research; STTR; Validation; Pathologic; digital; design; designing; clinical efficacy; Treatment Efficacy; intervention efficacy; therapeutic efficacy; therapy efficacy; manufacturing process; Population; treatment response; response to therapy; response to treatment; therapeutic response; therapy response; conventional therapy; conventional treatment; drug candidate; targeted treatment; targeted drug therapy; targeted drug treatments; targeted therapeutic; targeted therapeutic agents; targeted therapy; diagnostic assay; companion diagnostics; targeted agent; curative treatments; curative intervention; curative therapeutic; curative therapy; microdevice; microfabricated device; Drug Screening; manufacturability; patient response; patient specific response; responsive patient; microfluidic technology; µfluidic technology; cost estimate; cost estimation
