The Fast and Non-Spurious: High-content screening without artefact in barrier tissues on a chip

Lead Supervisor: Kevin Webb

The PhD project is aimed at improving data acquisition speed and quality in multimodal, label-free microscopy in high-throughput and high-content screening. Current methods are vulnerable to focus drift, which requires extra scanning time to correct and thus slows assays down. The meniscus formed at the culture well wall distorts and misaligns transmitted-light imaging, leading to difficulties in image analysis and segmentation. Quantitative, reproducible data must be generated that can be relied upon to consistently deliver endpoints that can be analysed and presented in a preclinical research program. 

The project will draw on and combine a set of simple technologies developed within the Webb lab to monitor and correct for defocus, meniscus artefact, and which provide multimodal, label-free quantitative phase imaging for endpoint interpretation.  

In partnership with UK SME Cairn Research Ltd, using a condenser-free illumination paradigm, the student will elaborate, optimise, validate, and combine these technologies into a monolithic illumination unit capable of bright field, dark field, quantitative phase imaging on any microscope, at any magnification.  

A minimum three-month placement at Cairn in the final year will produce a validated full manufacturable prototype and the experience of working within a design team to deliver a novel enabling solution that will speed up biomedical research by making imaging faster, higher quality, and information rich.  

The student will validate the technology using cutting-edge microphysiological models of barrier tissues (the “µSIM”) to capture high-content screening data and produce the first data to demonstrate applicability in models of the blood-retinal barrier produced within the Webb lab.  

Success will enable new endpoint assays to be developed to provide barrier tissue models for preclinical toxicology, endpoint analysis, and efficacy.  

The new technology developed is intended to be commercialised in partnership with UK (Cairn Research) and international (Etaluma Inc) SMEs. The novel illuminator design may also see service in the OpenFrame open-source microscope community, and eventually be evaluated for launch into space in a CubeSat or even the International Space Station (collaborators Etaluma currently have units in orbit, benefitting from their compact, light, and simple designs.“ 

 Check your eligibility and apply here

 Funding details:

  • This opportunity is open to both Home and International students. Funding is available for four years from October 2024.
  • The award covers tuition fees at the home rate (currently £4712) plus an annual stipend (currently £18,622 for 2023/2024). This is set by the Research Councils. 

Biotechnology and Biological Sciences Doctoral Training Programme

The University of Nottingham
University Park
Nottingham, NG7 2RD

Tel: +44 (0) 115 8466946