Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia
Sickle cell disorder (SCD) is a multisystem disease with heterogeneous phenotypes. Although all patients have the mutated hemoglobin (Hb) in the SS phenotype, the severity and frequency of complications are variable. When exposed to low oxygen tension, the Hb molecule becomes dense and forms tactoid...
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MDPI AG
2022-04-01
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author | Marcus Inyama Asuquo Emmanuel Effa Oluwabukola Gbotosho Akaninyene Otu Nicole Toepfner Soter Ameh Sruti-Prathivadhi Bhayankaram Noah Zetocha Chisom Nwakama William Egbe Jochen Guck Andrew Ekpenyong |
author_facet | Marcus Inyama Asuquo Emmanuel Effa Oluwabukola Gbotosho Akaninyene Otu Nicole Toepfner Soter Ameh Sruti-Prathivadhi Bhayankaram Noah Zetocha Chisom Nwakama William Egbe Jochen Guck Andrew Ekpenyong |
author_sort | Marcus Inyama Asuquo |
collection | DOAJ |
description | Sickle cell disorder (SCD) is a multisystem disease with heterogeneous phenotypes. Although all patients have the mutated hemoglobin (Hb) in the SS phenotype, the severity and frequency of complications are variable. When exposed to low oxygen tension, the Hb molecule becomes dense and forms tactoids, which lead to the peculiar sickled shapes of the affected red blood cells, giving the disorder its name. This sickle cell morphology is responsible for the profound and widespread pathologies associated with this disorder, such as vaso-occlusive crisis (VOC). How much of the clinical manifestation is due to sickled erythrocytes and what is due to the relative contributions of other elements in the blood, especially in the microcapillary circulation, is usually not visualized and quantified for each patient during clinical management. Here, we used a microfluidic microcirculation mimetic (MMM), which has 187 capillary-like constrictions, to impose deformations on erythrocytes of 25 SCD patients, visualizing and characterizing the morpho-rheological properties of the cells in normoxic, hypoxic (using sodium meta-bisulfite) and treatment conditions (using hydroxyurea). The MMM enabled a patient-specific quantification of shape descriptors (circularity and roundness) and transit time through the capillary constrictions, which are readouts for morpho-rheological properties implicated in VOC. Transit times varied significantly (<i>p</i> < 0.001) between patients. Our results demonstrate the feasibility of microfluidics-based monitoring of individual patients for personalized care in the context of SCD complications such as VOC, even in resource-constrained settings. |
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spelling | doaj.art-09c8d48495fd41ad8d4a84156d0b538d2023-11-23T07:48:25ZengMDPI AGApplied Sciences2076-34172022-04-01129439410.3390/app12094394Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell AnemiaMarcus Inyama Asuquo0Emmanuel Effa1Oluwabukola Gbotosho2Akaninyene Otu3Nicole Toepfner4Soter Ameh5Sruti-Prathivadhi Bhayankaram6Noah Zetocha7Chisom Nwakama8William Egbe9Jochen Guck10Andrew Ekpenyong11Department of Hematology, Faculty of Medicine and Dentistry, University of Calabar, Calabar 540001, NigeriaDepartment of Medicine, Faculty of Medicine and Dentistry, University of Calabar, Calabar 540001, NigeriaVascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Medicine, Faculty of Medicine and Dentistry, University of Calabar, Calabar 540001, NigeriaDepartment of Pediatric Hemato-Oncology, Carl Gustav Carus University Hospital, Technische Universität Dresden, 01307 Dresden, GermanyBiostatistics Unit, Department of Community Medicine, University of Calabar, Calabar 540001, NigeriaDepartment of Physics, Creighton University, Omaha, NE 68178, USADepartment of Physics, Creighton University, Omaha, NE 68178, USADepartment of Physics, Creighton University, Omaha, NE 68178, USAJoseph Ukpo Hospitals and Research Institutes (JUHRI), Afua Site, Ibiono Ibom 520115, NigeriaBiotechnology Centre, Technische Universität Dresden, 01307 Dresden, GermanyDepartment of Physics, Creighton University, Omaha, NE 68178, USASickle cell disorder (SCD) is a multisystem disease with heterogeneous phenotypes. Although all patients have the mutated hemoglobin (Hb) in the SS phenotype, the severity and frequency of complications are variable. When exposed to low oxygen tension, the Hb molecule becomes dense and forms tactoids, which lead to the peculiar sickled shapes of the affected red blood cells, giving the disorder its name. This sickle cell morphology is responsible for the profound and widespread pathologies associated with this disorder, such as vaso-occlusive crisis (VOC). How much of the clinical manifestation is due to sickled erythrocytes and what is due to the relative contributions of other elements in the blood, especially in the microcapillary circulation, is usually not visualized and quantified for each patient during clinical management. Here, we used a microfluidic microcirculation mimetic (MMM), which has 187 capillary-like constrictions, to impose deformations on erythrocytes of 25 SCD patients, visualizing and characterizing the morpho-rheological properties of the cells in normoxic, hypoxic (using sodium meta-bisulfite) and treatment conditions (using hydroxyurea). The MMM enabled a patient-specific quantification of shape descriptors (circularity and roundness) and transit time through the capillary constrictions, which are readouts for morpho-rheological properties implicated in VOC. Transit times varied significantly (<i>p</i> < 0.001) between patients. Our results demonstrate the feasibility of microfluidics-based monitoring of individual patients for personalized care in the context of SCD complications such as VOC, even in resource-constrained settings.https://www.mdpi.com/2076-3417/12/9/4394sickle cell disordervaso-occlusive crisishydroxyureamicrocirculationmicrofluidicspersonalized medicine |
spellingShingle | Marcus Inyama Asuquo Emmanuel Effa Oluwabukola Gbotosho Akaninyene Otu Nicole Toepfner Soter Ameh Sruti-Prathivadhi Bhayankaram Noah Zetocha Chisom Nwakama William Egbe Jochen Guck Andrew Ekpenyong Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia Applied Sciences sickle cell disorder vaso-occlusive crisis hydroxyurea microcirculation microfluidics personalized medicine |
title | Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia |
title_full | Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia |
title_fullStr | Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia |
title_full_unstemmed | Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia |
title_short | Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia |
title_sort | microfluidic microcirculation mimetic as a tool for the study of rheological characteristics of red blood cells in patients with sickle cell anemia |
topic | sickle cell disorder vaso-occlusive crisis hydroxyurea microcirculation microfluidics personalized medicine |
url | https://www.mdpi.com/2076-3417/12/9/4394 |
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