date: 2022-05-05T09:24:50Z pdf:unmappedUnicodeCharsPerPage: 0 pdf:PDFVersion: 1.7 pdf:docinfo:title: Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia xmp:CreatorTool: LaTeX with hyperref Keywords: sickle cell disorder; vaso-occlusive crisis; hydroxyurea; microcirculation; microfluidics; personalized medicine; deformation; transit time access_permission:modify_annotations: true access_permission:can_print_degraded: true subject: 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 (p < 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. dc:creator: Marcus Inyama Asuquo, Emmanuel Effa, Oluwabukola Gbotosho, Akaninyene Otu, Nicole Toepfner, Soter Ameh, Sruti-Prathivadhi Bhayankaram, Noah Zetocha, Chisom Nwakama, William Egbe, Jochen Guck and Andrew Ekpenyong dcterms:created: 2022-04-27T07:04:31Z Last-Modified: 2022-05-05T09:24:50Z dcterms:modified: 2022-05-05T09:24:50Z dc:format: application/pdf; version=1.7 title: Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia Last-Save-Date: 2022-05-05T09:24:50Z pdf:docinfo:creator_tool: LaTeX with hyperref access_permission:fill_in_form: true pdf:docinfo:keywords: sickle cell disorder; vaso-occlusive crisis; hydroxyurea; microcirculation; microfluidics; personalized medicine; deformation; transit time pdf:docinfo:modified: 2022-05-05T09:24:50Z meta:save-date: 2022-05-05T09:24:50Z pdf:encrypted: false dc:title: Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Blood Cells in Patients with Sickle Cell Anemia modified: 2022-05-05T09:24:50Z cp:subject: 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 (p < 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. pdf:docinfo:subject: 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 (p < 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. Content-Type: application/pdf pdf:docinfo:creator: Marcus Inyama Asuquo, Emmanuel Effa, Oluwabukola Gbotosho, Akaninyene Otu, Nicole Toepfner, Soter Ameh, Sruti-Prathivadhi Bhayankaram, Noah Zetocha, Chisom Nwakama, William Egbe, Jochen Guck and Andrew Ekpenyong X-Parsed-By: org.apache.tika.parser.DefaultParser creator: Marcus Inyama Asuquo, Emmanuel Effa, Oluwabukola Gbotosho, Akaninyene Otu, Nicole Toepfner, Soter Ameh, Sruti-Prathivadhi Bhayankaram, Noah Zetocha, Chisom Nwakama, William Egbe, Jochen Guck and Andrew Ekpenyong meta: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 and Andrew Ekpenyong dc:subject: sickle cell disorder; vaso-occlusive crisis; hydroxyurea; microcirculation; microfluidics; personalized medicine; deformation; transit time meta:creation-date: 2022-04-27T07:04:31Z created: 2022-04-27T07:04:31Z access_permission:extract_for_accessibility: true access_permission:assemble_document: true xmpTPg:NPages: 13 Creation-Date: 2022-04-27T07:04:31Z pdf:charsPerPage: 3977 access_permission:extract_content: true access_permission:can_print: true meta:keyword: sickle cell disorder; vaso-occlusive crisis; hydroxyurea; microcirculation; microfluidics; personalized medicine; deformation; transit time 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 and Andrew Ekpenyong producer: pdfTeX-1.40.21 access_permission:can_modify: true pdf:docinfo:producer: pdfTeX-1.40.21 pdf:docinfo:created: 2022-04-27T07:04:31Z