Báo cáo khoa học: Electrochemical biosensing with nanoparticles Arben Merkoci pot

MINIREVIEW
Electrochemical biosensing with nanoparticles
Arben Merkoc¸i
Institut Catala
`
de Nanotecnologia and Universitat Auto
`
noma de Barcelona, Spain
Introduction
Electrochemical sensing (ES) techniques are playing a
growing part in various fields in which an accurate,
low cost, fast and online measuring system is required.
With regard to quality and cost, ES is better than not
only standard analytical methods ⁄ assays but also sen-
sors based on other transducing mechanisms. Beside
the relatively low cost compared with optical instru-
mentation, advantages such as the possibility of minia-
turization as well as in-field applications make ES
devices very attractive in several fields such as environ-
mental monitoring, food quality control and clinical
analysis. The ES field, as also mentioned in a recent
review by Bakker & Qin [1], is relatively mature and
has found its way into commercial products and
advanced integrated sensing systems.
The use of ES in DNA and immunoanalysis is well
known. Electrochemical affinity biosensors based on
DNA hybridizations [2] or immunoreactions are
playing a more and more important role in DNA and
protein analysis. Several ES methodologies for DNA
and proteins based on either label-free or the use of
enzymes as labels have been reported [1].

The recent developments of bottom-up nanotechno-
logy approaches are offering novel materials such as
nanoparticles (NPs) with special interest for (bio)analy-
sis. This minireview will focus on current progress in
applying NPs to DNA sequence determination as well
as immunosensing systems based on electrochemical
schemes. It first covers some aspects related to electro-
chemical properties of metal NPs and then their appli-
cations as labels in a variety of DNA electrochemical
detection schemes.
Electrochemical properties of metal
NPs
Research on metal and semiconductor NPs [Group II–
VI compound semiconductors such as CdSe, ZnSe,
CdTe, etc. called also quantum dots, (QDs)] [3] as well
as gold NPs (AuNPs) has increased rapidly in recent
Keywords
conductometric techniques; DNA analysis;
differential pulse voltammetry;
electrochemical analysis; gold nanoparticles;
labelling technologies; nanotechnology;
protein analysis; stripping voltammetry
Correspondence
A. Merkoc¸i, Institut Catala
`
de
Nanotecnologia, Campus UAB, 08193
Bellaterra, Barcelona, Catalonia, Spain
E-mail:
(Received 26 September, accepted

8 November 2006)
doi:10.1111/j.1742-4658.2006.05603.x
This minireview looks at the latest trends in the use of nanoparticles (NPs)
in electrochemical biosensing systems. It includes electrochemical characteri-
zation of NPs for use as labels in affinity biosensors and other applications.
DNA analysis involving NPs is one of the most important topics of current
research in bionanotechnology. The advantages of the use of NPs in
designing novel electrochemical sensors for DNA analysis are reviewed.
Electrochemical NPs can also be used in designing immunoassays, offering
the possibility of easy, low cost and simultaneous detection of several pro-
teins. Research into NP applications in electrochemical analysis is in its
infancy. Several aspects related to sensitivity as well integration of all the
assay steps into a single one need to be improved.
Abbreviations
CV, cyclic voltammetry; DPV, differential pulse voltammetry; ES, electrochemical sensing; HBsAb, hepatitis B surface antibody; HBsAg,
hepatitis B surface antigen; MPC, monolayer-protected cluster; QD, quantum dot.
310 FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS
years because of interest in size-dependent and shape-
dependent tailoring of their physical and chemical
properties and their potential in applications in
catalysis, sensors, and molecular electronics. Finally,
research on the electrochemical properties of NPs has
received special attention with regard to applications
in the electrochemical biosensor field.
Quin et al. [4] have studied differential pulse voltam-
metry (DPV) responses of thiolate monolayer-protec-
ted Au clusters (Au
147
MPCs). They showed 15 evenly
spaced (DV) peaks characteristic of charge injection

