Seconds-Resolved, In Situ Measurements of Plasma Phenylalanine Disposition Kinetics in Living Rats

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 phenylalan...

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Published inAnalytical chemistry (Washington) Vol. 93; no. 8; pp. 4023 - 4032
Main Authors Idili, Andrea, Gerson, Julian, Kippin, Tod, Plaxco, Kevin W
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 02.03.2021
Subjects
analytical chemistry
Animals
Aptamers
Aptamers, Nucleotide
biochemical pathways
Chemical sensors
Chemistry
Electrochemistry
In situ measurement
Kinetics
Metabolic disorders
Metabolic response
Metabolism
Metabolites
pharmacokinetics
Phenylalanine
Rats
Sensors
Statistical analysis
Statistical methods
Temporal resolution
Time measurement
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Summary: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.
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A.I. and J.G. contributed equally to this work.
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.
ISSN:0003-2700
1520-6882
1520-6882
DOI:10.1021/acs.analchem.0c05024