Amperometry: January 2018
Amperometry: January 2018
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Amperometry
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This is an update of S.B. Adeloju, Amperometry, Editor(s): Paul Worsfold, Alan Townshend, Colin Poole, Encyclopedia of Analytical Science (Second Edition),
Elsevier, 2005, Pages 70–79, ISBN 9780123693976.
Introduction 1
Principles of Amperometry 1
Chronamperometry 2
Characteristics of Amperometric Measurements 2
Applications 3
Amperometric Titrations 3
Amperometric Sensors 5
Amperometric Biosensors 6
Amperometric Detectors in Flow Analysis 8
Flow injection analysis (FIA) 8
Chromatography analysis 10
Conclusion 11
References 11
Further Reading 14
Introduction
The present edition of this chapter discusses amperometry as an analytical technique, and critically examines a range of applications
using different amperometric transducers and updates the previous edition published by Adeloju.3 Amperometry is an electroan-
alytical technique that involves the application of a constant reducing or oxidizing potential to an indicator (working) electrode and
the subsequent measurement of the resulting faradaic current.
During the measurement, the optimized value of the potential is fixed and the current as a function of time is noted.47,67,122,136
The current obtained is proportional to the concentration of the analyte. Nonelectroactive compounds also may be identified by
indirect derivatization measurements or amperometric titrations.3
The advantages of controlled-potential techniques include high sensitivity and selectivity towards electro- active species, a wide
linear concentration range, portable and low-cost instrumentation, speciation capability, and a wide range of electrodes that permit
analyses in unusual environments.
Recently, amperometric techniques have become more attractive and advantageous due to the introduction of new sensing
concepts combined with numerous technological innovations which have led to the development of a new generation of sensors
and biosensors that are most frequently used in combination with flow analysis. Accordingly, some have reached the commercial
phase and are used in clinical, pharmaceutical, environmental, industrial, and agricultural applications.91,121
Principles of Amperometry
The electrochemical oxidation or reduction of an electro-active species by the application of an appropriate potential of a suitable
electrode results in either a steady-state anodic or cathodic current. However, it is important to note that the current measured
amperometrically is distinctly different from measured in the so-called “galvanic cell,” which does not require the application of a
potential.
In amperometry, the current generated from a faradaic reaction is directly proportional to the concentration of the analyte.55,122
The simplest reaction that can occur at the working electrode surface polarized at appropriate potential might take the following
form:
Ox þ ne>R ed
At constant potential, the electron transfer occurs at a diffusion controlled rate, so the process becomes controlled by mass
transfer.6,67 The diffusion controlled current “i” depends on the thickness of the diffusion layer d, the analyte diffusion coefficient
diffusion D, the electron transfer number n, the surface area A of the electrode, the concentration of the analyte, and F the Faraday
number (96,480C mol1), as in Eq. (1):
☆
Change History: September 2018. Aziz Amine and Hasna Mohammedi updated the text and references and added an abstract and keywords.
nFAD Cbulk Cx¼0
i¼ (1)
d
where Cbulk and Cx ¼ 0 represent the analyte concentration in the bulk solution and the concentration at the surface of the electrode
respectively.
Chronamperometry
Chronamperometry utilizes pulsed amperometric detection, which can be used with a few mL of solution when stirring is not
required. The potential is varied from a value at which no faradaic reaction occurs to a potential at which the surface concentration
of the electro-active species is effectively zero (Fig. 1).
For a chronamperometric sensor with a stationary electrode and unstirred solution the current–time dependence has been
reported by.122 One of the advantages of chronoamperometry is that it allows the diffusion coefficient to be determined even when
slow heterogeneous electron transfer kinetics occurs as the potential can be stepped to a sufficiently positive or negative value where
the process is under diffusion control.
Since the mass transport under these conditions is only controlled by diffusion, the current as function of the time reflects the
concentration gradient in the vicinity of the electrode surface. As a result, the current decreases with time, as given by the Cottrell
equation:
nFACD1=2
iðtÞ ¼ ¼ kt1=2 (2)
p1=2 t 1=2
where n, F, A, C, D, and t are the number of electron transitioned, Faraday’s constant, the surface area, the concentration, the
diffusion coefficient, and time.
