About the Project
Development of a electrochemical sensor platform in order to thermally measure antimicrobial resistance (involving antibiotic compounds and bacteria). This combines polymerization techniques to functionalize sensors and biological aspects to measure biological compounds. The applicant will have the possibility to work with cutting-edge thermal technology.
Aims and objectives
The World Health Organization recently stated that antimicrobial resistant (AMR) bacteria pose a fundamental threat to human health. Over 3 million European patients suffer from hospital acquired infections and approximately 50,000 patients die annually from these infections. Current gold standard techniques to determine bacterial strains are time-consuming. These include either conventional culture-based assays, which require a minimum of 48 hours to obtain a result, or genotyping-based methods, which depend upon access to expensive laboratory infrastructure and have a measurement time of ~2h.
The goal of this project is to develop a sensor platform that would make a step change by reducing measurement time to <15 min, and faster diagnosis enables earlier initiation of treatment which will improve clinical outcome and will lead to cost reductions4. In addition, the developed sensor platform will be compatible for the simultaneous in-situ monitoring of various analytes, including antibiotics and bacteria. This is complicated by variation in size and structure of these compounds, and conventional methods are not able to monitor them in-situ. Monitoring these analytes is key to combatting drug resistant infections and will provide insight into factors that trigger the development of AMR bacteria. The ability to measure under extreme environments (pH, organic solvents) will make the developed sensor platform attractive for various industries, such as environmental analysis, clinical applications and the food industry.
Therefore, we will focus on the development of a biosensor tool for the determination of bacteria and antibiotic compounds in this proposal. Molecularly Imprinted Polymers (MIPs) are synthetic receptors that are prepared via imprinting technology and can be tailored towards their analyte. These MIPs have commercial applications in chromatography columns and in the cosmetics, but are not used currently in biosensor platforms. The key issues that need to be addressed to move towards commercial applications are mass-production of MIP sensors and the development of fast and low-cost sensing technologies that offer straightforward detection.
In this proposal, we will use electrochemical methods to miniaturize the imprinted layers and to directly deposit MIPs onto SPEs, which will enhance the suitability of the sensors for diagnostics. Preliminary work was performed using pyrrole as monomer and a methicillin-susceptible S. aureus strain as a template molecule. This strain from Prof. Enright’s library is an isolate of the UK-EMRSA 15-clone, which is of high relevance since it is the most tenacious and most rapidly spreading clone. Upon optimization of various parameters, sensors with 200 nm thick MIP layers were obtained after 60s of polymerization. These sensors were subsequently mounted into the developed device and the thermal resistance was measured, showing this sensor platform is suitable as a tool for screening.
We will use electropolymerization to deposit MIP layers onto SPEs, which allows control over the surface architecture by adapting the reaction time, voltage and monomer concentration. It is essential for the selective detection of bacteria to have imprint sites that correspond to the size and shape of the template molecule, and contain chemical functionalities that specifically target the cell wall-anchored proteins of a particular bacterial strain. We have identified five amino-functionalised monomers (e.g. pyrrole, 4-aminophenol, 4-aminothiophenol, aniline and dopamine) from databases as potential agents. The positive charge of the amino group is able to form hydrogen bonds or ionic interactions with the anionic charge of the surface proteins.
The proposed research aims to develop a polymer-based bio-sensing platform for the detection of bacteria and antibiotic compounds. The primary objectives of this project are to manufacture MIP-based biosensor platforms using electrochemical methods and use those to measure bacterial strains and their antimicrobial resistant counterparts. Furthermore, we will explore the commercial potential of the developed thermal biosensor platform by Dr. Peeters and build collaborations with relevant industrial partners.
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