stim responsive HG
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Transcript of stim responsive HG
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Volum
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COMMUNICATIONKazunoriKataokaet al.pH-dependentpermeabilitychangeandreversiblestructuraltransitionofPEGylatedpolyioncomplexvesicles(PICsomes)inaqueousmedia
ISSN1744-683X
PAPERStefanHoworkaet al.SelectiveproteinandDNAadsorptiononPLL-PEGfilmsmodulatedbyionicstrength
Soft Matter
1744-683X(2009)5:3;1-J
Volume5|Number3|7February2009|Pages481692
As featured in:
SeeIhorTokarevandSergiyMinko,Soft Matter,2009,5,511.
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Stimuli-responsivehydrogelthinfilmsserveaversatileplatformforthefabricationofsmartresponsivesurfaces,cellculturesupports,autonomousdrugdeliverysystems,microfluidicdevicesandflowswitches,miniaturizedsensorswithvarioustransductionmechanisms,micro/nanoactuators,andmanyotherfunctionalsystems
Title: Stimuli-responsive hydrogel thin films
Showcasing a review from the Minko lab at Clarkson University, USA.
www.softmatter.org
COMMUNICATIONKazunori Kataoka et al.pH-dependent permeability changeand reversible structural transition ofPEGylated polyion complex vesicles(PICsomes) in aqueous media
ISSN 1744-683X
PAPERStefan Howorka et al.Selective protein and DNA adsorptionon PLL-PEG films modulated by ionicstrength
Soft Matter
1744-683X(2009)5:3;1-J
Volume 5 | Number 3 | 7 February 2009 | Pages 481692
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Stimuli-responsive hydrogel thin films
Ihor Tokarev and Sergiy Minko*
Received 8th August 2008, Accepted 15th October 2008
First published as an Advance Article on the web 17th November 2008
DOI: 10.1039/b813827c
In this brief review we address a range of interesting applications and prospects of responsive hydrogel
thin films for the fabrication of smart responsive surfaces, membranes, sensors with various
transduction mechanisms, micro/nanoactuators, and capsules. We show that hydrogel thin films
compete with grafted polymers and demonstrate strong advantages for the fabrication of robust
multifunctional and multiresponsive surfaces. This article reviews recent publications on the synthesis
of responsive hydrogel thin films and hybrid films with entrapped nanoparticles and reagents by the
chemical crosslinking of reactive polymers, layer-by-layer deposition, and block-copolymer self-
assembly, as well as examining those publications to determine a ran
1 Introduction
and applications of responsive hydrogel thin films for sensors,
lation, and controlled release.
2004 from Technische Uni-
ergiy Minko is Egon Matijevic
haired Professor of Chemistry
t the Department of Chemistry
nd Biomolecular Science
Clarkson University, NY,
USA). Dr Minko received his
Department of Chemistry and Biomolecular Science, Clarkson University,
REVIEW www.rsc.org/softmatter | Soft Matter
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His research is in the fields of
nanostructured materials, self-
assembled and stimuli-respon-
sive polymer thin films, sensing
and actuating devices.
Sergiy Minko
DSc in Chemistry from the
National Academy of Sciences
of Ukraine in 1993. His research
is in the fields of thin polymer
films, polymer brushes, polymer
gels and membranes, colloidal
particles and self-assembly.gating devices, actuators, encapsu
Ihor Tokarev is a Research
Assistant Professor of Chem-
istry at Clarkson University in
Potsdam, NY. Dr Tokarev
received his PhD in Chemistry in
S
C
a
a
(
Potsdam, NY 13699, USA. E-mail: [email protected] hydrogels have been the focus of research for the past
several decades because of their range of important properties,
such as biocompatibility, responsive behavior (volumetric
changes) in changeable surrounding environments, ability to
store and immobilize reactive functional groups, chemicals or
cells, and low interfacial tension at the gel-aqueous solution
interface.112 The responsive behavior of hydrogels is of special
concern in this review. If the hydrogel is synthesized from stimuli-
responsive polymers, then changes in the surrounding aqueous
solution (for example, temperature, pH, salt concentration or
concentration of some chemicals) may cause conformation
transition of the polymer chains, which form strands between
crosslinking points in the polymer gel. The globule-to-coil tran-
sition of the strands is observed as volumetric changes of the gel
material, specifically in the swelling degree of the gel in the
solution. This change in swelling degree refers to changes of many
properties of the materials: refractive index, permeability, elastic
modulus, interfacial tension, adhesion, etc. The mechanism
required to change the physical properties of hydrogels uponThis journal is The Royal Society of Chemistry 2009ge of applications.
external stimuli has been explored for the tunable and switchable
transport of ions and molecules across the material, controlled
uptake and release of chemicals by bulk hydrogels, and various
kinds of sensors and actuators as discussed in this review.
Recent advances in nanotechnology have led to increased
interest in hydrogel thin films. The advantages of hydrogel thin
films have been explored for the fabrication of miniaturized
devices with fast response times. Hydrogel thin films have also
attracted interest as an approach to responsive surfaces and
interfaces, where they compete with grafted polymer layers. A
3D polymer network is much more stable at interfaces when
compared with polymer brushes, where polymer chains are
grafted to the surface via only one functional group while the
polymer network is linked to the surface by multiple anchoring
points. Unlike polymer brushes, the thin gel film can be trans-
ferred from the surface of one material to the surface of another
material or used as a free-standing film. The storage function of
the hydrogel thin films (their ability to accommodate various
nanoparticles, chemicals, dyes, enzymes, etc.) can be explored for
the substantial increase in the range of functional properties they
will demonstrate and external signals they will respond to.