If the concentration is known, chronoamperometry is used to measure the diffusion coefficient of an electro-active chemical
element and/or to calculate the surface area of the working electrode or the concentration if D and A are known or by reference to a
calibration curve. In addition, chronoamperometry is commonly used to investigate the mechanisms of electrode processes where
chemical steps or other processes accompany electron transfer. However, there are some limitations to the chronoamperometric
method; very short and very long times should be avoided.
Amperometry and chronoamperometry have commonly been used to develop either chemical or bio-transducers (biosensors)
for direct evaluation of the concentration of the electro-active compounds, for use in amperometric titrations and combined with
flow analysis as a hydrodynamic amperometric detector.
The amperometric method provides the ability to distinguish selectively between a number of electroactive species in solution by
judicious selection of the applied potential and/or choice of electrode material. In cases where a nonspecific potential is applied, the
resulting current may contain a contribution from several electroactive species, with the number of oxidized species likely to
increase with increasingly positive applied potential and the number of reduced species increases the more negative the applied
potential. Thus, in order to avoid interferences low applied potentials in the range 0.2 V to þ0.2 V are highly desirable for analyte
detection. On this basis, the use of mediators that have low redox potentials are highly recommended. For example, direct oxidation
of hydrogen peroxide requires a potential of þ0.65 V versus Ag/AgCl at a platinum electrode and over þ1 V versus Ag/AgCl at a
glassy carbon electrode. However, reaction with the mediator Prussian Blue allows its’ interference free determination to be
undertaken at 0 V.44,57,106
Since the potential in amperometry is not scanned, voltammograms must be obtained from separate experiments. However, the
applied potential should be slightly greater than the maximum voltammetric current of the analyte and in a region with minimal
Fig. 1 A typical chronoamperometric experimentation: (A) potential as a function of time: (B) change in concentration profile as a function of time: (C) the resulting
current of a function of time.
Amperometry 3
Electrode material Potential window (vs. SCE) Advantages and limitations References
Glassy carbon 0.8 V to þ1.2 V (pH 4.5) Wide potential range, low background current, inexpensive 113
Carbon paste 1.6 V to þ1.1 V Wide potential range, low background current 113
(pH 4.5) Inexpensive
Unstable in flow cells and cannot be used in organic solvents
Mercury 2 V to þ0.4 V (pH ¼ 4.5) Excellent cathodic window 113
1.8 V to þ0.25 V in acid or 2.3 V in basic Limited anodic window due to mercury oxidation 3
media Highly toxic
Platinum 0.5 V to þ1.2 V (pH 4.5) Available wire, flat plate and tube, large range of sizes
Low hydrogen overvoltage so cathodic potential range limited 113
Expensive
Boron-doped 1 V to þ2.5 V (pH ¼ 2) An extremely wide potential window in aqueous and nonaqueous 137,138
diamond electrolytes
Excellent anodic window
An inert surface with low adsorption properties
Very low background current
Highly expensive
residual current from the electrolyte, working electrode etc., and should be performed within the potential window of the electrode
material. Thus, in aqueous media, the potential range available is limited in the positive (anodic) potential region by the oxidation
of electrolyte or water to oxygen and in the negative (cathodic) potential region by reduction of the electrolyte or the liberation of
hydrogen. This potential window is dependent on the electrode material as indicated in Table 1. Careful choice of the composition
of the supporting electrolyte also may be useful in broadening the potential window of amperometric methods. In cases where
oxygen reduction interferes, its removal by purging the solution with an inert gas such as nitrogen or argon may be necessary.
Even though amperometry has several advantages, it also has some weakness. For example, a gradual loss of detection sensitivity
may occur due to a heterogeneous electrochemical reaction occurring at the interface between the surface of the electrode and the
solution. This occurs when the product of the reaction is adsorbed onto the surface of the electrode and blocks electron transfer.
Other problems can be encountered such as the deterioration of the electrode surface quality and an increase in the baseline noise.
