Journal
SMALL
Volume 14, Issue 6, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201702832
Keywords
blood separation; diabetes; inflammation; microfluidics; neutrophils
Categories
Funding
- Lee Kong Chian School of Medicine
- Nanyang Technological University Start Up Grant
- MOE AcRF [2015-T1-001-258]
- NTU-NHG Metabolic Diseases Collaboration Grant [MDCG/15006, MDCG/15004]
- Lee Kong Chian School of Medicine (LKCMedicine) Postdoctoral Fellowship
- Singapore Ministry of Health's National Medical Research Council [CBRGNIG (NMRC/BNIG/2038/2015)]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available