In this review we analyze the recent results in synthesis, study,Soft Matter, 2009, 5, 511524 | 511
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close to the pKa of the acidic groups. The introduction of
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2.1 Theory of swelling
When a polymer material is immersed in a good solvent, the free
energy of mixing in the form of osmotic pressure causes the
solvent to diffuse into the materials body. The solvent absorp-
tion continues until the complete dissolution of the polymer
occurs unless its chains are held together by chemical or physical
crosslinks, thus forming a 3D polymer network. In the cross-
linked polymer material, the solvent absorption leads to the
expansion (swelling) of the network. This swelling is possible due
to the elastic stretching of the polymer chain fragments (strands)
between the crosslinking points. This stretching of the chain
fragments (away from the Gaussian conformation) increases the
elastic retractive force of the entropic origin, which counteracts
the networks expansion. The balance of these two opposing
contributions governs the equilibrium volume of the polymer
network. The ratio of the swollen volume to the dry volume
determines the swelling degree of the polymer network. A
network imbibed with a solvent is called a gel. The equilibrium
swelling behavior of isotropic, neutral polymer gels is well
described by the Flory-Rehner theory, which is generally
a combination of the thermodynamic theory and the theory of
rubber elasticity.1315
When a polymer network is swollen in water, it is referred to as
a hydrogel. A polyelectrolyte (PE) gel is a special kind of
hydrogel. In the simplest case, the PE gel has ionizable groups of
only one sign (or their large excess). Such a gel may swell to
a significantly greater extent compared to neutral gels due to the
additional osmotic pressure arising from mobile counterions
trapped in the gel as well as the electrostatic repulsion of similarly
charged PE segments. The difference in mobile ion concentra-
tions inside the gel and in the outer solution is determined by the
Donnan equilibrium. For highly ionized PE gels, the osmotic
contribution of counterions to the swelling is dominating. The
corresponding osmotic term was included in the Flory-Rehner
theory16 and the theory proposed by Ricka and Tanaka17 to
describe the equilibrium swelling properties of a wide range of PE
gels. However, in many cases, these theories demonstrated strong
deviations from the experiment, indicating that the electrostatic
interactions in PE gels cannot be ignored. As a result, alternative
theories and models have evolved to account for the long-range
repulsive electrostatic interactions between the PE segments
(favoring swelling), attractive electrostatic interactions between
salt counterions and the charged polymer segments (favoring
shrinking), counterion condensation (leading to an inhomoge-
neous charge distribution and the formation of ion pairs), the
non-Gaussian conformation of charged polymer segments, and
other effects.1820
Stimuli-responsive hydrogels often exhibit sharp volume phase
transitions triggered by specific chemical or physical stimuli.
Such reversible transitions between the swollen and shrunken
phases are often referred to in the literature as swelling-shrinking
transitions. Hydrogels that demonstrate large-scale volumetric
changes in response to small levels of stimuli are obviously of the
most practical interest. The typical stimuli and mechanisms
of response are discussed below in Section 2.2. Fast kinetics of
swelling and shrinking is the prerequisite of most applications512 | Soft Matter, 2009, 5, 511524hydrophobic comonomers shifts the transition to higher pH
values. In contrast, an increase in the pH causes the deproto-
nation of the basic groups in a polycationic gel. At a certain point
this leads to the transition of the gel into a shrunken state.
The swelling degree of a weak PE gel can be altered by adding
salt to an aqueous solution. Theoretical descriptions of the salt-
induced volume phase transitions can be found in several
studies.2224 As an example, consider the case of a gel comprised
of a weak polyacid. At low ionic strength, protons are the major
counterions in the gel. They are trapped in the gel, maintaining
its electroneutrality. The degree of ionization of the gel is
controlled by the pKa of the acidic groups, the local pH, and ionic
strength. In fact, it is lower than the degree of ionization of the
corresponding acid in the bulk solution due to the lower local
pH. As the ionic strength increases, the protons exchange with
the salt ions from the surrounding solution. This causes a shift in
the chemical equilibrium accompanied by an increase in the
ionization degree of the acid groups and in the osmotic pressure
of the mobile counterions in the gel. As a result, at medium ionic
strengths, the gel undergoes additional swelling. The dilution ofof stimuli-responsive hydrogels. The volume phase transition is
a diffusion-limited process, which implies that at least one of the
dimensions of a hydrogel material must be decreased to such
a level that the transition occurs within a reasonable amount of
time (from the point of view of practical applications). Tanaka
and Fillmore have proposed a theory in which the swelling is
explained by the collective diffusion of a polymer network into
a solvent while the local motion of the network obeys a diffusion
equation.21 The theory predicts that the characteristic time of the
swelling transition is directly proportional to the square of the
linear size of the gel and inversely proportional to the diffusion
coefficient of the network (D). D is defined as a ratio of the
longitudinal bulk modulus of the network to the coefficient of
friction between the network and the solvent; it is of the order of
106108 cm2/s for common hydrogels. Simple calculations show
that a response time of less than 1 second is achieved for a gel in
which at least one of the dimensions is less than ten micrometres.
Therefore, we set this value as an arbitrary limit for the thickness
of stimuli-responsive hydrogel thin films selected for overview
from the literature.
2.2 Mechanisms of response
Volume phase transitions in hydrogels have been induced using
various physical and chemical stimuli. Typical examples of
physical stimuli are temperature and light. Chemical stimuli
include pH, ions, and molecules that interact specifically with
a polymer network (molecular recognition).
PE gels bearing weak acidic or basic (or both) pendant groups
demonstrate pH-induced volume phase transitions. For example,
the protonation of the ionized acidic groups of a polyanionic gel
upon lowering the pH of an aqueous solution causes a decrease in
the content of mobile counterions in the gel and in the strength of
electrostatic repulsions of PE chain segments. As the hydro-
phobic interactions arising from the hydrophobic backbone
begin to dominate, the swollen network shrinks into a compact
state. The volume phase transition occurs in a narrow pH rangeThis journal is The Royal Society of Chemistry 2009
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the degree of dissociation of the acidic groups in accordance with
Ostwalds dilution law, thus facilitating further swelling. On the
other hand, the increase in the concentration of the counterions
in the gel leads to the Debye screening of the electrostatic
interactions of the ionized acidic groups. Thus, at high ionic
strengths, the screening effects dominate and the gel starts
shrinking upon salt addition. Since the ionization degree is
independent of the pH in polymers bearing strong acidic/basic
groups, only the shrinking tendency is observed for the corre-
sponding gels. In addition to pH and ionic strength, the degree of
ionization can be tuned by light (isomerization of spiropyran
functional groups)25 or electrochemically (for functional groups
changing their charge state in a redox reaction).2629
In the case of neutral hydrogels, it has been demonstrated that
the swelling degree of an ultrathin hydrogel film immersed in an
electrolyte solution could be tuned by applying a voltage across
the film.30The film swelled or contracted depending on the voltage
polarity. The variations of the swelling degreewere rationalized by
the migration of mobile ions into or from the film with corre-
sponding changes in the osmotic pressure inside the film.
Temperature-responsive hydrogels are prepared from poly-
mers that exhibit the temperature-induced transition from the
state of preferential polymer-water interaction to the state of
preferential polymer-polymer interaction. The characteristic
temperature of the volume phase transition for the most studied,
specially tailored hydrogels is in the biologically relevant range of
temperatures (3040 C). Depending on the chemical structure ofthe polymer chains, some hydrogels shrink if the temperature
rises above a critical point, a lower critical solution temperature
(LCST), while others shrink if the temperature lowers below
a critical point, an upper critical solution temperature (UCST).
