A Novel Bioimpedance Sensor for Intracellular Hemoglobin Analysis in Single Sickle Cells

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Sickle cell disease is an inherited red blood cell disorder that affects hemoglobin, the oxygen-carrying protein inside the red blood cells. Sickle hemoglobin is the fundamental cause of abnormalities in sickle cell shape, deformability and blood flow behavior, leading to various symptoms and complications. Variabilities in complications and disease severity are expected over time. A major challenge in understanding the extreme heterogeneities of sickle cell disease is the inability to measure the sickle hemoglobin within the single sickle cells. This research aims to overcome this challenge by developing a microfabricated sensor that can measure the amount of abnormal sickle hemoglobin without breaking down cell membranes. This interdisciplinary project provides research training to women and underrepresented minority students, in biosensing, cell biophysics, microfabrication, and microfluidics. The research findings and technological development are incorporated into course development and disseminated to students at undergraduate and graduate levels. Sickle cell disease is known for its extreme heterogeneities in cell morphology, deformability, hemorheology, and severity of clinical symptoms and complications, which are linked to the intracellular hemoglobin variations. This project develops a microfluidics-based single-cell assay of intracellular sickle hemoglobin, using a sequential bioimpedance sensing of sickle cells under controlled oxygen levels in a microflow cytometry setting. Integration of hypoxic microenvironment with impedance sensing allows selective measurement of intracellular sickle hemoglobin variant from the induced cell sickling process in single cells. Three research objectives include: (i) establishment of a bioimpedance analysis of hemoglobin solution; (ii) design and development of a sequential impedance sensing of sickle cells under low and high oxygen levels; (iii) modeling of single cell bioimpedance and method validation for characterization of cell volume, membrane and intracellular hemoglobin composition from the multi-frequency impedance signal of single sickle cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.