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dc.contributor.author
Frutiger, Andreas
dc.contributor.supervisor
Vörös, Janos
dc.contributor.supervisor
Fattinger, Christof
dc.contributor.supervisor
Sandoghdar, Vahid
dc.date.accessioned
2021-03-15T07:53:40Z
dc.date.available
2021-03-13T16:11:32Z
dc.date.available
2021-03-15T07:53:40Z
dc.date.issued
2021
dc.identifier.uri
http://hdl.handle.net/20.500.11850/474270
dc.identifier.doi
10.3929/ethz-b-000474270
dc.description.abstract
Holograms have fascinated humans ever since their first creation nearly 70 years ago. On the other hand, label-free optical biosensors are an invaluable tool for molecular interaction analysis. This thesis is about applying holographic detection to biomolecular interaction analysis and by this overcoming many of the drawbacks of state-of-the-art biosensors. Over the past 30 years, refractometric biosensors, and in particular surface plasmon resonance, have matured to the de facto standard of this field. However, since their introduction no fundamental technological breakthrough that could address the major problems of refractometric transducers occured. Sensor equilibration, temperature drifts, buffer change artefacts and nonspecific binding are still significantly lowering throughput, limit the application scope and complicate the analysis of molecular binding experiments. Most importantly, the stabilization requirements and the cross-sensitivity of refractometric biosensors have impeded label-free (bio-)sensors to truly extend their scope beyond the controlled conditions of a laboratory environment. Molecular holograms or diffractometric biosensors should finally enable this step and create biosensors that can analyze molecular interactions in their natural habitat - the crowded environment of body fluids, tissues, cells and membranes. This thesis provides the physical explanation and the experimental evidence why this is not just a dream but actually very well possible. First, I introduce the spatial affinity lock-in and use signal processing to explain why diffractometric biosensors are finally solving the inherent stability problems of refractometric biosensors. Second, by simulation and experiments I show that molecular holograms achieve diffraction-limited focusing and derive mass quantification formulas and an optimization criterion for diffractometric biosensors. Third, I demonstrate that waveguide based diffractometric biosensors can function as a combined refractometric sensor. In addition, in a direct comparison of a state-of-the-art biosensor system to an unstabilized diffractometric biosensor I show that diffractometric biosensors surpass refractometric biosensors in terms of mass resolution and require less precise readout instrumentation. Lastly, I end with an in-depth noise analysis to identify the intrinsic noise limit of biosensors in general and the extrinsic noise limits of the setups developed in this thesis. In summary, this thesis provides the explanation why molecular holograms at optical frequencies are the physical principle to build robust and sensitive molecular sensors.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.subject
Biosensors
en_US
dc.subject
DIFFRACTION (OPTICS)
en_US
dc.subject
Focal molography
en_US
dc.subject
Molecular Sensors
en_US
dc.subject
HOLOGRAPHY (OPTICS)
en_US
dc.subject
Phase masks
en_US
dc.subject
Waveguides, planar
en_US
dc.title
Molecular Holograms - Design principles of robust biosensors at the example of focal molography
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2021-03-15
ethz.size
266 p.
en_US
ethz.code.ddc
DDC - DDC::6 - Technology, medicine and applied sciences::600 - Technology (applied sciences)
en_US
ethz.code.ddc
DDC - DDC::5 - Science::530 - Physics
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
en_US
ethz.identifier.diss
27337
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02140 - Dep. Inf.technologie und Elektrotechnik / Dep. of Inform.Technol. Electrical Eng.::02631 - Institut für Biomedizinische Technik / Institute for Biomedical Engineering::03741 - Vörös, Janos / Vörös, Janos
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02140 - Dep. Inf.technologie und Elektrotechnik / Dep. of Inform.Technol. Electrical Eng.::02631 - Institut für Biomedizinische Technik / Institute for Biomedical Engineering::03741 - Vörös, Janos / Vörös, Janos
en_US
ethz.date.deposited
2021-03-13T16:11:42Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-03-15T07:53:52Z
ethz.rosetta.lastUpdated
2023-02-06T21:36:05Z
ethz.rosetta.versionExported
true
ethz.COinS
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