Poly(N-isopropylacrylamide) (PNIPAM), poly(vinyl methyl
ether) (PVME), poly(N-vinylcaprolactam) (PNVC), and
hydroxypropyl cellulose (HPC) are a few examples of hydrogels
exhibiting a LCST. For these hydrogels, water molecules form
hydrogen-bonds with the polar groups of the polymer network
below the critical temperature, causing its expansion. However,
the efficiency of the hydrogen-bonding decreases with the rise in
temperature and, above the critical temperature (LCST), the
hydrophobic interactions of the hydrophobic groups and back-
bone start dominating and the polymer network shrinks,
expelling water from the material. The LCST of temperature-
responsive hydrogels and their swelling behavior can be strongly
altered by incorporating weak acidic or basic comonomers into
the polymer network.
Hydrogels from polymers bearing acrylamide and acrylic acid
groups are examples of hydrogels exhibiting an UCST.31 These
groups form insoluble hydrogen-bond complexes which disso-
ciate above the critical temperature, thus triggering the transition
into the swollen state.
Certain hydrogels can be loaded with small molecules that are
known to produce specific interactions with active groups of
a polymer network. For example, the well-known property of
boronic acids to form a reversible covalent complex with cis-diols
was used to prepare hydrogels sensitive to glucose. In particular,
it has been demonstrated that glucose induces the volume phase
transition in hydrogels that contain acrylamidophenylboronic
acid comonomers.32,33This journal is The Royal Society of Chemistry 2009A copolymer bearing both phenylboronic acid and tertiary
amine groups forms a stable complex with poly(vinyl alcohol)
(PVA).35 The polymer-polymer complex involving the interac-
tions between the phenylboronic acid and hydroxyl groups of
PVA dissociates with the addition of glucose and forms a new
complex between the phenylboronic acid groups and the
hydroxyl groups of glucose. The amino groups stabilize the
complex formation through the charge transfer from nitrogen to
boron. As a result, thin films of the complex demonstrate changes
in their swelling degree in response to changes in the concen-
tration of glucose.
Some stimuli-responsive hydrogels exhibit hysteresis loops
between swelling and shrinking curves.3644 The hysteretic
behavior has been linked to the different kinetics of processes
occurring in the gel phase during swelling and shrinking transi-
tions, the existence of activation barriers for protonation/
deprotonation of ionizable groups, and the effects of confor-
mational memory. For example, the formation of intramolecular
and intermolecular hydrogen-bonds and the hydrophobic inter-
actions in a copolymer gel with PE fragments may suppress their
ionization. The mechanisms of hysteretic behavior of the
hydrogels are often poorly understood. Because hysteresis affects
the signal reproducibility and response time of hydrogel-based
chemical sensors, it has to be minimized if possible.39 On the
other hand, hysteretic behavior can be exploited for the creation
of threshold sensors and actuators.36
2.3 Effects of thin film confinement
If the swelling of isotropic bulk gel materials is uniform in all
directions, the swelling of surface-attached hydrogel thin films
and thin film patterns is highly anisotropic. Indeed, chemical
attachment of the network to a surface prohibits in-plane
(lateral) swelling, and the volumetric expansion of the network is
possible only in the direction normal to the substrate plane. It has
a strong impact on the swelling properties of the network. Thus,
the surface-attached polymer gels swell to a much lesser degree
than the bulk gels of the same crosslink density. For example,
bulk PNIPAM gels showed a 100-fold change in their total
volume compared to the 15-fold volume change for the 4 mm
thick surface-attached PNIPAM gel films.45
The swelling behavior of surface-attached poly
(dimethylacrylamide) (PDMAM) gel films was found to be inThe specificity of hydrogels toward target molecules can be
substantially increased by imprinting the molecules in a polymer
network. In particular, the imprinting refers to a process in which
the polymer network is synthesized in the presence of the target
molecules.3 The molecules are held in the highly crosslinked
network by interactions with the functional groups of the poly-
mer. Removing the molecules from the gel produces binding sites
(often referred as to molecular recognition sites, MRSs). These
sites make possible the subsequent rebinding of the target
molecules with high specificity.
Incorporation of enzymes in a hydrogel is an alternative route
for achieving specificity toward substances that are metabolized
by this enzyme.34 For example, glucose oxidase (GOx) can
catalyze oxidation of glucose, resulting in the formation of glu-
conic acid; the latter may induce the volume phase transition in
a weak PE hydrogel.Soft Matter, 2009, 5, 511524 | 513
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either spin-coated onto a planar substrate or confined between
two planar substrates (one of them is non-sticky) using micro-
metre-thick spacers and polymerized in situ.45 Among the
free-radical polymerization techniques, a UV-initiated polymer-
ization technique has gained popularity because it allows
micro-patterning of films via a projection mask.55,56 Peppas and
attached (circles) and unconstrained bulk PDMAM (squares) networks.
Fig. 2 The transition temperature (a) and refractive index in the
collapsed state (b) of the surface-attached PNIPAM gel films are shown
as functions of the film thickness with different crosslinking densities; the
crosslinking degree of the PNIPAM gels increases in the following order:
squares, circles, and triangles. The arrow shows the refractive index of the
films in the swollen state. Reprinted with permission from ref. 49,
copyright (2003) American Chemical Society.
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particular, this theory, which was modified to describe one-
dimensional swelling, predicts that the linear extent of the
swelling scales with the density of crosslinks to the 1/3 power(as opposed to 3/5 for the bulk gel). Fig. 1 presents the overalldegree of swelling of the surface-attached and unconstrained
bulk PDMAM gels as a function of the degree of crosslinking.
Although the bulk gel undergoes much greater volumetric
changes than the surface-attached gel, the latter shows greater
linear expansion when considering the changes in one dimension
only.
The constraints for lateral swelling affected the transition
temperature of the surface-attached PNIPAM gel films, espe-
cially for those at high crosslinking density and for those con-
taining a high concentration of ionizable comonomers.45,4749 In
particular, the temperature of the volume phase transition star-
ted decreasing above some critical film thickness (Fig. 2a). The
presence of a substrate also limited the collapse of the thin gel
films at temperatures above the transition temperature (as
deduced from the dependence of the refractive index on the film
thickness, Fig. 2b).
A strong osmotic force in the lateral dimension puts a swollen
gel film under biaxial compressive stress. Such mechanical stress
can be large enough to overcome the adhesion forces and to
The X-axis denotes the molar concentration of 4-methacryloylox-
ybenzophenone (MaBP), a photocrosslinkable monomer, in the
PDMAM networks. Reprinted with permission from ref. 46, copyright
(2004) American Chemical Society.Fig. 1 Comparison of the overall degree of swelling between the surface-cause delamination of the film from a substrate.50,51 It may also
cause wrinkling of the free surface of the film. In particular, the
wrinkling was observed in 100 mm thick gel films52 and 150nm thick gel membranes.53,54
3 Synthesis of hydrogel thin films
Thin films of chemically crosslinked stimuli-responsive hydrogels
reported in the literature were prepared by the following
methods: (1) crosslinking copolymerization (adding multifunc-
tional comonomers), (2) crosslinking (co)polymers with reactive
groups, and (3) crosslinking with high-energy irradiation. Phys-
ically crosslinked films were prepared by (4) PE complexation
and (5) block-copolymer self-assembly.
