title: Real-time, aptamer-based tracking of circulating therapeutic agents in living animals.
abstract: 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.
authors.affiliation: Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Brian Scott
authors.initials: BS
authors.lastname: Ferguson
authors.forename: David A
authors.initials: DA
authors.lastname: Hoggarth
authors.forename: Dan
authors.initials: D
authors.lastname: Maliniak
authors.forename: Kyle
authors.initials: K
authors.lastname: Ploense
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: White
authors.forename: Nick
authors.initials: N
authors.lastname: Woodward
authors.forename: Kuangwen
authors.initials: K
authors.lastname: Hsieh
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bonham
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenstein
authors.forename: Tod E
authors.initials: TE
authors.lastname: Kippin
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Plaxco
authors.forename: Hyongsok Tom
authors.initials: HT
authors.lastname: Soh
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide; D015374:Biosensing Techniques / Q000379:methods*; D003920:Diabetes Mellitus / Q000097:blood; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007612:Kanamycin / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D044085:Microfluidics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052157:Aptamers, Nucleotide; D007612:Kanamycin; D004317:Doxorubicin