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Diese Dissertation beschäftigt sich mit der Entwicklung eines neuartigen Konzepts für Herstellung und Handhabung von Mikrofluidiksystemen auf der Basis akustischer Oberflächenwellen (SAW) sowie der Nutzung dieses Konzepts zur Fertigung anwendungsrelevanter Teststrukturen. Schwerpunkte sind dabei unter anderem eine hohe Leistungsbeständigkeit und Lebensdauer der Chipbauelemente und eine hohe technologische Flexibilität bezüglich Herstellung und Einsatz. Ausgehend von einer modularen Betrachtungsweise der Bauelemente wurden vielseitig einsetzbare, elektrisch-optimierte Interdigitalwandler entworfen, verschiedene Herstellungsvarianten für vergrabene Interdigitalwandler hoher Leistungsbeständigkeit auf piezoelektrischen Lithiumniobat-Substraten entwickelt und experimentell verifiziert, ein Sputterverfahren für amorphe SiO2-Dünnschichten hoher Qualität optimiert und eine Federstiftkontakt-Halterung entworfen. Durch Kombination dieser Technologien wurden SAW-Bauelemente für die mikrofluidische Aktorik mit hoher Performance und Reproduzierbarkeit entworfen, charakterisiert und beispielhaft für das elektroakustische Zerstäuben von Fluiden und das Mischen in Mikrokanälen eingesetzt.

I den här rapporten undersöks hur en vävd textil kan fungera som ett hjälpmedel i analys av vätskor, såsom förorenat vatten eller blod från människor och djur. Det finns i dagsläget ett stort forskningsområde, kallat mikrofluidik, som behandlar förflyttning av vätska i kanaler på mikrometerstora ytor, där det här projektet till viss del kan hjälpa forskningen på området att komma framåt ytterligare ett steg.   Undersökningen har genomförts med hjälp av tester i laboratorium där en väv i polyeten, med kanaler i Coolmax® (polyester) för att transportera vätskan har använts. En mängd olika testomgångar med olika fokus, har genomförts: test i bitar med raka kanaler, test där wickingen avbrutits med hjälp av sax, test där wickingen har pausats på olika sätt för att sedan startas på nytt samt ett mindre antal tester där försök till styrning av vätskan. Syftet har varit att undersöka huruvida alla sex utvalda vätskor (metylenblått, mjölk, nötblod, olivolja, Poly(3,4-ethylenedioxythiophene) och syntetisk urin) har en förmåga att wicka och om det finns skillnader mellan hur långt vätskorna förflyttar sig.   Wickingtesterna har genomförts i både horisontellt och vertikalt läge, detta för att se om och i så fall hur mycket det skiljer, gällande hur långt en vätska flödar i kanalen. Det som framkommit i projektet är att alla vätskorna hade en förmåga att wicka. Metylenblått förflyttade sig längst i horisontellt läge medan urin förflyttades längst i vertikalt läge. Nötblodet förflyttade sig kortast sträcka i både horisontellt och vertikalt läge. Det som däremot har varit svårt att fastställa är vad skillnaderna egentligen beror på. Baserat på matematiska formler för wicking har det konstaterats att vätskornas kontaktvinkel bör ha betydelse, men detta har dessvärre inte kunnat undersökas i det här projektet. / This thesis examines how a woven textile can act as an aid in the analysis of fluids, such as contaminated water or blood from humans and animals. There is currently a large research area, called microfluidics, which deals with the movement of fluid in channels on micrometer-sized surfaces, where this project can, to some extent, fill some gaps and open for further questions in other parts.   The study has been carried out by using laboratory tests where a polyethylene weave, with channels in Coolmax® (polyester) for transporting the liquid has been used. Several different test rounds with a little different focus have been carried out: test in straight pieces, tests where the wicking has been interrupted by scissors, tests where the wicking has been paused and then restarted, and a smaller number of tests where attempts to control and navigate the fluid has been tested. The purpose has been to investigate whether all six selected fluids (methylene blue, milk, blood from bovine, olive oil, poly (3,4-ethylenedioxythiophene) and synthetic urine) have the ability of wicking and if there are differences between the fluids, and how far they reach.   The wicking tests have been carried out in both horizontal and vertical positions, to see if and if so, how much it differs, how far a fluid reaches. What emerged from the project is that all the liquids had the ability to wick. Methylene blue was the fluid that moved furthest in the horizontal position while urine moved furthest in the vertical position. The blood from bovine moved the shortest distance in both horizontal and vertical positions. What has, however, been difficult to determine is what the differences really depend on. Based on mathematical formulas for wicking, it has been found that the contact angle of the liquids should be important, but this have not been investigated in this project.

