First-generation amperometric glucose biosensors are the most commonly used method for glucose monitoring in neuroscience. Nevertheless, biosensors of this genre suffer from the so-called "oxygen deficit". This problem is particularly acute when the oxygen concentration is low, as is the case in brain extracellular fluid. In the present work we use different fluorocarbons, such as Nafion and H700, to mitigate the oxygen deficit. These fluorocarbon-derived materials display a remarkable solubility for oxygen, and are able to act as oxygen reservoirs supporting the enzymatic reaction. Different biosensor configurations are presented, evaluating their sensitivity, linear range and oxygen dependence. Optimized Nafion- and H700-modified biosensors displayed a remarkable oxygen tolerance, with K-M(O-2) values as low as 11 and 4 mu mol L-1, respectively, and an appropriate sensitivity for in-vivo applications. Finally, in-vivo data are reported in order to illustrate the application of such devices in neuroscience applications. (C) 2014 The Electrochemical Society. All rights reserved.