The reliable quantitative detection of biomarkers and pathogens at picomolar or even lower concentration would be a great help in point-of-care testing but is not readily available today. Integrated optical waveguides, which interact with the biochemical species to be monitored, are promising candidates for the detection of such ultra-low concentrations.
The focus of this thesis is on optical waveguides in the shape of micro-ring or micro-racetrack resonators that are manufactured by UV-assisted nanoimprint lithography. This replica manufacturing technology is analyzed using analytical and numerical models in order to identify and quantify the main influence factors that determine the limit of detection of such biosensors. Potential biosensor applications are evaluated and general design rules are derived.
The resulting measurements confirm the high potential of the chosen approach with respect to excellent sensitivity, low limit of detection and high dynamic range. With suitable optimization of the sensor layout, a further improvement of the performance by one to two orders of magnitude is possible.:Editor’s Preface
Variables and constants
Abbreviations
1 Introductions
1.1 Medical laboratory diagnostics
1.2 Biosensor technologies for point-of-care testing
1.3 Integrated optical waveguides and microresonators
1.4 Outline of the thesis
2 Basics
2.1 Guided waves in planar optical waveguides
2.1.1 Planar optical waveguides
2.1.2 Propagation of optical waves
2.1.3 Coupled modes in waveguides
2.2 Planar optical microresonators
2.2.1 Basic layouts and parameters
2.2.2 Manufacturing
2.2.3 Biosensing
2.3 Functionalization and biofunctionalization
3 UV-NIL Polymer Microresonator Biosensor Design
3.1 UV-assisted nanoimprint lithography
3.2 Waveguide cross-sections and refractive indices
3.2.1 Analytical waveguide modeling
3.2.2 Mode diagrams
3.2.3 Conclusions
3.3 Waveguide coupling
3.4 Waveguide losses
3.4.1 Absorption loss
3.4.2 Roughness loss
3.4..3 Substrate loss
3.4.4 Radiation loss due to bending
3.5 Sensitivity of the effective index to analyte binding
3.6 Overall sensitivity and detection limit
3.7 Generic design guidelines
3.8 Parameter selection for UV-NIL polymer waveguides
3.9 Comparison of polymer and silicon-based waveguides
3.9.1 Waveguide geometry
3.9.2 Radiation loss due to bending
3.9.3 Material damping
3.9.4 Surface roughness
3.9.5 Coupling channel widths and coupling coefficients
3.9.6 Conclusions
4 Characterization and Proof of Concept
4.1 Manufacturing-based design limits and chosen designs
4.2 Measurement setup and characterization process
4.3 Optical properties of UV-NIL polymer microresonators
4.4 Proof of concept
4.4.1 Sensitivity to bulk solutions
4.4.2 Reproducibility and drift
4.4.3 Comparison with theory
4.4.4 Comparison with literature
4.4.5 Sensitivity improvement
4.5 Asymmetry of the resonance curves
4.5.1 Cavity lifetime
4.5.2 Thermal influence
4.5.3 Summary
4.6 Conclusions
5 Integration into a biosensor platform
5.1 Chemical functionalization by oxygen plasma
5.2 Preparation of a biosensor characterization assay
5.2.1 Binding of fluorescent nanoparticles onto polymer surfaces
5.3 Microfluidic system
5.3.1 Programmable microfluidic system
5.3.2 System evaluation and improvement
5.4 Conclusions
6 Conclusions
Declaration of authorship
Acknowledgements
Publications and awards / Der zuverlässige quantitative Nachweis von Biomarkern und Krankheitserregern in pikomolarer oder noch niedrigerer Konzentration wäre eine große Hilfe bei Tests am Point-of-Care, ist aber heute nicht ohne weiteres verfügbar. Integrierte optische Wellenleiter, die mit den zu überwachenden biochemischen Spezies interagieren, sind vielversprechende Kandidaten für den Nachweis solcher ultraniedriger Konzentrationen.