into the metal core (Fig. 1, left). This was clear confir-
mation that MPCs behave as multivalent redox spe-
cies, in which the number of observable charge states
is limited by the size of the available potential window.
The electrochemistry of QD-size Au MPCs has also
been studied by Murray and coworkers [5]. According
to these authors, Au MPCs behave as multivalent
redox species as charge injection into the core is quant-
ized [6].
Using the ‘particle in a box’ model, Brus [7] predic-
ted the dependence of redox potential on particle size
for CdS QDs. However, this model has not been tested
by electrochemical measurements of QDs in solution,
largely because of the limited solvent window of many
solvent ⁄ electrolyte systems and the instability of the
particles.
Haram et al. [8] have reported the novel use of elec-
trochemistry of CdS QDs in N,N¢-dimethylformamide.
They were able to show a direct correlation between
the electrochemical band gap and the electronic spectra
of CdS NPs in N,N¢-dimethylformamide. In the light
of this and the irreversibility of oxidation and reduc-
tion of Q-CdS, the authors propose a multielectron
transfer process in which the electrons are consumed
by fast-coupled chemical reactions through decomposi-
tion of the cluster. Essentially, the electron is scav-
enged immediately after injection into the particle,
and, unlike the case of thiol-capped metal particles,
the CdS QDs can accept additional electrons at the
same potential, giving rise to higher peak currents. The

appearance of additional cathodic and anodic peaks in
the middle of the potential window supports this. A
typical cyclic voltammetry (CV) for thioglycol-capped
CdS Q-particles at the Pt electrode is given in Fig. 1
(right) where clear oxidation and reduction peaks are
apparent at )2.15 V (A1) and 0.80 V (C1), respect-
ively. This is compared with the response of the sup-
porting electrolyte alone.
DNA analysis
The development of sensitive nonisotopic detection
systems has significantly affected the DNA sensor field.
Affinity electrochemical biosensors based on enzyme
labeling solved the problems of radioactive detection
(e.g. health hazards and short lifetimes) and opened up
new possibilities in ultrasensitive and automated bio-
logical assays. Nevertheless, biological research and
other application fields need a broader range of more
12
0
1-
2-
0.0
1.
0
2.0
V2.1
ERQsusr
e
v
V

/E/E
-I / nA
0.1
0.0
0.
1
-
0
.
2
-
0.
3
-
E
H
N
su
s
r
e
v
V
0
.
2-
0.0
0.2
Current (µA)
SdC-Q

etylortceleesaB
1C
2C
3C
3A
2A
1
A
Fig. 1. Left, DPV responses for MPC solutions measured at a Pt microelectrode; as-prepared 177 lM C6S-Au
147
(upper) showing 15 high-
resolution QDL peaks, and 170 l M C6S-Au
38
(lower) showing a HOMO-LUMO gap. It can be seen that the as-prepared solution contains a
residual fraction of Au
38
which smears out the charging response in E regions where quatized double layer charging (QDL) peaks overlap.
The electrode potential scanned negative to positive. The caption single electron-transfer events are termed quantized double layer charging.
Adapted from [4]. Right, CV response in the absence and presence of thioglycol-capped CdS Q-particles (1 mgÆmL
)1
fraction IV) at a Pt
electrode. Sweep rate, 50 mVÆs
)1
and tetrahexylammonium perchlorate (THAP), 0.05 M. Adapted from Fig. 1 of reference [8].
A. Merkoc¸i Electrochemical biosensing with nanoparticles
FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS 311
reliable, more robust labels to enable high-throughput
bioanalysis and simultaneous determination of mul-
tiple-molecule types present in a sample [9].
The DNA-recognition event can be detected using

