Label-free screening of sickle cell disease patients based on their red blood cell stiffness.

Saurabh kaushik

Understanding the morphological and mechanical parameters of red blood cells are important for diagnostic and treatment methods in various hematological diseases. Sickle Cell Disease (SCD) is one of many such hematological genetic diseases that is caused by point mutation of the Hemoglobin β-globin (HBB) gene. The mutated hemoglobin (HbS) has propensity to aggregate inside the red blood cells, making them rigid and sickle-shaped. The stiffened RBCs have been in general reported to block the blood flow and break apart, causing chronic anemia, episodes of pain, and multiple organ damage. High-Performance Liquid Chromatography (HPLC) is the most widely used technique for the screening of the hemoglobin variants present in the RBCs. For disease management, a population-wide screening of SCD using HPLC is neither economical nor logistically possible. In this work, we present a label-free, cost-effective, high-throughput electro-fluidic technique to study changes in the mechanical and morphological characteristics of red blood cells. We apply our device to characterize the mechanical properties of RBCs as a function of RBC cell volume, storage time & temperature, as well as dependence on the stiffness altering drug (Latrunculin-A). Further, we demonstrate the on-site application of our system by screening SCD patients. Identification was based on their RBC stiffness changes and a possible correlation with the patient’s HbS content. Our measurements open the possibility for the whole cell stiffness to be used as a preliminary screening parameter for many haematological conditions and show promise of applications in other areas such as tumor cell identification, veterinary sciences as well as hydrogel technologies.