Contents
Preface v
Contents vii
1. Introduction 1
1.1 Introduction................................ 1
1.2 MicromachiningofBiomaterials .................... 3
1.3 BiomedicalMicrodevices......................... 5
1.4 Organizationofthebook......................... 7
2. Spider Silk as a MEMS Material 11
2.1 Introduction................................ 11
2.2 Thin-Film Spider Silk Preparation . . . . . . ............. 13
2.3 Characterization.............................. 13
2.3.1 SEMandEDS .......................... 13
2.3.2 TEM................................ 16
2.3.3 FTIR................................ 16
2.3.4 Squid ............................... 20
2.3.5 Micromachining and Mechanical Testing of a Spider Silk
Microbridge ........................... 20
2.3.6 ActuationofaMagneticSpiderSilkMicrostructure..... 24
2.4 ConclusionsandOutlook ........................ 27
2.5 Acknowledgments ............................ 28
3. Biodegradable Elastomeric Polymers
and MEMS in Tissue Engineering 33
3.1 Introduction................................ 33
3.1.1 TissueEngineering ....................... 33
3.1.2 Mechanical Considerations for Tissue Engineering Scaffolds 35
3.2 DesignCriteriaforBiodegradableElastomericPolymers ...... 36
3.2.1 PolymerizationMechanisms.................. 36
3.2.2 MethodstoIncorporateElasticity ............... 36
3.2.3 DesignConcerns......................... 37
3.3 BiodegradableElastomericPolymers.................. 39
3.3.1 Polyesters............................. 39
3.3.2 Polyurethanes .......................... 47
3.3.3 Polycarbonates.......................... 51
vii
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3.4 MEMSPrinciplesinTissueEngineering ................ 55
3.5 MEMsApplicationsinTissueEngineering .............. 55
4. MEMS in the Nervous System 65
4.1 In Vitro Devices .............................. 67
4.1.1 MicroelectrodeArrays ..................... 67
4.1.2 MicroperfusionDevices..................... 69
4.1.3 MicrofluidicDevices ...................... 70
4.2 In Vivo Devices .............................. 70
4.2.1 TheUtahElectrodeArray.................... 71
4.2.2 MichiganProbes......................... 72
4.2.3 CustomElectrodesandCombinationDevices........ 73
4.2.4 DeepBrainStimulationElectrodes .............. 74
4.2.5 PeripheralProstheticDevices ................. 75
4.2.6 VisualProsthetics ........................ 75
4.2.7 AuditoryProsthetics ...................... 76
4.2.8 SpinalCordElectrodes ..................... 77
4.2.9 BrainComputerInterfaces ................... 78
4.3 DeviceConcernsandTissueResponse................. 80
4.4 ConcludingRemarks........................... 82
5. Hydrogel-Based Microfluidic Cell Culture 89
5.1 Introduction................................ 89
5.1.1 TraditionalCellCultureMethods ............... 90
5.1.2 Two-dimensional Versus Three-dimensional Culture
Methods ............................. 90
5.1.3 MicroscaleCellCultureUsingHydrogels .......... 92
5.2 Hydrogels ................................. 92
5.2.1 NaturallyDerivedHydrogels ................. 93
5.2.2 Alginate . . ............................ 94
5.2.3 Agarose.............................. 95
5.2.4 SyntheticHydrogels....................... 96
5.2.5 Pluronic.............................. 96
5.2.6 N-isopropylacrylamidePolymers(NiPAAm) ........ 97
5.3 Microfabrication.............................. 97
5.4 Hydrogel-basedMicrofluidicCellCulture............... 99
5.4.1 On-chip Alginate Cell Encapsulation .............101
5.4.2 MicrofluidicAgaroseCellCulture...............102
5.4.3 DropletEncapsulation .....................104
5.4.4 OtherConfigurations ......................106
5.4.5 TransportConsiderations....................107
5.5 Applications................................108
5.6 ConclusionsandOutlook ........................109
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6. Flow Control in Biomedical Microdevices using Thermally Re-
sponsive Fluids 115
