ANALYTICAL SCIENCES DECEMBER 2010, VOL.

26 1219
2010 The Japan Society for Analytical Chemistry

Reviews

Polymer-functionalized Gold Nanoparticles as Versatile Sensing

Materials
Nobuo UEHARA

Department of Applied Chemistry, Graduate School of Engineering, Utsunomiya University,

7-1-2 Yoto, Utsunomiya, Tochigi 3218585, Japan

In this brief review, gold nanoparticles conjugated with functional polymers are described from the viewpoint of application
to sensing materials. The optical properties of gold nanoparticles, the synthesis of polymer-functionalized gold
nanoparticles, and their analytical applications are discussed. Polymer-functionalized gold nanoparticles are categorized
into two classes: biopolymer-conjugated gold nanoparticles and artificial-polymer conjugated gold nanoparticles.
Fluorometric and colorimetric sensing using gold nanoparticles are focused; fluorometric detection enables us to exploit
sensitive assays for practical use. Furthermore, chemical amplification using gold nanoparticles is also discussed for the
sensitive probing.

(Received October 9, 2010; Accepted October 25, 2010; Published December 10, 2010)

1 Introduction 1219 41 Sensors based on bridging structures

2 Optical Properties of Gold Nanoparticles 1220 42 Sensors based on spontaneous aggregation
21 Surface plasmon resonance 43 Chemical amplification
22 Luminescence 5 Analytical Application of Gold Nanoparticles
3 Fabrication of Gold Nanoparticles Functionalized with Synthetic Polymers 1224
Functionalized with Polymers 1221 6 Fluorometric Nano-sensors with Polymer-
31 Grafting from fabrication functionalized Gold Nanoparticles 1224
32 Grafting to fabrication 61 Quenching control
33 Post modification 62 Molecular beacon
4 Analytical Application of Gold Nanoparticles 7 Perspective 1226
Functionalized with Biopolymers 1222 8 References 1226