One sophisticated method for overcoming the adsorption of the product of a reaction onto the electrode surface is based on the use
of pulsed potential as an alternative to a continuously applied potential.14,59 In this approach the amperometric detector measures
current only during the short sampling interval of the pulse, giving less time for electrode fouling. In addition, much more negative
or positive values of potential can be used than the potential for measurement as a means of cleaning or activating the surface to
improve the detection response. The carbon paste electrode (CPE) introduced by Adams in 1958 may overcome the fouling and
adsorption problems generated from reaction products on electrode surfaces because that the electrode surface can be renewed after
each use. Chemically modified carbon-paste electrodes have also been advantageously used in various fields of electrochemistry
including amperometry.71,76
Recently, amperometric sensors based on the use of screen-printed electrodes have become promising analysis tools with the
requirements for in situ monitoring devices; minimal sample preparation, simple apparatus and fast result readout.37 In addition,
modification of the surface of the transducer with new materials at the nanoscale level has led to enhanced sensor performance with
increased sensitivity and lower detection limits. With nanomaterials, a general benefit is that highly specific surfaces enable the
immobilization of an enhanced amount of the biomolecules required for biosensor preparations. Compared to conventional
electrodes, those modified with nanomaterials also offer advantages such as higher surface area and enhanced electronic
conductivity.41,92,127
Applications
Amperometric Titrations
In amperometric titrations, the current varies as the titrant is added. Recalling the fundamental principles of amperometric
titrations: the measured current at a suitable applied potential is evaluated as a function of the added titrating solution volume
and the titration end point is the intersection of two lines associated with the change of current before and after the equivalence
point (Fig. 2). Different situations are presented in Fig. 2. In the first situation, the titrand is reducible but the titrant and product are
not (Fig. 2A). For example, the titration of Pb2þ ion with SO2 4 ion leads to the formation of PbSO4 which is an insoluble product.
In the second situation, the titrant is reducible but titrand and product not (Fig. 2B); for example the titration of Mgþ2 with a
reducible species such as 8-hydroxy quinolone. In the third situation, both the titrant and titrand are reducible but the product is not
(Fig. 2C): for example the titration of Pb2þ ions with K2Cr2O2 7 . Apart from the selection of an appropriate electrode material and
4 Amperometry
Fig. 2 Typical amperometric titration curves where (A) only analyte is reduced; (B) only the reagent is reduced; and (C) both analyte and reagent are reduced but
not the product.
titrant concentration, the main requirement in an amperometric titration is the choice of either a single or dual polarizable electrode
system. Amperometric titrations with single and dual polarizable electrodes have been discussed with detail in the second edition of
this chapter.3
The amperometric titration method has several advantages; the titration can be usually done rapidly and titration methods can
be used in cases where potentiometric methods are unsatisfactory because of solubility or dilution problems (Table 2).
Amperometric titrations are widely applicable for analytical determinations. Since the determination of chloride (Cl) in human
blood is clinically important, particularly for estimating blood hyperchloremia, several amperometric titration methods have been
developed to measure the chloride content in biological fluids.9
Amperometric titration is also a standard online method for the determination of free and bound chlorine in water. Usually free
chlorine, bound in hypochlorous acid or the hypochlorite ion is determined in water. For wastewater, analyses are made commonly
for total residual chlorine (chlorine and chloramines).
The most commonly used procedures for routine measurement of total chlorine in water and wastewater have been described in
standard methods.46
Amperometric titration is a standard analytical method since it provides adequate accuracy throughout over a wide range of the
chlorine concentrations. For example, the analytical procedure for the determination of chlorine at low concentration levels using
standard water and wastewater amperometric titration apparatus such as the Wallace and Tiernan amperometric titrator is reliable
over the range of 3–1000 mg/L of chlorine.46
Amperometry has been used for automated oxygen titration.38 For example the automated Winkler method has been used for
routine dissolved oxygen analysis using a microcomputer controlled piston buret coupled with amperometric end-point detection
and a platinum electrode polarized at 200 mV. Under optimized conditions, the standard deviation is 0.3 mM and analysis time is
3 min per sample.
The determination of Pd(II) and Pt(IV) was efficaciously performed with thioglycolic acid as titrant, with ammonium and
acetate buffers employed for Pd(II) and Pt(IV) respectively.73
Amperometric Sensors
The development of gas sensors in recent decades has led to important improvements in environmental protection and pollution
monitoring. The first amperometric sensors were Clark electrodes used for dissolved oxygen analysis in aqueous solutions35 and the
first used in hydrogen determination were proposed by Conti and Maget.70 Since the early 1970s, sustained studies have been
conducted on oxygen sensors.104 Subsequently, amperometric sensors have been applied to food, clinical and pharmaceutical
analysis and for environmental monitoring (Table 3).
