Bloch Surface Wave Biosensing: Study of Optical Elements for the Early Detection of Protein Aggregation
The process of protein aggregation, due to an incorrect protein folding, has very important implications in medicine. An increasing number of pathologies, including Alzheimer's and Parkinson's diseases, are associated unambiguously with the formation of large aggregates of misfolded proteins. Yet are the causes and conditions for which aggregates become pathogenic unclear. Increasing evidences point towards the early stages of fibril formation. Of interest are hence the early dynamic events in the aggregation process. The scope of this thesis is the study of two types of optical components, based on periodic multilayer structures, and aimed at the early detection of protein aggregation. These are 1) a Bloch surface wave (BSW) sensor and 2) a type of narrow-band wire-grid polarisers (WGP) for the mid-infrared range. In the first part, the computational methods used to investigate these components theoretically are presented. A derivation of approximate analytical results regarding BSW sensing in Kretschmann configuration is proposed. These results are suggested as guidelines for the efficient design of BSW sensing structures. The second part details the experimental application of BSW sensing to the detection of protein aggregation. As an example, two types of proteins are studied : Hen Egg White Lysozyme (HEWL) and Alzheimer's amyloid beta 1-42 (Aβ1-42). Measurements on HEWL are shown to demonstrate the ability of the BSW sensing scheme to detect aggregates from monomeric proteins in a label-free way. Then, dynamic measurements conducted on Aβ1-42 reveal the ability of the sensor to observe the early events of the aggregation process. In the last part, the study of multilayer WGP as cost-effective filtering components in the mid-infrared (MIR) is presented. The presence of specific protein absorption bands in the MIR is a potential mean for selective label-free detection using BSW sensing. A simple modal model describing a particular class of multilayer WGP is proposed. A suitable fabrication method is proposed. The developed methods are illustrated by an example designed at a wavelength λ = 4.36 µm. Measurements on the transmission characteristics of the structures show good agreement with the theoretical model.
Keywords: surface wave resonance ; biomedical optics ; detectors ; sensors ; protein aggregation ; degenerative diseases ; mid-infrared ; narrow-band polariser ; résonance d'ondes de surface ; optique biomédicale ; détecteurs et senseurs ; agrégation de protéines ; maladies dégénératives ; infra-rouge moyen ; polariseur à bande étroiteThèse École polytechnique fédérale de Lausanne EPFL, n° 5022 (2011)
Section de microtechnique
Faculté des sciences et techniques de l'ingénieur
Institut de microtechnique
Laboratoire d'optique appliquée
Record created on 2011-03-03, modified on 2016-08-09