University of Groningen
Monitoring endothelial cells in microfluidic systems
Grajewski, Maciej
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Publication date: 2018
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Grajewski, M. (2018). Monitoring endothelial cells in microfluidic systems. Rijksuniversiteit Groningen.
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Monitoring Endothelial Cells
in Microfluidic Systems
2
Cover design:
Pieter E. Oomen ©
ISBN:
978-94-034-0430-1 (printed)
ISBN:
978-94-034-0429-5 (electronic)
Printed by:
Gildeprint – The Netherlands
The work published in this thesis was carried out in the Pharmaceutical Analysis group of the
Groningen Research Institute of Pharmacy (GRIP) at the University of Groningen, the Netherlands.
This research received funding from European Commission (LiPhos – Living Photonics, Contract
No. 317916) .
Copyright © 2018 by Maciej Grajewski. All rights reserved. No part of this thesis may be reproduced,
stored in a retrieval system or transmitted in any form or by any means without the prior written
permission of the author.
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Monitoring Endothelial Cells
in Microfluidic Systems
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnificus Prof. E. Sterken
and in accordance with
the decision by the College of Deans
This thesis will be defended in public on
Friday 16
thof March 2018 at 16.15 hours
by
Maciej Grajewski
born on 30
thof April 1988
in Poznań, Poland
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Supervisor
Prof. E. Verpoorte Prof. G. Molema
Assessment Committee
Prof. A.M. van Oijen Prof. W.R. Browne Prof. G. Garcia-Cardena
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Table of content
PART I - GENERAL INTRODUCTION AND LITERATURE REVIEW ON OPTICAL METHODS FOR
CELL AND TISSUE CULTURE MONITORING ... 9
Chapter 1 - General introduction and the outline of the thesis ... 11
1.1. General introduction ... 11
1.2. References ... 12
1.3. Outline of the thesis ... 12
Chapter 2 - Optical research tools for real-time cell and tissue culture monitoring ... 13
2.1. Introduction ... 14
2.2. State-of-the-art optical methods for cell and tissue culture ... 17
2.3. Applicability of optical methods to real-time cell and tissue culture research ... 25
2.4. Future directions of development for optical methods in cell and tissue research ... 27
2.5. Acknowledgements ... 28
2.6. References ... 29
PART II - DESIGN, DEVELOPMENT AND TESTING OF A MICROFLUIDIC CELL CULTURE SYSTEM ... 33
Chapter 3 - Geometry optimization of microfluidic channels for endothelial cell cultures ... 35
3.1. Introduction ... 36
3.2. Materials and Methods ... 37
3.3. Results and Discussion ... 44
3.4. Conclusions ... 48
3.5. Acknowledgements ... 48
3.6. References ... 49
Chapter 4 - Effects of channel width combined with flow on endothelial cell culture in microchannels51 4.1. Introduction ... 52
4.2. Theory ... 52
4.3. Material and Methods ... 55
4.4. Results and Discussion ... 63
4.5. Acknowledgements ... 70
4.6. References ... 70
PART III - MONITORING OF MICROMOTION WITH A NOVEL LABEL FREE APPROACH ... 75
Chapter 5 - Localized optical monitoring of cellular micromotion through confluent endothelial cell layers ... 77
5.1. Introduction ... 78
5.2. Materials and methods ... 80
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5.4. Conclusions ... 93
5.5. Acknowledgements ... 94
5.6. References ... 94
Appendix ... 96
Chapter 6 - Localized optical monitoring of cytoskeletal changes in confluent endothelial cell layers upon exposure to xenobiotics ... 99
6.1. Introduction ... 100
6.2. Material and methods ... 101
6.3. Results and discussion ... 107
6.4. Conclusions ... 112
6.5. Acknowledgements ... 113
6.6. References ... 113
Appendix ... 115
Chapter 7 - Integrated cell culture platform for real-time monitoring of adherent cell cultures ... 117
7.1. Introduction ... 118
7.2. Materials and Methods ... 119
7.3. Results and discussion ... 126
7.4. Conclusions ... 128
7.5. Acknowledgements ... 129
7.6. References ... 129
PART IV - 3D PRINTING ... 133
Chapter 8 – Fused deposition modeling 3D printing for (Bio)Analytical device fabrication: procedures, materials and applications ... 135
8.1. Introduction ... 136
8.2. Materials and Methods ... 137
8.3. Results and discussion ... 138
8.4. Conclusion ... 148 8.5. Acknowledgements ... 148 8.6. Supporting information... 148 8.7. References ... 149 Supporting Information ... 151 PART V - Wrap up ... 175
Chapter 9 - General discussion and future outlook ... 177
9.1. Optical methods for real-time cell monitoring ... 177
9.2. Toolbox for work with microfluidic endothelial cell cultures ... 178
9.3. The optical chip for cell monitoring ... 178
9.4. Setup optimization ... 180
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Summary... 182
Nederlandse Samenvatting ... 184
Acknowledgements ... 186
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