Real-time, aptamer-based tracking of circulating therapeutic agents in living animals.

TitleReal-time, aptamer-based tracking of circulating therapeutic agents in living animals.
Publication TypeJournal Article
Year of Publication2013
AuthorsFerguson BScott, Hoggarth DA, Maliniak D, Ploense K, White RJ, Woodward N, Hsieh K, Bonham AJ, Eisenstein M, Kippin TE, Plaxco KW, Soh HTom
JournalSci Transl Med
Date Published2013 Nov 27
KeywordsAnimals, Aptamers, Nucleotide, Biosensing Techniques, Diabetes Mellitus, Doxorubicin, Humans, Kanamycin, Male, Microfluidics, Rats, Rats, Sprague-Dawley

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients' health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at subminute temporal resolution. We show that MEDIC can also obtain pharmacokinetic parameters for individual animals in real time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe that MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters.

Alternate JournalSci Transl Med
PubMed ID24285484
PubMed Central IDPMC4010950
Grant List1S10RR022585-01A1 / RR / NCRR NIH HHS / United States
R01 AI076899 / AI / NIAID NIH HHS / United States
R01 DA027525 / DA / NIDA NIH HHS / United States
R01 EB007689 / EB / NIBIB NIH HHS / United States
R01A1076899 / / PHS HHS / United States
U01HL099773-01 / HL / NHLBI NIH HHS / United States
U54 DK093467 / DK / NIDDK NIH HHS / United States