A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus
Neutrophil dysfunction is strongly linked to type 2 diabetes mellitus (T2DM) pathophysiology, but the prognostic potential of neutrophil biomarkers remains largely unexplored due to arduous leukocyte isolation methods. Herein, a novel integrated microdevice is reported for single-step neutrophil sor...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/87040 http://hdl.handle.net/10220/44287 |
| _version_ | 1826114777118670848 |
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| author | Tay, Hui Min Dalan, Rinkoo Li, Holden King Ho Boehm, Bernhard Otto Hou, Han Wei |
| author2 | School of Mechanical and Aerospace Engineering |
| author_facet | School of Mechanical and Aerospace Engineering Tay, Hui Min Dalan, Rinkoo Li, Holden King Ho Boehm, Bernhard Otto Hou, Han Wei |
| author_sort | Tay, Hui Min |
| collection | NTU |
| description | Neutrophil dysfunction is strongly linked to type 2 diabetes mellitus (T2DM) pathophysiology, but the prognostic potential of neutrophil biomarkers remains largely unexplored due to arduous leukocyte isolation methods. Herein, a novel integrated microdevice is reported for single-step neutrophil sorting and phenotyping (chemotaxis and formation of neutrophil extracellular traps (NETosis)) using small blood volumes (fingerprick). Untouched neutrophils are purified on-chip from whole blood directly using biomimetic cell margination and affinity-based capture, and are exposed to preloaded chemoattractant or NETosis stimulant to initiate chemotaxis or NETosis, respectively. Device performance is first characterized using healthy and in vitro inflamed blood samples (tumor necrosis factor alpha, high glucose), followed by clinical risk stratification in a cohort of subjects with T2DM. Interestingly, "high-risk" T2DM patients characterized by severe chemotaxis impairment reveal significantly higher C-reactive protein levels and poor lipid metabolism characteristics as compared to "low-risk" subjects, and their neutrophil chemotaxis responses can be mitigated after in vitro metformin treatment. Overall, this unique and user-friendly microfluidics immune health profiling strategy can significantly aid the quantification of chemotaxis and NETosis in clinical settings, and be further translated into a tool for risk stratification and precision medicine methods in subjects with metabolic diseases such as T2DM. |
| first_indexed | 2024-10-01T03:44:42Z |
| format | Journal Article |
| id | ntu-10356/87040 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:44:42Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/870402020-11-01T05:15:19Z A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus Tay, Hui Min Dalan, Rinkoo Li, Holden King Ho Boehm, Bernhard Otto Hou, Han Wei School of Mechanical and Aerospace Engineering Lee Kong Chian School of Medicine (LKCMedicine) Blood Separation Diabetes Neutrophil dysfunction is strongly linked to type 2 diabetes mellitus (T2DM) pathophysiology, but the prognostic potential of neutrophil biomarkers remains largely unexplored due to arduous leukocyte isolation methods. Herein, a novel integrated microdevice is reported for single-step neutrophil sorting and phenotyping (chemotaxis and formation of neutrophil extracellular traps (NETosis)) using small blood volumes (fingerprick). Untouched neutrophils are purified on-chip from whole blood directly using biomimetic cell margination and affinity-based capture, and are exposed to preloaded chemoattractant or NETosis stimulant to initiate chemotaxis or NETosis, respectively. Device performance is first characterized using healthy and in vitro inflamed blood samples (tumor necrosis factor alpha, high glucose), followed by clinical risk stratification in a cohort of subjects with T2DM. Interestingly, "high-risk" T2DM patients characterized by severe chemotaxis impairment reveal significantly higher C-reactive protein levels and poor lipid metabolism characteristics as compared to "low-risk" subjects, and their neutrophil chemotaxis responses can be mitigated after in vitro metformin treatment. Overall, this unique and user-friendly microfluidics immune health profiling strategy can significantly aid the quantification of chemotaxis and NETosis in clinical settings, and be further translated into a tool for risk stratification and precision medicine methods in subjects with metabolic diseases such as T2DM. MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) Accepted version 2018-01-09T09:10:57Z 2019-12-06T16:33:48Z 2018-01-09T09:10:57Z 2019-12-06T16:33:48Z 2017 Journal Article Tay, H. M., Dalan, R., Li, H. K. H., Boehm, B. O., & Hou, H. W. (2017). A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus. Small, 14(6), 1702832-. 1613-6810 https://hdl.handle.net/10356/87040 http://hdl.handle.net/10220/44287 10.1002/smll.201702832 en Small © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the author created version of a work that has been peer reviewed and accepted for publication by Small, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1002/smll.201702832]. 28 p. application/pdf |
| spellingShingle | Blood Separation Diabetes Tay, Hui Min Dalan, Rinkoo Li, Holden King Ho Boehm, Bernhard Otto Hou, Han Wei A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus |
| title | A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus |
| title_full | A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus |
| title_fullStr | A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus |
| title_full_unstemmed | A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus |
| title_short | A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus |
| title_sort | novel microdevice for rapid neutrophil purification and phenotyping in type 2 diabetes mellitus |
| topic | Blood Separation Diabetes |
| url | https://hdl.handle.net/10356/87040 http://hdl.handle.net/10220/44287 |
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