Rapid and reliable diagnostics of a disease represents one of the main focuses of today’s academic and industrial research in the development of new sensor prototypes and improvement of existing technologies. With respect to demographic changes and inhomogeneous distribution of the clinical facilities worldwide, especially in rural regions, a new generation of miniaturized biosensors is highly demanded offering an easy deliverability, low costs and sample preparation and simple usage. This work focuses on the integration of nanosized electronic structures for high-specific sensing applications into adequate microfluidic structures for sample delivery and liquid manipulation. Based on the conjunction of these two technologies, two novel sensor platforms were prototyped, both allowing label-free and optics-less electrochemical detection ranging from molecular species to eukaryotic micron-sized human cells.:Table of Figures List of Tables Abbreviations List of Symbols 1 Introduction 1.1 Motivation 1.2 State of the art 1.3 Scope of this thesis 2 Fundamentals 2.1 Sensors at the nanoscale 2.2 Transistors technology 2.2.1 p-n junction 2.2.3 The MOSFET 2.2.4 The ISFET and BioFET 2.3 Impedance measurements for biodetection 2.3.1 Electrical impedance spectroscopy 2.3.2 Electrical impedance cytometry 2.4 Microfluidics 2.4.1 Definition 2.4.2 Droplet-based microfluidics 2.5 Biomarkers for sensing applications 2.5.1 Peripheral blood mononuclear cells (PBMCs) 2.5.2 Physical parameters 3. Material and methods 3.1 General 3.1.1 Materials and chemicals 3.1.2 Surface cleaning 3.2 Lithography 3.2.1 Electron beam lithography 3.2.2 Laser lithography 3.2.3 UV lithography 3.2.4 Soft lithography 3.3 Thermal deposition of metals 3.4 APTES functionalization 3.4.1 Fluorescent labeling of APTES 3.5 Measurement devices 3.5.1 SiNW FET measurements 3.5.2 Electrical Impedance cytometry measurements 3.6 Bacteria and cell cultivation 3.6.1 PBMC purification and treatment 3.6.2 Bacteria cultivation 4. Compact nanosensors probe microdroplets 4.1 Overview 4.2 Fabrication 4.2.1 SiNW FET fabrication 4.2.2 SiNW FET modification for top-gate sensing 4.3 Electrical characterization 4.4 Flow-focusing droplet generation 4.4.1 Flow-focusing geometry 4.4.2 Flow-focusing droplet characterization 4.4.3 Microfluidic integration 4.5 Deionized water droplet sensing 4.6 Phosphate-buffered saline (PBS) droplet sensing 4.6.1 Influence of the droplet’s ionic concentration 4.6.2 Plateau formation in dependence of the droplet’s settling time 4.6.3 Droplet analysis by their ratio 4.6.4 Dependence on pH value 4.6.5 Long time pH sensing experiment 4.6.6 Dependence on ionic concentration 4.7 Tracking of reaction kinetics in droplets 4.7.1 Principle and setup of the glucose oxidase (GOx) enzymatic test 4.7.2 GOx enzymatic assay 4.8 Stable baseline by conductive carrier phase 5. Impedance-based flow cytometer on a chip 5.1 Overview 5.2 Overview of the fabrication of the sensor device 5.3 COMSOL simulation of sensing area 5.3.1 Prototyping of the sensing geometry 5.3.2 Optimization of the sensing geometry 5.3.3 Evaluation of the working potential 5.3.4. Scaling of the sensing area 5.4 Fabrication of the nanoelectronic sensing structure 5.4.1 Nanofabrication and analysis 5.4.2 Evaluation of the proximity effect 5.5 Microcontacting of nanostructured sensing structures 5.6 Electrical characterization of the sensing structure 5.6.1 Characterization in alternating current 5.6.2 Characterization in direct current (DC) 5.7 Scaling effect of nanostructures in static sensing conditions 5.8 Multi-analyte detection on the sensor 5.9 Microfluidic focusing system 5.9.1 1D focusing using FITC-probed deionized water 5.9.2 2D Focusing using fluorescent microparticles 