The review is devoted to the analysis of the physical mechanisms of signal transduction in wearable sensors for non-invasive monitoring of biomarkers (glucose, acetone, water vapor, and other). The transition from metal oxides to graphene-biopolymer composites is considered. The advantages of the biomass of the cyanobacterium Spirulina platensis are substantiated: built-in redox centers (phycocyanin) and a hierarchical porous structure provide multimodal detection. It is shown that the operation of the sensors is based on reversible physical adsorption, determined by the energy of the surface and the geometry of the pores of the matrix. It has been established that binding selectivity is ensured not simply by adsorption, but by the synergy of electrostatic, donor-acceptor, and dimensional interactions that modulate charge transfer in the graphene percolation network. It is noted that the effect of concentration dominance in combination with the high differential sensitivity of the composite provides reliable detection of acetone against a background of high humidity at room temperature, which is promising for non-invasive diagnostic tasks.