Development of Original and Notable Techniques for Protein Analysis, Native Identification, and Characterisation

This thesis is a compilation of multiple techniques developed to characterise solutions of proteins, or proteins themselves. Proteins are the building blocks of life, and thus they are interesting to study for a deeper understanding of the mechanisms of life but also for developing diagnostic tools as well as medical therapies. The first chapter is a general overview of the thesis with an explanation of the different points developed further in the thesis such as proteins, protein aggregation, microfluidics, and optics. The second chapter describes a microfluidic platform for performing a 2D characterisation, separating the particles using capillary electrophoresis and diffusional sizing. This allowed to characterise the components of heterogenous solutions in function of their size and the mobility of the proteins. The third chapter is looking at existing well-known microfluidic techniques, like free-flow electrophoresis and diffusional sizing, combined with confocal microscopy. The single molecule detection allows to distinguish particles in function of their brightness, breaking the homogenous limitation of these microfluidic techniques under classical epifluorescence microscopy. The fourth chapter shows an elegantly simple way to characterise an exponential decrease of the residence time distribution within a nanocavity trap. The explanation is based only on a random walk assumption without requesting potential interactions. The fifth chapter describes a new method to size particles in solution based on interferometry scattering microscopy by looking at the correlation of the intensity of the interferometric term. The last chapter before the overall conclusion is based on a study of SARS-COV2 seroprevalence in the swiss canton of Zürich between December 2019 and January 2021. This study was conducted on two cohorts, the University Hospital patients, and the blood donation services of Zürich.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Jacquat, Raphaël Philippe Bernard

Advisor dc:contributor.advisor

• Knowles, Tuomas

• biophysics
• proteins characterisation
• capillary electrophoresis
• alpha-synuclein
• center of misfolding disease
• confocal microscopy
• microfluidics
• protein aggregation
• diffusional sizing
• SARS-COV2

Licence

• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.81576

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/334165