In the first category, solvent-based free-radical polymerization
techniques are broadly used. A reaction mixture containing
monomers, a crosslinking agent, and a free-radical initiator is
514 | Soft Matter, 2009, 5, 511524coworkers used a mask aligner to precisely position hydrogel
patterns on a substrate surface.56 The photoinitiator is either
added to a reaction mixture or chemically immobilized on
a substrate. In the latter case, the growth of a film is initiated
from a surface, and the thickness can be controlled by varying the
exposure time.45 This method is also suitable for coating
substrates with complex geometry.57 Another free-radical poly-
merization technique is electrochemically-induced polymeriza-
tion. For example, the polymerization of PNIPAM hydrogel thin
films was initiated by electron transfer from a conducting
substrate to a redox-active initiator (potassium persulfate).58 In
another example, the hydrogel thin films of an m-acryl-
amidophenylboronic acid-acrylamide copolymer were grown by
Zn(II)-catalyzed electropolymerization.32 In both cases, the film
thickness was controlled by the electrolysis time. Recently,
a simple method for the generation of hydrogel films with
a thickness gradient has been reported.59 In this method, Zn(II)-
catalyzed electropolymerization of poly(acrylic acid) (PAA) was
This journal is The Royal Society of Chemistry 2009
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microchannels.41 Hollow PE capsules were prepared by LbL
assembly on a surface of sacrificial colloidal particles.82,83 The
LbL assembly can be carried out in the presence of charged
analyte molecules to allow their imprinting in a film and selective
recognition.84
Weak PE can be assembled with a high percentage of segments
comprised of loops and tails by adsorbing under pH conditions
of incomplete charge. The resulting LbL films exhibit pH-
responsive swelling behavior. For example, poly(allylamine
hydrochloride)/poly(styrene sulfonate) (PAH/PSS) films were
rendered pH-sensitive by selecting appropriate assembly condi-
tions (pH).36 A strong excess of COO-groups can be built into
multilayers by using partially esterified PAA. As the assembly of
a multilayer is completed, the ester groups are hydrolyzed to
yield carboxyl groups.85
LbL films of water-soluble non-ionic polymers and PEs can
also be obtained via hydrogen-bonded self-assembly.86 For
example, the hydrogen-bonded LbL assembly was utilized to
produce temperature-responsive films.87,88
In highly acidic and basic solutions, LbL films become
unstable due to internal ionization, large swelling forces, and
partial dissociation of ionic bonds, resulting in film detachment,
decomposition, or phase separation.8992 In order to secure their
stability, the films are chemically attached to substrates and
internally crosslinked. For example, PE chains were functional-
ized with photoreactive groups (e.g., benzophenone) to enable
crosslinking with UV light.93,94 Condensation reactions (e.g.
carbodiimide chemistry) were used for crosslinking polymers
their size and the applied radiation dose. Reprinted with permission from
ref. 78, copyright (2006) Wiley-VCH.
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potential gradient applied to a resistive working electrode.
Plasma polymerization is an attractive one-step, solvent-free,
vapor-phase deposition technique used for producing highly
crosslinked hydrogel thin films (typically ranging from tens to
hundreds of nanometres thick) without the use of crosslink
agents (crosslinking occurs due to ion/electron bombardment of
the material during the deposition).6064 Film thickness is
conveniently controlled by polymerization time and plasma
power. The substrates are often surface modified with an adhe-
sion promoter (e.g., self-assembled monolayer or polymer brush)
to improve the stability of the films. Some monomers (e.g., N-
isopropylacrylamide) have to be heated to achieve an appro-
priate vapor pressure during plasma polymerization. Initiated
chemical vapor deposition (iCVD) is another solvent-free, one-
step technique suitable for the generation of uniform thin films of
crosslinked polymers.65
In the second and third categories, polymer crosslinking is
carried out after thin film deposition in the dry state. The
crosslinking of copolymers containing photoreactive pendent
groups or monomers (e.g., benzophenone or 4-cinnamoylphenyl
methacrylate) with UV irradiation is a popular approach.40,47,66
69 It is compatible with photolithography and is suitable for the
preparation of films with a wide range of thicknesses in the dry
state (from tens of nanometres to tens of micrometres).70,71
Photocrosslinkable films can also be obtained by mixing a poly-
mer with a photoinitiator.72 Alternatively, polymer thin films are
immobilized to the substrates surface and internally crosslinked
by plasma treatment.44,73
Thin films of a PVA/PAA miscible blend can be thermally
crosslinked via the esterification reaction to produce pH-sensitive
hydrogels.37,74 Furthermore, polymers containing tertiary amine
or pyridine groups can be crosslinked via the quaternization
reaction using bifunctional alkyl-halides (e.g., 1,4-diiodobutane).
Thin films from these polymers are usually crosslinked in the
vapor of a crosslinking agent.75 It also has been demonstrated
that the quaternized reaction between poly(2-vinyl pyridine)
(P2VP) and 1,4-diiodobutane in a solution led to the binding of
1,4-diiodobutane molecules to the nitrogen of the pyridine
groups, preferably by one end, hence converting P2VP into
a crosslinkable polymer. Spin-coated films were crosslinked by
annealing above the glass transition temperature of P2VP.53,76
High-energy irradiation (e.g., electron beam, g-rays, UV-light)
of a polymer causes random chain scission (radiolysis) and
recombination of the formed free-radicals, leading to the
formation of a crosslinked network. Crosslinking-agent-free
techniques based on electron beam7780 and UV irradiation81
were used to produce gel films (e.g., PNIPAM, PVME, HPC, and
poly(4-vinyl pyridine) (P4VP)) and patterns (Fig. 3) with a high
lateral resolution (100 nm). The degree of crosslinking ismainly controlled by the irradiation dose.