Hydrogen peroxide (H2O2) is used as an oxidizing agent in numerous industrial processes as a bleaching and sterilizing agent
and is the enzymatic reaction product, catalyzed by several enzymes.129 Accordingly H2O2 detection is essential in environmental
and biomedical fields.
Amperometric sensors based on a platinum electrode have been extensively used for the determination of hydrogen peroxide
(H2O2).53 Recently, to overcome platinum electrode drawbacks such as the over-potential and interference problems, approaches
based on modifications of the electrode with nanoparticles, nanomaterials and polymers have been explored.33,41,92,127
In another approach, the detection of H2O2 at low applied potential was successfully achieved using Prussian Blue modified
electrodes.106 Prussian Blue was used as an electrochemical mediator for H2O2 reduction at around 0 V in order to avoid
interference from other electrochemical species.
The amperometric analysis of chlorine was evaluated on-line and compared to the colorimetric method77 with results confirm-
ing the usefulness of this method in process control. A general scheme for the oxido-reduction occurring in amperometric systems is
given below. The anodic material (Me) employed corresponds to gold or platinum.
The electrochemical determination of nitric oxide (NO) in solution in biological applications has been broadly applied.25
Because of properties related to the physiological messenger, high reactivity (free radical modulator) and low concentrations, real
time measurement of NO is required in biological systems. Among the strategies that permit direct, real time and label free detection
of NO are those founded on the use of ultra-microelectrodes modified with nanomaterials. These strategies provide a rapid response
and high sensitivity.28,110 For the same reason, a carbon fiber modified microelectrode has been employed for the evaluation of
nitric oxide in brain tissue.108 A real-time determination of NO along with oxygen consumption in rat neocortex in vivo by the
amperometric NO/O2 dual microelectrode configuration has been explored by Park el al.95. The method was successfully used for
Platinum nanoparticle decorated reduced graphene oxide screen printed electrodes:Pt/rGO/SPES, screen-printed electrodes: SPE,
tridodecylmethylammonium tetrakis(4-chlorophenyl) borate:TDMATPBCl.
6 Amperometry
the measurement of the NO and O2 contents in vivo. This study provided details of the dynamic role of NO in the regulation of the
cerebral hemodynamics, particularly those associated with tissue oxygenation.
Glucose oxidation with new materials have been developed by use in nonenzymatic electrochemical sensors as reviewed in
2010.116 Direct oxidation of glucose on metal substrates, particularly with platinum modified electrodes has been investigated.51,58
Much interest has centered on using carbon as an inexpensive substrate for electrochemical techniques. However, hydrazine,
ascorbic acid, L-cysteine, nitrite, bisphenol A or phenolic compounds electro-chemical detection is kinetically sluggish with a
significant over-potential at carbon materials. Numerous approaches have been proposed to minimize this problem such as the use
of pretreated glassy carbon electrode to improve hydrazine detection69,90,98,105 or the modification of the electrodes by carefully
selected redox mediators.106
Since chloride ion monitoring is essential in clinical, industrial and environmental applications, this has been widely studied.
Solid silver and AgNO3 modified carbon paste electrodes (CPE) have been investigated by Libuse Trnkova et al., who reported that a
silver nano-particle modified CPE exhibits high sensitivity towards chloride ions with a limit of detection of 500 nM.118
Amperometric Biosensors
Amperometry has found many applications in electrochemical biosensing. The first bio-amperometric sensor is regarded as the one
developed by Clark in 1956 to measure dissolved O2 in blood consumed during the enzymatic reaction of glucose oxidase catalysis
(1st generation biosensor: Fig. 3).
In general, a biosensor can be defined as an analytical device containing two units intimately in contact: a biological recognition
element and the transducer. The biological element (enzymes, proteins, antibodies, nucleic acids, cells, tissues or receptors)
selectively reacts with the target analyte and produce an electrical signal that is measured by an appropriate transducer (electro-
chemical, optical, thermal etc.). The signal response is related to the concentration of the analyte. Owing to the high sensitivity of an
amperometric transducer and to the high selectivity of the enzyme, amperometric enzyme electrodes are widely employed in
medical diagnosis, drug discovery, food safety, and environmental monitoring (Tables 4 and 5).