5.10 Microfluidic integration of the two technologies 5.11 Dynamic SiO2 particle detection 5.11.1 Single particle detection 5.11.2 Scatter plot representation 5.11.3 Effect of the sensing area in dynamic particle detection 5.11.4 Dynamic detection of SiO2 particles with different diameters 5.12 Detection of peripheral blood mononuclear cells (PBMCs) 5.12.1 Overview 5.12.2 PBMC classification detected by impedance cytometry 5.12.3 PBMC Long-time detection 5.13 Detection of acute myeloid leukemia by impedance cytometry 5.13.1 Manual analysis of the output response 5.13.2 Learning algorithm for automatic cell classification 5.14 Exploring the detection limit of the device 6. Summary and outlook Scientific output References Acknowledgements / Rasche und zuverlässige biologische Krankheitsdiagnostik repräsentiert eines der Hauptfokusse heutiger akademischer und industrieller Forschung in der Entwicklung neuer Sensor-Prototypen und Verbesserung existierender Technologien. In bezug auf weltweite demographische Änderungen und hohe Distanzen zu Kliniken, besonders in ländlichen Gegenden, werden zusätzliche Anfordungen an neue miniaturisierte Biosensor-Generationen gestellt, wie zum Beispiel ihre Transportfähigkeit, geringe Kosten und Probenpräparation, sowie einfache Handhabung. Diese Dissertation beschäftigt sich mit der Integration nanoskalierter Strukturen zur Detektion chemischer und biologischer Spezies und mikrofluidischen Kanälen zu deren Transport und zur Manipulation der Ströme. Basierend auf der Verbindung dieser beiden Technologien wurden zwei Sensor-Plattformen entwickelt, die eine markierungsfreie und nicht-optische elektrische Detektion von Molekülen bis zu eukaryotischen menschlichen Zellen erlauben.:Table of Figures List of Tables Abbreviations List of Symbols 1 Introduction 1.1 Motivation 1.2 State of the art 1.3 Scope of this thesis 2 Fundamentals 2.1 Sensors at the nanoscale 2.2 Transistors technology 2.2.1 p-n junction 2.2.3 The MOSFET 2.2.4 The ISFET and BioFET 2.3 Impedance measurements for biodetection 2.3.1 Electrical impedance spectroscopy 2.3.2 Electrical impedance cytometry 2.4 Microfluidics 2.4.1 Definition 2.4.2 Droplet-based microfluidics 2.5 Biomarkers for sensing applications 2.5.1 Peripheral blood mononuclear cells (PBMCs) 2.5.2 Physical parameters 3. Material and methods 3.1 General 3.1.1 Materials and chemicals 3.1.2 Surface cleaning 3.2 Lithography 3.2.1 Electron beam lithography 3.2.2 Laser lithography 3.2.3 UV lithography 3.2.4 Soft lithography 3.3 Thermal deposition of metals 3.4 APTES functionalization 3.4.1 Fluorescent labeling of APTES 3.5 Measurement devices 3.5.1 SiNW FET measurements 3.5.2 Electrical Impedance cytometry measurements 3.6 Bacteria and cell cultivation 3.6.1 PBMC purification and treatment 3.6.2 Bacteria cultivation 4. Compact nanosensors probe microdroplets 4.1 Overview 4.2 Fabrication 4.2.1 SiNW FET fabrication 4.2.2 SiNW FET modification for top-gate sensing 4.3 Electrical characterization 4.4 Flow-focusing droplet generation 4.4.1 Flow-focusing geometry 4.4.2 Flow-focusing droplet characterization 4.4.3 Microfluidic integration 4.5 Deionized water droplet sensing 4.6 Phosphate-buffered saline (PBS) droplet sensing 4.6.1 Influence of the droplet’s ionic concentration 4.6.2 Plateau formation in dependence of the droplet’s settling time 4.6.3 Droplet analysis by their ratio 4.6.4 Dependence on pH value 4.6.5 Long time pH sensing experiment 4.6.6 Dependence on ionic concentration 4.7 Tracking of reaction kinetics in droplets 4.7.1 Principle and setup of the glucose oxidase (GOx) enzymatic test 4.7.2 GOx enzymatic assay 4.8 Stable baseline by conductive carrier phase 5. Impedance-based flow cytometer on a chip 5.1 Overview 5.2 Overview of the