Developing biophysical markers for anemic disorders through advancing interferometric microscopy

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.Cataloged from PDF version of thesis.Includes bibliographical references (pages 89-98).Erythrocytes, better known as red blood cells, among various functions, are mainly tasked with the oxygen transport in vertebrates through blood circulation. Red blood cells are packed with the hemoglobin, an oxygen-binding molecule, and have unique biophysical properties that are critical in enabling the oxygen delivery and optimization of the blood flow in large vessels and capillaries. These properties such as cellular deformability, biconcave shape, and proper hemoglobin function are compromised in a range of diseases known as anemic disorders. Quantifying these alterations provides a tool for studying pathobiology of these diseases and guides the search for the cure or novel treatments. Interferometric microscopy in various forms has been suggested as a tool for measuring some of these biophysical properties. However, current interferometric techniques suffer from one or a combination of the following shortcomings: (1) precision of the biophysical measurements is limited due to limits on the measurement sensitivity, (2) absence of a practical solution for clinical settings to conduct high-throughput and comprehensive biophysical measurements on a cellular basis, (3) ignoring cell-to-cell variability in molecular specific information such as cellular hemoglobin concertation in conventional interferometric measurements, In several steps, we have made advancements to the state-of-the-art technology in each of these areas. We have particularly shown the capabilities of our platforms in studying a genetic anemic disorder known as sickle cell disease (SCD). Through these studies and in collaboration with our clinical partners, we have investigated the treatment effects on SCD patients, and have introduced novel biomarkers relevant in quantifying the pathophysiology of the anemic disorders. These technology developments open new horizons in which interferometric microscopy serves as a powerful platform for studying anemic disorders and potentiallyby Poorya Hosseini.Ph. D