Since the discovery of (bio) sensors in the early 1960s, considerable progress in bio-transducer development and application has
led to significant advances. First-generation biosensors measured the reactant or product concentration. In the second-generation
the biosensor architecture contained a redox mediator so the concentration of the analyte involved in the reaction is related to the
response for the oxidation or reduction of the mediator. Finally, in the third-generation biosensors, the bio-component directly
switches the electrons between the enzyme active site and the transducer. Consequently, the analyte concentration is directly
proportional to the redox current generated at a polarized electrode set at a low operating potential (generally close to the enzyme’s
reversible redox potential) without the need for a mediator. Fig. 3 illustrates the principles of the three generations for glucose
oxidase sensing with an enzyme biosensor
Fig. 3 The three generations of biosensors (glucose oxidase—GOx) used for the determination of glucose. First-generation is based on the measurement of
hydrogen peroxide concentration produced or oxygen concentration consumed, second-generation is based on the use of redox mediators (Mox and MRED), and third-
generation is based on the direct electron transfer between a GOx-FADH2-nanomaterial conjugate and the electrode.
Amperometry 7
Glutamate Platinum Covalent immobilization of GluOx on poly (5,20 :50 ,200 -terthiophene-30 - Extracellular glutamate 102103
microelectrode carboxylic acid
Dopamine AuNPs layer EDTA immobilized onto poly (1,5-DAN/GO/AuNPs layer) PC12 cells 81
Lactate Printed tattoo electrode Lactate oxidase Saliva 107
Skin-worn enzymatic 63
Glucose Flexible oxygen GOx Tear 61
Electrode Blood 91
Platinum working or
oxygen
electrode
Phosphate CoPC-SPCE PyOd cellulose membranes immobilization Biomedical and 48
environmental
samples
Phenolic Carbon black paste Tyrosinase Olive oil 88
compounds electrode
Sulfite Platinum disk Entrapment SOX into ultrathin polypyrrole (PPy) films Food 8
Glutamate oxidase, GluOx; Ethylenediaminetetraacetic, EDTA; Horseradish peroxidase, HRP; Self-assembled monolayer/SAM, sulfite oxidase: SOX; tridodecylmethylammonium
tetrakis(4-chlorophenyl) borate: TDMATPBCl, cobalt phthalocyanine screen-printed carbon electrode: CoPC-SPCE. immobilization of the enzyme pyruvate oxidase (PyO), EDTA
immobilized-poly(1,5-diaminonaphthalne) (poly-DAN) layer comprising graphene oxide (GO) and gold nanoparticles (GO/AuNPs).:EDTA immobilized onto poly (1,5-DAN/GO/
AuNPs layer).
Drugs
Tacrine Pt/AchE – 97
Codeine SPE/TTF/AchE Urine and pharmaceutical 18
tablets
Neostigmine TTF-TCNQ-IL/AchE Tap water 131
Donepezil GE/BODT-co-FMOC/Cho/AchE Tap water 120
Allopurinol SPE/PB/Nafion/XO Medicinal plants 44
Methimazole SPE-CNTs/Tyr Commercial preparations 78
Leupeptin CNPE/Tyr – 45
Naproxen Clark electrode/COx Pharmaceutical drug 30
Heavy metals
Methyl mercury Pt/invertase biosensor inhibition Fish tissue 11, 12
Hg2þ Platinum ultra-microelectrode invertase/glucose oxidase – 21
Platinum/invertase/glucose oxidase/mutarotase 84
Pb2þ and Hg2þ Pt/CeO2/urease inhibition at specific potentials of 0.03 and Water 52
0V
Chromium Carbon film electrode 17
Cr(III)/Cr(VI) HPP inhibition
Pesticides
Malathion NPGE/carbon nanotubes/acetylcholinesterase – 42
Simultaneous detection of paraoxon and AChE-multisensors: with chemometric data – 19
carbofuran
Carbamic/Organophosphorous AChE and BChE/Prussian Blue-modified screen-printed Water 16
electrodes
Toxins
Cyanobacterial toxins Protein phosphatases/polyethersulfone/SPE Water and food 31
Microcystins AchE/PVA-SbQ
Anatoxin Matrix/SPE
Other
Sulfides HRP/gold electrode Water 130
H2S, HS and S2
Sulfamethoxazole Tyrosinase/SPE/gold nanoparticles Water
Acetylcholinesterase: AchE, Tetrathiafulvalene: TTF; Tetracyanoquinodimethane ionic liquid gel: TCNQ-IL, 5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)benzo[c][1,2,5]oxadiazole(BODT) with
(2-(((9H-fluoren-9-yl)methoxy)carbonylamino) acetic acid (FMOC): BODT-co-FMOC, Screen-printed electrode: SPE, Prussian blue: PB, xanthine oxidase: XO, Tyrosinase: Tyr, carbon
nanotubes: CNTs, Carbon nanopowder paste electrode: CNPE. The nanoporous gold film electrode: NPGE, horseradish peroxidase: HRP.
