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Development and characterization of an implantable biosensor for telemetric monitoring of ethanol in the brain of freely moving rats

Significance Statement

In the last decades, ethanol has assumed the role of the most widespread psychotropic agent in Western society because of its availability to the youth and adults and also because it is widely legally accepted. It has been largely demonstrated that acute and subchronic exposure to ethanol may have important repercussions on the Central Nervous System (CNS), therefore, it becomes significative to monitor the toxicokinetics and the effects of ethanol on the brain with the most appropriate techniques [1]. Biosensors are the emerging tool for the preclinical study of neurochemical changes in the brain. Recently, minimally invasive electrochemical biosensors have been developed for monitoring the real-time variations of ethanol concentrations in the brain of animal models. The ethanol biosensor exploits the presence of a biological element, the alcohol oxidase enzyme, to selectively transform ethanol into a directly-oxidizable by-product (hydrogen peroxide), amperometrically detectable on the surface of a platinum transducer [1, 2]. The main characteristics of this biosensor is represented by its capability of monitoring variations of ethanol in seconds or fractions of these, and over a period of two weeks. This tool have proved to be successful, especially when it have been associated with a miniaturized telemetric system, so that animals are allowed to be totally free to move. According to the results of this study, the developed ethanol biosensor has been demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in CNS extracellular fluids. The implantable biosensor, integrated into a low-cost telemetry system, represents a new generation of analytical tools for studying ethanol pharmacokinetics in early stages of addiction [3] and the effect of drugs on CNS ethanol levels in real time.


Further References

[1] Rocchitta G., Serra P.A. (2013). Direct monitoring of ethanol in the brain. OA Alcohol. 01;1(2):15. ISSN: 2053-0285.

[2] Secchi O., Zinellu M., Spissu Y., Pirisinu M., Bazzu G., Migheli R., Desole M.S., O’Neill R.D., Serra P.A. and Rocchitta G. (2013) Further in-vitro characterization of an implantable biosensor for ethanol monitoring in the brain. Sensors. 13(7), 9522-9535. ISSN: 1424-8220.

[3] Fellet M. Electrode Measures Brain Alcohol Levels In Tipsy Rats (Biosensors: Implantable wireless electrode could help track ethanol’s changes to rat brain chemistry). Chemical and Engineering News. August 2012. ISSN 0009-2347.


Development and Characterization of an Implantable Biosensor for Telemetric Monitoring of Ethanol in the Brain of Freely Moving Rats- Global Medical Discovery









Rocchitta G, Secchi O, Alvau MD, Migheli R, Calia G, Bazzu G, Farina D, Desole MS, O’Neill RD, Serra PA.

Anal Chem. 2012 Aug 21;84(16):7072-9.

Department of Clinical and Experimental Medicine, Medical School, University of Sassari, Viale S. Pietro 43/b, 07100 Sassari, Italy.



Ethanol is one of the most widespread psychotropic agents in western society. While its psychoactive effects are mainly associated with GABAergic and glutamatergic systems, the positive reinforcing properties of ethanol are related to activation of mesolimbic dopaminergic pathways resulting in a release of dopamine in the nucleus accumbens. Given these neurobiological implications, the detection of ethanol in brain extracellular fluid (ECF) is of great importance. In this study, we describe the development and characterization of an implantable biosensor for the amperometric detection ofbrain ethanol in real time. Ten different designs were characterized in vitro in terms of Michaelis-Menten kinetics (V(MAX) and K(M)), sensitivity (linear region slope, limit of detection (LOD), and limit of quantification (LOQ)), and electroactive interference blocking. The same parameters were monitored in selected designs up to 28 days after fabrication in order to quantify their stability. Finally, the best performing biosensor design was selected for implantation in the nucleus accumbens and coupled with a previously developed telemetric device for the real-time monitoring of ethanol in freelymoving, untethered rats. Ethanol was then administered systemically to animals, either alone or in combination with ranitidine (an alcohol dehydrogenase inhibitor) while the biosensor signal was continuously recorded. The implanted biosensor, integrated in the low-cost telemetry system, was demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in brain ECF and represents a new generation of analytical tools for studying ethanol toxicokinetics and the effect of drugs on brain ethanol levels.


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