In Brain and in Vein Detection of Antibiotics Using Electrochemical-DNA Biosensors

Abstract

Current approaches towards drug dosing rely on venous draws measurements performed on test patients which are laboratory-analyzed and returned the following days. This practice forces physicians to administer potentially toxic or ineffective concentrations of drugs to patients since dosages are determined based on weight and age of this test group even though pharmacokinetics may differ in each individuals. Having a technology that would in contrast allow, direct, continuous, real-time monitoring of drugs in the living body would revolutionize healthcare and allow personalized drug dosage and adjustment while enabling the development of artificial organs responsible of adjusting these levels.Motivated by this goal, we have developed a class of electrochemical aptamer-based (E-AB) sensors[1]. These sensors are comprised of a redox-reporter-modified DNA “probe” that is attached by one terminus to a self-assembled monolayer deposited on an interrogating gold electrode. The binding of an analyte to this probe alters the kinetics with which electrons exchange to/from the redox reporter via binding-induced conformational changes producing an easily measured change in current when the sensor is interrogated using square-wave voltammetry (see Figure) [2]. E-AB sensors are capable of detecting with high specificity their molecular targets in flowing whole blood and directly in the living body. I will present during this presentation some of these sensors deployed in the vein [3] and in the brain of sedated rats to monitor the pharmacokinetics of the antibiotic, vancomycin. The ability of acquiring high frequency measurements of drug plasma levels using these biosensors has also allowed us to develop a technology that improves our ability to deliver them [3]. Due to their small size, these sensors can also be deployed directly in the brain of freely moving animals to monitor molecules with unmatched temporal resolution [4]. All these advancement in developing E-AB sensors are aimed towards developing new analytical tools for personalized medicine while improving our understanding of drug metabolism.[1]: Dauphin Ducharme, P. and Plaxco, K. W. Anal. Chem. 2016 88: 11654–11662.[2]: Li, H., Dauphin Ducharme, P., Ortega, G., Plaxco, K. W. J Am. Chem. Soc. 2017, 139, 11207-11213.[3]: Dauphin-Ducharme, P., Yang, K., Arroyo-Currás, N., Ploense, L. K., Zhang, Y., Gerson, J., Kurnik, M., Kippin, T. E., Stojanovic, M., Plaxco, K. W. ACS Sensors 2019, 4, 2832-2837.[4]: Ploense, K. L., Dauphin-Ducharme, P., Arroyo-Currás, N., Curtis, S. D., Williams, S., Schwarz, N., Kippin, T. E., Plaxco, K. W. 2019 In preparation. Figure 1