Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus
Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using s...
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sg-ntu-dr.10356-838052022-02-16T16:27:58Z Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus Hou, Han Wei Petchakup, Chayakorn Tay, Hui Min Tam, Zhi Yang Dalan, Rinkoo Chew, Daniel Ek Kwang Li, King Ho Holden Boehm, Bernhard Otto School of Mechanical and Aerospace Engineering Lee Kong Chian School of Medicine (LKCMedicine) microfluidic neutrophil diabetes mellitus Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings. MOE (Min. of Education, S’pore) Published version 2016-09-21T04:25:46Z 2019-12-06T15:32:26Z 2016-09-21T04:25:46Z 2019-12-06T15:32:26Z 2016 Journal Article Hou, H. W., Petchakup, C., Tay, H. M., Tam, Z. Y., Dalan, R., Chew, D. E. K., et al. (2016). Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus. Scientific Reports, 6, 29410-. 2045-2322 https://hdl.handle.net/10356/83805 http://hdl.handle.net/10220/41457 10.1038/srep29410 27381673 en Scientific Reports © 2016 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 12 p. application/pdf |
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microfluidic neutrophil diabetes mellitus Hou, Han Wei Petchakup, Chayakorn Tay, Hui Min Tam, Zhi Yang Dalan, Rinkoo Chew, Daniel Ek Kwang Li, King Ho Holden Boehm, Bernhard Otto Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
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Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings. |
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School of Mechanical and Aerospace Engineering |
author_facet |
School of Mechanical and Aerospace Engineering Hou, Han Wei Petchakup, Chayakorn Tay, Hui Min Tam, Zhi Yang Dalan, Rinkoo Chew, Daniel Ek Kwang Li, King Ho Holden Boehm, Bernhard Otto |
format |
Article |
author |
Hou, Han Wei Petchakup, Chayakorn Tay, Hui Min Tam, Zhi Yang Dalan, Rinkoo Chew, Daniel Ek Kwang Li, King Ho Holden Boehm, Bernhard Otto |
author_sort |
Hou, Han Wei |
title |
Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
title_short |
Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
title_full |
Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
title_fullStr |
Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
title_full_unstemmed |
Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
title_sort |
rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus |
publishDate |
2016 |
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https://hdl.handle.net/10356/83805 http://hdl.handle.net/10220/41457 |
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1725985577257402368 |