Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood

Abstract The separation of leukocytes from whole blood is a prerequisite for many biological assays. Traditional methods require significant sample volumes and are often undesirable because they expose leukocytes to harsh physical or chemical treatment. Existing microfluidic approaches can work with...

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Autores principales: Quan Guo, Simon P. Duffy, Kerryn Matthews, Emel Islamzada, Hongshen Ma
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/5074f8f2f4a3494a9d7cd6b70d5341fa
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spelling oai:doaj.org-article:5074f8f2f4a3494a9d7cd6b70d5341fa2021-12-02T16:08:21ZDeformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood10.1038/s41598-017-06865-x2045-2322https://doaj.org/article/5074f8f2f4a3494a9d7cd6b70d5341fa2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06865-xhttps://doaj.org/toc/2045-2322Abstract The separation of leukocytes from whole blood is a prerequisite for many biological assays. Traditional methods require significant sample volumes and are often undesirable because they expose leukocytes to harsh physical or chemical treatment. Existing microfluidic approaches can work with smaller volumes, but lack selectivity. In particular, the selectivity of microfluidic systems based on microfiltration is limited by fouling due to clogging. Here, we developed a method to separate leukocytes from whole blood using the microfluidic ratchet mechanism, which filters the blood sample using a matrix of micrometer-scale tapered constrictions. Deforming single cells through such constrictions requires directionally asymmetrical forces, which enables oscillatory flow to create a ratcheting transport that depends on cell size and deformability. Simultaneously, oscillatory flow continuously agitates the cells to limit the contact time with the filter microstructure to prevent adsorption and clogging. We show this device is capable of isolating leukocytes from whole blood with 100% purity (i.e. no contaminant erythrocytes) and <2% leukocytes loss. We further demonstrate the potential to phenotypically sort leukocytes to enrich for granulocytes and lymphocytes subpopulations. Together, this process provides a sensitive method to isolate and sort leukocytes directly from whole blood based on their biophysical properties.Quan GuoSimon P. DuffyKerryn MatthewsEmel IslamzadaHongshen MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Quan Guo
Simon P. Duffy
Kerryn Matthews
Emel Islamzada
Hongshen Ma
Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood
description Abstract The separation of leukocytes from whole blood is a prerequisite for many biological assays. Traditional methods require significant sample volumes and are often undesirable because they expose leukocytes to harsh physical or chemical treatment. Existing microfluidic approaches can work with smaller volumes, but lack selectivity. In particular, the selectivity of microfluidic systems based on microfiltration is limited by fouling due to clogging. Here, we developed a method to separate leukocytes from whole blood using the microfluidic ratchet mechanism, which filters the blood sample using a matrix of micrometer-scale tapered constrictions. Deforming single cells through such constrictions requires directionally asymmetrical forces, which enables oscillatory flow to create a ratcheting transport that depends on cell size and deformability. Simultaneously, oscillatory flow continuously agitates the cells to limit the contact time with the filter microstructure to prevent adsorption and clogging. We show this device is capable of isolating leukocytes from whole blood with 100% purity (i.e. no contaminant erythrocytes) and <2% leukocytes loss. We further demonstrate the potential to phenotypically sort leukocytes to enrich for granulocytes and lymphocytes subpopulations. Together, this process provides a sensitive method to isolate and sort leukocytes directly from whole blood based on their biophysical properties.
format article
author Quan Guo
Simon P. Duffy
Kerryn Matthews
Emel Islamzada
Hongshen Ma
author_facet Quan Guo
Simon P. Duffy
Kerryn Matthews
Emel Islamzada
Hongshen Ma
author_sort Quan Guo
title Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood
title_short Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood
title_full Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood
title_fullStr Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood
title_full_unstemmed Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood
title_sort deformability based cell sorting using microfluidic ratchets enabling phenotypic separation of leukocytes directly from whole blood
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/5074f8f2f4a3494a9d7cd6b70d5341fa
work_keys_str_mv AT quanguo deformabilitybasedcellsortingusingmicrofluidicratchetsenablingphenotypicseparationofleukocytesdirectlyfromwholeblood
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AT kerrynmatthews deformabilitybasedcellsortingusingmicrofluidicratchetsenablingphenotypicseparationofleukocytesdirectlyfromwholeblood
AT emelislamzada deformabilitybasedcellsortingusingmicrofluidicratchetsenablingphenotypicseparationofleukocytesdirectlyfromwholeblood
AT hongshenma deformabilitybasedcellsortingusingmicrofluidicratchetsenablingphenotypicseparationofleukocytesdirectlyfromwholeblood
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