6.1 Introduction................................115
6.2 TransportinMicrofluidicChannels...................116
6.3 FlowControlMechanisms........................117
6.3.1 MicrovalvePrinciples......................117
6.3.2 Hydrogel-basedMicrovalvePrinciples ............118
6.4 ThermallyResponsiveFluidsforMicroflowControl.........119
6.4.1 TemperatureResponsiveMaterials ..............119
6.4.2 PropertiesofPluronicSolutions ................120
6.5 FlowControlusingThermallyResponsiveFluids ..........124
6.5.1 ActiveValving..........................124
6.5.2 PassiveValving .........................128
6.5.3 Cross-ChannelTransport....................132
6.6 Conclusions ................................135
7. Application of MEMS in Drug Delivery: The Dynamic Between
Biocompatibility and Biofunctionality 143
7.1 Introduction................................143
7.1.1 CurrentTherapiesinDrugDelivery..............143
7.1.2 TheBioMEMSSolution.....................144
7.1.3 TheHost-deviceContinuum..................145
7.2 BioMEMSinDrugDelivery:TheStateoftheField..........146
7.2.1 AcceptanceofBioMEMS ....................146
7.2.2 ThestateoftheBioMEMSField ................146
7.3 The dynamic between Biocompatibility and Biofunctionality . . . . 151
7.3.1 Overview.............................151
7.3.2 Tissue Biocompatibility and Effect on Biofunctionality . . . 152
7.3.3 Hemocompatibility and Effect on Biofunctionality . . . . . 159
7.4 BioMEMS Design Parameters Affecting Biocompatibility and Bio-
functionality................................159
7.4.1 Materialselection ........................159
7.4.2 FabricationMethods.......................161
7.5 BioMEMSinDrugDelivery:TheReality................163
7.6 ConcludingRemarks...........................167
8. Polymer-Based Biocompatible Surface Coatings 173
8.1 Introduction................................173
8.2 Non-foulingSurfacesBasedonPoly(EthyleneGlycol)........174
8.2.1 Physical Adsorption of PEG-containing Copolymers . . . . 174
8.2.2 Chemisorption of PEG Containing Thiol or Sulfide Groups 175
8.2.3 Covalent Grafting of Poly (ethyelene glycol) .........178
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8.2.4 Surface Initiated Polymerization of PEG-containing
Monomers ............................183
8.3 Non-foulingSurfacesBasedonZwitterionicGroups.........185
8.3.1 Self-assembled Monolayers Containing Zwitterionic
Groups ..............................186
8.3.2 Surface Initiated Polymerization of Zwitterionic Group
ContainingMonomers .....................188
8.4 Poly(meth)acrylateBasedNon-foulingSurfaces ...........190
8.5 Poly(meth)acrylamideBasedNon-foulingSurfaces .........190
8.6 Hyperbranched Polyglycidol Based Non-fouling Surfaces .....193
8.7 PeptideandProteinGraftedPolymericSurfaces ...........194
8.8 Conclusions ................................197
9. Vibration-based Anti-Biofouling of Implants 203
9.1 Introduction................................203
9.2 ProteinsVisualization ..........................206
9.3 InteractionsbetweenProteinsandSurface ..............207
9.4 ShearStressontheProtein .......................212
9.5 MicroFabrication .............................216
9.6 ConclusionsandOutlook ........................220
10. Characterization of Biomaterials 223
10.1 Introduction................................223
10.2 BulkAnalysisMethods..........................225
10.2.1 X-rayMicro-computedTomography .............225
10.2.2 X-rayMicrodiffractionTechnique ...............226
10.3 SurfaceAnalysisMethods........................227
10.3.1 MicroscopicMethods......................227
10.3.2 SpectroscopyMethods .....................232
10.3.3 Microspectroscopy and Spectral Imaging Methods . . . . . 237
10.3.4 ThermodynamicMethods ...................240
10.3.5 EmergingOpticalMethodsforinvivoAnalysis.......241
10.4 ConcludingRemarks...........................245
Color Inserts 251
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