Doctoral dissertation
Development of new anti-bioadhesive surfaces for specific neurodegenerative agents
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Abstract
The research work presented in this thesis considers the development of new
biocompatible surfaces that are able to control the adhesion of specific proteins
responsible for the development of neurodegenerative diseases such as Creutzfeldt–Jakob,
Alzheimer, Parkinson and Lewis body disease. Our approach was focused on problems
prior to the detection step, which were never considered before, particularly on the
improvement of Eppendorf tubes that are used for the storage of body fluids like
cerebrospinal fluid and blood. Namely these tubes made of polypropylene induce high
depletion of biological material, in some cases even over 70%, resulting in a low
concentration of these biomarkers for the further immunoenzymatic detection.
With the purpose to reduce the adhesion, two courses of treatments were anticipated. The
first one consists of surface modification by highly reactive fluorine plasma treatment and
the second one incorporates development of new hydrophilic surfaces by coupling two
techniques: plasma activation and subsequent grafting of polymer-surfactant complexes.
With the latter approach, an original way of surface modification has been attained that
permits controlled configuration of nanostructured surfaces. All steps of surface
modifications were well characterized by different physicochemical methods. The surface
hydrophilic/hydrophobic character was determined by measurements of polar and apolar
surface energy, surface charge by magnitude of zeta potential, surface chemistry was
evaluated by x-ray photoelectron spectroscopy (XPS), while the surface roughness and
topography were monitored by atomic force microscopy (AFM). The interactions between
functional groups of treated supports and proteins were interpreted referring to different
models of adhesion established for a range of pH values close to the classical biological
protocols.
Finally, in order to validate the non-adhesive properties of newly developed Eppendorf
tubes, immunoenzymatic analyses were carried out in hospital centres of partners that were
participating to the project STREP NEUROSCREEN n° LSHB-CT-2006-03 7719 (Centre
de Recherche sur les Protéines Prion; Liege (ULG), Hospices Civils de Lyon (CHUL) and
Lancaster University (L-UNI)).
In-vitro analyses have shown that these tubes lead to a decrease of antigen adsorption up
to 100%. Obtained results are contributing importantly to the neurodegenerative protein
standardisation, sampling, storage and more importantly to ambitious plans in early
detection of neurodegenerative diseases.