PhD Projects
Investigation of the propagation of laser beams with non-Gaussian spatial and phase profiles through turbulent atmospheres and obscuration
The propagation of laser beams through the atmosphere is of keen interest for energy transfer. As a dynamic system, the atmosphere changes on a range of temporal and spatial scales leading to attenuation, spatial beam break up, and scintillation, that can limit the range and efficacy of energy transfer using laser beams. This project will investigate the generation and propagation of a variety of laser beams with differing spatial intensity and phase profiles to understand any benefits over traditional Gaussian profiled beams. One such beam is a Vortex laser beam that carries orbital angular momentum with unique properties and often possess doughnut-shaped spatial intensity profiles. The project will be a combination of experimental and simulation of vortex beam propagation through turbulence (& cloud/fog) and comparison across vortices with different topological charge, Gaussian beams, coherently-coupled beams, and consideration of other possible spatial profiles.
This PhD is part of the EPSRC Energy Transfer Technologies Doctoral Training Hub. As a student of the Hub, you receive an enhanced stipend of £23,237 per year, plus additional funds of £7,000 a year for travel, conferences and research equipment. This project is co-funded and co-supervised by industry partner DSTL.
Eligibility: PhD Candidates must hold a minimum of an upper Second-Class UK Honours degree or international equivalent in a relevant science or engineering discipline. Candidates must be UK Nationals and be willing to apply for and able to obtain Baseline Personnel Security Standard (BPSS) clearance.
For more information please contact Prof Mike Damzen.
Electrically Pumped Intense Hollow-core Optical Fiber Gas Laser (EPIc-HOFGLAS): A New Approach For Highly Efficient Mid-Infrared Laser Sources
This project will develop an Electrically Pumped Intense Hollow-core Optical Fiber Gas LASer (EPIc-HOFGLAS): a completely new mid-infrared laser architecture based on a combination of cutting-edge gas filled hollow-core fibre technology and novel mid-infrared optical materials.
The concept is based on the electrical excitation of N2O gas in an anti-resonant hollow-core optical fiber providing optical gain at 4.6 µm. This approach has the potential to greatly reduce the size, power consumption and thermal issues associated with current state-of-the-art high power MIR lasers. The EPIc-HOFGLAS 4.6 µm emission wavelength is optimal for long range propagation through atmospheric windows, with greatly improved penetration of cloud, fog, haze and other weather, providing an entirely new, highly efficient, and ultra-scalable approach for next generation MIR directed energy and electronic warfare sources. Alternative gases can provide gain at other wavelengths throughout the MIR, and thus, this platform could be hugely beneficial for other applications requiring high pulse energies in the MIR e.g. precision oncological surgery – another ongoing research thread in the Dr Murray’s lab.
The project will be involve working closely with external partners in the UK/EU and US, under the guidance of the PI, and extended research exchange trips to partner sites in the US (multiple weeks-months) will be encouraged. The international network of project collaborators includes industry (BAE Systems US), United States Airforce (USAF) Government Laboratories (AFRL Dayton/Albuquerque US), US universities and UK/EU universities (Cambridge/Lille). This is a very exciting opportunity to join this project at the beginning and be part of the development of a new class of paradigm shifting mid-infrared laser sources, with a huge number of potential applications across medicine, defence and industry. The USAF have just funded this work through a $0.75m grant to Dr Murray’s lab, to fund the necessary equipment and infrastructure for the work, as well as an PDRA to work alongside the PhD student. The project would suit a candidate with a Physics/Electrical Engineering/Engineering background, and the work will primarily be experimental, involving hollow-core optical fibres, gas filled fibres, novel infrared materials, high voltage pulse power systems and mid-infrared diagnostics. Supporting numerical and theoretical work is essential to guide the experiments and will be carried out in collaboration with world leading gas laser modelling experts from the US.
For more information please contact Dr Robbie Murray.
Development of a single-cell infrared-laser driven mass spectrometric imaging platform
This project will lead the development of a cross-faculty mass spectrometry imaging (MSI) platform, capable of single-cell resolution and live-cell analysis at Imperial College London (ICL). We will combine an industrial class picosecond infrared laser system with the latest technology in high-resolution mass spectrometry, enabling a single-cell resolution molecular imaging platform for users across the biomedical sciences. The laser will achieve spatial resolutions of < 5 um, translating directly to the possibility of single-cell analysis, allowing unprecedented classification of cell metabolic states in their original tissue context. Coupled with this, the infrared laser makes use of water molecules naturally present in biological tissue to drive the desorption and ion plume creation and since no sample preparation is needed, this facilitates the analysis of live cells, opening a suite of new applications not previously possible.
By integrating single-cell spatial metabolomics with our recent capabilities in single-cell genomics, spatial transcriptomics and imaging mass cytometry, we will be in a unique position to transform the understanding of molecular and cell biology in a new multi-omics centre. Our platform will be available to diverse groups across disciplines and applied to the study of non-alcoholic fatty liver disease, type 2 diabetes, cardiovascular disease, dementia research and cancer. With Imperial's Microbiome Network, we will finely map the spatial distribution of microbial products and their metabolites in biofilms, organs-on-chip and host tissues. Our flexible setup will be tunable for single-cell resolution or ablating larger tissue regions facilitating ex vivo and real-time surgical diagnostics - impossible with the current technology at ICL and more broadly in the UK. These studies will pave the way for "Personalised Medicine" approaches to tackle disease, whilst bridging the gap between cellular and organ-level understanding of biological processes.