include chemical inertness, easy preparation, easy modification,

1 Introduction
Gold nanoparticles (AuNPs) are colloidal gold particles ranging
from ca. 1 nm to ca. 100 nm in size. AuNPs have several
distinctive physical and chemical attributes; their optical and
electrochemical properties and catalytic activity are not
characteristic of bulk gold.1 Other versatile features of AuNPs
Nobuo UEHARA received his bachelor and
master degrees, and a D.Sc. degree in
Material Chemistry from Tohoku University.
He joined as a lecturer in the Department
of Applied Chemistry, Utsunomiya
University in 1988 and is presently
Associate Professor since 1998. His main
area of research involves the fabrication,
characterization and application of new
analytical systems for trace metal analysis.
He is currently, engaged in the development
of versatile and novel chemical sensing
systems using stimuli-sensitive polymers
and colloidal gold for biological analysis.
E-mail: ueharan@cc.utsunomiya-u.ac.jp
and easy control of particle size. These properties have
facilitated the use of AuNPs as key materials for nanoscientific
and nanotechnological applications.2,3 Moreover, AuNPs are
commonly used in everyday life, e.g., in red stained glass and as
a red marker in diagnostic tests for influenza.
The dispersion of AuNPs affects their practical applications.
Dispersed AuNPs are thermodynamically unstable because of
their high surface energy, and they tend to spontaneously form a
precipitate under external stimuli. The conjugation of AuNPs
with water-soluble polymers is an effective way to prevent the
assembly of AuNPs because it decreases the high surface energy
of the AuNPs, and it inhibits the contact between individual
AuNPs. Indeed, the first AuNP solution prepared by Faraday
was stabilized using gelatin, a water-soluble biopolymer, and it
has retained its reddish color.4 Thus, water-soluble polymers
have been used as effective stabilizers for disassembled AuNPs.
Water-soluble polymers often exhibit versatile analytical
properties. For example, water-soluble biopolymers such as
polypeptides, nucleic acids, and polysaccharides play important
roles in specific recognition in homeostasis processes. Artificial
water-soluble polymers have also been used as functional
materials in chemical analyses, e.g., typical thermoresponsive
1220
Fig. 1Conjugation of gold nanoparticles with functional polymers.
polymers such as poly(n-isopropylacrylamide) and poly-
(methylvinylether). They exhibit a change in conformation at
different solution temperatures. The thermoresponsive property
has facilitated the use of such polymers as key materials in
actuators,57 micro-TAS,8 and drug delivery systems.9,10
A combination of two different types of functional materials
results in the inadvertent development of new functions that are
not characteristic of the individual materials. A typical example
is the conjugation of AuNPs with functional polymers, as shown
in Fig. 1. The recognition of analytes by the functional polymers
in the resulting AuNP results in a morphological change in the
gold cores, which is indicated a colorimetric change. In this
review, the optical properties of AuNPs and conjugation of
AuNPs are focused, first. Next, the applications of
polymer-functionalized AuNPs to analytical systems are
discussed. Furthermore, homogeneous sensing systems using
polymer-functionalized AuNPs are emphasize; hence,
heterogeneous sensors based on electrochemical sensing using
electrodes modified with AuNPs are ruled out. Readers may
refer to various informative reviews of electrochemical sensors
based on AuNPs.11,12
2 Optical Properties of Gold Nanoparticles
21 Surface plasmon resonance
Surface plasmon is the coherent oscillation of the surface
electrons of metal nanoparticles; it propagates at the surface of
the metal nanoparticles along with an evanescent wave. When
an incident electromagnetic wave whose frequency is identical
to that of the metal nanoparticle surface plasmon passes near the
surface of the metal nanoparticles, the resonance between the
electromagnetic wave and the surface plasmon occurs to
decrease the intensity of the incident electromagnetic wave.13,14
Although the following model may be a quantitative expression,
it is a convenient representation of the surface plasmon band.
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
The undulation of electrons existing on the surface of metal
nanoparticles causes a decrease in the radii of the nanoparticles
from bulk (e.g., milli meter order) size to nano size. The
undulation of electrons interacts with the incident light to
decrease the intensity of the light as a result of the energy
transferred from the light to the plasmon, resulting in extinction
of the incident light.
The surface plasmon resonance of AuNPs is influenced by
their morphology (shape, size, and degree of aggregation).
Spherical AuNPs whose particle sizes are above ca. 10 nm
exhibit an extinction band around 520 nm due to their inherent
surface plasmon band when disassembled in a solution.1517 The
maximum wavelength of the extinction spectra of AuNPs is
correlated to the morphology of AuNPs by Mie theory.18,19 The
addition of ionic substances or other external stimuli causes the
assembly of AuNPs because of the instability of disassembled
AuNPs. Once the AuNPs assemble, their surface plasmons are
coupled to generate a new extinction band at a longer wavelength,
resulting in a bluish color. This is the principle of colorimetric
sensors of AuNPs, which will be discussed in later sections (41
and 42).
22 Luminescence
Unlike conventional size AuNPs (above several nanometers),
AuNPs with particle sizes below ca. 2 nm, which are referred to
as gold nanoclusters, luminesce, as quantum dots do.2022 The
luminescence of inorganic nanoparticles provides new
possibilities for cell staining. Although common organic