In the fourth category, thin films are mainly assembled by
multiple layer-by-layer (LbL) adsorption of oppositely charged
PE chains. The polymer films fabricated in this way are multi-
layered PE complexes.82 The main advantages of the LbL tech-
nique are in the fine control of a films structure and chemical
composition, and in the fact that LbL films can be assembled on
substrates of any shape and in confined environments. For
example, LbL deposition was used to modify the walls ofThis journal is The Royal Society of Chemistry 2009Fig. 3 (a) Scanning probe microscopy (SPM) image of irradiated stripes
(250 nm) at various doses, and (b) SPM image of irradiated squares with
lateral sizes ranging from 1.2 1.2 mm2 to 250 250 nm2 at variousradiation doses. (c) Three-dimensional plot of the SPM image of the
irradiated small squares representing the lateral resolution as well as the
pad height. (d) Pad heights of the submicrometre squares as a function ofSoft Matter, 2009, 5, 511524 | 515
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(majority component) and a stimuli-sensitive polymer middle
block (minority component) leads to the formation of micro-
phase-segregated structures of hydrophobic polymer domains
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sensitive polymer, where the hydrophobic domains serve as
physical crosslinks. For example, temperature-responsive thin
gel films of PS-b-PNIPAM-b-PS, where PS is polystyrene, were
prepared by spin-coating deposition on porous substrates.97 The
subsequent annealing of the films (showing spherical and gyroid
morphologies in the bulk) in the solvents vapor was carried out
to improve their microphase ordering.
Stimuli-responsive hybrid and composite hydrogel thin films
have been reported in several studies. The two-component hybrid
thin films with a dual response (temperature and pH) were
prepared by the grafting of a PNIPAM brush on top of a PAH/
PAA multilayer.98 Composite thin films that contain functional
nanoparticles were prepared using (1) an LbL approach where
PEs and the nanoparticles were co-assembled to formmultilayers
and (2) a PE gel matrix served as a reactor for the synthesis of
inorganic nanoparticles.
In the LbL approach, the nanoparticles function either as
stimuli-responsive inclusions or as crosslinks. For example, PE
chains served as linkers for assembling multilayers of tempera-
ture-responsive drug-impregnated PNIPAM-co-PAA microgel
particles (300 nm in size).99,100 In another example, goldnanoparticles and weak PE chains were co-assembled to form
pH-responsive composite LbL films.101 The incorporation of
monolayers of gold nanoparticles into LbL layers has been
demonstrated to make them extremely robust so that they can be
freely suspended over submillimetre openings.102,103
To demonstrate the second approach, we examined the
synthesis of gold nanoparticles inside the crosslinked P2VP thin
films.104 The films were pre-loaded with gold salt, and afterwards
the salt was reduced in the presence of citric acid. Gold nano-
particles were formed in the voids of the polymer network, and
they had an insignificant effect on the gels swelling properties. In
this example, the gold nanoparticles enabled the optical detection
of swelling transitions in the films.
4 Applications of stimuli-responsive polymerhydrogel films
4.1 Storage and regulation of mass-transport
Tunable ion-selective permeability (ion gating). Harris and
Bruening observed the pH-dependent ionic permeability of PAH/
PAA and PAH/PSS LbL multilayers.105 The tunable perme-
ability was attributed to the pH-dependent swelling of the
multilayers. The chemical crosslinking of the PAA/PAHcontaining carboxylic acids and amines.95 PAH/PAA LbL films
were also crosslinked via a heat-induced amidation reaction.85
Amphoteric PMAA hydrogel thin films were prepared by the
hydrogen-bonded assembly of poly(methacrylic acid) (PMAA)
and poly(N-vinylpyrrolidone) (PNVP), the crosslinking of
PMAA with carbodiimide and ethylenediamine, and the subse-
quent removal of PVPON.96
In the fifth category, self-assembly in amphiphilic triblock-
copolymers comprised of hydrophobic polymer end blocks516 | Soft Matter, 2009, 5, 511524multilayers allowed stabilization of the films, which otherwise
showed delamination at basic pH because of strong swelling.85
Reversible temperature-induced modulation of ion transport
across LbL multilayers assembled from ionically modified PNI-
PAM random copolymers (PAH-co-PNIPAM and PSS-co-
PNIPAM) has been demonstrated by Jaber and Schlenoff.106
Because of the high density of ionic crosslinks, the multilayers
showed very limited swelling with no delamination problem.
Highly stable ion-permselective membranes based on chemi-
cally crosslinked LbL multilayers and hydrogel thin films have
been reported by several groups. Akashi and coworkers have
demonstrated the switching on/off of ionic permeability of
crosslinked LbL multilayers (PAA-co-PNIPAM/PVAm, where
PVAm is poly(vinylamine hydrochloride)) below and above the
LCST of PNIPAM.95 Advincula and coworkers have reported
on pH-sensitive bipolar ion-permselective hydrogel films
prepared by LbL assembly and photo-crosslinking of benzo-
phenone-modified PAA and PAH.93 The ionization degree of the
groups in the multilayers was controlled by pH, thereby allowing
the switching on/off of ion transport for either cationic or anionic
species. Ion permselectivity occurs because the charges present in
the multilayer reject ions of the same sign and favor transport of
ions of the opposite sign. This approach was later extended to
films having the dual response.98 The films had a binary archi-
tecture, where a temperature-sensitive brush (PNIPAM) was
grafted atop a pH-sensitive LbL multilayer (PAH/PAA), thus
enabling a dual control mechanism for ionic permeability across
the films. pH-switchable permselective membranes from photo-
crosslinked LbL multilayers containing carboxylic acid and
imine groups have also been reported by Sun and coworkers.94
Aoyagi and coworkers prepared photo-crosslinked hydrogel
films of PNIPAM-co-poly(2-carboxyisopropylaclylamide) and
demonstrated that the ion transport across the films was strongly
affected by temperature and pH.68
Regulation of flow and permeability (chemical valves). A
responsive hydrogel material immobilized inside a microfluidic
channel can operate as a valve which opens and closes the
channel for a water flow. Smart hydrogel valves eliminate
the need for external power and external control and thus allow
the creation of autonomous lab-on-a-chip systems for
analytics. The hydrogel material can also be incorporated in
a MEMS-based microvalve to work as an actuator that deforms
an elastic diaphragm wall of a flow channel, thus altering its
cross-section.38,40 Such devices are suggested as components of
autonomous drug delivery systems. Since the size of a micro-
fluidic channel is typically larger than 100 mm, a hydrogel layer
has to be of the order of tens of micrometres thick in order to be
able to close the channel upon swelling. Hydrogel components
with even larger dimensions are needed to actuate mechanical
microvalves. Since hydrogels of this thickness are beyond the
scope of this review, we refer the interested reader to reviews on
this subject.107,108
An alternative approach for the pH-controlled switching of
the direction of an electroosmotic flow (EOF) in a microchannel
coated with a responsive ultrathin LbL multilayer was suggested
by Sui and Schlenoff.109 The reversal of the EOF direction was
attributed to pH-induced changes in the surface charge in
the multilayer (PSS/PDADMA + PDADMA-co-PAA, whereThis journal is The Royal Society of Chemistry 2009
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PDADMA is poly(diallyldimethylammonium chloride)). Fine
control of the EOF has been demonstrated for these films by
varying the pH of solutions.