different strategies, including intrinsic electroactivity of
the nucleic acid [10], DNA duplex intercalators [13],
electroactive markers [14], enzyme labels [15], etc. The
existing labeling techniques have several drawbacks;
the markers used have short life times and a limited
number of combinations that can be practically used
for simultaneous analysis of various analytes.
Fluorescent labeling of biological materials with
small organic dyes is also widely used in the life sci-
ences and has been used in a variety of DNA-sensing
systems based on optical detection. Organic fluoroph-
ores, however, have characteristics that limit their
effectiveness for such applications. These limitations
include narrow excitation bands and broad emission
bands with red spectral tails, which can make simulta-
neous evaluation of several light-emitting probes
problematic because of spectral overlap. Also, many
organic dyes exhibit low resistance to photodegrada-
tion. To improve assay sensitivity and achieve better
and more reliable analysis, there is a great demand for
labels with higher specific activity.
The electrochemical properties of NPs make them
extremely easy to be detected with simple instrumenta-
tion. Sensitivity, long life time, and multiplexing capa-
bility have led to the explosive growth of NP-based
DNA electrochemical assays in recent years [11,12,16–
18]. NPs are made of a series of semiconductor NPs
which are easily detected by highly sensitive techniques
such as stripping methods among others. In addition,
these electrochemical properties may allow simple and

inexpensive electrochemical systems to be designed for
detection of ultrasensitive, multiplexed assays.
Conductometric techniques
Detection of DNA hybridization used in connection
with conductometric measurements after labeling
with AuNPs has been successfully demonstrated by
Mirkin’s group [19]. They exploited the silver-deposition
technique to construct a sensor based on conductivity
measurements. A small array of microelectrodes with
gaps (20 lm) between the electrodes leads is construc-
ted. DNA probe sequences are then immobilized on the
substrate between the gaps. By using a three-component
sandwich approach, hybridized target DNA is used
to recruit AuNP-tagged reporter probes between the
electrode leads. The NP labels are then developed in the
silver enhancer solution leading to a sharp fall in
the resistance of the circuit (Fig. 2A).
Electrochemical stripping
Other electrochemical techniques for DNA detection
have been reported. Voltammetric or potentiometric
stripping analysis using mercury film electrode depos-
ited on a pencil graphite or glassy carbon electrode has
been used. The intrinsic electrochemical signals of
AuNPs, observed after dissolving these with HBr ⁄ Br2,
are then related to DNA. This is achieved by pre-con-
centration of gold(III) ions through electrochemical
reduction and subsequent determination by anodic-
stripping voltammetry [20] (Fig. 2B).
Going further to lower the detection limits, gold tra-
cer ‘amplification’ by silver deposition on the surface

has also been applied [21,22]. This is a clever way of
achieving higher sensitivities for DNA detection
(Fig. 2C).
The labeling of probes bearing different DNA
sequences with different NPs enables the simultaneous
detection of more than one DNA target in a sample.
The number of targets that can be readily detected
simultaneously (without the use of high level multi-
plexing) is controlled by the number of voltammetri-
cally distinguishable NP markers. A multitarget
sandwich hybridization assay involving a dual hybrid-
ization event, with probes linked to three tagged inor-
ganic crystals and to magnetic beads has been reported
[23]. The DNA-connected QDs yielded well-defined
and resolved stripping peaks at )1.12 V (Zn), )0.68 V
(Cd) and )0.53 V (Pb) at the mercury-coated glassy
carbon electrode (versus the Ag ⁄ AgCl reference elec-
trode) after acidic dissolution of the above metal NPs
(Fig. 2D).
Single nucleotide polymorphisms were also detected
recently by Liu et al. [24]. They used ZnS, CdS, PbS,
and CuS NPs linked (using phosphoramidite chemistry
through a cysteamine linker) to adenosine, cytidine,
guanosine, and thymidine mononucleotides, respect-
ively. They introduced the monobase-conjugated nano-
crystals to the hybrid-coated magnetic-bead solution.
Each mutation thus captures different nanocrystal-
mononucleotides and in this way the unknown single
nucleotide polymorphisms were detected on the basis
of distinct voltammetric stripping signals.

Making the DNA ⁄ NP detection system more
integrated
The use of NPs as electrochemical labels for DNA sens-
ing has several advantages. The related technique –
stripping voltammetry – is cheaper, faster and easier
to use in field analysis than optical ones. Moreover
it offers the possibility of simultaneous detection of
Electrochemical biosensing with nanoparticles A. Merkoc¸i
312 FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS
several biological molecules in the same sample using a
unique sensor because of the distinct voltammetric
waves produced by different electrochemical tracers.
The advantages offered along with the possibility of
being used in several biosensing systems based on
electrochemical techniques require the development of
novel NP-detection strategies that avoid dissolution of
NPs before detection thereby integrating the whole
assay.
A novel NP-based system for detection of DNA
hybridization based on magnetically induced direct
electrochemical detection of a 1.4-nm Au67 QD tag
linked to the target DNA has been reported by our
group [25]. The Au67 NP tag is directly detected after
the DNA hybridization event, without the need for
acidic (i.e. HBr ⁄ Br
2
) dissolution. In this way, the NP-
detection event is integrated into the biosensor system.
The binding of a DNA probe to paramagnetic beads
was achieved by streptavidin–biotin interaction. The