fluorescent dyes are expected to stain cells with high sensitivity,
easy decomposition with an excitation light and interference
from the background of coexisting organic substances should be
overcome for the practical cell staining with high sensitivity.
The fluorescent staining with inorganic nanoparticles, on the
other hand, can overcome the drawbacks because of the
resistance of photo degradation by UV-irradiation.23 Because
irradiation of strong UV light decomposes organic fluorescent
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
Fig. 2Scheme of functionalization of gold nanoparticle through grafting from (A), grafting to
(B), and post modification (C) techniques.
substances, the irradiation prior to fluorescent detection of
stained cells enables us to reduce background noise from the
coexisting substances and improve S/N ration (i.e., sensitivity).
3 Fabrication of Gold Nanoparticles
Functionalized with Polymers
The conjugation of AuNPs with functional polymers is the first
step toward fabricating functional gold nanocomposites. Many
investigations involving with the fabrication of gold nanoparticles
functionalized with polymers have been reported. The reported
fabrication methods can be classified into the following three
representative categories illustrated in Fig. 2.
31 Grafting from fabrication
Grafting from fabrication is a technique in which polymer
chains extend from scaffolds attached to the surface of AuNPs
(Fig. 2(A)).2428 This technique provides the following
advantages: precise control of the molecular weight (i.e.,
polymer layer thickness) of introduced polymers, versatile
structural design of a polymer layer, and effective introduction
of polymer chains with high density. Chemically-bonded
scaffolds are superior to physically-adsorbed ones in terms of
robustness of the resulting gold nanocomposites.
Although most polymers introduced by the grafting from
method are artificial polymers,2426 representative biopolymers
such as oligonucleotides and peptides can also be introduced.
To introduce single-strand oligonucleotide chains, primers
having thiol groups were attached to the AuNPs surface
followed by the extension of single-stranded DNA (ssDNA)
chains conducted by rolling circle polymerization using DNA
polymerase.27 Since the molecular size of the primer is small,
effective introduction of ssDNA chains can be achieved. To
graft peptides onto AuNPs, sulfhydryl amines are introduced
onto AuNPs surface followed by elongation of peptide chains
with a ring opening polymerization. Higuchi and coworkers28
demonstrated the introduction of poly(gamma-methyl
1221
L-glutamate-co-L-glutamic acid)s grafted onto AuNPs to form
bio-conjugating gold nanocomposites. The molecular weight of
the grafted peptides was ca. 73 kDa and the morphology of the
peptides was an -helix structure in an aqueous solution.
32 Grafting to fabrication
The evolution of gold cores in polymer aggregates, which is
referred to as grafting to fabrication, is another potential
method for producing polymer-modified gold nanoparticles.
Advantages of this method are the availability of many kinds of
polymers and the easy synthesis (one-pot synthesis). The
one-pot synthesis enables us to reduce laborious steps that
grafting-from modification requires.
Polymers to be used for the grafting to modification are
categorized into two types: one is a polymer terminated with a
sulfur-containing group and the other is a polymer terminated
with a sulfur-free group. Polymers terminated with a sulfur
containing group (dithioester, trithioester, thiol, thioether and
disulfide) provide chemical-bonded shell layers around the gold
cores, which also occurs in the grafting from method.29,30 The
polymers terminated with sulfur containing groups can be
synthesized by a radical polymerization using chain transfer
reagents containing sulfur atoms.31
The evolution of gold cores in aggregates composed of
conventional polymers without sulfur atoms results in gold
nanocomposites in which the polymers interact with gold cores
through multi-point physical adsorption.32 Not only artificial
polymers, such as poly(N-vinylpyrrolidine),33 poly(vinylpyridine),34
poly(ethyleneglycol),35 poly(vinyl alcohol),36 poly(vinyl
methylether),37 poly(ethyleneimine),38 poly(dialyl dimethyl-
ammonium),39 but also biopolymers, were examined for the
grafting to fabrication. The drawback of using the polymer
terminated with a sulfur-free group is instability of the resulting
gold nanocomposites. The polymer-coated AuNPs are prone to
being detached because of a lack of chemical bonds, resulting in
assembly of the AuNPs when the polymer micelles that surround
the AuNPs collapse. Crosslinking between the polymer
networks in the polymer layer is an effective way to suppress
1222
Fig. 3Aggregation of AuNPs through ridging structure via (A) hybridized DNA, (B) chelating bond,
(C) supermolecule, (D) biological interaction, and (E) covalent bond.
the instability of the resulting gold nanocomposites. The use of
unimolecular micelles40 or stabilized micelles with crosslinking
networks provides another promising strategy for overcoming
the instability because the morphology of these micelles is not
influenced by solution conditions.41
33 Post modification
Conjugation of as-prepared AuNPs with as-prepared polymers
is the most common and the simplest method for preparing gold
nanocomposites because mixing both of the as-prepared
materials can eliminate uncertain factors in fabricating gold
nanocomposites, such as the dispersion of AuNP size and
molecular weight. Drawbacks of the post modification
method, however, are low efficiency of polymer introduction of
due to the steric hindrance of the conjugated polymers and
unintended adsorption through functional groups in the
polymers. As well as the other modifications reviewed in this
section, conjugation of AuNPs with the polymers having