fabrication of the sensor device 5.3 COMSOL simulation of sensing area 5.3.1 Prototyping of the sensing geometry 5.3.2 Optimization of the sensing geometry 5.3.3 Evaluation of the working potential 5.3.4. Scaling of the sensing area 5.4 Fabrication of the nanoelectronic sensing structure 5.4.1 Nanofabrication and analysis 5.4.2 Evaluation of the proximity effect 5.5 Microcontacting of nanostructured sensing structures 5.6 Electrical characterization of the sensing structure 5.6.1 Characterization in alternating current 5.6.2 Characterization in direct current (DC) 5.7 Scaling effect of nanostructures in static sensing conditions 5.8 Multi-analyte detection on the sensor 5.9 Microfluidic focusing system 5.9.1 1D focusing using FITC-probed deionized water 5.9.2 2D Focusing using fluorescent microparticles 5.10 Microfluidic integration of the two technologies 5.11 Dynamic SiO2 particle detection 5.11.1 Single particle detection 5.11.2 Scatter plot representation 5.11.3 Effect of the sensing area in dynamic particle detection 5.11.4 Dynamic detection of SiO2 particles with different diameters 5.12 Detection of peripheral blood mononuclear cells (PBMCs) 5.12.1 Overview 5.12.2 PBMC classification detected by impedance cytometry 5.12.3 PBMC Long-time detection 5.13 Detection of acute myeloid leukemia by impedance cytometry 5.13.1 Manual analysis of the output response 5.13.2 Learning algorithm for automatic cell classification 5.14 Exploring the detection limit of the device 6. Summary and outlook Scientific output References Acknowledgements

Diese Dissertation beschäftigt sich mit der Entwicklung eines neuartigen Konzepts für Herstellung und Handhabung von Mikrofluidiksystemen auf der Basis akustischer Oberflächenwellen (SAW) sowie der Nutzung dieses Konzepts zur Fertigung anwendungsrelevanter Teststrukturen. Schwerpunkte sind dabei unter anderem eine hohe Leistungsbeständigkeit und Lebensdauer der Chipbauelemente und eine hohe technologische Flexibilität bezüglich Herstellung und Einsatz. Ausgehend von einer modularen Betrachtungsweise der Bauelemente wurden vielseitig einsetzbare, elektrisch-optimierte Interdigitalwandler entworfen, verschiedene Herstellungsvarianten für vergrabene Interdigitalwandler hoher Leistungsbeständigkeit auf piezoelektrischen Lithiumniobat-Substraten entwickelt und experimentell verifiziert, ein Sputterverfahren für amorphe SiO2-Dünnschichten hoher Qualität optimiert und eine Federstiftkontakt-Halterung entworfen. Durch Kombination dieser Technologien wurden SAW-Bauelemente für die mikrofluidische Aktorik mit hoher Performance und Reproduzierbarkeit entworfen, charakterisiert und beispielhaft für das elektroakustische Zerstäuben von Fluiden und das Mischen in Mikrokanälen eingesetzt.:i Kurzzusammenfassung . 5 ii Abstract. 5 iii Inhaltsverzeichnis . 7 iv Abkürzungen und Symbole . 9 1 Überblick . 11 2 Grundlagen und Stand der Technik . 13 2.1 Mikrofluidik . 13 2.1.1 Vom Labor zum Chiplabor . 13 2.1.2 Besonderheiten in miniaturisierten Fluidvolumina . 16 2.2 SAW-basierte Mikrofluidiksysteme . 18 2.2.1 Akustische Oberflächenwellen (SAW) . 18 2.2.2 SAW-Mikrofluidik . 19 2.2.3 SAW-induzierte Strömung ("Acoustic Streaming") . 22 2.2.4 Anforderungen an SAW-basierte Mikrofluidiksysteme . 24 2.2.5 Schädigung SAW-basierter Mikrofluidiksysteme . 26 2.3 Dünnschichten für SAW-basierte Mikrofluidiksysteme . 28 2.3.1 Überblick . 28 2.3.2 Metallisierungssysteme für Interdigitalwandler . 28 2.3.3 Amorphe SiO2-Schichten . 30 2.3.4 Deck- und Funktionsschichten . 32 3 Analysemethoden . 35 4 Technologiekonzept für SAW-basierte Mikrofluidiksysteme . 47 4.1 Modulare Systembeschreibung . 47 4.2 Substratmodul . 50 4.3 Transducermodul . 52 4.3.1 Layout der PSAW-Chipbauelemente . 