Porous inorganic and polymeric filtration membranes with
pore sizes ranging from 10 nm to a few micrometres can be
coated with responsive hydrogel thin layers to produce flow
valves and filters with size-selective permeability. Several groups
have explored this approach.110113 For example, PNIPAM
hydrogel layers were graft-polymerized on the surface of porous
polymer materials (inside pores and/or on the outer surfaces) to
produce composite membranes with temperature-controlled
permeability. The swelling and shrinking of the surface-attached
PNIPAM layers changed the effective pore size and hence altered
the flow rate or permeation rate for diffusional species. As
compared to stimuli-responsive polymer brushes, hydrogel layers
allowed for a much larger range of pore size changes and hence
a wider range of porous materials were suitable as substrates.
Chu et al. have reported chemical valves with the temperature
response opposite to that found in PNIPAM-based systems.31 To
achieve this behavior, they modified a porous nylon 6 membrane
with a layer of an interpenetrated polymer network (IPN)
composed of PAM and PAA (Fig. 4). The resulting gel exhibited
UCST behavior due to the temperature-induced dissociation of
the zipper-type H-bond complex between the polymers.
Rubner, Cohen, and coworkers have fabricated pH-controlled
valves from commercial track-etch membranes whose pores were
modified with PAH/PSS LbL multilayers.41 The valve showed
with relatively low molecular cutoff values (660 g/mol). Thepermeability of the membranes and their responsive properties
depended strongly on their morphology (spherical, cylindrical,
gyroid, and lamellar morphologies were studied).
Encapsulation and the triggered release of active substances.
The swelling properties of stimuli-responsive hydrogels can be
used for encapsulation and the triggered release of active
substances (e.g., drugs, fragrances, and flavor additives). In the
past two decades, bulk hydrogels and hydrogel microparticles
have been widely explored as potential responsive carrier mate-
rials.1,9,114,115 In recent years, numerous publications have
emerged in which hydrogel thin films were suggested for the same
purposes. In most studies, a hydrogel film forms a semipermeable
capsule which isolates water-soluble guest molecules (low
molecular weight or macromolecular) from their environment.
The permeability of the gel capsule for the molecules can be
regulated by an external stimulus (e.g., temperature, pH, ionic
strength, or light). A typical example of such a release system is
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permeability of high molecular weight poly(ethylene oxide)
(PEO) caused by pH-induced swelling and shrinking of the
multilayer. The swelling of the multilayer was found to be
Fig. 4 Schematic illustration of the temperature-responsive gating
membrane and the fabrication procedure: (a) porous membrane support;
(b) membrane support after plasma-graft polymerization of PAM; (c) the
subsequent synthesis of PAA results in the formation of PAM/PAA
hydrogel gate inside the membranes pores; (d) below the UCST the
membranes pores open as a result of the formation of an insoluble
hydrogen-bonded complex between PAM and PAAC; (e) above the
UCST the membranes pores close because of the complex dissociation
and swelling of the hydrogel. Reprinted with permission from ref. 31,
copyright (2005) Wiley-VCH.This journal is The Royal Society of Chemistry 2009hysteretic, meaning an open or closed state of the valve could be
attained at a single pH value.
An alternative approach to chemical valves based on macro-
porous hydrogel thin filmmembranes has been recently suggested
by our group.76 The 100 to 200 nm thick membranes (chemically
crosslinked P2VP) were prepared on a planar substrate and then
transferred onto 200 nm pore size polycarbonate track-etch
support membranes to form a pH-responsive skin layer (Fig. 5).
The pore size was altered (from wide open pores to completely
closed pores) by the expansion/shrinkage of the entire hydrogel
body of the membranes. This property was explored for
controlling the water transport through the membranes.
Temperature-responsive, self-assembled thin film hydrogel
membranes from PS-b-PNIPAM-b-PS triblock-copolymer
(Fig. 6a) have been reported by Ruokolainen and coworkers.97
The membranes were spin-cast directly on top of meso/macro-
porous polyacrylonitrile (PAN) support membranes (Fig. 6b).
The PS end blocks were the minor component and served as
physical crosslinks (see the fifth category in Section 3). The
membranes showed a switchable on-off permeability for poly(-
ethylene glycol) (PEG) below and above the LCST of PNIPAM
Fig. 5 (a) SPM images (7.5 7.5 mm2) of a P2VP gel membrane underwater of pH 5.5 (left) and 2 (right). (b) Schematic representation of the gel
membrane with the open (left) and closed (right) pores; the gel membrane
is deposited on the surface of a porous substrate.Soft Matter, 2009, 5, 511524 | 517
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repeated many times. This encapsulation approach is of a limited
practical value because of the small capacity of thin films as
compared to bulk hydrogels. However, this approach has
scientific significance because it allows study of the processes of
the loading and release of guest molecules and nanoparticles in
responsive hydrogels, as well as the permeability of the hydrogels
for low molecular weight and macromolecular species using the
various techniques of thin film characterization (e.g., ellipsom-
etry, UV-vis and fluorescence spectroscopies, microgravimetric,
and electrochemical techniques).
Lyon and coworkers have demonstrated the temperature-
triggered pulsatile and the extended release of insulin99 and
doxorubicin100 from LbL films composed of alternating layers of
drug-impregnated crosslinked hydrogel nanoparticles (PNI-
PAM-co-PAA)/drug) and PAH (Fig. 7). The reversible stimuli-
controlled loading and release of guest molecules using hydrogel
films have been reported by several groups. For example, Hiller
and Rubner demonstrated that an anionic dye (as a model drug)
can be rapidly loaded (within minutes) into swollen PAH/PSS
LbL films (having an excess of free amine groups) at acidic pH
while it releases very slowly (on a time scale of weeks) from the
shrunken films (pH 611).36 This property of the films can be
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with desired substances by diffusion from concentrated solu-
tions. The diffusion is possible either through a swollen LbL shell
or through the nanoscopic holes in the shell. Afterwards, the
capsule shell is switched to the impermeable state by changing
environmental conditions or by chemical crosslinking, and the
loaded capsules are transferred to a medium of interest. The
release of the encapsulated substance is triggered by an appro-
priate stimulus. The triggered release of polyelectrolyte capsules
was reviewed by Sukhishvili82 and Smedt and coworkers.83 The
description of different types of hydrogel-based colloidal carriers
can be found in a review by Nayak and Lyon.115
A hydrogel film can also function as a container itself. An
active substance can be added to a hydrogel solution before the
film deposition, or it can even serve as a building block in the case
of LbL multilayers. As the film is prepared, the substance is held
(stored) in the deswollen hydrogel body. Alternatively, a hydro-
gel film can absorb the substance from the solution. When the
loading is complete, the hydrogel is caused to shrink by an
external stimulus. The stored substance can be released from the
film to a solution by applying the stimulus (trigger), which causes
the hydrogel to swell. The loading and release steps can be
utilized for the sustained release of drugs. The pH and ionic
strength dependent release of anionic dyes from chemically
Fig. 6 (a) Chemical structure of PS-b-NIPAM-b-PS triblock-copol-
ymer. On the right, a schematic illustration of the temperature-induced
conformation transition of a hydrogel having a self-assembled
morphology with spherical PS domains. These domains act as physical
crosslinks for the hydrogel, and as the temperature is raised above the
LCST the PNIPAM chains become hydrophobic and the gel collapses.