8 Amperometry
The use of the amperometric biosensors can be divided into three categories: (1) sensors based on enzyme immobilization for
bioselectivity of metabolic analytes, hazardous component analysis and drug therapy, (2) immune-sensors for pathogenic and toxin
bacteria determination, (3) geno-sensors based on nucleic acid immobilization which are commonly employed for pathogen
determination89 and cancer marker diagnosis.83 Some of these sensors have reached the commercial stage and are routinely applied
in clinical, environmental, industrial, and agricultural applications.121
For metabolic analyte evaluation such as Lactate and Glucose, the monitored signal is produced after enzyme recogni-
tion.23,61,91,107 The glucose biosensor represents a major success in the realization of biosensing. For many diabetes patients, the
health and the quality of their life depends on the correct monitoring of the concentration levels of glucose in their blood by a
glucose biosensor.91,121,123
Food analytes evaluated with enzymatic biosensors include L-lysine, ascorbate, ethanol, glucose, fructose, sulfite, and phenols.
Sulfite oxidase entrapped in polypyrrole films improved the amperometric biosensing of sulfite in wine as reported by Ameer
and Adeloju. In the range of 0.9–400 mM, phenol concentrations as low as 6 nmol L1 of phenols was detected in olive oil using
tyrosinase immobilized onto a carbon black paste electrode.88 The content of phenolic content of compounds also had been
evaluated using a laccase biosensor.141
In biosensor analysis of dairy foods, lactose and lactate are the products of highest interest. Lactate is the most investigated,
owing to the accessibility of lactate dehydrogenase and lactate oxidase.134 For clinical analysis, such as the diagnosis of lactate
acidosis resulting from of metabolic, respiratory, or haemodynamic disturbance, lactate determination is essential.57,63,107 Hickey
and coworkers have investigated the use of redox mediators to avoid a large applied potential.57 Moscone et al., measured lactulose
in milk in order to distinguish between pasteurized, UHT and sterilized milks.87 Other biosensors based on antibody-antigen
recognition are less common in the field of milk quality control. However,79 reported a highly sensitive immunosensor for the
detection of aflatoxin M.
Amperometric neurotransmitter bio-sensors have been used to determine neurotransmitters that include amino acids such as
glutamic acid, biogenic amines like dopamine and histamine, acetyl choline (acetyl-choline and choline), and soluble gases such as
nitric oxide and hydrogen sulfide.86
In vivo glutamate detection using glutamate oxidase covalently immobilized on a poly-thiophene derivative has been devel-
oped.102,103 In-vivo dopamine has also evaluated by incorporating Cibacron Blue into poly (1,5-diaminonaphtalen).2 Dopamine
released from PC12 cells upon extracellular stimulation of Kþ ions was monitored using a nano-biosensor.81
Real-time non-invasive and cost effective monitoring of electrolytes and metabolites in sweat, tears, or saliva as indicators of the
wearer’s health status gained attention recently.23,63,107
The analysis of phosphate is highly important for environmental monitoring. Traditional methods are based on color developed
upon formation of a phospho-molybdate complex. However, these methods cannot be used in turbid and colored samples.114 have
developed on amperometric sensor for the evaluation of the reduction signal of the phospho-molybdate complex, which allows the
determination of phosphate in the mmolar range using SPE. The specific enzyme pyruvate oxidase also was successfully applied by
Gilbert et al., for phosphate determination in water samples.48
Hazardous components such as heavy metals, pesticides, pollutants and drugs were evaluated using amperometric biosensors
based on enzyme inhibition.5,10–12,17,43 In these methods, the biosensor evaluation is recorded before and after addition of an
inhibitor thereafter. Subsequently, the degree of inhibition that correlates directly with the hazardous component concentration,
can be calculated.