52 4.3.2 Reinigungsverfahren . 53 4.3.3 Übersicht der untersuchten Herstellungsverfahren . 54 4.3.4 Nasschemisches Ätzverfahren für Al/Ti . 56 4.3.5 Lift-Off Verfahren für Al/Ti . 62 4.3.6 Damaszentechnik für Al2O3/Cu/Ta-Si-N . 65 4.3.7 Vergleich der Herstellungsverfahren . 72 4.4 Funktionsmodul . 75 4.4.1 Hochqualitative SiO2-Schichten . 75 4.4.2 Mikrokanäle . 88 4.4.3 Silanisierung. 88 4.5 Handlingmodul . 90 5 Realisierung und Charakterisierung SAW-basierter Fluidaktoren . 93 5.1 Flexibles Layout für Aktorik-Chipbauelemente . 93 5.2 Chiplayouts für spezielle Anwendungen . 95 5.2.1 Chiplayouts zur IDT-Charakterisierung . 95 5.2.2 Chiplayouts für stehende Wellenfelder . 96 5.2.3 Chiplayouts für "SAW-Stabmixer" . 98 5.2.4 Chiplayouts für tropfenbasierte Fluidik auf Oberflächen . 99 5.3 Wärmeeintrag in Fluide durch "acoustic streaming" . 101 5.4 SAW-basierte Fluidzerstäubung . 104 6 Zusammenfassung & Ausblick . 111 v Literaturverzeichnis . 115 vi Abbildungsverzeichnis . 123 vii Tabellenverzeichnis . 128 viii Selbstständigkeitserklärung . 129 ix Anhang . 131 A1 Bestimmung der Abtragsrate beim Cu-CMP . 131 A2 Ellipsometrie-Modell . 133 A3 "Thin plate spline" Methode für räumlich verteilte Messwerte . 134 A4 Modell des Kammerdrucks . 134 A5 Verzeichnis weiterer Formeln . 136 A6 Visual Basic Programm zur Aerosolcharakterisierung . 138 A7 Visual Basic Programm zur Steppplan-Generierung . 144

In this work, a design platform for the modeling, simulation and optimization of fluidic components and their interactions in larger systems is developed. A hydrogel-based stimulus-sensitive microvalve is the core element of the microfluidic toolbox. Essential material properties as swelling-stimuli functions and the cooperative diffusion are extracted from measurements. The results provide necessary input data for finite element simulations in order to extract characteristic properties of the mechanical and fluid domains. Finally, the behavior of the microvalve and other fluidic library elements is implemented in Matlab Simscape for component and system simulations. Case studies and design optimization can be realized in a very short time with high accuracy. The toolbox is suitable for research and development and as software for academic education. The library elements are evaluated for a chemofluidic NAND gate, a chemofluidic decoder and a chemofluidic oscillator.:1 Introduction to Microfluidic Systems 1.1 Chemofluidic Enables Scalable and Logical Microfluidics 1.2 Focus of this Work 2 Fundamentals for Hydrogel-based Lab-on-Chip Systems 2.1 Basic Hydrogel Material Behavior 2.1.1 Basic Swelling Behavior 2.1.2 General Properties of Hydrogels 2.2 Overview of the used Microtechnology 2.2.1 Synthesis of P(NIPAAm-co-SA) 2.2.2 Microfabrication of a Microfluidic Chip 2.3 Introduction to Modeling and Simulation Techniques 2.3.1 Computer-aided Design Methodologies 2.3.2 Model Abstraction Levels for Computer-Aided Design 2.3.3 Modeling Techniques for Microvalves in a Fluidic System 3 Analytical Descriptions of Swelling 3.1 Quasi-Static Description 3.1.1 Physical Static Chemo-Thermal Description 3.1.2 Finite Element Routine for Static Thermo-Elastic Expansion 3.1.3 Static System Level Design for Hydrogel Swelling 3.2 Transient Description 3.2.1 Physical Dynamic Chemo-Thermal Description 3.2.2 Finite Element Routine for Dynamic Thermo-Elastic Expansion 3.2.3 Transient System Level Design for Hydrogel Swelling 3.3 Swelling Hysteresis Effect 3.3.1 Quasi-static Hysteresis 3.3.2 Transient Hysteresis 4 Characterization of Hydrogel 4.1 Data Acquisition through Automated Measurements 4.1.1 Measuring the Swelling of Hydrogels 4.1.2 Contactless Measurement Concept to Determine the Core Stiffness of Hydrogels 4.2 Data Evaluation with Image