Advancing the Development of Subcutaneous Glucose Biosensors: Cargo‐Carrying Adhesive Biosensor Systems (CABs)

The development of an injectable, subcutaneous glucose biosensor may be advanced by utilizing optical glucose sensing assays. However, this requires a strategy to effectively house small-sized assay molecules. Herein, "CABs" or cargo-carrying adhesive biosensors were constructed via the electrostatic adhesion of a hollow rod membrane (whose cavity could store a liquid optical-assay) and hydrogel caps. For the CAB 'wall', the hollow rod leveraged a comb double network (DN) design previously shown to limit biofouling and reduce mesh size. To regulate the mesh size, poly(AMPS)-methacrylate (PAMPS_n-MA) comb macromers were incorporated into the 1st network. To improve electrostatic adhesivity, anionic 2-acrylamido-2-methylpropane sulfonic acid (AMPS) was incorporated into the second network of the DN hydrogels at varying concentrations. For the CAB 'cap' with a cationic surface, a semi-interpenetrating polymer network was formed, comprised of crosslinked polyampholyte and non-crosslinked cationic polyelectrolyte. A CAB was constructed with a CAB wall based on a DN hydrogel composition shown to exhibit the requisite thermosensitivity, mechanical robustness, glucose diffusivity, low mesh size (4 nm < ξ < 7 nm), and adhesivity to the CAB cap. Using FITC-dextran solutions, the CAB was shown to retain ∼90% of molecules of low hydrodynamic diameters (D_h ∼ 7 nm and D_h ∼ 10 nm).