Although short term experiments suggest that foulants in serum can further stabilize the monolayer, over multiple days these foulants locally promote desorption, which can also be resolved by increased alkylthiolate chain length (Figure ). While electrochemical aptamer sensors have been shown to operate in complex biofluid media, such as blood and serum, demonstrations have previously been limited to several hours and longer-term studies for more than 24 hours have been limited to more hydrophobic monolayers, such as those employing 1-hexanethiol, which are known to exhibit superior monolayer stability but foul much more severely. It is known that biofouling of the electrode surface by large solutes such as albumin can alter sensor performance and electron transfer kinetics. Typically, for aptamer sensors with hydroxyl-terminated alkylthiolates such as MCH or MCO, a rapid exponential loss of sensor redox tag current (~30-50%) is seen within the first 3 hours, followed by a period of slow and more linearly stable current loss for several hours thereafter. It has also been shown that the foulants in serum driving this loss in current are passivating unoccupied sites on the gold surface, thus flattening the baseline in the range of the potentials where otherwise oxygen reduction would be pronounced. The results here show that while foulants can initially passivate larger defects in the monolayer, over the long term the biofouled layer actually caused desorption of the monolayer at a faster rate compared to experiments performed in PBS.