Multimodal contrast agents for MSOT and Ultrasound


Contact Dr Kevin Critchley to discuss this project further informally

Project description

The aim is to develop multimodal microbubble (MB)/nanorod (NR) constructs, which will be used for in-vivo ultrasound (US) and near-IR photoacoustic (PA) imaging. Firstly, you will synthesize ultrathin Au NRs using wet-chemical methods. The NRs will be fully characterised by TEM, EDAX, UV-NIR-IR spectroscopy, XRD, DLS, Zeta potential, and AAS.  These techniques will be used to montor batch variation by providing the geometry, composition, optical absorption, charge, and concentration of the NRs.  Importantly, the NRs will be optimised to ensure strong absorption in the near-IR (biological window 650 nm- 1400 nm), but also within the range of the iThera Multispectral optoacoustic tomography (MSOT) instrument. MSOT measurements in a “phantom” cell will determine their PA response. 

Secondly, targeting antibodies (ABs) will be conjugated to the NR surfaces either via COOH-PEG-thiols or polymers (with COOH groups) using NHS/EDC linking.  Colorectal cancer tissue will be targeted using the ABs to VEGFR2.  Targeting specificity, efficiency, and uptake will be investigated by in-vitro assays.  In addition, we will use an Anti-VEGFR2 mimic, developed in Leeds, called an Adhiron.

Thirdly, the student will be trained in the production of lipid stabilised fluorcarbon microbubbles (MBs) using our microfluidic chip-based design.[2-3]  Prof. Evans (2nd physics supervisor) will lead this. This instrument produces C3F8 MBs for in-vivo US imaging and drug delievery. In this project, instead of loading the MBs with liposomes or QDs, NRs will be conjugated to the MB shell, along with the targeting ABs.  NR loaded MBs will be characterised by US spectroscopy, fluoresence and optical microscopy, and DLS. In vivo imaging will be performed on phantom models and subsequesntly in mice with xenografts[5].  The animal preparation and subsequent tail injection will be performed by a dedicated PDRA, from Coletta’s group.  US imaging will be performed using a VisualSonics Vevo 2100 and the iThera US prototype (at iThera).  MSOT imaging will be performed at both sites.

Finally, we will develop fluorocarbon nanodroplets stabilized by lipids, or surfactants, using microfluidics. The Au NRs will be attached to the droplets.  The nanodroplets will be undetected in US, but detectable using PA imaging.  When the nanodroplets are irradiated (in-vivo) by a NIR laser, the NRs heat the liquid nanodrolet, which phase changes into MBs; enabling US contrast to be switched on. A US destruction pulse of the MB will cause sonoporation, resulting in enhanced uptake of the NRs for photothermal treatment.


Entry requirements

Applications are invited from candidates with, or expecting, a minimum of a UK upper second class honours degree (2:1) in a relevant discipline, a Master's degree in a relevant discipline, or both.

Additional staff contact

Steve Evans and Louise Colletta

How to apply

If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements.

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is 'Multimodal contrast agents for MSOT and Ultrasound' as well as Dr Kevin Critchley as your proposed supervisor.

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates.  All scholarships will be awarded on the basis of merit.

If you require any further information please contact the Graduate School Office