resulting DNA-modified paramagnetic beads were then
hybridized with the DNA target labeled with Au67 NP
in a 1 : 1 ratio. The resulting Au67-DNA probe–DNA
target paramagnetic bead conjugate was collected mag-
netically on the surface of a transducer with built-in
magnet (Fig. 3). The two main highlights of this novel
genosensor are that: (a) the direct voltammetric detec-
tion of metal QDs obviates the need for their chemical
dissolution; (b) the Au67 QD–DNA probe ⁄ DNA tar-
get-paramagnetic bead conjugate does not create the
interconnected 3D network of Au-DNA duplex–para-
magnetic beads as in previously developed NP DNA
assays. In this way, the sensitivity of the assay is not
decreased by the sharing of one gold tag by several
DNA strands, achieving lower detection limits. The
magnetically triggered Au67 NP direct detection meth-
odology described above can be applied to different
bioassays (including isoelectric immunoassay). Current
efforts in our laboratory are aimed at broadening the
application range of the QD direct detection protocol
and the development of a microfluid device to integ-
rate all the steps of the genomagnetic protocol on a
lab-on-a-chip platform.
The integration of nanotechnology with biology and
electrochemistry is going to produce major advances in
dC
+2
C
d
S

uC
+
2
nZ
+
2
A
g
A
u
A
u
3
+
A
u
e
-
gA
uA
gA
uA
Z
n
S
C
u
S
A
B

C
D
PM
PM
PM
gA
+
Fig. 2. Strategies used for DNA detection by labeling with metallic NPs. Usually a probe DNA has been immobilised on a transducing plat-
form and then hybridized with target DNA and further with NP-modified DNA probes. (A) Conductivity assay in which gold is accumulated in
the gap and later on a silver enhancement procedure in the presence of hydroquinone is performed. (B) Electrochemical stripping assays
based on labeling with AuNPs which were then dissolved with HBr ⁄ Br
2
and detected by stripping techniques. (C) The same as (B) but the
AuNPs are first covered with silver by a deposition treatment and then detected by stripping techniques via a silver enhanced signal. (D)
Multilabelling by the use of three different NPs (QDs) and the simultaneous detection of the three DNA targets.
A. Merkoc¸i Electrochemical biosensing with nanoparticles
FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS 313
the field of electrochemical DNA sensors. Research on
the application of these systems to real samples is in
progress and is expected to produce novel alternatives
for DNA analysis.
Protein analysis
Electrochemical immunosensors, based on the coupling
of immunochemical reactions with electrochemical
transduction, have attracted considerable interest in
recent years. The use of NPs as either immobilization
platforms or labels in immunosensing systems has been
reported.
NPs as protein immobilization platforms
The combination of self-assembly with NPs has attrac-

ted researchers to develop novel immunosensors. A
hepatitis B surface antigen (HBsAg) immunosensor
has been developed by self-assembling AuNPs to a
thiol-containing sol–gel network. The hepatitis B sur-
face antibody (HBsAb) was adsorbed to the surface of
the AuNPs and used later to detect HBsAg in human
serum based on the specific reaction of HBsAb with
HBsAg. The electrochemistry of the ferricyanide redox
reaction was used as a marker to probe the interface
and as a redox probe to determine HBsAg [26].
Self-assembly to immobilize HBsAb on a platinum
disk electrode based on AuNPs, Nafion, and gelatin as
matrices has also been demonstrated. Detection is
based on the change in the electric potential before
and after the antigen–antibody reaction. The proposed
hepatitis B immunosensor provides a novel tool for
directly monitoring the concentration of HBsAg in
serum samples [27].
NPs as labels for proteins
The study of immunoreactions through labeling with
metallic ions after a long period of using only enzymes
or dyes opened up new possibilities. The interaction of
human serum albumin with its antibody was used as a
model system, with bismuth ion serving as the metal
label that is detected by potentiometric stripping
analysis [28]. The concept of this single-use stripping
immunosensor opened up the way to improving the
AB CDE
Fig. 3. Schematic representation of the analytical protocol (not in scale). (A) Introduction of streptavidin-coated paramagnetic beads; (B)
immobilization of the biotinylated probe (DNA2) on the paramagnetic beads; (C) addition of the 1 : 1 Au67–DNA1 target; (D) accumulation of

