Figure 4.

When placed in situ in the body EAB sensors drift.^19,21,22 To correct this, we employed kinetic differential measurements (KDM).^19,29 (A) Normalized signals collected at 300 Hz (black) and 10 Hz (red) square-wave frequencies drift in concert, such that taking their difference via KDM eliminates the drift. (B) Using KDM we can easily see the results of serial increasing intravenous injections of phenylalanine in an anesthetized rat. The 12 s time resolution achieved in these measurements is sufficient to monitor both the injection itself and the subsequent distribution of the metabolite within the body. This reflects a 30-fold improvement over the time resolution of the best prior studies of phenylalanine metabolism kinetics in either rats or humans.^{31,36,38–42} (C) As expected, the in-vivo sensor does not respond to intravenous injections of either a saline “blank” or the aromatic amino acids tyrosine or tryptophan at the indicated dosages.