Real-time measurement of small molecules directly in awake, ambulatory animals

Significance The ability to monitor arbitrary molecules directly in living subjects as they undergo their daily routines remains one of the “holy grails” of bioanalytical chemistry. Such a technology would, for example, vastly improve our knowledge of physiology, pharmacokinetics, and toxicology by allowing the high-precision measurement of drugs and metabolites under realistic physiological conditions. Real-time molecular measurements would also provide an unparalleled window into health status (e.g., kidney function) and would facilitate “therapeutic drug monitoring,” in which dosing is personalized to the specific metabolism of each individual patient. Finally, the ability to measure molecules in the body in real time would provide unprecedented new routes by which drugs with dangerously narrow therapeutic windows could be safely and efficiently administered.