Effects of Erythrocyte Aggregation on Blood Rheology in Regard to Future Sepsis Diagnosis Application Darren Burley Courtney Campagna Aislinn Harte Samantha Kelly Max Spiegelhoff Advisors: Prof Raymond Page Prof Ahmet Can Sabuncu May 7th, 2020 Contents Authorship .................................................................................................................................................... 1 Acknowledgements ...................................................................................................................................... 2 Abstract ........................................................................................................................................................ 3 Chapter 1: Introduction ................................................................................................................................ 4 Chapter 2: Background ................................................................................................................................. 5 2.1 Sepsis Overview .................................................................................................................................. 5 2.2 Current Diagnostic Methods ............................................................................................................... 7 2.2.1 Blood Culture ............................................................................................................................... 7 2.2.2 Protein Analysis ............................................................................................................................ 8 2.2.3 Prothrombin and Partial Thromboplastin Time/Platelet Counts ................................................. 8 2.3 Potential Biological Tests for Sepsis Diagnosis ................................................................................... 9 2.3.1 Biomarkers ................................................................................................................................... 9 2.4 Potential Mechanical Tests for Sepsis Diagnosis .............................................................................. 16 2.4.1 Red Blood Cell Deformability ..................................................................................................... 16 2.4.2 RBC Aggregation ........................................................................................................................ 20 2.4.3 White Blood Cells ....................................................................................................................... 23 Chapter 3: Project Strategy ........................................................................................................................ 26 3.1 Client Statement ............................................................................................................................... 26 3.2 Design Requirements ........................................................................................................................ 27 3.2.1 Standards ................................................................................................................................... 27 3.3 Revised Project Statement ................................................................................................................ 29 Chapter 4: Design Process .......................................................................................................................... 30 4.1 Needs Analysis .................................................................................................................................. 30 4.2 Conceptual Designs and Prototype Testing ...................................................................................... 31 4.2.1 Erythrocyte Sedimentation Rate ................................................................................................ 32 4.2.2 Capillary Fill ................................................................................................................................ 34 4.2.3 Vibration Syllectometry ............................................................................................................. 36 4.3 Alternative Designs ........................................................................................................................... 37 2 4.4 Final Design Selection ....................................................................................................................... 38 4.4.1 Blood Preparation ...................................................................................................................... 38 4.4.2 Micro-ESR Methodology & Materials ........................................................................................ 39 4.4.3 Capillary Fill Methodology & Materials...................................................................................... 40 4.4.4 Laser Syllectometry Methodology & Materials ......................................................................... 42 Chapter 5: Design Verification ................................................................................................................... 44 5.1 Micro-ESR Results ............................................................................................................................. 44 5.2 Capillary Fill Results........................................................................................................................... 46 5.3 Laser Syllectometry Results .............................................................................................................. 47 Chapter 6: Final Design and Validation ..................................................................................................... 55 6.1 Final Design CAD Prototype .............................................................................................................. 55 6.2 Standards .......................................................................................................................................... 56 6.3 Economics ......................................................................................................................................... 57 6.4 Environmental Impact ....................................................................................................................... 58 6.5 Societal Influence .............................................................................................................................. 58 6.6 Political Ramifications ....................................................................................................................... 59 6.7 Ethical Concerns ................................................................................................................................ 59 6.8 Health and Safety .............................................................................................................................. 59 6.9 Manufacturability ............................................................................................................................. 60 6.10 Sustainability ................................................................................................................................... 61 Chapter 7: Discussion/Future .................................................................................................................... 62 7.1 Micro-ESR .......................................................................................................................................... 62 7.1.1 Implications ................................................................................................................................ 62 7.1.2 Limitations .................................................................................................................................. 62 7.1.3 Future ......................................................................................................................................... 63 7.2 Capillary Fill ....................................................................................................................................... 64 7.2.1 Implications ................................................................................................................................ 64 7.2.2 Limitations .................................................................................................................................. 64 7.2.3 Future ......................................................................................................................................... 65 7.3 Syllectometry .................................................................................................................................... 66 3 7.3.1 Implications ................................................................................................................................ 66 7.3.2 Limitations .................................................................................................................................. 67 7.3.3 Future ......................................................................................................................................... 68 7.4 Device Discussion .............................................................................................................................. 69 Chapter 8: Conclusions and Recommendations .......................................................................................