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Cell Surface Interaction on a Multi – Scale

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Cell Surface Interaction on a Multi – Scale.

ABSTRACT

The increasing rate of cancer patients worldwide, and especially Africa has led to numerous efforts to battle it. One approach to this has been localized drug delivery to reduce the quantity of drugs needed for therapeutic effect. Poly-di-methyl-siloxane (PDMS) is an elastomer with much focus on it as a microfluidic device.

PDMS is one polymer of choice for localized drug delivery due to its biocompatibility, transparency, and ease of fabrication.

However, its highly hydrophobic nature does not allow it to be used without modification. This work presents results of experimental and computational methods for PDMS surface modification.

Also computational results of shear assay model for the effects on surface modification on cell adhesion is present. Modifying the surface of the PDMS was done by varying the mix ratio and curing temperatures after fabrication.

The results from the experiment shows that low base to curing agent ratio and increasing curing temperature gives a highly stiff PDMS.

Also, the PDMS treatment via boiling water and Ultraviolet Ozone (UVO) methods makes it hydrophilic with the generation of hydroxyl (OH) group on the substrates.

These studies provided understanding of cell-surface interaction on a multi-scale. Morphological studies with Scanning Electron Microscope (SEM) reveal a layer and textured featured formed on UVO treated and PLGA coated PDMS.

Shear assay model showed that cells on modified PDMS surface low energy release rate on application of shear load. This signifies that cells adhered to the modified surfaces better, thus could not be easily detached.

TABLE OF CONTENTS

DEDICATION………………. iii
ACKNOWLEDGEMENTS ……….. iv
ABSTRACT ………….. v
Table of Contents ………… vi
LIST OF FIGURES ………… ix
LIST OF TABLES ……….. xiii

1.0 CHAPTER ONE

1.1 INTRODUCTION……………. 1
1.1.2 Objectives ……….. 2
1.1.3 Scope of work……. 3
1.2 Reference for Chapter One …….. 4

2.0 CHAPTER TWO: LITERATURE REVIEW

2.1 Introduction ………………… 8
2.2 Microfluidic systems … 8
2.3 PDMS ………… 9
2.3.1 Surface Modification of PDMS ……….. 10
2.3.2 Mechanical characterization of PDMS ……… 12
2.4 Cell/surface interaction ………. 14
2.4.1 Cell ……………….. 14
2.5 The Effects of Surface Morphology on Cell/Surface Interaction ….19
2.5.1 Roughness ………… 19
2.5.2 Surface Texture ………………….. 20
2.6 The Effects of Surface Chemistry on Cell/Surface Interaction …. 20
2.7 Methods for Studying Cell/Surface Adhesion ……….. 22
2.7.1 Micro-pipette Aspiration …. 22
2.7.2 Laser tweezers ………… 24
2.7.3 AFM ……… 25
2.7.4 Cell Traction Measurements …………… 26
2.7.5 Shear Assay Measurement in Parallel-Plate Flow Chambers ….. 26
2.8 Summary …………….. 28
2.9 Reference for chapter two ……… 29

3.0 CHAPTER THREE: METHODOLOGY

3.1 Introduction 3.1 Introduction 3.1 Introduction 3.1 Introduction ……. 41
3.2 Materials and Methods ……………. 42
3.3.1 Fabrication ………………….. 42
3.3.2 Preparation of PDMS ……… 42
3.3.3 Surface Modification of PDMS …… 44
3.3.3.1 UV/Ozone Treatment ………… 45
3.3.3.2 Boiling water treatment ………… 46
3.3.3.3 Coating with PLGA ………….. 47
3.3.4 Surface Chemistry Assay ………… 48
3.3.5 Topographical Analysis of PDMS …….. 48
3.4 Reference for Chapter three ………… 48

4.0 CHAPTER FOUR: MODELLING

4.1 Introduction ……….. 50
4.2 Analytical Modelling …………. 50
4.2.1 Residual and Applied Stresses ………. 52
4.3 Computational Modelling …………….. 53
4.3.1 Au/PDMS Buckling Model …… 53
4.3.2 Shear Assay Model………….. 54
4.4 Reference for chapter four ……………. 55

5.0 CHAPTER FIVE: RESULTS AND DISCUSSION

5.1 Introduction …………………… 57
5.2 Tensile …… 57
5.3 FTIR Results …………….. 63
5.3 SEM Result ………… 67
5.4 Analytical Model Results …………… 68
5.4.1 Stress Analysis of Analytical Model .. 68
5.5 Computational Model Results…………… 70
5.5.1 Buckling Profile as a Function of Pre-Strain and Substrate Elastic Modulus ……………… 70
5.6 Effect of Surface Modification on Cell Adhesion ……… 71
5.7 Reference for chapter five ……………. 74

6.0 CHAPTER SIX

6.1 Implications of the Results……….. 75
6.2 Conclusion ………… 76
6.3 Future Work …….. 76
6.4 Reference for Chapter Six …….. 78

INTRODUCTION

The treatment of injury, disease and congenital malformation from traditional to scientific has been part of the human experience. Better ways are sought to improve human life. One disease that is currently taking human lives is cancer.

Cancer is second only to cardiovascular disease [1, 2], and with current trends is likely to become the leading cause of death globally by 2030 [1].

In a quest to battle this globally threatening disease, research is being done to improve on conventional methods of detection and treatment [3-6].

This is to reduce the various side effects that accompany existing methods based on surgical procedures, radiation therapy, including bulk systemic chemotherapy.

It is important to explore alternative approaches that can reduce the killing of normal or healthy cells during the cancer treatments.

An emerging field, tissue engineering, which provides an approach for the repair and fabrication of tissue from living cells [7] offers a better approach to cancer treatment.  Soft tissue engineering plays a vital role in the treatment of cancer through implantable device.

REFERENCES

Bowden, S. Brittain, A.G. Evans, J.W. Hutchinson, G.M. Whitesides, “Spontaneous Formation of ordered structures in thin films of metals supported on an elastomeric polymer,” Nature, vol. 393, (6681), pp. 146-149, 1998.

Mei and R. Huang, “Wrinkling and Delamination of Thin Films on Compliant Substrates,” 13th International Conference on Fracture, June 16–21, Beijing, China, 2013 J. W. Hutchinson, and Z. Suo. “Mixed mode cracking in layered materials,” Advances in applied mechanics, vol. 29, pp. 63-191, 1991.

Ebata, A. B. Croll and A. J. Crosby, “Wrinkling and strain localizations in polymer thin films,” Soft Matter, vol. 8, pp. 9086-9091, 2012.

H. Kim, et al., “Stretchable, curvilinear electronics based on inorganic materials,” Advanced Materials, vol. 22, no.19, pp. 2108-2124, 2010.

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