Recognition 4.3 Data Fitting and Model Adaption 4.3.1 Quasi-static Response 4.3.2 Transient Response 4.3.3 Hysteresis Response 5 Modeling Swelling in Finite Elements 5.1 Validity of the Model and Simulation Approach 5.2 Thermo-Mechanical Model of the Hydrogel Expansion Behavior 5.2.1 Change of the Length by Thermal Expansion 5.2.2 Stress-Strain Relationship for Hydrogels 5.2.3 Thermal Volume Expansion and Parameter Adaptation 5.2.4 Heat Transfer Coefficient 5.3 Volume Phase-Transition of a Hydrogel implemented in ANSYS 5.4 Computational Fluid Dynamics 5.4.1 Analytic Mesh Morphing 5.4.2 One-way Fluid Structure Interaction Modeling 5.4.3 Towards a Two-way Fluid Structure Interaction Model in CFX 6 Lumped Modeling 6.1 The Chemical Volume Phase-transition Transistor Model 6.1.1 Static Hysteresis 6.1.2 Equilibrium Swelling Length – Quasi-static Behavior 6.1.3 Kinematic Swelling Length - Transient Behavior 6.1.4 Stiffness and Maximum Closing Pressure 6.1.5 Calculation of the Fluidic Conductance 6.1.6 Modeling of the Fluid Flow through the Valve 6.2 Circuit Descriptions Analogy for Microfluidic Applications 6.2.1 Advantages and Limitations of Combined Simulink-Simscape Models 6.2.2 Requirements for Microfluidic Circuits 6.2.3 Graphical User Interfaces and Library Element Management 6.3 Modeling Techniques for the Chemical Volume Phase-transition Transistor (CVPT) 6.3.1 Network Description of CVPT 6.3.2 Signal Flow Description of CVPT 6.3.3 Mixed Signal Flow and Network Model for CVPT 7 Micro-Fluidic Toolbox 7.1 Microfluidic Components 7.1.1 Fluid Sources and Stimuli Sources 7.1.2 Fluidic Resistor with Bidirectional Stimulus Transport 7.1.3 Junctions 7.1.4 Chemical Volume Phase-transition Transistor 7.2 Microfluidic Matlab Toolbox 7.3 Modeling Chemofluidic Logic Circuits 7.3.1 Chemofluidic NAND Gate 7.3.2 Chemofluidic Decoder Application 7.3.3 Chemo-Fluidic Oscillator 7.4 Layout Synthesis 8 Summary and Outlook Appendix A 2D Thermo-Mechanical Solid Element for the Finite Element Method B Thermal Expansion Equation for ANSYS C Linear Regression of the Thermal Expansion Equation for ANSYS D Comparing different Mechanical Strain Definitions E Supporting Documents E.1 Analytic Static Swelling E.2 FEM - Matrix Method E.3 8 Node Finite Element Routine E.4 FEM - Script to create the CTEX table data E.5 Comparison of Solid Mechanics / In dieser Arbeit wird eine Entwurfsplattform für die Modellierung, Simulation und Optimierung von fluidischen Komponenten und deren Wechselwirkungen in größeren Systemen entwickelt. Ein Mikroventil auf der Basis von stimuli-sensitiven Hydrogelen ist das Kernelement des Entwurfstools. Wesentliche Materialeigenschaften wie das Quellverhalten und der kooperative Diffusionskoeffizient werden zu Beginn mit Messungen ermittelt. Mit Finite-Elemente-Simulationen werden aus diesen Daten charakteristische Kennwerte für das mechanische und fluidische Verhalten bestimmt. Sie bilden die Basis für komplexe Systemmodelle in Matlab Simscape, welche das Mikroventil und weitere fluidische Grundelemente in ihrem Zusammenwirken beschreiben. Verschiedene Konzepte können in kurzer Zeit und mit hoher Genauigkeit analysiert, optimiert und verglichen werden. Die Toolbox eignet sich für die Forschung und Entwicklung sowie als Software für die akademische Ausbildung. Sie wurde für den Entwurf eines chemofluidischen NAND-Gatters, für einen chemofluidischen Decoder und für einen chemofluidischen Oszillator eingesetzt.:1 Introduction to Microfluidic Systems 1.1 Chemofluidic Enables Scalable and Logical Microfluidics 1.2 Focus of this Work 2 Fundamentals for Hydrogel-based Lab-on-Chip Systems 2.1 Basic Hydrogel Material Behavior 2.1.1 Basic Swelling Behavior 2.1.2 General Properties of Hydrogels 2.2 Overview