Development of microfluidics-based neutrophil migration analysis systems for research and clinical applications
| dc.contributor.author | Wu, Jiandong | |
| dc.contributor.examiningcommittee | Morrison, Jason (Biosystems Engineering) Goertzen, Andrew (Radiology) Ren, Carolyn (University of Waterloo) | en_US |
| dc.contributor.supervisor | Lin, Francis (Physics and Astronomy) Levin, David (Biosystems Engineering) | en_US |
| dc.date.accessioned | 2016-04-06T16:43:32Z | |
| dc.date.available | 2016-04-06T16:43:32Z | |
| dc.date.issued | 2013 | en_US |
| dc.date.issued | 2014 | en_US |
| dc.date.issued | 2015 | en_US |
| dc.date.issued | 2016 | en_US |
| dc.degree.discipline | Biosystems Engineering | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Immune cell migration and chemotaxis plays a key role in immune response. Further research to study the mechanisms of immune cell migration and to develop clinical applications requires advanced experimental tools. Microfluidic devices can precisely apply chemical gradient signals to cells, which is advantageous in quantifying cell migratory response. However, most existing microfluidic systems are impractical to use without specialized facilities and research skills, which hinders their broad use in biological and medical research communities. In this thesis, we integrated several new developments in microfluidic gradient generating devices, compact imaging systems, on-chip cell isolation, cell patterning, and rapid data analysis, to provide an easy-to-use and practical solution for immune cell migration and chemotaxis experiments. Using these systems, we quantitatively studied neutrophil migration for both research and clinical applications. First, we developed a compact USB microscope-based Microfluidic Chemotaxis Analysis System (UMCAS), which integrates microfluidic devices, live cell imaging, environmental control, and data analysis to provide an inexpensive and compact solution for rapid microfluidic cell migration and chemotaxis experiments with real-time result reporting. To eliminate the lengthy cell preparation from large amounts of blood, we developed a simple all-on-chip method for magnetic isolation of untouched neutrophils directly from small volumes of blood, followed by chemotaxis testing on the same microfluidic device. Using these systems, we studied neutrophil migration in gradients of different chemoattractants, such as interleukin-8 (IL-8), N-formyl-methionyl-leucyl-phenylalanine (fMLP), and clinical sputum samples from Chronic Obstructive Pulmonary Disease (COPD) patients. Previous studies have shown that COPD is correlated with neutrophil infiltration into the airways through chemotactic migration. The thesis work is the first application of the microfluidic platform to quantitatively characterizing neutrophil chemotaxis to sputum samples from COPD patients. Our results show increased neutrophil chemotaxis to COPD sputum compared to control sputum from healthy individuals. The level of COPD sputum induced neutrophil chemotaxis was correlated with the patient’s spirometry data. Collectively, the research in this thesis provides novel microfluidic systems for neutrophil migration and chemotaxis analysis in both basic research and clinical applications. The developed microfluidic systems will find broad use in cell migration related applications. | en_US |
| dc.description.note | May 2016 | en_US |
| dc.identifier.citation | J.D. Wu, X. Wu and F. Lin, “Recent developments in microfluidics-based chemotaxis studies". Lab on Chip. 2013, 13(13):2484-99. | en_US |
| dc.identifier.citation | J.D. Wu and F. Lin, “Recent developments in electrotaxis assays". Advances in Wound Care, 2014, 3(2):149-155. | en_US |
| dc.identifier.citation | J.D. Wu, L.P. Ouyang, N. Wadhawana, J. Li, M. Zhang, S. Liao, D. Levin and F. Lin, "A compact microfluidic system for cell migration studies", Biomedical Microdevices, 2014, 16(4): 521-528 | en_US |
| dc.identifier.citation | J.D. Wu, C. Hillier, P. Komenda, R. Lobato de Faria, D. Levin, M. Zhang and F. Lin, “A microfluidic platform for evaluating neutrophil chemotaxis induced by sputum from COPD patients”, PLoS ONE, 2015 May 11;10(5):e0126523. | en_US |
| dc.identifier.citation | J.D. Wu, C. Hillier, P. Komenda, R. Lobato de Faria, S. Santos, D. Levin, M. Zhang, F. Lin, “An all-on-chip method for testing neutrophil chemotaxis induced by fMLP and COPD patient’s sputum”, Technology, 2016, accepted. | en_US |
| dc.identifier.citation | J.D. Wu, L.P. Ouyang, M. Zhang, S. Liao, C. Hillier, P. Komenda, R.L. de Faria and F. Lin, “Assessing neutrophil chemotaxis in COPD using a compact microfluidic system”, The 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’14), Chicago, U.S.A., August 26-30, 2014. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/31179 | |
| dc.language.iso | eng | en_US |
| dc.publisher | Royal Society of Chemistry | en_US |
| dc.publisher | Mary Ann Liebert, Inc. | en_US |
| dc.publisher | Springer | en_US |
| dc.publisher | Public Library of Science | en_US |
| dc.publisher | World Scientific Publishing | en_US |
| dc.publisher | IEEE Engineering in Medicine and Biology Society (EMBC’14) | en_US |
| dc.rights | open access | en_US |
| dc.subject | Microfluidics | en_US |
| dc.subject | Chemotaxis | en_US |
| dc.subject | Cell migration | en_US |
| dc.subject | COPD | en_US |
| dc.subject | Neutrophil | en_US |
| dc.title | Development of microfluidics-based neutrophil migration analysis systems for research and clinical applications | en_US |
| dc.type | doctoral thesis | en_US |