Frequency/Linear
Analyte Electrode Sample range References
Boron-doped diamond: BDD, microdialysis-coupled flow injection amperometric sensor: mFIAS. Meldola’s Blue-Reinecke Salt: MBRS-SPCE, Lactate dehydrogenase: NAD, F-doped
lead dioxide modified electrode.
level was 2 mg/L.13,54 The linear range of the method is 2.0–5000 mg/L cyanide using a 200-mL sample loop. The linearity can be
modified via changing the sample loop volume or dilution.
A F-PbO2 modified electrode combined with flow injection analysis has been studied and validated by Jiaqing et al. for the
oxygen demand measurement. A linear concentration range 100–1200 mg L1 was achieved, and a limit of oxygen detection of
15 mg L1 was obtained.142
A highly sensitive flow injection acetylcholinesterase-sensor for the detection of pesticides using layered double hydroxides as
the immobilization matrix and a thin-layer flow cell has been developed.50 Methyl parathion was chosen as a model system; the
degree of inhibition of methyl parathion was proportional to its concentration over the range of 0.005–0.3 mg mL1 with a methyl
parathion detection limit of 0.6 ng mL1.
L-lactate in milk and in yoghurt has been studied using the FIA flow-through cell combined with an amperometric lactate oxidase
biosensor.94 The limit of detection was lower than mM and up to the1 mm L1 range could be determined.
Sequential injection analysis (SIA) has been proposed as an alternative to FIA due to its lower reagent consumption and multiple
sample capability.
The simultaneous analysis of lactose, galactose and glucose in milk was realized with a multianalyte biosensor and sequential
injection. The biosensor was based on an enzyme-catalyzed reaction in combination with three well-established analytical
techniques: microdialysis sampling, flow injection analysis and amperometric detection.101
A chip-based biosensor with flow-injection analysis has been investigated for the simultaneous determination of glutamate,
glucose and glutamine.22 In this work, a good correlation between measured glutamate, glutamine and glucose concentrations has
been demonstrated. These experiments were carried out in a cell culture medium in the differential-mode and with commercially
available instrumentation.
The detection of nitrites and nitrates in water has been realized using a poly-diaminonaphthalene modified platinum electrode
combined with batch and flow injection analysis.20
In another approach, glucose oxidase modified platinum and copper modified glassy carbon electrodes were used for mercury
determination. The method is based on invertase enzyme inhibition coupled with batch injection analysis (BIA) with low sample
and reagent consumption and allows mercury determination in the ng mL1 range.85
BIA was invented by Wang in the early 1990s. This technique is based on the use of a large volume wall-jet cell allowing high
throughput analysis without employment of a pump, injection valve and connecting tubes.125
Sulfite determination based on gas diffusion sequential injection (GDSIA) coupled with use of a boron-doped diamond (BDD)
electrode was developed.34 The data showed that the sequential injection system was simple and easy to manipulate, and
furthermore provided high sample throughput and low reagent consumption. This system was suitable for use in the concentration
range for 0.2–20 mg SO2 2
3 /L. A detection limit of 0.05 mg SO3 /L was achieved with this system. The GDSIA method also was
successfully applied to the evaluation of sulfite in wines with relative standard deviations in the range of 1.0%–4.1% with a
sampling frequency of 65 h1.
10 Amperometry
Recently,117 have developed a simple, high-throughput, and portable electrochemical system for H2O2 analysis. This system is
based on the use of a screen-printed transducer combined with batch injection analysis. A throughput of 150 injections of H2O2 per
hour was obtained with the BIA system and no fouling effects or gradual loss of mediator molecules stress was observed.
A high throughput system was used for the determination of lactate in serum using a FIA thin-layer cell. In this approach, a
Meldola’s Blue lactate dehydrogenase modified SPE was combined with the aforementioned system.96
Chromatography analysis
The amperometric method has been widely used for the direct determination of oxidizable and reducible species when combined
with chromatographic separation methods (Table 7). The working electrode is placed in a suitable flow-cell, through which the
eluent passes. The analyte to be detected undergoes a faradaic reaction at an appropriate applied potential.