(b) Schematic view of the multilayer composite filter used for the
permeability studies. Reprinted with permission from ref. 97, Copyright
(2007) American Chemical Society.
518 | Soft Matter, 2009, 5, 511524crosslinked PNIPAM-co-PAA/PVAm LbL films was observed
by Akashi and coworkers.116 The reversible temperature-depen-
dent loading and release of a dye was documented for hydrogen-
bonded PNIPAM/PAA LbL films by Quinn and Caruso.87
Sukhishvili and coworkers fabricated PMAA hydrogel films with
pH-dependent polyampholytic swelling properties by the
hydrogen-bonded LbL assembly of PNVP and PMAA followed
by the crosslinking of PMAA with ethylenediamine as well as the
removal of PNVP. The pH-dependent loading and release of
dyes and macromolecules was demonstrated for these films.96
Fig. 7 Schematic representation of the LbL films composed of PAH and
temperature-responsive microgel particles (PNIPAM-co-PAA). The films
were loaded with doxorubicin (DX) by deswelling/swelling the film in
a buffered, pH 7.0 DX solution. DX was released from the films in pH 3.0
buffer by deswelling the film upon heating. Reprinted with permission
from ref. 100, copyright (2005) American Chemical Society.This journal is The Royal Society of Chemistry 2009
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presence of the anionic nucleotide (adenosine monophosphate,
deformation of thin distortable membranes and microcanti-
levers.43,119,120
Commercial piezoresistive pressure sensor chips were used as
electromechanical transducers by Guenther and coworkers.38
The micrometres-thick hydrogel layers (PAA/PVA and PNI-
PAM) sensitive to pH and organic solvent concentration were
either deposited onto a distortable silicon membrane of the
sensor chip or placed in a cavity under the membrane. In the
latter case, the thickness of a hydrogel layer was determined by
the size of the cavity (250 mm). The swelling-induced deflection of
the membrane was converted into an electrical signal by pie-
zoresistive elements.
An ultrasensitive pH sensor based on micromachined canti-
levers has been reported by Peppas group.56,121 Patterned layers
of PMAA/poly(ethylene glycol) dimethacrylate were formed on
silicon wafers containing cantilevers by free-radical UV poly-
merization. pH-induced swelling/shrinking of a hydrogel
attached to one side of the cantilever created surface stress,
causing the cantilever to bend (Fig. 8). The use of an optical
laser-based reflection system (such as the one used in atomic
force microscopy) for monitoring of the cantilever bending
response resulted in a maximum deflection sensitivity of 1 nm/5105 DpH. The hydrogel coated microcantilevers were also
fabricated by other groups for sensing pH (PMAA-co-PAM,120
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AMP from the multilayer yielded the swollen hydrogel from the
cation-excess polyion complex. Rebinding of AMP neutralized
the complex, and thus the hydrogel shrank. The swelling-
shrinking of the hydrogel was sensed using a QCM resonator.
Transducers based on microelectromechanical systems
(MEMS). The swelling forces exerted by stimuli-sensitive
hydrogel thin layers are sufficient to cause the mechanical4.2 Chemical sensors based on hydrogel films
The stimuli-triggered volumetric transition in hydrogel layers
was explored for various sensors. The recent review by Richter
et al. describes hydrogel-based pH sensors.43 Here, we focus on
studies in which hydrogel thin films were used to sense temper-
ature, pH, and various kinds of analytes. Sensors are classified by
a scheme used to transduce analyte-induced chemical or physical
changes in a hydrogel into an electrical or optical signal.
Microgravimetric transducers. Several groups used mass-
sensitive quartz crystal microbalance (QCM) resonators coupled
with stimuli-responsive hydrogel coatings to monitor changes in
hydrogel swelling. Absorption and release of water by the
hydrogel are followed by changes in the surface load, which
results in a shift of the resonance frequency of a QCM resonator.
The response is typically nonlinear because both stiffness and
density of the hydrogel coating decrease upon swelling. Such
changes in the mechanical properties also cause damping of the
signal amplitude, which can be monitored in parallel with the
frequency. Richter et al. discussed physical aspects of the oper-
ation of hydrogel-based QCM sensors and their limitations.37
Their pH sensor, based on PVA/PAA hydrogel, showed high pH-
sensitivity but suffered from swelling hysteresis. The pH-sensitive
thin films of crosslinked P4VP prepared on QCM crystals have
been also reported by Ramstrom, Yan, and coworkers.81
Willners group used the QCM technique to study the selective
sensing of triazine herbicides,117 nucleotides, mono-
saccharides,118 and glucose,32 using hydrogels (electro-
polymerized acrylamide-methacrylic acid copolymers and
acrylamide-based copolymers containing boronic acid groups).
Herbicides were imprinted in the hydrogels to allow their selec-
tive detection. The boronic acid groups enabled the selective
binding of glucose. The combination of the boronic acid groups
and MRS provided the selective detection of nucleotides and
monosaccharides. The formation of negatively charged boronate
complexes with the analyte molecules was responsible for the
swelling of the hydrogel.32,118 In the case of herbicides, the density
of the MRS in the hydrogel was insufficient to provide a detect-
able surface load to the QCM surface. However, the binding was
found to be accompanied by the hydration of the MRS and
thereby it led to the additional swelling of the molecularly
imprinted hydrogel.117 Faradaic impedance spectroscopy, chro-
nopotentiometry, and surface plasmon resonance (SPR) spec-
troscopy were used as complementary techniques to monitor the
hydrogel swelling.32,118
Shinkai and coworkers prepared a nucleotide-sensitive
molecularly imprinted multilayer by carrying out the LbL depo-
sition of boronic acid containing polyanion and polycation in theThis journal is The Royal Society of Chemistry 2009where PAM is polyacrylamide, and polyelectrolytes with
amino groups122), Pb2+-ions (acrylamides containing benzo-18-
crown-6),123 CrO42-ions (polymers containing tetraalkylammo-
nium salt),124 and glucose (poly(methacrylamidophenylboronic
acid)-co-PAM120 and GOx/polycation LbL multilayers125).