Au67–DNA1 ⁄ DNA2–paramagnetic bead conjugate on the surface of the magnetic electrode; (E) magnetically triggered direct DPV electro-
chemical detection of Au QD tag in Au67–DNA1 ⁄ DNA2–paramagnetic bead conjugate. Also shown is the schematic of the integrated geno-
sensor based on labeling with Au67 NPs. The magnetic field produced by a tiny magnet introduced inside a graphite epoxy composite
electrode attracts the resulting Au67 QD–DNA hybrid–paramagnetic bead conjugate. In situ electrochemical oxidation of the AuNPs followed
by differential pulse voltammetry of the gold ions is then performed and the signal obtained related to the quantity of the DNA target found
in the sample. Adapted from reference [25].
Electrochemical biosensing with nanoparticles A. Merkoc¸i
314 FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS
performance of immunoassays by incorporating electro-
chemical NPs as labels.
NP-based electrochemical biosensors for disease-
related glycan markers based on their interaction with
surface-functionalized lectins have been developed [29].
The assay has been optimized and tested using a model
system. It involves immobilization of the lectin, the
carbohydrate-recognition element, on the gold surface
and the following competition between a nanocrystal
(CdS)-labeled sugar and the target sugar for the carbo-
hydrate-binding sites on lectins. Finally, the extent
of competition is monitored by highly sensitive
electrochemical stripping detection of the captured
nanocrystal.
An electrical immunoassay-coding protocol for the
simultaneous measurement of multiple proteins based
on the use of different inorganic nanocrystal tracers
has been developed. The concept is demonstrated for a
simultaneous immunoassay of b
2
-microglobulin, IgG,
BSA, and C-reactive protein in connection with ZnS,

CdS, PbS, and CuS colloidal crystals, respectively [30].
The assay shows the efficient coupling of the multipro-
tein electrical detection with the amplification feature
of electrochemical stripping transduction yielding fem-
tamolar detection limits. In addition, the proposed
method is combined with efficient magnetic separation
so as to minimize nonspecific binding effects.
NPs as aptamer labels
Aptamers offer great promise for sensitive displace-
ment assays, as the tagged protein has a significantly
lower affinity for the aptamer than for the unmodified
analyte. The use of nanocrystal tracers for designing
multianalyte electrochemical aptamer biosensors with
subpicomolar (attomolar) detection limits has been
demonstrated. A simple single-step displacement assay
was used. Several thiolated aptamers were first immo-
bilized on the gold substrate. The corresponding
QD-tagged proteins were then bound and this was
followed by the addition of the protein sample. The
displacement was monitored through electrochemical
detection of the remaining nanocrystals (PbS and
CdS). The concept has been demonstrated for dual-
analyte sensing (thrombin and lysozyme) and could
easily be expanded for the simultaneous measurement
of a large panel of proteins [31].
Conclusions
The integration of nanotechnology with biology and
electrochemistry is expected to produce major advan-
ces in the field of electrochemical biosensors. Recent
progress has led to the possibility of the application of

