An important difference between observations in PBS and serum at 37˚C is that the redox-tag currents eventually increase for both the MCH and MCO sensors at 37˚C in serum (Figure ), whereas in PBS at 37˚C (Figure ) the redox tag currents monotonically decreased with time. We speculate that once protein molecules interact with the surface of a sensor, they undergo full or partial unfolding with a high degree of freedom to reposition and rearrange. Some of the protein molecules will adsorb directly onto the surface of the gold electrode where the passivation layer has partially desorbed. Due to their large size and the ability to undergo rearrangement, the biofouled protein/peptide layer is rich in imperfections, such as pinholes and large uncoordinated gold domains, that are readily available for efficient electron-transfer due to a lower charge-transfer resistance. This results in the increase in the redox-tag and oxygen reduction currents seen in Figure . Furthermore, all of these thermally-governed processes are largely impeded at 4 ˚C, resulting in much more stable redox-tag currents and lower oxygen reduction currents over multiday operation (Figure ). Also of interest, the initial ~30-50% exponential loss in redox tag current typically seen at 37 ˚C over the first ~3 hours (Figure ) occurs more slowly over ~24 hours at the lower temperature of 4 ˚C. Furthermore, the first 12 hours at 37 ˚C and the first several days at 4 ˚C both reveal the 'exponential' and subsequent 'linear' phases of degradation previously described in the literature, as data from sensors tested at both temperatures closely mirror one other and differ only in the timescales over which the aforementioned phases occur (see Supplemental Figure ). This observation demonstrates the energetic dependence governing biofouling kinetics as dictated by the rate of protein unfolding and rearrangement. This is further illustrated by the finding that the rate of fouling is somewhat dependent on periodicity of electrochemical scanning (Figure ), a process that locally imparts energy and likely drives rearrangement of the biofouled layer.