Manufacturing and Analytical Validation of the Microfluidic Impedance Red Cell Assay (MIRCA) for Commercial Viability

PROJECT SUMMARY Sickle cell disease (SCD) is an autosomal recessive disorder that significantly contributes to morbidity and mortality among affected populations. In individuals with SCD, red blood cells (RBCs) undergo drastic morphological and structural changes. These alterations lead to decreased deformability, increased adhesiveness, and altered viscosity, which in turn can trigger vascular complications and various co-morbidities, including painful crises, stroke, acute chest syndrome, and organ failure. Despite being known for more than a century, curative therapies for SCD remain limited. Recently, there has been a growing effort to develop pharmaceutical agents targeting the abnormal properties of RBCs. Some new drugs have recently become commercially available for a limited patient population, including novel pharmacologic and gene-based therapies. Conventional clinical laboratory tests do not suffice to measure the efficacy of these new drugs. Therefore, there is a high demand and unmet need for new devices capable of testing RBC functionality and health. We recently developed a new in vitro diagnostic technology to measure cellular obstruction in microcapillary networks due to abnormal RBC deformability through electrical impedance readouts. The Microfluidic Impedance Red Cell Assay (MIRCA), which features embedded microcapillary network-based micropillar arrays and integrated electrodes for electrical impedance measurement, may provide a promising solution in SCD. To clinically utilize the MIRCA technology, it is necessary to scale up the manufacturing of the microfluidic biochip component with appropriate specifications and tight tolerances under regulated manufacturing quality controls. It is also required to complete all the validation steps necessary to ensure a robust, precise, and reproducible system. This STTR Phase I/II Fast-Track project aims to manufacture MIRCA biochips, which will allow us to complete the analytical validation of the device for commercial viability and lay the groundwork for the application for FDA approval. STTR PHASE I SPECIFIC AIM AND MILESTONE. Aim 1: Manufacture alpha-prototype MIRCA biochips: We will finalize the design and product requirements for the commercial manufacturing of the MIRCA biochips. The alpha-prototype with integrated electrodes will be produced and tested. STTR PHASE II SPECIFIC AIMS AND MILESTONES. Aim 2: Manufacture beta-prototype MIRCA biochips: The manufactured beta-prototype will be tested and validated. Release and acceptance criteria will be established for further production. Aim 3: Outline the design of the MIRCA Reader as a standalone device. The initial design of an alpha-prototype as a standalone device of the MIRCA Reader will be completed. Our goal is to establish the commercial manufacturability of MIRCA, which will allow us to complete the analytical validation, determine the robustness, precision, and reproducibility of the device for commercial viability, and lay the groundwork for a future application for FDA approval.