Der Schwerpunkt dieser Arbeit liegt auf optischen Wellenleitern in Form von Mikro-Ring- oder Mikro-Spur-Resonatoren, die durch UV-unterstützte Nanoimprint-Lithographie hergestellt werden. Diese Replika-Herstellungstechnologie wird mit Hilfe analytischer und numerischer Modelle analysiert, um die wichtigsten Einflussfaktoren zu identifizieren und zu quantifizieren, die die Nachweisgrenze solcher Biosensoren bestimmen. Potenzielle Biosensoranwendungen werden bewertet und allgemeine Designregeln abgeleitet.
Die daraus resultierenden Messungen bestätigen das hohe Potenzial des gewählten Ansatzes in Bezug auf ausgezeichnete Empfindlichkeit, niedrige Nachweisgrenze und hohen Dynamikbereich. Bei geeigneter Optimierung des Sensorlayouts ist eine weitere Verbesserung der Leistung um ein bis zwei Größenordnungen möglich.:Editor’s Preface
Variables and constants
Abbreviations
1 Introductions
1.1 Medical laboratory diagnostics
1.2 Biosensor technologies for point-of-care testing
1.3 Integrated optical waveguides and microresonators
1.4 Outline of the thesis
2 Basics
2.1 Guided waves in planar optical waveguides
2.1.1 Planar optical waveguides
2.1.2 Propagation of optical waves
2.1.3 Coupled modes in waveguides
2.2 Planar optical microresonators
2.2.1 Basic layouts and parameters
2.2.2 Manufacturing
2.2.3 Biosensing
2.3 Functionalization and biofunctionalization
3 UV-NIL Polymer Microresonator Biosensor Design
3.1 UV-assisted nanoimprint lithography
3.2 Waveguide cross-sections and refractive indices
3.2.1 Analytical waveguide modeling
3.2.2 Mode diagrams
3.2.3 Conclusions
3.3 Waveguide coupling
3.4 Waveguide losses
3.4.1 Absorption loss
3.4.2 Roughness loss
3.4..3 Substrate loss
3.4.4 Radiation loss due to bending
3.5 Sensitivity of the effective index to analyte binding
3.6 Overall sensitivity and detection limit
3.7 Generic design guidelines
3.8 Parameter selection for UV-NIL polymer waveguides
3.9 Comparison of polymer and silicon-based waveguides
3.9.1 Waveguide geometry
3.9.2 Radiation loss due to bending
3.9.3 Material damping
3.9.4 Surface roughness
3.9.5 Coupling channel widths and coupling coefficients
3.9.6 Conclusions
4 Characterization and Proof of Concept
4.1 Manufacturing-based design limits and chosen designs
4.2 Measurement setup and characterization process
4.3 Optical properties of UV-NIL polymer microresonators
4.4 Proof of concept
4.4.1 Sensitivity to bulk solutions
4.4.2 Reproducibility and drift
4.4.3 Comparison with theory
4.4.4 Comparison with literature
4.4.5 Sensitivity improvement
4.5 Asymmetry of the resonance curves
4.5.1 Cavity lifetime
4.5.2 Thermal influence
4.5.3 Summary
4.6 Conclusions
5 Integration into a biosensor platform
5.1 Chemical functionalization by oxygen plasma
5.2 Preparation of a biosensor characterization assay
5.2.1 Binding of fluorescent nanoparticles onto polymer surfaces
5.3 Microfluidic system
5.3.1 Programmable microfluidic system
5.3.2 System evaluation and improvement
5.4 Conclusions
6 Conclusions
Declaration of authorship
Acknowledgements
Publications and awards
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:92546 |
| Date | 15 July 2024 |
| Creators | Landgraf, René |
| Contributors | Gerlach, Gerald, Mertig, Michael, Technische Universität Dresden |
| Publisher | THELEM Universitätsverlag und Buchhandlung GmbH & Co. KG |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | urn:nbn:de:bsz:14-qucosa-95647, qucosa:26134 |
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