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. The development of a technology capable of tracking the levels of drugs, metabolites, and biomarkers in the body continuously and in real time would advance our understanding of health and our ability to detect and treat disease. It would, for example, enable therapies guided by high-resolution, patient-specific pharmacokinetics (including feedback-controlled drug delivery), opening new dimensions in personalized medicine. In response, we demonstrate here the ability of electrochemical aptamer-based (E-AB) sensors to support continuous, real-time, multihour measurements when emplaced directly in the circulatory systems of living animals. Specifically, we have used E-AB sensors to perform the multihour, real-time measurement of four drugs in the bloodstream of even awake, ambulatory rats, achieving precise molecular measurements at clinically relevant detection limits and high (3 s) temporal resolution, attributes suggesting that the approach could provide an important window into the study of physiology and pharmacokinetics.
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