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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/12/9/4394
_version_ 1797505642548690944
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.
first_indexed 2024-03-10T04:21:32Z
format Article
id doaj.art-09c8d48495fd41ad8d4a84156d0b538d
institution Directory Open Access Journal
issn 2076-3417
language English
last_indexed 2024-03-10T04:21:32Z
publishDate 2022-04-01
publisher MDPI AG
record_format Article
series Applied Sciences
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
work_keys_str_mv AT marcusinyamaasuquo microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT emmanueleffa microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT oluwabukolagbotosho microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT akaninyeneotu microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT nicoletoepfner microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT soterameh microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT srutiprathivadhibhayankaram microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT noahzetocha microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT chisomnwakama microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT williamegbe microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT jochenguck microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia
AT andrewekpenyong microfluidicmicrocirculationmimeticasatoolforthestudyofrheologicalcharacteristicsofredbloodcellsinpatientswithsicklecellanemia