Current
knowledge of the disposition kinetics of endogenous metabolites
is founded almost entirely on poorly time-resolved experiments in
which samples are removed from the body for later, benchtop analysis.
Here, in contrast, we describe real-time, seconds-resolved measurements
of plasma phenylalanine collected in situ in the body via electrochemical
aptamer-based (EAB) sensors, a platform technology that is independent
of the reactivity of its targets and thus is generalizable to many.
Specifically, using indwelling EAB sensors, we have monitored plasma
phenylalanine in live rats with a few micromolar precision and a 12
s temporal resolution, identifying a large-amplitude, few-seconds
phase in the animals’ metabolic response that had not previously
been reported. Using the hundreds of individual measurements that
the approach provides from each animal, we also identify inter-subject
variability, including statistically significant differences associated
with the feeding status. These results highlight the power of in vivo
EAB measurements, an advancement that could dramatically impact our
understanding of physiology and provide a valuable new tool for the
monitoring and treatment of metabolic disorders.