electroactive NPs to simple and low cost analytical sys-
tems for analysis of biological molecules, such as pro-
teins and nucleic acids.
NPs show great promise for electrobioanalytical
applications. They can be used as labels for affinity
biosensors, biomolecule immobilization platforms, and
biocatalysts in various bioassays.
The electrochemical detection of NP labels in affinity
biosensors using stripping methods allows the detailed
study of DNA hybridization as well as immunoreac-
tions, with possible genosensor and immunosensor
applications. The use of diverse NPs for the simulta-
neous detection of several biomolecules is expected to
open up new opportunities for DNA diagnostics. The
developed electrochemical coding is being adapted to
other multianalyte biological assays, particularly immu-
noassays. The electrochemical coding technology is thus
expected to open up new opportunities not only for
DNA diagnostics but for bioanalysis in general.
NPs have a promising future in the design of electro-
chemical sensors, but their use will be driven by the
need for smaller detection platforms with lower limits
of detection.
The use of electrocatalytic NPs, already demonstrated
in the ultrasensitive micro RNA assay [32], can be exten-
ded to several other applications. Future applications in
biosensors may aim to reduce the oxidation overpoten-
tial in novel electrochemical recognition biosensors.
Acknowledgements
This work was financially supported by the Spanish

‘Ramo
´
n Areces’ foundation (project ‘Bionanosensores’)
and MEC (Madrid) (projects MAT2005-03553 and
NANOBIOMED, CONSOLIDER).
References
1 Bakker E & Qin Y (2006) Electrochemical sensors. Anal
Chem 78, 3965–3983.
2 Pividori MI, Merkoc¸ i A & Alegret S (2000) Electroche-
mical genosensor design: immobilisation of oligonucleo-
tides onto transducer surfaces and detection methods.
Biosensors Bioelectronics 15, 291–303.
3 Murphy CJ (2002) Optical sensing with quantum dots.
Anal Chem 520A–526A.
4 Quinn BM, Liljeroth P, Ruiz V, Laaksonen T & Kont-
turi K (2003) Electrochemical resolution of 15 oxidation
states for monolayer protected gold nanoparticles. JAm
Chem Soc 125, 6644–6645.
5 Balasubramanian R, Guo R, Mills AJ & Murray RW
(2005) Reaction of Au
55
(PPh
3
)
12
C
l6
with thiols yields
A. Merkoc¸i Electrochemical biosensing with nanoparticles
FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS 315

thiolate monolayer protected Au75 clusters. J Am Chem
Soc 127, 8126–8132.
6 Chen S, Ingram RS, Hostetler MJ, Pietron IJ, Murray
RW, Schaaff TG, Khoury JT, Alvarez MM & Whetten
RL (1998) Gold nanoelectrodes of varied size. Transi-
tion molecule-like charging. Science 280, 2098–2101.
7 Brus LE (1983) A simple model for the ionization
potential, electron affinity, and aqueous redox potentials
of small semiconductor crystallites. J Chem Phys 79,
5566–5571.
8 Haram SK, Quinn BM & Bard AJ (2001) Electrochem-
istry of CdS nanoparticles: a correlation between optical
and electrochemical band gaps. J Am Chem Soc 123,
8860–8861.
9 Merkoc¸ i A, Aldavert M, Tarraso
´
n G, Eritja R & Ale-
gret S (2005) Toward an ICPMS-linked DNA assay
based on gold nanoparticles immunoconnected through
peptide sequences. Anal Chem 77, 6500–6503.
10 Jelen F, Yosypchuk B, Kourilova A, Votny L & Palecek
E (2002) Label-free determination of picogram quanti-
ties of DNA by stripping voltammetry with solid copper
amalgam or mercury electrodes in the presence of cop-
per. Anal Chem 74, 4788–4793.
11 Wang J, Kawde A-N, Erdem A & Salazar MA (2001)
Magnetic-beads based. Label-free electrochem detection
DNA hybridization. Analyst 126, 2020–2024.
12 Wang J & Kawde A-N (2002) Magnetic-field stimulated
DNA oxidation. Electrochem Commun 4, 349–352.

