PMID- 29168915 OWN - NLM STAT- MEDLINE DCOM- 20190912 LR - 20190912 IS - 1613-6829 (Electronic) IS - 1613-6810 (Linking) VI - 14 IP - 6 DP - 2018 Feb TI - A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus. LID - 10.1002/smll.201702832 [doi] AB - 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. CI - (c) 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Tay, Hui Min AU - Tay HM AD - Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Clinical Sciences Building Level 11, Singapore, 308232, Singapore. FAU - Dalan, Rinkoo AU - Dalan R AD - Endocrine and Diabetes, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. FAU - Li, King Ho Holden AU - Li KHH AUID- ORCID: 0000-0001-6187-6434 AD - School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Block N3, Singapore, 639798, Singapore. FAU - Boehm, Bernhard O AU - Boehm BO AD - Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Clinical Sciences Building Level 11, Singapore, 308232, Singapore. AD - Endocrine and Diabetes, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. FAU - Hou, Han Wei AU - Hou HW AD - Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Clinical Sciences Building Level 11, Singapore, 308232, Singapore. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171123 PL - Germany TA - Small JT - Small (Weinheim an der Bergstrasse, Germany) JID - 101235338 RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Biomarkers/blood MH - Biomimetics MH - Cell Separation/*instrumentation MH - Chemotaxis, Leukocyte MH - Diabetes Mellitus, Type 2/*blood/drug therapy MH - Extracellular Traps MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Immunophenotyping MH - Lab-On-A-Chip Devices MH - Metformin/therapeutic use MH - Neutrophils/*cytology/immunology MH - Proof of Concept Study OTO - NOTNLM OT - blood separation OT - diabetes OT - inflammation OT - microfluidics OT - neutrophils EDAT- 2017/11/24 06:00 MHDA- 2019/09/13 06:00 CRDT- 2017/11/24 06:00 PHST- 2017/08/16 00:00 [received] PHST- 2017/09/21 00:00 [revised] PHST- 2017/11/24 06:00 [pubmed] PHST- 2019/09/13 06:00 [medline] PHST- 2017/11/24 06:00 [entrez] AID - 10.1002/smll.201702832 [doi] PST - ppublish SO - Small. 2018 Feb;14(6). doi: 10.1002/smll.201702832. Epub 2017 Nov 23.