SH-terminated groups form covalent-bonded type gold
nanocomposites while the conjugation with other polymers
without thiol groups form physically-adsorbed gold
nanocomposites.
4 Analytical Application of Gold Nanoparticles
Functionalized with Biopolymers
In this section, an overview of the analytical applications of
biopolymer-functionalized gold nanoparticles to chemical
sensing and chemical magnification is provided. The chemical
inertness of AuNPs provides them with low bio-toxicity, which
is an advantage in biological and medical applications. In
addition to the inherent inertness of AuNPs, the conjugation of
biopolymers further increases the biocompatibility of the
resulting gold nanocomposites. Since the conjugation of
biopolymer confers recognizing functions to the resulting
polymer-functionalized AuNPs, the resulting gold
nanocomposites have been investigated as bio-sensing probes
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
for the last decade.42,43 Based on the recognition abilities of the
biopolymers, cell staining has been investigated with the
biopolymer-functionalized AuNPs discussed earlier (Sect. 22).
41 Sensors based on bridging structures
As mentioned in Sect. 21, disassembled and assembled
AuNPs, which develop a reddish and bluish-purple solution
color, respectively, due to their surface plasmon bands of the
corresponding morphology, have been utilized for fabrication of
colorimetric sensors. The formation of bridging structures
between AuNPs facilitates a linkage for assembling the AuNPs,
resulting in a change in solution color from red to blue-purple.
Figure 3 depicts representative bridging structures for linking
AuNPs.44 After Mirkin and coworkers first reported the
assembly of AuNPs linked through double-stranded DNAs,45
related bridging structures have been developed for colorimetric
sensors of DNAs with AuNPs.46,47 In addition to DNA
hybridization,4547 interactions such as antigen-antibody,48,49
avidin-biotin,50,51 lectin-sugar,5254 and generation of a chemical
bond55 have been investigated for the formation of bridging
structures. Chelation56 and the formation of supermolecular
structure57,58 have been also studied.
42 Sensors based on spontaneous aggregation
Non-crosslinking aggregation based on the enthalpic
destabilization of gold nanocomposites is another potential
approach for developing the colorimetric sensors. Since
negative charges on the surface of AuNPs stabilize the AuNPs,
cancellation of negative charges or shrinkage of the electric
double layers surrounding gold nanoparticles cause the
spontaneous non-crosslinking aggregation. Although the
cancellation of the negative charges on gold nanocomposites is
easy to achieve by adding counter ionic, i.e., cationic substances,
the control of the selectivity is difficult in practice.59
The shrinkage of electric double layers surrounding AuNPs is
another potential approach to serve a platform of colorimetric
sensors. Increasing the ionic strength of a solution by adding of
an inorganic salt compresses the electric double layers of gold
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
Fig. 4Spontaneous aggregation of gold nanocomposites based on salting out assisted with
destabilization. A) Hybridization with complement, B) disruption of bonded polymer.
nanocomposites to destabilize the nanocomposites, resulting in
spontaneous aggregation.60,61 Introduction of the mechanisms
that can be manipulated externally allows us to develop selective
colorimetric assays with the gold nanocomposites. Typical
mechanisms for spontaneous aggregation based on salting out
are shown in Fig. 4. Single-stranded oligonucleotides, acting as
anionic and flexible biopolymers, were examined to verify the
spontaneous aggregation. The single-stranded oligonucleotides
stabilize AuNPs even under saline conditions. Hybridization
with the complementary single-stranded oligonucleotides forms
rigid double-stranded oligonucleotides with reduced the
flexibility, causing the gold nanocomposites to assemble due to
entropic instability with the aid of salting out. Single nucleotide
polymorphisms (SNPs) form imperfect double strands, which
do not cause the assembly of the oligonucleotides and hence
stabilize AuNPs. Based on the different responses of the SNPs
and the complementary DNA, the SNPs could be discerned with
the naked eye (Fig. 4A).62
Cleavage of aptamers, engineered nucleotides, provides
another sensing platform for non-crosslinking. When specific
substances cleave aptamers bonded onto AuNPs to generate
single-stranded fragments, the resulting AuNPs with cleaved
aptamers become unstable and assemble with the addition of
salts. Thus, the specific substances can be quantified by the
colorimetric change in the solution.63 Because the liberated
fragments of aptamers work as anionic soluble polymers which
coat and stabilize AuNPs through multi-point interaction to
prevent aggregation by the salting out effect, another sensing
system platform can be designed using the cleaved fragments.64,65
Since the original aptamers are rigid, they do not stabilize the
AuNPs, leading to the spontaneous aggregation by salting out.
Subsequently, the specific substances were assayed
colorimetrically after the addition of sodium chloride.
43 Chemical amplification
Chemical amplification prior to assay is an important
technique for the sensitive assay. Because the electric
1223
amplification magnifies the background noise as well as signals
of analytes, it does not practically improve the signal-to-noise
ratio. On the contrary, the chemical amplification has the
potential to amplify only signals of analytes to improve the
sensitivity of the whole analytical system. One of the most
effective chemical amplification systems utilizing gold
nanoparticles is a bio-barcode method, in which magnetic
particles play an important role along with the gold
nano-composites. The bio-barcode method is based on the
