Rapid Detection of Disease Biomarkers Using Novel Hydrogel Beads

Hydrogels are multifunctional biomaterials popularly used in a wide range of applications. In this thesis, calcium alginate hydrogels were thoroughly studied with a special focus on synthesizing calcium alginate hydrogel beads using a simple set up involving only a syringe and a gelation bath. By introducing an additional nonionic polymer component to the alginate solution during synthesis, the hydrogel beads exhibited greatly improved morphology with regard to uniformity and sphericity. These hydrogel beads also demonstrated excellent dye retention properties and stability in water. Additionally, they exhibited a gel-sol transition process in response to external stimuli such as calcium chelators. Taking advantage of these properties, the novel hydrogel beads were integrated in diagnostics applications for point-of-care detection of metabolic alkalosis and biomarkers in bacterial infections, with the degradation of gel and release of dye as disease indicators. For metabolic alkalosis detection, the assay utilized the reaction of sodium bicarbonate and citric acid to produce citrate, a metal chelator capable of competitively binding to calcium cations in the gel matrix to trigger hydrogel degradation. This resulted in successful detection of elevated bicarbonate concentrations in less than one hour. For detection of biomarkers in bacterial infections, novel hydrogel beads were synthesized with an additional enzyme substrate component in their gel matrix, which allowed for substrate cleavage and gel degradation to occur in the presence of bacterial enzymes. Results from preliminary studies showed that the gel-sol response of the hydrogel beads towards the bacterial enzymes α-amylase and trypsin was successfully achieved