Nitric oxide (NO) electrochemical sensors - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 2

characterized by Joseph Priestly in 1772. However, until the mid-1980s, NO was
regarded as an atmospheric pollutant and bacterial metabolite. Nitric oxide (NO) is
a hydrophobic, highly labile free radical that is catalytically produced in biological
systems from the reduction of L-arginine by nitric oxide synthase (NOS) to form
L-citrulline, which produces NO in the process. In biological systems NO has long
been known to play various roles in physiology, pathology and pharmacology [2].
In 1987 NO was identifi ed as being responsible for the physiological actions of
endothelium-derived relaxing factor (EDRF) [3]. Since that discovery, NO has been
shown to be involved in numerous biological processes such as: vasodilatation and
molecular messaging [3]; penile erection [4]; neurotransmission [5, 6]; inhibition of
platelet aggregation [7]; blood pressure regulation [8]; immune response [9]; and
as a mediator in a wide range of both anti-tumor and anti-microbial activities [10,
11]. In addition, NO has been implicated in a number of diseases including diabe-
tes [12], and Parkinson's and Alzheimer's diseases [13]. The importance of NO was
confi rmed in 1992 when Science magazine declared NO the “Molecule of the Year”
and in 1998, F. Furchgott, Louis J. Ignarro, and Ferid Murad were awarded the
Nobel Prize in Physiology and Medicine for unraveling the complex nature of this
simple molecule. Despite the obvious importance of NO in so many biological proc-
esses, less than 10% of the thousands of scientifi c publications over the last decade
dedicated to the fi eld of NO research involve its direct measurement.

1.1.2 Methods of measurement of nitric oxide in physiology
As stated above, NO plays a signifi cant role in a variety of biological processes where
its spatial and temporal concentration is of extreme importance. However, the meas-
urement of NO is quite diffi cult due to its short half-life (

5 sec) and high reactivity
with other biological components such as superoxide, oxygen, thiols, and others. To
date, several techniques have been developed for the measurement of NO including:
chemiluminescence [14, 15]; Griess method [16]; paramagnetic resonance spectrome-
try [17]; paramagnetic resonance imaging; spectrophotometry [18]; and bioassay [19].
Each of these techniques has certain benefi ts associated with it but suffer from poor
sensitivity and the need for complex and often expensive experimental apparatus. In
addition, the above NO sensing techniques are limited when it comes to continuous
monitoring of NO concentration in real time and most importantly in vivo .

1.1.3 Advantages of electrochemical sensors for determination of NO
To date, electrochemical (amperometric) detection of NO is the only available technique
sensitive enough to detect relevant concentrations of NO in real time and in vivo and suf-
fers minimally from potential interfering species such as nitrite, nitrate, dopamine, ascor-
bate, and L-arginine. Also, because electrodes can be made on the micro- and nano-scale
these techniques also have the benefi t of being able to measure NO concentrations in
living systems without any signifi cant effects from electrode insertion.
The fi rst amperometric NO electrode used for direct measurement was described
in 1990 [20]. In 1992, the fi rst commercial NO sensor system was developed. Over