formation of linkages composed of analytes between the
magnetic nanocomposites and gold nanocomposites that hold
barcode DNAs on their surface, as shown in Fig. 5.66 The
resulting sandwich-type magnetic conjugates are separated and
isolated from a solution with an external magnetic field. After
the isolation of the conjugates with the magnetic field, the
barcode DNAs from the gold nanocomposites are liberated by
heating the solution as a result of dehybridization. Since one
target molecule is converted to the liberated barcode DNAs
through the bio-barcode process, the number of barcode ssDNAs
in the gold nanocomposites corresponds to the amplification
ratio of the bio-barcode amplification, at least in principle. The
amplification ratio of bio-barcodes is comparable to polymerase
chain reaction (PCR) amplification.67 The principle of
bio-barcodes worked on the amplification of proteins that
act as specific and stable linkers through antigen-antibody
interactions.68 After the first investigation reported by Mirkins
group,68 various modifications of bio-barcodes have been
reported.66
The bio-barcode amplification technique has been combined
with a chip-based DNA detection. In the chip-based detection,
liberated barcode DNAs are hybridized to a microarray slide
followed by capture of universal gold nanocomposites through
further hybridization. Catalytic deposition of silver ions on
AuNPs further enhances the sensitivity of the chip-based
detection. The combination of PCR amplification and
bio-barcodes also achieved high sensitivity for a protein with
the detection limit at the atto molar level.68
1224
Fig. 5Bio-barcode amplification. Step 1, Formation of gold-magnetic conjugates; step 2, magnetic
separation; step 3, liberation of hybridized barcode DNA (e.g. heating).
5 Analytical Application of Gold Nanoparticles
Functionalized with Synthetic Polymers
Synthetic polymers also provide versatile functions to gold
nanoparticles to be used as chemical sensors.
Poly(ethyleneglycol), which is a typical synthetic polymer
composed of a repeating oxyethylene unit, is one of the most
promising candidates to be conjugated with AuNPs for the
development of chemical sensors due to the high
bio-compatibility and the stable dispersibility. AuNPs linked
with lactose through poly(ethyleneglycol) were examined as a
colorimetric sensor of lectin.6971 RCA120, a bivalent lectin that
recognizes the -D-galactose specifically, accumulates
lactose-linked AuNPs, resulting in the alteration of the solution
color from red to blue-purple. The addition of excess galactose
releases the lactose-linked AuNP from the aggregates of AuNPs
and RCA120, leading to disassembly of the AuNPs. Based on the
lectin-sugar interaction, antimicrobial susceptibility,71 Cholera
toxin,72 and ConA52,73 were assayed with the sugar-bonded
AuNPs.
Thermoresponsive polymers reveal a reversible phase
transition between hydration and dehydration in response
to the solution temperature. Conjugation of AuNPs with
poly(n-N-isopropylacrylamide), a typical thermoresponsive
polymers, produces a novel type of colorimetric sensing
material. A layer of thermoresponsive polymer surrounding the
AuNPs swells below the phase transition temperature and
shrinks above the phase transition temperature.74 The
temperature-controlled thickness of the polymer layer is applied
to the fabrication of a nano-sized thermometer based on
fluorometry.75 The nano-sized thermometer is composed of the
temperature-controlled polymer containing fluorophores and
gold nano-cores. Fluorescence of the fluorophores in the
polymer layer is influenced by energy transfer from excited
fluorophers to AuNPs (referred to as florescence resonance
energy transfer, FRET) that can be controlled by thermal stimuli
externally. Fluorophores in the shrunken polymer layer come
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
close to the surface of AuNPs to enhance FRET, leading to
suppression of the fluorescence, and vice versa.
The phase transition of thermoresponsive polymers attached
to AuNPs alters not only the polymer configuration but also the
morphology of gold cores in nanocomposites. The present
authors group has developed a unique colorimetric sensor using
gold nanocomposites conjugated with thermoresponsive
copolymers possessing poly(ethyleneamine).76 Figure 6
illustrates the schematic of the colorimetric sensor whose color
changes from blue-purple to red by thermal stimuli (heating
followed by cooling). Although the gold nanocomposites
aggregate initially due to the poly(ethyleneamine) groups, they
do not precipitate owing to the conjugated polymers. Heating a
solution facilitates shrinkage of polymer chains on the AuNPs
surface to expand the inter-particle distance of the AuNPs like a
wedge. After the solution is cooled, the aggregated gold
nanoparticles become disassembled, leading to a change in the
solution color to red. Cysteine, a sulfhydryl monopeptide,
inhibits the disassembly through replacement of the polymer
adsorbed on the gold nanocomposites. As the concentration of
cysteine added into the solutions increases, the resulting
solutions exhibit gradation from red to blue-purple. The
gradation could be quantified with the L*a*b* color coordinates
to determine the concentration of cysteine. Further studies
indicated that the addition of glutathione induced the spontaneous
disassembly of the polymer-conjugated AuNPs without the
thermal stimuli.77
6 Fluorometric Nano-sensors with Polymer-
functionalized Gold Nanoparticles
61 Quenching control
AuNPs whose particle sizes exceed ca. 10 nm work as an
effective fluorescence quencher.78,79 The quenching efficiency
of AuNPs is much larger than that of conventional organic
quenching substances. The quenching is caused by FRET,
which occurs when a fluorophore and an AuNP locate closely
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26 1225

