Monitoring drug levels through responsive hydrogel sensors

 

Outline, including interdisciplinary dimension

The monitoring of drug levels in complex samples such as blood or urine is challenging. Many active substances have a narrow therapeutic window of concentration over which they are effective. Below these levels, no therapeutic effect is observed, but above these levels toxic side-effects become prevalent. This can be particularly problematic for neonates, where dosage regimens for many drugs of this type are not well-established. Typically, to monitor these substances, an involved laboratory process of separation and assay can lead to results taking longer to obtain than the duration of effect of the drug itself. In such circumstances, therapeutic monitoring is impossible to achieve.

In this project, we will build on previous collaborative interdisciplinary work by the applicants on selective soft-matter sensing to develop rapid-response systems which are practically interference free and require no sample preparation. We will exploit the applicants’ extensive experience in design of selectively-assembled hydrogels to design drug-selective gelating materials, which will contain lanthanide-based sensors to read-out the degree of gelation, and hence drug concentration, via ultrasensitive detection of light emission. The lanthanide sensors, which are the expertise of the Gunnlaugsson group, have considerable advantages in read-out of concentration; emission is of a long lifetime, and is long wavelength, which mitigates against background autofluorescence from blood or urine. Additionally, emission can be finely-tuned to switch ‘on’ or ‘off’ in the presence or absence of the analyte respectively.

The synergistc application of materials science from the McCoy group with the sensing expertise of the Gunnlaugsson group will provide an outstanding training environment in industrially-relevant fields.

The materials developed will allow, for the first time, real-time monitoring of circulating blood concentrations of drugs to be available to clinicians, to inform more effectively dosing regimens. This in turn, will have impact in clinical outcomes for patients.

Key words/descriptors

theraupeutic monitoring, sensing, drugs, monitoring, polymers, light, selectivity

First supervisor

Professor Colin McCoy - School of Pharmacy

Secondary supervisor from a complementary discipline

Professor Thorfinnur Gunnlaugsson - Trinity College Dublin

Supervisors’ track record of PhD completions, plus excellence and international standing in the project area

Professor Colin McCoy has supervised 18 PhD students, 14 of whom have graduated and 4 are in their first, second or third year of PhD study. He has also co-supervised 14 PhD students, 12 to completion and 2 of whom are completing their studies. He has published more than 100 peer-reviewed articles in journals including Nature, and has a citation rate of over 100 citations/paper over his career. His research has attracted more than £4M in funding from RCUK, The Royal Society, The Wellcome Trust and international medical devices companies.

Professor Gunnlaugsson has supervised more than 40 PhD students to completion. He is an acknowledged world leader in the field of luminescent sensors and has published over 200 papers in the field. He is one of the most highly-cited scientists in Ireland and has received in excess of €6M in research funding.

The supervisors have published a series of high-impact papers together on soft matter sensing over the last ten years, and currently collaborate on a €3M SFI-funded programme in the field.

Intersectoral exposure and/or international mobility

(e.g. secondments to/collaboration with partner organizations)

The PhD student will be primarily based in Queen’s, but will have the opportunity for secondment to the Gunnlaugsson lab in Trinity College Dublin to avail of their facilities, training environment and supervision. There will be significant intersectoral exposure, with the student experiencing biomaterials, materials science and advanced materials characterisation sectors in Belfast, and synthesis, luminescence and molecular assembly fields in Dublin. The student will be involved with existing industrial relationships in both laboratories, which span the medical device and sensor sectors across both sites.

Describe briefly the international profile of the partner

Professor Gunnlaugsson is a principal investigator at the Trinity Biomedical Sciences Institute. He was appointed as the Kinerton (IPSEN) Lecturer in Medicinal Organic Chemistry at the School of Chemistry, University of Dublin, Trinity College, in October 1998 and a Lecturer in Organic Chemistry in 2000. He was made a Fellow of Trinity College Dublin in 2003. In October 2004 he was appointed as an Associate Professor of Organic Chemistry at the same department amd in 2008 a personal chair and Professor in Chemistry. He was a Visiting Professor at Faculty of Science and Technology- School of Life and Environmental Sciences. Deakin University, Victoria, Australia in 2005. In 2008 he was a visiting Professor in Bordeaux I CNRS in 2008. His research interests are in theareas of supramolecular organic and inorganic chemistry and bio and medicinal chemistry, with emphasis on the recognition and targeting of biologically important ions and molecules. He has given numerous invited keynote addresses at international conferences.

Training that will be provided through the research project itself

The project will give a diverse and interdisciplinary training in pharmaceutical and materials science, together with partner input in supramolecular chemistry, sensor development and characterisation. Training will be in the fields of organic synthesis, sensor fabrication, spectroscopy, materials characterisation, separation science and microscopy.

Examples of additional training in non-research transferable skills

Additional training will be given in presentation skills, scientific writing skills and general communication skills. Additionally, training in business and intellectual property, which are important aspects of the project, will be given. The ability to liaise with two teams of scientists and lay audiences such as industrial partners will also be given. McCoy recently received a Postgraduate Supervisory Excellence Award for his comprehensive and holistic approach to postgraduate supervision and career development.

Expected dissemination of results: peer-reviewed journals, seminars, workshop and conferences at European/international level

(e.g. public talks, visits to schools, open days, QUB impact showcase)

The project is anticipated to result in several high-impact peer-reviewed publications. The application collaboration to date has a proven track record of this. Additionally, attendance at international conferences is expected from students in both groups, with oral and poster presentations likely to arise. The groups will meet regularly and the student will give seminars in both institutions.

Expected impact activities

(e.g. public talks, visits to schools, open days, QUB impact showcase)

Such partnerships make excellent showpieces for our research and network activities. As such, the work is likely to attract school audiences (McCoy presents at a W5 School event already, and this material will make an excellent showcase), and be highlighted by both institutions in Open events. As IP is expected to arise from the project, the exploitation of this will potential industrial commercialisation partners is also anticipated to have societal and economic impact also.