Electrochemical Nitric Oxide Sensors for Biological Samples – Principle, Selected Examples and Applications

Abstract

The discoveries made in the 1980s that NO could be synthesized by mammalian cells and could act as physiological messenger and cytotoxic agent had elevated the importance of its detection. The numerous properties of NO, that enable it to carry out its diverse functions, also present considerable problems when attempting its detection and quantification in biological systems. Indeed, its total free concentration in physiological conditions has been established to be in nanomolar range. Thus, detection of nitric oxide remains a challenge, pointing out the difficult dual requirements for specificity and sensitivity. Exception made for the electrochemical techniques, most of the approaches (namely UV-visible spectroscopy, fluorescence, electron paramagnetic resonance spectroscopy) use indirect methods for estimating endogenous NO, relying on measurements of secondary species such as nitrite and nitrate or NO-adducts. They also suffer from allowing only ex situ measurements. So, the only strategies that allow a direct and in vivo detection of NO are those based on the use of ultramicroelectrodes. The reality is that surface electrode modification is needed to make the ultramicroelectrode material selective for NO. Therefore, the design of modified electrode surfaces using organized layers is very attractive and provides the ideal strategy. This review addresses a global description of the various approaches that have involved chemically modified microelectrodes specially designed for the electrochemical detection of NO in biological media. Selected significant examples of applications in biological tissues are also reported in order to highlight the importance of this approach in having new insights into the modulatory role of NO in physiology and pathophysiology.

Nitric oxide in brain: diffusion, targets and concentration dynamics in hippocampal subregions

“…Considering the role of NO Å as a diffusible messenger in the brain, the need to achieve a dynamic detection of NO Å at low nM levels in tissues with appropriate spatial and temporal resolution led to the development of selective electrochemical microsensors in connection with diverse electrochemical techniques (reviewed in Bedioui and Villeneuve, 2003). Commonly, electrochemical sensors exhibit a detection limit in the vicinity of 1-10 nM, a linear response up to lM range and an accuracy of 5-10%.…”

“…A second hallmark in the development of microsensors was the introduction of catalytic electrode surfaces by Malinski and Taha (1992), who used a carbon fiber electrode modified by the electropolymerization of Ni(II)-porphyrin. Following this advance, the deposition of polymeric films that catalyse NO Å oxidation at the electrode surface became an attractive approach and several materials have been proposed, including different types of metalloporphyrins, metallophtalocyanines, copper-platinum microparticles, palladium and iridium oxide (Bedioui and Villeneuve, 2003). In most cases, the catalytic films are combined with molecular/ionic filters in order to achieve higher selectivity, including, as the most common, Nafion â , o-phenylenediamine (Friedemann et al, 1996;Pontie et al, 1999), polylysine and polypyridinium (Mitchell and Michaelis, 1998).…”

“…Amperometry is a highly sensitive analytical electrochemical technique (although suffering from lack of selectivity) often selected to detect NO Å in vivo, but, under conditions of high NO Å concentrations, selectivity can be improved by using fast cyclic voltammetry (FCV) (Ledo et al, 2002) and differential pulse voltammetry (Bedioui and Villeneuve, 2003). The oxidation and reduction peaks obtained with FCV provide the ''redox signature'' of the active species.…”

Real-time electrical detection of nitric oxide in biological systems with sub-nanomolar sensitivity

“…To this end, the reliable and specific detection of NO with high spatiotemporal resolution is essential. However, the accurate determination of NO concentration is of significant challenge because of its low concentration (nanomolar scale) and relatively short half-life time (6-50 s) in biological systems 6,7 . Indirect detection methodswhich rely on sensing secondary species such as nitrite and nitrate-are inherently ineffective for real-time detection.…”

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

“…A variety of amperometric sensors specifically developed for the analysis of NO recently has been reviewed [325,326,328,329]. In combination with CE, the ECD techniques (CEECD) expand the range of accessible analytes without derivatization.…”