Monitoring through Tissue the De-gelation of Alginate Gels by Different De-gelling Agents

Alginate gels are widely used for drug delivery and implanted devices. The rate at which these gels break down is important for controlling drug release. However, it is challenging to monitor the gel through tissue due to optical scattering and tissue autofluorescence. Herein we describe a method to detect through tissue the gelation and de-gelation processes of alginate gel using magnetically modulated optical nanoprobes (MagMOONs). The MagMOONs are fluorescent magnetic microspheres coated with a thin layer of opaque metal on one hemisphere. The metal layer prevents excitation and emission light from passing through one side of the MagMOONs, which creates an orientation-dependent fluorescence intensity. These magnetic particles also align in an external magnetic field and give blinking signals when they rotate to follow the magnetic field modulation. The blinking signals from these MagMOONs are distinguished from background autofluorescence and can be tracked on a single particle level in the absence of tissue, or by averaging an ensemble of particles through tissue. When these MagMOONs are dispersed in alginate gel, they become sensors for the detection of either the gelation with the addition of a multivalent cation (Ca

2 + 

, Cu

2 + 

) or the de-gelation as de-gelling agents like ammonium chloride, sodium citrate, or alginate lyase are added. Herein the release of copper ion as an antimicrobial from the gel can be tracked. Our method also can potentially be applied to detect bacterial biofilm formation and other biosensors and drug delivery systems based on enzyme-catalyzed breakdown of gel components.