Developing quick, sensitive and cheap methods for detecting protein and molecular biomarkers of disease is a continuing challenge. There are a number of aspects in the design of biosensing systems that can act to limit their response. In particular, the reaction kinetics of the affinity reagents of interest, but also the amplification mechanisms used to indicate the presence of a biomarker of interest.
This PhD project, working between the Thomas (http://www.thethomaslab.com
) and Chudasama (http://www.chudasama-group.eu
) labs at University College London, aims to investigate the potential of two approaches for improving the sensitivity and speed of paper-based rapid tests for infectious disease. Conformational flexibility and dynamic response of nanomaterials represent two complimentary approaches towards realising better diagnostic performance in rapid test assays where short time frames are of the essence. Conventionally, nanomaterials for lateral flow diagnostics tend to rely on hard structures with affinity reagents bound to the interface with short flexible linkers or physisorbed passively. While numerous different nanomaterial compositions have been explored for this, the interplay between their overall morphology and flexibility has been unexplored. In addition to shape and flexibility, there is also potential in designing structures that are capable of providing additional function beyond colouration or fluorescence, where more advanced sensor designs can be envisaged.
The project will involve the design and synthesis of flexible, self-assembled nanomaterials capable of eliciting a structural amplification in paper-based rapid tests (as opposed to a chemical amplification) and conventional plate-based assay formats. Particles with a triggerable degradation pathway will be explored to promote amplification of detection events with a view to generating colourimetric rapid tests capable of sufficient sensitivity to detect fg/mL concentration of HIV viral capsid protein antigens.
• Establish methods for the production of nano/micro-scale flexible particles capable of reconfigurability
• Incorporate triggered cleavage mechanisms into the nanoparticle design to facilitate the generation of multiple, biorthogonal targets for detection.
• Design paper-based and microfluidic devices capable of maximising the sensitivity of the structural amplification approach.
• Extend these concepts towards single protein detection.
The PhD project will be affiliated to the i-sense EPSRC IRC Next Steps Award in Agile Early Warning Sensing Systems for Infectious Disease and Antimicrobial Resistance (www.i-sense.org.uk).
Interested candidates should submit a formal application through UCL’s Application portal to the Research Degree: Biochemical Engineering programme [RRDBENSING01], noting in the statement section that they are applying for this particular project. Applicants should also send their CV and covering letter to Dr Michael Thomas ([email protected]
), outlining your interest in and suitability for, researching the suggested topic.
Applications will be accepted until 15th May 2020 but the position will be filled as soon as a suitable candidate has been identified. The project will commence in September/October 2020. Any inquiries for further information about the studentship should be emailed to [email protected]