Characterising individual proteins is essential for understanding their functions associated with health and disease. For example, many age-associated diseases are caused by a small population of the misbehaviour of intrinsically disordered proteins. To detect and characterise these abnormal proteins, traditional single-molecule approaches suffer from several drawbacks; they either can only monitor proteins outside their physiological environment (e.g. electron microscopy), or require protein modification.
Tiny devices with pores with nanoscale diameters so-called “nanopores”, have attracted attention rapidly over the past decades due to their appealing applications in the real-time detection of single proteins in aqueous solutions. Nanopore sensors provide information about the size, shape, charge, and rigidity of a protein sample, as well as the dynamics of their assembly/disassembly without [1-3]. However, nanopore-based protein sensors are not yet fully functional because most protein translocation events are too fast to be recorded experimentally.
This PhD project aims to develop the next generation of single-protein sensors by combining nanopore and optical detection technologies. Nanoscale antennas will be designed and fabricated in such novel sensors to trap and detain the proteins [4-6] without influencing them and the electrical readings. As a result, one can significantly increase the detection resolution by nanopores.
Specifically, the primary objectives of this project are:
- To combine nanopore and optical sensing and synchronise the optical signals with the ionic current signals for an improved understanding of proteins at the single-molecule level.
- To increase the residence time of individual proteins inside a nanopore by nano-optical trapping, allowing rich information about the target protein.
- To interrogate the conformation changes of disease-related proteins, understanding their contribution to the development of chronic diseases, such as Alzheimer's and Parkinson's.