13 Kara P, Kerman K, Ozkan D, Meric B, Erdem A,
Ozkan Z & Ozsoz M (2002) Electrochemical genosensor
for the detection of interaction between methylene blue
and DNA. Electrochem Commun 4, 705–709.
14 Wang J, Polsky R, Merkoc¸ i A & Turner KL (2003)
‘Electroactive beads’ for ultrasensitive DNA detection.
Langmuir 19, 989–991.
15 Caruana DJ & Heller A (1999) Enzyme-amplified
amperometric detection of hybridization and of a single
base pair mutation in an 18-base oligonucleotide on a
7-lm-diameter microelectrode. J Am Chem Soc 121,
769–774.
16 Hernandez-Santos D, Gonzales-Garcia MB & Costa
Garcia AC (2002) Metal-nanoparticles based electroana-
lysis. Electroanalysis 14, 1225–1235.
17 Katz E, Willner I & Wang J (2004) Electroanalytical
and bioelectroanalytical systems based on metal semi-
conductor nanoparticles. Electroanalysis 16, 19–44.
18 Merkoc¸ i A, Aldavert M, Marı
´
n S & Alegret S (2005)
New materials for electrochemical sensing. V.
Nanoparticles for DNA labeling. Trends Anal Chem 24,
341–349.
19 Park SJ, Taton TA & Mirkin CA (2002) Array-based
electrical detection of DNA with nanoparticle probes.
Science 295, 1503–1506.
20 Wang J, Xu D, Kawde AN & Polsky R (2001) Metal
nanoparticle-based electrochemical stripping potentio-
metric detection of DNA hybridization. Anal Chem 73,

5576–5581.
21 Wang J, Polsky R & Xu D (2001) Silver-enhanced col-
loidal gold electrochemical stripping detection of DNA
hybridization. Langmuir 17, 5739–5741.
22 Wang J, Xu D & Polsky R (2002) Magnetically-induced
solid-state electrochemical detection of DNA hybridiza-
tion. J Am Chem Soc 124, 4208–4209.
23 Wang J, Liu G & Merkoc¸ i A (2003) Electrochemical
coding technology for simultaneous detection of multi-
ple DNA targets. J Am Chem Soc 125, 3214–3215.
24 Liu G, Lee TMH & Wang J (2005) Nanocrystal-based
bioelectronic coding of single nucleotide polymorphisms.
J Am Chem Soc 127, 38–39.
25 Pumera M, Castan
˜
eda MT, Pividori MI, Eritja R, Mer-
koc¸ i A & Alegret S (2005) Magnetically trigged direct
electrochemical detection of DNA hybridization based
Au67 Quantum Dot – DNA – paramagnetic bead con-
jugate. Langmuir 21, 9625–9629.
26 Lianga R, Qiua J & Caib P (2005) A novel ampero-
metric immunosensor based on three-dimensional sol–
gel network and nanoparticle self-assemble technique.
Anal Chim Acta 534, 223–229.
27 Tang DP, Yuan R, Chai YQ, Zhong X, Liu Y, Dai JY
& Zhang LY (2004) Novel potentiometric immunosen-
sor for hepatitis B surface antigen using a gold nanopar-
ticle-based biomolecular immobilization method. Anal
Biochem 333, 345–350.
28 Wang J & Tian B (1998) Thick-film electrochemical

immunosensor based on stripping potentiometric detec-
tion of a metal ion label. Anal Chem 70, 1682–1685.
29 Dai Z, Kawde AN, Xiang Y, La Belle JT, Gerlach J,
Bhavanandan VP, Joshi L & Wang J (2006) Nanoparti-
cle-based sensing of glycan–lectin interactions. JAm
Chem Soc 128, 10018–10019.
30 Liu G, Wang J, Kim J & Jan MR (2004) Electrochemi-
cal coding for multiplexed immunoassays of proteins.
Anal Chem 76, 7126–7130.
31 Hansen JA, Wang J, Kawde AN, Xiang Y, Gothelf KV
& Collins G (2006) Quantum-dot ⁄ aptamer-based ultra-
sensitive multi-analyte electrochemical biosensor. JAm
Chem Soc 128, 2228–2229.
32 Gao Z & Yang Z (2006) Detection of microRNAs using
electrocatalytic nanoparticle tags. Anal Chem 78, 1470–
1477.
Electrochemical biosensing with nanoparticles A. Merkoc¸i
316 FEBS Journal 274 (2007) 310–316 ª 2006 The Author Journal compilation ª 2006 FEBS