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OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability

Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. Howev...

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Autores principales: Man, Yuncheng, An, Ran, Monchamp, Karamoja, Sekyonda, Zoe, Kucukal, Erdem, Federici, Chiara, Wulftange, William J., Goreke, Utku, Bode, Allison, Sheehan, Vivien A., Gurkan, Umut A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452903/
https://www.ncbi.nlm.nih.gov/pubmed/36091387
http://dx.doi.org/10.3389/fphys.2022.954106
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author Man, Yuncheng
An, Ran
Monchamp, Karamoja
Sekyonda, Zoe
Kucukal, Erdem
Federici, Chiara
Wulftange, William J.
Goreke, Utku
Bode, Allison
Sheehan, Vivien A.
Gurkan, Umut A.
author_facet Man, Yuncheng
An, Ran
Monchamp, Karamoja
Sekyonda, Zoe
Kucukal, Erdem
Federici, Chiara
Wulftange, William J.
Goreke, Utku
Bode, Allison
Sheehan, Vivien A.
Gurkan, Umut A.
author_sort Man, Yuncheng
collection PubMed
description Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up to 1% volume fraction; ektacytometry detected no significant change in Elongation Index (EI), while the OcclusionChip showed significant differences in Occlusion Index (OI). OcclusionChip detected a significant increase in OI in RBCs from an individual with sickle cell trait (SCT) and from a subject with SCD who received allogeneic hematopoietic stem cell transplant (HSCT), as the sample was taken from normoxic (pO2:159 mmHg) to physiologic hypoxic (pO2:45 mmHg) conditions. Oxygen gradient ektacytometry detected no difference in EI for SCT or HSCT. These results suggest that the single cell-based OcclusionChip enables detection of sickle hemoglobin (HbS)-related RBC abnormalities in SCT and SCD, particularly when the HbS level is low. We conclude that the OcclusionChip is complementary to the population based ektacytometry assays, and providing additional sensitivity and capacity to detect modest abnormalities in red cell function or small populations of abnormal red cells.
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spelling pubmed-94529032022-09-09 OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability Man, Yuncheng An, Ran Monchamp, Karamoja Sekyonda, Zoe Kucukal, Erdem Federici, Chiara Wulftange, William J. Goreke, Utku Bode, Allison Sheehan, Vivien A. Gurkan, Umut A. Front Physiol Physiology Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up to 1% volume fraction; ektacytometry detected no significant change in Elongation Index (EI), while the OcclusionChip showed significant differences in Occlusion Index (OI). OcclusionChip detected a significant increase in OI in RBCs from an individual with sickle cell trait (SCT) and from a subject with SCD who received allogeneic hematopoietic stem cell transplant (HSCT), as the sample was taken from normoxic (pO2:159 mmHg) to physiologic hypoxic (pO2:45 mmHg) conditions. Oxygen gradient ektacytometry detected no difference in EI for SCT or HSCT. These results suggest that the single cell-based OcclusionChip enables detection of sickle hemoglobin (HbS)-related RBC abnormalities in SCT and SCD, particularly when the HbS level is low. We conclude that the OcclusionChip is complementary to the population based ektacytometry assays, and providing additional sensitivity and capacity to detect modest abnormalities in red cell function or small populations of abnormal red cells. Frontiers Media S.A. 2022-08-25 /pmc/articles/PMC9452903/ /pubmed/36091387 http://dx.doi.org/10.3389/fphys.2022.954106 Text en Copyright © 2022 Man, An, Monchamp, Sekyonda, Kucukal, Federici, Wulftange, Goreke, Bode, Sheehan and Gurkan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Man, Yuncheng
An, Ran
Monchamp, Karamoja
Sekyonda, Zoe
Kucukal, Erdem
Federici, Chiara
Wulftange, William J.
Goreke, Utku
Bode, Allison
Sheehan, Vivien A.
Gurkan, Umut A.
OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
title OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
title_full OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
title_fullStr OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
title_full_unstemmed OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
title_short OcclusionChip: A functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
title_sort occlusionchip: a functional microcapillary occlusion assay complementary to ektacytometry for detection of small-fraction red blood cells with abnormal deformability
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452903/
https://www.ncbi.nlm.nih.gov/pubmed/36091387
http://dx.doi.org/10.3389/fphys.2022.954106
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