In order to develop methods with high analytical performances, special attention has been placed on sample throughput,
reliability and robustness of analysis. Since analysis of bodily fluids in clinical laboratories is of great diagnostic importance to
discover diseases in an early stage, these methods are important in this area. Recently, diagnostic methods for Parkinson’s disease
have been developed using reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric
detection.93 A number of tumor and cardiovascular markers have been analyzed using a dedicated transducer combined with
chromatographic separation. Thus, the catecholamines and their metabolites have been widely determined with high-performance
liquid chromatography (HPLC) combined with electrochemical detection owing of high sensitivity and selectivity.93,119 This form
of detection has been established as a fast, reproducible and reliable system for routine catecholamine and metabolite determina-
tion in plasma and urine.
The optimized Monier-Williams Method (AOAC Method 990.28) has some drawbacks for sulfate determination in food/
beverage products such as time-consuming, labor-intensive, and less than ideal reproducibility.65 To improve the sulfate determi-
nation, Kim and Kim have developed an efficient and accurate method to evaluate total sulfite which is based on using an alkaline
medium followed by ion-exclusion chromatography and amperometric detection.15,64 However, a loss of sensitivity of the detector
occurs frequently when the working electrode is contaminated. In order to minimize errors, the calibration standards and samples
must be measured sequentially.66 Modification of the AOAC method has been achieved by employing pulsed amperometric
detection (PAD) in order to overcome the working electrode-fouling problem.126
High-performance anion exchange (HPAE) chromatography was investigated to separate carbohydrates and coupled with
pulsed amperometric detection (PAD) to allow the direct quantification of non-derivatized carbohydrates at low pM levels with
minimal sample preparation and clean-up. Pulsed amperometric detection represents a universal detection method for all
carbohydrates.
HPAE chromatography provides highly selective separations of carbohydrates at high pH using a strong anion-exchange
stationary phase by taking advantage of the acidic nature of carbohydrates. Zhao and coworkers using high-performance anion-
exchange chromatography coupled with pulsed amperometric detector for the simultaneous determination of several carbohy-
drates. The limits of detection and limits of quantification for carbohydrates were 0.02–0.10 and 0.2–1.2 mg/kg, respectively.132
A major problem in measuring nitrite (NO
2 ) and nitrate (NO3 ) in food or biological and environmental samples arises from
matrix interference. Amperometric detection requires the capability to oxidize only selected compounds. Accordingly ion-exchange
or reversed-phase chromatography coupled with amperometric detection can be utilized in to indirectly determine nitrite and
nitrate complex samples by means of the photolytic step. Several methods have been investigated for the determination of nitrite by
high-performance liquid chromatography with electrochemical detection (HPLC–ED).40 The measurement of NO
2 and NO3 have
been reported using HPLC–ED in food, biological and environmental samples and demonstrated to be more sensitive, selective and
faster than methods based on UV absorption, photometry, fluorometry or chemiluminescence. Amperometric detectors have the
Reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection: RP-HPLC-IPAD.
Amperometry 11
advantage of superior sensitivity.99,143 They also have a wide linear dynamic range, a rapid response time and are readily
miniaturized to match micropacked and capillary columns, while potentiometric detection has a slower response time and a less
stable baseline.82
Ion chromatography with pulsed amperometric detection (PAD) has been used for the direct determination of free cyanide in
drinking water.115 The recovery of added cyanide was >80%. With a limit of detection of 1.0 mg L1, this method determines
cyanide concentrations below the reportable limit of free cyanide in drinking water.
High-performance liquid chromatography and capillary electrophoresis are widely used for the separation of sulfonamides prior
to their detection using amperometric sensors.29 The electro-analysis of sulfonamides by flow injection system/high-performance
liquid chromatography coupled with amperometric detection using boron-doped diamond electrode and thin layer-cell also has
been investigated.100
Recently, a diagnostic method for Parkinson’s disease was developed by simultaneously analyzing biogenic amines and their
metabolites using reverse-phase high-performance liquid chromatography coupled with an integrated pulsed amperometric
detection method. Dopamine, 3,4-dihydroxyphenylacetic acid, serotonin (5-HT), 5-hydroxyindolacetic acid, and homovanillic
acid were used as biomarkers in the diagnosis of Parkinson’s disease.93
Conclusion
Significant research activity recently has been devoted to the development of amperomatric sensors. New strategies with the use of
nanomaterials, polymers and mediators are advantageous due to their rapid response and high sensitivity. Amperometric detection
combined with flowing solutions is now successfully applied in routine analysis. Coupling of electrochemical detectors with
advanced separation procedures makes it possible to process very complex samples for simultaneous analysis.
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