Fig. 6Thermal stimuli-induced disassembly of aggregated gold nanocomposites conjugated with

thermoresponsive polymer.

FL B

FL

FRET A
FRET
FL
C
FL FL
Gold
FL nanoparticle
FRET

FRET
FL

SH
FL
FL FRET FL

E
D

Fig. 7Fluorometric sensing based on suppression of fluorescence resonance energy transfer (FRET).

(<2 nm). When analytes isolate fluorophores and AuNPs with
enough distance to suppress FRET, the fluorophores regain their
inherent fluorescence. Based on the recovery of the fluorescence,
the fluorescent sensors attain high sensitivity because a blank
fluorescence can be suppressed effectively by AuNPs.
Figure 7 depicts the five representative assay systems of the
quenching control of fluorescence. A target single-stranded
DNA replaces a fluorophore-connected DNA possessing the
same sequence (system A). Competition of complexation with
a target metal ion releases a bound complex connecting with a
fluorophore (system B). A target substance disrupts a linkage
between a fluorophore and an AuNP, leading to liberation
of the fluorophore (system C). A target substance releases a
fluorophore in a super-molecular structure bound with an AuNP
(system D). A target sulfhydryl compound releases a fluorophore
adsorbed on an AuNP through replacement (system E).
1226
Fig. 8Molecular beacon probe (A) and its stemmed molecular probe (B).
62 Molecular beacon
Molecular beacon (MB), a typical molecular switching
method, is categorized as a fluorophore quenching control
method. Since MB methods for the detection of DNA were
originally developed by Klamer and coworkers,80 many related
methods have been developed to detect DNA. Therefore, we
briefly review MB independently. Figure 8 shows two
representatives of the molecular switching methods, which
utilize changes in configuration and rigidity of hybridized
DNA.81 A key material of MB is a single-stranded DNA that
possesses complementary sequences at each terminal to form a
hairpin-like configuration through hybridization. To prepare a
MB probe, a quencher and a fluorophore are attached at each
end of the single-stranded DNA followed by the formation of a
hairpin. Energy is transferred from the fluorophore to the
quencher in the MB probe due to their proximity, quenching the
fluorescence. Hybridization of a fully complementary DNA
with the probe conjugate opens the hairpin to alienate both the
quencher and the fluorophore, resulting in inhibition of the
energy transfer to recover the fluorescence (Fig. 8A). The
opposite type of sensor molecule in which a fluorophore and
a quencher are aligned closely to facilitate energy transfer can
also be designed (Fig. 8B).
Dubertret and coworkers were the first to introduce AuNPs
into MBs probes as a quencher.82 The introduction of a gold
nanoparticle enhanced the sensitivity up to 100-fold and
improved the detectability for a single mismatch eight-fold
compared to conventional MBs.83
7 Perspective
Gold nanocomposites composed of gold nano-cores and
water-soluble polymer shells serve as highly functional
nano-materials that exhibit versatile properties arising from not
only the features of each original constituent but also from the
synergistic effects of both. Gold nanocomposites conjugated
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
with biopolymers have provided potential bio-sensing materials
for labeling, imaging, and assaying. Also, the conjugation of
thermoresponsive polymers has introduced a thermoresponsive
property in the resulting gold nanocomposites, allowing us to
fabricate unique colorimetric sensors. The changes in the
morphology of the thermoresponsive gold nanocomposites
between assembly and disassembly, which are read by
colorimetric changes, can be controlled externally by the
solution temperature with reversibility. In this review, distinctive
and versatile properties of polymer-functionalized gold
nanoparticles have been discussed in terms of their analytical
