Hydrogel Beads for the Detection of Disease Biomarkers in Resource-Limited Settings

Point-of-care (POC) diagnostics are easy-to-use, low-cost devices that can rapidly detect a biomarker of interest without the need for highly trained personnel or expensive equipment. In resource-limited settings, POC testing is often the only viable option for patients, which highlights the importance of developing sensitive technologies for early disease detection and monitoring of treatment methods. Hydrogels are flexible 3D structures made with crosslinked hydrophilic components that absorb large amounts of water. These systems are sensitive to different chemical or physical stimuli, and the magnitude of their response is usually directly proportional to the magnitude of the applied external stimuli. In the diagnostics field, hydrogels are mostly being used for enzyme detection and immunodiagnostics. For these applications, the biomarker acts as a signal that triggers a volume, color, or state change of the hydrogel, an example of the latter being a gel-sol transition or vice versa. This technology often requires the chemical modification of at least one of the main hydrogel components so that the system is specific towards the molecule of interest. Accordingly, these devices need to be manufactured in a laboratory setting with complex equipment and often expensive reagents, and they also require personnel with extensive knowledge and experience to conduct the assay and its analysis. Thus, it would be desirable to design a hydrogel system that is responsive to the presence of the biomarker of interest without the need for chemical modification of the reagents to design a robust, POC-friendly device that can be manufactured in all parts of the world. To develop this system, we focused on calcium alginate dextran hydrogels beads for the detection of abnormal concentrations of ions, such as bicarbonate and phosphate, in patient samples. This system can be synthesized by a simple ionic crosslinking method based solely on the complexation of the oppositely charged species, i.e., alginate and calcium, which comprise the gel matrix. For disease detection, we took advantage of a calcium depletion mechanism based on the reaction of the biomarkers of interest with the divalent calcium cation in the calcium alginate gel matrix. The timeframe for hydrogel degradation was therefore correlated with the sample’s ion concentration, making our POC device semi-quantitative. To our knowledge, this is the first demonstration of the use of nonionic polymers to improve the morphology of calcium alginate hydrogel beads using a simple processing method that involves minimal labor, equipment, and reagents. The simplified bead synthesis protocol combined with a user-friendly device that we developed allows for the rapid detection of high serum bicarbonate or urine phosphate levels at the POC