DETECTION OF OLIGOMERIC FORMS OF AMYLOID-BETA USING REFRACTIVE INDEX INTERFEROMETRIC FIBER-OPTIC SENSORS FUNCTIONALIZED WITH BIOTINYLATED PEPTIDES IN THE CONTEXT OF PROBE SIGNATURE APPROACH AND ITS POTENTIAL TO DIFFERENTIATE BETWEEN AMYLOID “STRAINS”

Abstract

The topic of the thesis is a possible new way of detection of Alzheimer’s disease (AD) biomarkers for early and more precise diagnostics based on the recent advances in the study of “strains” of amyloid beta and utilization of peptides for functionalization of RI sensors instead of antibodies. The main goal is to make the sensor more economical and robust in application, as well as to enable additional modalities for further study going beyond the primary detection of the analyte (e.g. detection of concentration vs mere presence of the target using machine learning), with probe signature approach further enhancing these possibilities. Using peptides at the second stage of the work instead of antibodies as the biological recognition element (BRE) is a promising way to make sensors considerably cheaper in the context of diseases associated with peptide and/or protein aggregates. Nowadays, peptides are widely used in electrochemical biosensing, reports on their use in optical biosensing are present but mostly stem from surface plasmon resonance (SPR) measurements with very few covering interferometric detection of refractive index (RI) change. Also, investigation of possible detection of different “strains” bears promises for more precise diagnostics since there are so called mismatch cases where presence of the amyloid aggregates by itself does not lead to cognitive impairment. It is of paramount importance to be able to differentiate between such cases and focus on people who really need intervention without unnecessarily stigmatizing others.