of the used Microtechnology 2.2.1 Synthesis of P(NIPAAm-co-SA) 2.2.2 Microfabrication of a Microfluidic Chip 2.3 Introduction to Modeling and Simulation Techniques 2.3.1 Computer-aided Design Methodologies 2.3.2 Model Abstraction Levels for Computer-Aided Design 2.3.3 Modeling Techniques for Microvalves in a Fluidic System 3 Analytical Descriptions of Swelling 3.1 Quasi-Static Description 3.1.1 Physical Static Chemo-Thermal Description 3.1.2 Finite Element Routine for Static Thermo-Elastic Expansion 3.1.3 Static System Level Design for Hydrogel Swelling 3.2 Transient Description 3.2.1 Physical Dynamic Chemo-Thermal Description 3.2.2 Finite Element Routine for Dynamic Thermo-Elastic Expansion 3.2.3 Transient System Level Design for Hydrogel Swelling 3.3 Swelling Hysteresis Effect 3.3.1 Quasi-static Hysteresis 3.3.2 Transient Hysteresis 4 Characterization of Hydrogel 4.1 Data Acquisition through Automated Measurements 4.1.1 Measuring the Swelling of Hydrogels 4.1.2 Contactless Measurement Concept to Determine the Core Stiffness of Hydrogels 4.2 Data Evaluation with Image Recognition 4.3 Data Fitting and Model Adaption 4.3.1 Quasi-static Response 4.3.2 Transient Response 4.3.3 Hysteresis Response 5 Modeling Swelling in Finite Elements 5.1 Validity of the Model and Simulation Approach 5.2 Thermo-Mechanical Model of the Hydrogel Expansion Behavior 5.2.1 Change of the Length by Thermal Expansion 5.2.2 Stress-Strain Relationship for Hydrogels 5.2.3 Thermal Volume Expansion and Parameter Adaptation 5.2.4 Heat Transfer Coefficient 5.3 Volume Phase-Transition of a Hydrogel implemented in ANSYS 5.4 Computational Fluid Dynamics 5.4.1 Analytic Mesh Morphing 5.4.2 One-way Fluid Structure Interaction Modeling 5.4.3 Towards a Two-way Fluid Structure Interaction Model in CFX 6 Lumped Modeling 6.1 The Chemical Volume Phase-transition Transistor Model 6.1.1 Static Hysteresis 6.1.2 Equilibrium Swelling Length – Quasi-static Behavior 6.1.3 Kinematic Swelling Length - Transient Behavior 6.1.4 Stiffness and Maximum Closing Pressure 6.1.5 Calculation of the Fluidic Conductance 6.1.6 Modeling of the Fluid Flow through the Valve 6.2 Circuit Descriptions Analogy for Microfluidic Applications 6.2.1 Advantages and Limitations of Combined Simulink-Simscape Models 6.2.2 Requirements for Microfluidic Circuits 6.2.3 Graphical User Interfaces and Library Element Management 6.3 Modeling Techniques for the Chemical Volume Phase-transition Transistor (CVPT) 6.3.1 Network Description of CVPT 6.3.2 Signal Flow Description of CVPT 6.3.3 Mixed Signal Flow and Network Model for CVPT 7 Micro-Fluidic Toolbox 7.1 Microfluidic Components 7.1.1 Fluid Sources and Stimuli Sources 7.1.2 Fluidic Resistor with Bidirectional Stimulus Transport 7.1.3 Junctions 7.1.4 Chemical Volume Phase-transition Transistor 7.2 Microfluidic Matlab Toolbox 7.3 Modeling Chemofluidic Logic Circuits 7.3.1 Chemofluidic NAND Gate 7.3.2 Chemofluidic Decoder Application 7.3.3 Chemo-Fluidic Oscillator 7.4 Layout Synthesis 8 Summary and Outlook Appendix A 2D Thermo-Mechanical Solid Element for the Finite Element Method B Thermal Expansion Equation for ANSYS C Linear Regression of the Thermal Expansion Equation for ANSYS D Comparing different Mechanical Strain Definitions E Supporting Documents E.1 Analytic Static Swelling E.2 FEM - Matrix Method E.3 8 Node Finite Element Routine E.4 FEM - Script to create the CTEX table data E.5 Comparison of Solid Mechanics