uses. Because many kinds of metal nanoparticles and functional
polymers are available at the present time, the number of
possible combinations is immense. There are many more
remain excellent and innovative polymer-functional gold
nanoparticles; a limited number of examples are highlighted
here. The author hopes this brief review inspire readers to
develop novel functional materials.
8 References
1. G. Schmid, Clusters and Colloids: From Theory to
Applications, 1994, Wiley-VCH, New York.
2. Nanomaterials for the Life Sciences, ed. C. S. S. R.
Kumer, 2009, Vol. 1, Wiley-VCH, New York.
3. Colloidal Nanoparticles in Biotechnology, ed. A.
Elaissari, 2008, Wiley-Interscience A John Wiley and Sons,
New York.
4. M. Faraday, Philosophical Transactions, 1857, 147, 145.
5. M. J. N. Junk, R. Berger, and U. Jonas, Langmuir, 2010,
26, 7262.
6. M. E. Harmon, M. Tang, and C. W. Frank, Polymer, 2003,
44, 4547.
7. A. Buguin, M.-H. Li, P. Silberzan, B. Ladoux, and P. Keller,
J. Am. Chem. Soc., 2006, 128, 1088.
8. T. Saitoh, A. Sekino, and M. Hiraide, Chem. Lett., 2004,
ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
33, 912.
9. S. Dirk, Adv. Drug Delivery Rev., 2006, 58, 1655.
10. M. Nakayama and T. Okano, J. Drug Delivery Sci. Technol.,
2006, 16, 35.
11. T. Nagaoka, H. Shiigi, and S. Tokonami, Bunseki Kagaku,
2007, 56, 201.
12. M. T. Castaeda, S. Alegret, and A. Merkoci, Electroanalysis,
2007, 19, 743.
13. S. Link and M. A. El-Sayed, J. Phys. Chem. B, 1999, 103,
8410.
14. Z. Zhong, S. Patskovskyy, P. Bouvrette, J. H. T. Luong, and
A. Gedanken, J. Phys. Chem. B, 2004, 108, 4046.
15. W. Haiss, N. T. K. Thanh, J. Aveyard, and D. G. Fernig,
Anal. Chem., 2007, 79, 4215.
16. N. G. Khlebtsov, Anal. Chem., 2008, 80, 6620.
17. P. N. Njoki, I.-I. S. Lim, D. Mott, H.-Y. Park, B. Khan, S.
Mishra, R. Sujakumar, J. Luo, and C.-J. Zhong, J. Phys.
Chem. C, 2007, 111, 14664.
18. G. Gouesbet, J. Quant. Spectrosc. Radiat. Transfer, 2009,
110, 1223.
19. C. M. Cobley, S. E. Skrabalak, D. J. Campbell, and Y. Xia,
Plasmonics, 2009, 4, 171.
20. C.-C. Huang, C.-K. Chiang, Z.-H. Lin, K.-H. Lee, and
H.-T. Chang, Anal. Chem., 2008, 80, 1497.
21. C.-A. J. Lin, T.-Y. Yang, C.-H. Lee, S. H. Huang, R. A.
Sperling, M. Zanella, J. K. Li, J.-L. Shen, H.-H. Wang, H.-I.
Yeh, W. J. Parak, and W. H. Chang, ACS Nano, 2009, 3,
395.
22. X. Liu, C. Li, J. Xu, J. Lv, M. Zhu, Y. Guo, S. Cui, H. Liu,
S. Wang, and Y. Li, J. Phys. Chem. C, 2008, 112, 10778.
23. H. He, C. Xie, and J. Ren, Anal. Chem., 2008, 80, 5951.
24. Q. Huo and J. G. Worden, J. Nanoparticle Res., 2007, 9,
1013.
25. J. Shan and H. Tenhu, Chem. Commun., 2007, 4580.
26. M. Kaholek, W.-K. Lee, S.-J. Ahn, H. Ma, K. C. Caster, B.
LaMattina, and S. Zauscher, Chem. Mater., 2004, 16, 3688.
27. W. Zhao, Y. Gao, S. A. Kandadai, M. A. Brook, and Y. Li,
Angew. Chem., Int. Ed., 2006, 45, 2409.
28. M. Higuchi, K. Ushiba, and M. Kawaguchi, J. Colloid
Interface Sci., 2007, 308, 356.
29. Y. Liu, M. K. Shipton, J. Ryan, E. D. Kaufman, S. Franzen,
and D. L. Feldheim, Anal. Chem., 2007, 79, 2221.
30. A. Aqil, H. Qiu, J.-F. Greisch, R. Jerome, E. D. Pauw, and
C. Jerome, Polymer, 2008, 49, 1145.
31. Z. Wang, B. Tan, I. Hussain, N. Schaeffer, M. F. Wyatt, M.
Brust, and A. I. Cooper, Langmuir, 2007, 23, 885.
32. T. Sakai and P. Alexandridis, Langmuir, 2004, 20, 8426.
33. S. Yang, T. Zhang, L. Zhang, S. Wang, Z. Yang, and B.
Ding, Colloids Surf., A, 2007, 296, 37.
34. H. Dong, E. Fey, A. Gandelman, and W. E. Jones, Jr.,
Chem. Mater., 2006, 18, 2008.
35. P. Zhang, X. Jiang, X. Zhang, W. Zhang, and L. Shi,
Langmuir, 2006, 22, 9393.
36. M. Sakamoto, T. Tachikawa, M. Fujitsuka, and T. Majima,
Langmuir, 2006, 22, 6361.
37. R. R. Bhattacharjee, M. Chakraborty, and T. K. Mandal, J.
Phys. Chem. B, 2006, 110, 6768.
38. C. Note, S. Kosmella, and J. Koetz, Colloids Surf., A, 2006,
290, 150.
39. H. Chen, Y. Wang, Y. Wang, S. Dong, and E. Wang,
Polymer, 2006, 47, 763.
40. M. Filali, M. A. R. Meier, U. S. Schubert, and J.-F. Gohy,
