Biosensing Platforms to Detect Bacterial Lectins

Identifying bacteria, and biomarkers associated with their infection, remains a challenge in clinical settings. While many molecular targets are available, the complexity of bacterial analytes, particularly within chronic or polymicrobial infections makes it difficult to rely on classical ‘lock-and-key’ biosensors alone. Array-based sensing platforms are therefore better suited to capture this complexity.
Carbohydrates are particularly attractive recognition elements as they mediate many biological interactions at the host–pathogen interface. Nature has demonstrated how multivalency can be exploited to facilitate interactions that would not otherwise occur. Synthetic macromolecular scaffolds that present multiple sensing elements have been shown to differentiate between biological analytes. Moreover, cross-reactive sensor arrays that exploit these interactions have shown promise for rapid bacterial detection in clinically relevant contexts, though their full capabilities remain underexplored.
This thesis will investigate routes to synthesise glycopolymers with enhanced stability and conjugation efficiencies for potential use in a number of platforms. A novel monomer has been synthesised and incorporated into a variety of homopolymer and copolymer scaffolds. The stability and conjugation efficiency of the resulting polymers are compared to that of literature examples.
A fluorescent glycopolymer array has also been synthesised and applied to discriminate between Pseudomonas aeruginosa strains with known differences in phenotype including transposon-insertion mutants and clinical isolates from people with cystic fibrosis. Moreover, P. aeruginosa could be identified as unique from other common lung co-infectants, highlighting the sensors array’s potential applications in complex clinical problems.
Finally, glycopolymers were conjugated to screen printed graphite electrodes, enabling electrochemical biosensing on a widely available and low-cost platform. Initial studies of lectin sensing showed potential cross-reactivity, highlighting the promise of this approach for integration into array-based electrochemical platforms.