Active membranes with switchable pores that are based on hydrogels can be used to measure the cell size distribution in blood samples. The system investigated in the present research is based on a polyethylene terephthalate (PET) membrane that is surface polymerized with poly (N-isopropyl acrylamide) (PNiPAAm) to form active pores of arbitrary geometry. The PET membrane provides the functionality of a backbone for mechanical rigidity, while the soft PNiPAAm hydrogel forms the active pores. Modeling and simulation of the active hydrogel behavior proved to adequately predict the opening and closing of the pores under application of an activating stimulus, e.g. temperature. The applied model is called Temperature-Expansion-Model and uses the analogy of thermal expansion to model the volume swelling of hydrogels. The Normalized Extended Temperature-Expansion-Model can englobe arbitrary hydrogels and large geometric displacements. Studies of pore opening - performed by using commercial finite element tools - show good agreement of the experimentally measured shape change of active pores. Based on these studies, the particulate fluid flow through the switchable pores is analyzed. Through application of a membrane process, i.e. a given variation of applied pressure and switching stimulus for the hydrogel, the size profile of the blocking particles can be measured directly using the flux difference under constant pressure. This allows the measurement of the cell size distribution in blood samples, e.g. to detect circulating tumor cells or anomalies in the distribution that hint to anemia.

3-dimensional imaging often requires substantial effort since information along the optical axis is not straight forward gatherable. In many applications it is aimed for depth information along the direction of view. For example fluidic mixing processes and the environmental interaction on a microscopic scale are of particular importance for e.g. pharmaceutical applications and often demand for 3D information. This problem is often solved by stereoscopic approaches, where two cameras are used in order to gather depth information by triangulation technique. Another approach is to scan the object through the focal plane in order to get sharp images of each layer. Since the before mentioned approaches require a lot of video data to be evaluated it would be more convenient to get depth mapping within a single camera recording and without scanning. Here we present a tunable 3D depth-mapping camera technique in combination with dynamic aberration control. By using an incoherent light source, only one camera and a spatial light modulator (LCoS-SLM), it is a simply applicable and highly scalable technique. A double-helix point spread function (DH-PSF) is generated for light emerging from the bserved focal plane. Each object appears as a double-image on the camera. Within the orientation of the double-image, depth information along the optical axis is encoded. By using an additional adaptive element (deformable mirror) the technique is combined with wide-field aberration correction. Here we combine a tunable 3D depth camera with dynamic aberration control in one imaging system.

Stimuli-sensitive hydrogels have an outstanding potential for miniaturized, integrated sensor, and actuator systems and especially for lab-on-chip technology, but the application is still in its infancy. One major reason may be that design and realization of hydrogel-based systems are exceptionally complex and demanding. Here, the design parameters of a key component, the hydrogel-based valve, are discussed in their entirety. Key developments in the fields of stimuli-sensitive hydrogels are highlighted and the necessary know-how in material behavior, microstructuring technologies, modeling and name five essential design guidelines as well as scaling laws for hydrogelbased components, including microfluidic one-directional valves, microelectromechanical systems valves, self-regulating, chemomechanical valves, and chemofluidic transistors, is provided.