This project will be based jointly in the Blackett Laboratory in the Physics Department (ICL) and the Hammersmith Hospital site (ICL). The project is primarily aimed at transferring initial prototype technology recently developed in Physics to a hospital environment, to provide end-users across the biological and medical sciences with easy access to single-cell level metabolomic mass spectrometric imaging techniques. This project will be primarily experimental, involving mid-infrared laser source commissioning and development, high resolution microscope hardware and software implementation and the development of biological cell analysis routines with commercial mass spectrometers (Waters). It is an exciting opportunity to work in a highly inter-disciplinary environment spanning physics, analytical chemistry, and medicine. The work will also involve working closely with industrial and academic partners across the globe, with the potential to roll this technology out across different once the ICL platform has been demonstrated successfully.
For more information please contact Dr Robbie Murray.
Light sheet fluorescence microscopy
Light sheet fluorescence microscopy (LSFM) is a high-speed 3D fluorescence imaging method with the advantages of low photodamage to biological samples and low photobleaching of the fluorophores being imaged. However, conventional LSFM requires two microscope objectives placed at 90 degrees to one another to provide orthogonal illumination and detection. Oblique plane microscopy (OPM) is a technique developed in the Photonics Group at Imperial that uses a single high numerical aperture microscope objective to provide both the illumination light sheet and collection of fluorescence from the sample. In collaboration with the National Heart and Lung Institute, the current OPM system has been applied to image dynamic calcium events in isolated heart muscle cells at video volumetric imaging rates, which gives new insights into dynamic events that may trigger arrhythmias of the heart. It is also being applied in collaboration with the Institute of Cancer Research to achieve 3D imaging in 96 and 384 multi-well plates for higher throughput and time-lapse imaging of arrays of samples. Here, the aim is to study how different genes affect cancer cell morphology and the ability of cancer cells to change their shape over time, which is a factor that affecting metastasis in cancer. More recently, we have developed an optically folded version of OPM that enables two different views of the sample to be obtained that can then be fused together computationally, which we call dual-view OPM (dOPM). This approach improves the spatial resolution and provides a more isotropic point spread function more isotropic. There are three potential topics for PhD projects on OPM:
1) Development of dOPM to study mouse mammary organoid development. This would extend the work of an EPSRC-funded research project joint between Axel Behrens at the Institute of Cancer Research and Guillaume Salbreux at the University of Geneva. This project aims to develop dOPM to allow it to be used to study the growth of up to 50 healthy and cancerous organoids over a period of a week, to develop and apply code to segment – including deep-learning-based approaches – and track every individual cell. The resulting cell fate data will then be compared to physical models of cell and cell membrane behaviour, to study the stochasticity of organoid growth and to look for differences in behaviour between healthy and cancerous organoids.
2) Develop a dOPM system for 3D super-resolution microscopy using single-molecule localisation microscopy (SMLM) approaches. This project will include a detailed assessment of the spatial resolution of the dOPM system, develop improved optical systems to reduce aberrations and then investigate different approaches that correct for spatial variation in the system PSF during the localisation of individual fluorophores. The resulting system will be applied to high-throughput 3D SMLM in arrays of biological samples.
3) Develop a dOPM system optimised for imaging optically cleared fixed tissue specimens. This will involve detailed optical design of the required components, alignment, testing and characterisation. The resulting system will also be applied to study arrays of optically cleared biological samples with collaborators in biology. The cleared specimens will result in larger datasets and the associated challenge of data processing and analysis will require the application and development of automated image segmentation approaches.
For more information see Oblique Plane Microscopy or email Chris Dunsby.
Advanced, low-cost, modular microscopy for histopathology
Conventional histopathology relies on brightfield microscopy of H&E stained histological sections and immunofluorescence microscopy where specific proteins are labelled using antibodies. Where highre spatial resolution is required, e.g. to diagnose kidney disease, electron micrscopy may be utilised. Typically, histopathology entails manual microscopy and visual inspection, although there is an increasing trend to digitise histopthology images and apply image processing techniques, including machine learning for classification. We are working to enhance immunofluoescence by incresing the numbers of different proteins that can be mapped within a single image and by improving the spatial resolution to <50 nm using single molecule localisation microscopy. We are particulary keen to widen access to such advanced techniques and are developing a low-cost modular microscope platform "openFrame", implementing bright field and immunofluorescence microscopy with automated slide-scanning. The platform will include super-resolved imaging utilising our low-cost “easySTORM” technique to image key proteins with clinically validated antibodies. For this, we will complement low-cost instrumentation with practical protocols that will work with existing clinical biopsy samples. As well as being affordable to replicate, this instrument would be straightforward to maintain and would be tested in collaboration with colleagues from lower resources settings. We intend that it could be accessible by clinicians in low and middle-income countries (LMIC). This platform would be generally applicable in histopathology, although this project will focus on developing protocols for diagnosing kidney disease and cancer. As well as developing the hardware, the student would develop and optimise specific protocols for sample preparation and imaging, as well as suitable software tools for data acquisition and analysis, e.g. using MicroManager and ImageJ plug-ins.
The ideal candidate would have a keen interest in the development and application of new biophotonics technologies and would welcome the multidisciplinary nature of the project and the application to lower resourced settings. They would have a first degree in physics or engineering with strong practical skills and competence in programming for image data acquisition and analysis. They would be required to acquire an advanced knowledge of optics and data analysis in the project and to learn sample preparation techniques for histopathology, including immunofluorescnce.
For more information please contact Prof Paul French.