Langmuir, 2005, 21, 7995.
41. S. Liu, J. V. M. Weaver, M. Save, and S. P. Armes,
Langmuir, 2002, 18, 8350.
1227
42. N. L. Rosi and C. A. Mirkin, Chem. Rev., 2005, 105, 1547.
43. C. S. Thaxton, D. G. Georganopoulou, and C. A. Mirkin,
Clin. Chim. Acta, 2006, 363, 120.
44. N. Uehara and T. Nagaoka, Nanomaterials for the Life
Science, ed. C. S. S. R. Kumer, 2010, Vol. 8, Wiley-VCH,
119.
45. C. A. Mirkin, R. L. Letsinger, R. C. Mucic, and J. J.
Storhoff, Nature, 1996, 382, 607.
46. M. S. Han, A. K. R. Lytton-Jean, B.-K. Oh, J. Heo, and C.
A. Mirkin, Angew. Chem., Int. Ed., 2006, 45, 1807.
47. M. S. Han, A. K. R. Lytton-Jean, and C. A. Mirkin, J. Am.
Chem. Soc., 2006, 128, 4954.
48. Y. Liu, Y. Liu, R. L. Mernaugh, and X. Zeng, Biosens.
Bioelectron., 2009, 24, 2853.
49. C. Wang, Y. Chen, T. Wang, Z. Ma, and Z. Su, Chem.
Mater., 2007, 19, 5809.
50. K. Aslan, C. C. Luhrs, and V. H. Prez-Luna, J. Phys. Chem.
B, 2004, 108, 15631.
51. A. Gole and C. J. Murphy, Langmuir, 2005, 21, 10756.
52. M. Toyoshima and Y. Miura, J. Polym. Sci., Part A, 2009,
47, 1412.
53. Y. Sato, T. Murakami, K. Yoshioka, and O. Niwa, Anal.
Bioanal. Chem., 2008, 391, 2527.
54. C. L. Schofield, B. Mukhopadhyay, S. M. Hardy, M. B.
McDonnell, R. A. Field, and D. A. Russell, Analyst, 2008,
133, 626.
55. Y. Zhou, S. Wang, K. Zhang, and X. Jiang, Angew. Chem.,
Int. Ed., 2008, 47, 7454.
56. A. Sugunan, C. Thanachayanont, J. Dutta, and J. G.
Hilborn, Sci. Technol. Adv. Mater., 2005, 6, 335.
57. S. Kim, J. W. Park, D. Kim, D. Kim, I.-H. Lee, and S. Jon,
Angew. Chem., Int. Ed., 2009, 48, 4138.
58. S.-Y. Lin, S.-W. Liu, C.-M. Lin, and C.-h. Chen, Anal.
Chem., 2002, 74, 330.
59. Y.-M. Chen, C.-J. Yu, T.-L. Cheng, and W.-L. Tseng,
Langmuir, 2008, 24, 3654.
60. I.-I. S. Lim, D. Mott, W. Ip, P. N. Njoki, Y. Pan, S. Zhou,
and C.-J. Zhong, Langmuir, 2008, 24, 8857.
61. K. Sato, K. Hosokawa, and M. Maeda, J. Am. Chem. Soc.,
2003, 125, 8102.
62. K. Sato, K. Hosokawa, and M. Maeda, Nucleic Acids Res.,
2005, 33, e4.
63. J. Liu and Y. Lu, J. Am. Chem. Soc., 2007, 129, 8634.
64. Z. Wang, J. H. Lee, and Y. Lu, Adv. Mater., 2008, 20, 3263.
65. J. Wang, L. Wang, X. Liu, Z. Liang, S. Song, W. Li, G. Li,
and C. Fan, Adv. Mater., 2007, 19, 3943.
66. K. A. White and N. L. Rosi, Nanomedicine, 2008, 3, 543.
67. J.-M. Nam, S. I. Stoeva, and C. A. Mirkin, J. Am. Chem.
Soc., 2004, 126, 5932.
68. J. M. Nam, C. S. Thaxton, and C. A. Mirkin, Science, 2003,
301, 1884.
69. H. Otsuka, Y. Akiyama, Y. Nagasaki, and K. Kataoka, J.
Am. Chem. Soc., 2001, 123, 8226.
70. S. Takae, Y. Akiyama, H. Otsuka, T. Nakamura, Y. Nagasaki,
and K. Kataoka, Biomacromolecules, 2005, 6, 818.
71. S. Nath, C. Kaittanis, A. Tinkham, and J. M. Perez, Anal.
Chem., 2008, 80, 1033.
72. C. L. Schofield, R. A. Field, and D. A. Russell, Anal.
Chem., 2007, 79, 1356.
73. C. L. Schofield, A. H. Haines, R. A. Field, and D. A.
Russell, Langmuir, 2006, 22, 6707.
74. D. J. Kim, S. M. Kang, B. Kong, W.-J. Kim, H.-J. Paik, H.
Choi, and I. S. Choi, Macromol. Chem. Phys., 2005, 206,
1941.
75. H. Kobayashi, M. Nishikawa, C. Sakamoto, T. Nishio,
1228 ANALYTICAL SCIENCES DECEMBER 2010, VOL. 26
H.Kanazawa, and T. Okano, Anal. Sci., 2009, 25, 1043.
76. T. Shimada, K. Ookubo, N. Komuro, T. Shimizu, and N.
Uehara, Langmuir, 2007, 23, 11225. 80.
77. N. Uehara, K. Ookubo, and T. Shimizu, Langmuir, 2010, 81.
26, 6818.
78. N. Nerambourg, M. H. V. Werts, M. Charlot, and M. 82.
Blanchard-Desce, Langmuir, 2007, 23, 5563.
79. E. Dulkeith, A. C. Morteani, T. Niedereichholz, T. A. Klar, 83.
J. Feldmann, S. A. Levi, F. C. J. M. van Veggel, D. N.
Reinhoudt, M. Mller, and D. I. Gittins, Phys. Rev. Lett.,
2002, 89, 203002.
S. Tyagi and F. R. Kramer, Nat. Biotechnol., 1996, 14, 303.
G. Goel, A. Kumar, A. K. Puniya, W. Chen, and K. Singh,
J. Appl. Microbiol., 2005, 99, 435.
B. Dubertret, M. Calame, and A. J. Libchaber, Nat.
Biotechnol., 2001, 19, 365.
N. C. Cady, A. D. Strickland, and C. A. Batt, Mol. Cell.
Probes, 2007, 21, 116.