Supervisors: Dr Philip Hands / Dr Toby Hurd / Dr Ann Wheeler / Prof Baljean Dhillon
This PhD research project will develop newly-emerging tuneable and highly-customisable liquid crystal laser
sources, and apply them to the field of fluorescence-based retinal imaging, for the detection of age-related
macular degeneration and other ophthalmic diseases.
Autofluorescent (or fluorescent-tagged) biomarkers such as lipofuscin, within the retinal pigment epithelium,
can be optically probed using lasers to search for ophthalmic medical abnormalities. Despite the potential
capabilities of this technique, its clinical adoption is somewhat limited, restricted to specialist laboratories.
Each fluorescent biomarker has its own specific optical absorbance range, and so medical equipment must
compromise between detection versatility (i.e. containing multiple lasers with different wavelengths, each
targeting a different marker, and hence be large, bulky and expensive), or portability (i.e. contain only a single
laser source addressing a single fluorophore, and hence be small and portable). Compromised systems must
also be built around the availability of existing light sources, which do not cover the full colour spectrum,
resulting in poor signal strength and signal ambiguity due to overlapping absorbances between multiple
Newly-developed liquid crystal (LC) lasers use self-assembling chiral nanostructures to create tuneable laser
cavities only 10 μm thick, and when doped with organic dyes enable simple, highly efficient and customisable
laser emission over the visible spectrum (450-850 nm). They have great potential as small, low-cost,
switchable and tuneable light sources for medical imaging applications, thus eliminating the requirement to
compromise between versatility, portability and cost, and potentially enabling cheaper, smaller and more
effective diagnostics tools. Tuneable LC lasers can be designed to perfectly match the absorbance
requirements of the biomarkers, maximising detection capabilities. They also provide a simple route to
providing new modalities of detection, such as ratiometric imaging and fluorescence lifetime imaging,
through temporal control of rapidly changing pulsed wavelength patterns.
Working in collaboration with engineers, biomedical scientists, ophthalmic clinicians and a world-leading
microscopy manufacturer on a highly interdisciplinary project, the student will demonstrate a proof-ofconcept
system using LC lasers to perform clinically-relevant fluorescence imaging of the retina for disease
diagnostics. They will use cleanroom microfabrication, opto-mechanical and electro-optical approaches to
construct bespoke LC laser and microscope systems (with properties including tuneable wavelengths and
temporal control of single or multiple simultaneous beams). LC lasers will be designed to optimally probe
multiple common fluorescent retinal markers simultaneously, and their performance advantages compared
to conventional sources will be validated. Further investigations will also be made into the clinical
opportunities of techniques such as ratiometric imaging and fluorescence lifetime imaging, enabled by LC
lasers, to provide improved data to the field of point-of-care ophthalmic disease detection. Opportunities for
commercial development will also be explored, in collaboration with our industrial partners.
Michael Chen (School of Engineering, UoE), Bin-zhi Qian (Edinburgh Cancer Research Centre, UoE)
Tumours are populated with not only malignant cells but also many other resident cells such as macrophages. Normally, macrophages act as the first defence line of the immune system and are specialised to kill and remove disease cells or foreign substances that may be harmful to human body. However, the macrophages in the tumour is a “double edged sword” and can either inhibit or promote tumour growth depending on their polarisation to different phenotypes including pro-inflammatory macrophages (M1; suppress tumour growth) or anti-inflammatory macrophages (M2; promote tumour development). It has been demonstrated that cancer therapy can affect the population of tumour macrophages. A high M1/M2 ratio is linked with extended survival of cancer patients. Therefore, the population of macrophages and the M1/M2 ratio is very important in assessing therapeutic outcome and status of tumour. Our goal is to develop a non-invasive fluorescence nanoprobe (materials science and chemical engineering) to specifically target M1/M2 tumour macrophages (cancer biology). Through this, the population of tumour macrophages and the M1/M2 ratio can be determined via optical imaging (physical science). The information will be used to assess the outcome of anticancer therapy and the status of tumour to guide doctors in treatment.
Duncan Graham (Dept of Pure and Applied Chemistry, UoS), Mark Arends (Cancer Research UK Edinburgh Centre, UoE), Karen Faulds (Dept of Pure and Applied Chemistry, UoS)
This project proposes a new approach to understand the local environment of DNA, including damaged DNA, within cancer cells using an imaging approach. In particular, we are interested in understanding if we can image changes in the local DNA environment using a new class of environmentally sensitive probes and Raman spectroscopy. This project will focus on the development of these probes, which is based on a specific change in vibration of a tagged molecule, when DNA found within cancer cells changes environment. This change in environment could come about due to different types of DNA damage, DNA base mismatches (e.g. G: C to G: T), or structural rearrangements, following exposure to external stimuli such as radiation or oxidative or alkylating agents. We propose to build on some exciting preliminary data to test the hypothesis of generating a specific environmentally sensitive probe in a number of different cell models and then in vivo imaging environments using Raman spectroscopy with the view to ultimately moving to stimulated Raman scattering microscopy to provide a faster imaging approach. This is an ambitious collaborative project between a group specialising in spectroscopy and a group with expertise in DNA mismatch repair and its relationship to cancer.
Khellil Sefiane (School of Engineering, UoE), John Christy (School of Engineering, UoE), Chris Gregory (MRC Centre for Inflammation Research, UoE)
There is a growing need to provide diagnoses at the ‘point-of-care’ (PoC) (i.e. near patient) in settings outside specialized hospital laboratories or clinics on minute (ideally ‘pinprick’) volumes of drawn material (usually venous blood). The provision of such diagnostics requires the identification of viable biomarkers for health and disease states, capable of being exploited in simple tests, with rapid, automated operation and analysis, and minimal operator training/experience. This is particularly true with cancer diagnosis and treatment, where timely detection of biomarkers of the disease (e.g. in extracellular vesicles) can significantly alter the prognosis for the patient.
Recent work indicates that exploitable biomarkers may be found in the pathological or therapeutic modification of certain haemorheological phenomena. One such phenomenon involves the formation of complex structural patterns during the drying of drops of blood on solid substrates whose complex stain morphologies are influenced by the original blood composition and, potentially, clotting abnormalities. The proposed project combines experimental optical techniques to establish a fundamental understanding of bio-drops drying patterns as a basis for developing simple, inexpensive clinical tests, capable of being performed at the PoC. Our team will create, characterise and study the drying of model bio-fluids that allow us to analyse the influence of the constitutive components on pattern formation. The study will focus on the patterns generated by extracellular vesicles that are present in all bio-fluids. Because extracellular vesicles carry a broad array of biologically active cargoes, they have been identified as highly important sources of biomarkers for disease. Here, we will focus on the contributions of extracellular vesicles and their constituents to pattern formation in drying droplets.
It is anticipated that the proposed research will lead to the development of a prototype smartphone camera-based device that exploits pathological and therapeutic influences on the pattern morphologies left behind by drying bio-drops for rapid and reliable PoC medical diagnosis.