Electronic transducers. Willner and coworkers deposited the
molecularly imprinted hydrogels (the same as hydrogels
described in the subsection on microgravimetric transducers) on
the gate surface of ion-sensitive field-effect transistors
Fig. 8 (a) Cross-sectional schematic of the cantilever/polymer gel
structure with the typical dimensions and (b) scanning electron micros-
copy (SEM) images of the cantilever/polymer gel structure in the dry
state. The cantilever is bent upwards and hence the tip region is out of
focus. Reprinted with permission from ref. 56, copyright (2002) American
Institute of Physics.Soft Matter, 2009, 5, 511524 | 519
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Advincula et al. reported on the enhancement of an SPR signal
in pH-sensitive gold nanoparticle/PAH LbL multilayers.101 The
swelling/shrinking of these hybrid multilayers resulted in
a change in the spacing between individual Au nanoparticle
monolayers, which in turn strongly affected the propagation of
an SPR wave along the hybrid LbL film/metal substrate inter-
face. The introduction of an additional pH-sensitive LbL
multilayer (PAH/PSS) at the interface between the hybrid LbL
film and metal substrate was shown to further enhance the SPR
response towards pH changes. The enhanced SPR shifts were
rationalized by electromagnetic coupling between the individual
Au nanoparticle monolayers and the metal film of the SPR
detector.
A metallic thin film with a lithographically manufactured
periodic array of cylindrical nanoscopic wells (so-called plas-
monic crystal, Fig. 9a) is another promising sensing platform that
does not require a prism to excite the SPR by incident light. The
plasmonic crystal exhibits a complex, multi-peak transmission
spectrum in the visible and near-infrared regions. Mack et al.
immobilized a 500 nm thick pH-responsive hydrogel film(copolymer containing acrylic acid groups) on the surface of the
plasmonic crystal (Fig. 9b).131 They found that the pH-induced
swelling transitions occurring in the hydrogel film strongly
altered the positions and intensities of plasmon resonance peaks
in the spectra. Summing the absolute magnitudes of the differ-
ence spectra (as referenced to a spectrum acquired at a specific
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the metal gate electrode is eliminated and the gate insulator is
directly exposed to an electrolyte solution (a reference electrode
is used to complete the circuit). In the case above, the gate
insulator with the surface-immobilized molecularly imprinted
hydrogel layer is exposed to the electrolyte solution containing
the analyte. The binding of the ionized/protonated analyte
molecules to the MRS leads to changes in the charge distribution
in the hydrogel and hence the potential on the gate. The drain-
source current is very sensitive to the gate potential and is used as
an output signal.
Optical transducers. The surface plasmon resonance (SPR)
technique has been widely used to monitor changes in the
thickness of polymer thin films and multilayers. The basics of this
technique and its applications for chemical and biochemical
sensing can be found in a recent review by Homola.126 Briefly,
SPR is a collective density oscillation of free electrons confined to
and propagating along a metal (typically silver or gold) surface.
This density oscillation is coupled with an electromagnetic
(evanescent) wave whose electric field is decaying exponentially
from the surface. The SPR can be excited on the surface of a thin
metal film deposited on the base of a prism (the Kretschmann
configuration) by monochromatic light incident at the prism-film
interface. The SPR is detected through a narrow minimum in
the reflection coefficient at a particular angle of incident light.
The angle at which the minimum occurs depends strongly on the
refractive index and the thickness of the dielectric layer deposited
on the metal surface. Because of the evanescent nature of SPR,
the probing depth of this technique is limited to layers of two to
three hundred nanometres in thickness.
Frank and coworkers used the SPR technique to study the
effects of temperature and hydrostatic pressure on the swelling
degree of 4 mm thick (dry state) PNIPAM hydrogel films. They
detected broadening of the volume phase transition region and
a shift in the transition temperature to higher values with an
increase in pressure. It has been demonstrated that the film
confinement has a significant effect on the transition temperature
and the swelling degree (see also Section 2.2).45
Willner and coworkers measured the kinetics of swelling and
shrinking of the glucose-sensitive hydrogel film (acrylamide
copolymer containing boronic acid groups) using the SPR
technique.32 They found that the film swelling upon addition of
glucose was rapid, whereas the shrinking as a result of the glucose
depletion was a slow process (tens of minutes), which indicated
strong interactions between the sugar molecules and the boronic
acid groups.
In several studies, hydrogel thin films were used as platforms
for immobilization of various bioreceptors for SPR monitoring
of biomolecular binding events, including DNA hybridization,
DNA-protein, protein-protein, and other receptor-ligand pair
associations.127130 The hydrogel films (usually carboxylated
dextran and ethylendiamine) enable better surface coverage and
adhesion of the receptor groups than is usually achieved when
they are directly immobilized on a metal surface. Being highly
hydrophilic, the hydrogel layers demonstrate low non-specific
adsorption of proteins on the detector surface. Furthermore,
protein bioreceptors are less prone to denaturation on hydrogel
substrates.129520 | Soft Matter, 2009, 5, 511524pH value) over all wavelengths yielded an integrated plasmonic
response that directly correlated with pH-dependent changes in
the properties of the hydrogel film (Fig. 9c and d).
The SPR can also be excited in noble metal nanoparticles by
exposing them to light of a specific wavelength. This phenom-
enon, known as localized surface plasmon resonance (LSPR), is
Fig. 9 Schematic representation of a plasmonic crystal before (a) and
after modification with a pH-responsive hydrogel layer (b). (c) Spectral
sensitivity map consisting of difference spectra from the hydrogel-
modified crystal referenced to t 0 s, after which the analyte solution wascycled between pH 7.86 and 1.44. (d) The integrated plasmonic response
corresponding to reversible changes in analyte solution from pH 7.86 to
1.44 (blue), 6.42 to 5.13 (red), and 5.76 to 5.66 (black). The smallest pH
change (0.10) is well differentiated from the stable background signal
(inset). Reprinted with permission from ref. 131, copyright (2007)
American Chemical Society.This journal is The Royal Society of Chemistry 2009
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observed for surface immobilized nanoparticles (islands) and
colloidal dispersions. The LSPR leads to a pronounced extinc-
tion peak (or peaks) in a transmission UV-vis spectrum (also
referred to as a T-LSPR spectrum) that is noticeable even for
nanoparticle monolayers and sub-millimolar concentrations of
nanoparticle dispersions. The intensity and position of the peak
depend on the size and shape of nanoparticles, their size distri-
bution and spatial organization, shell thickness (for the core-shell
particles), and the dielectric constant of the surrounding
medium.132,133 If the metal nanoparticles are coupled with
a polymer, the stimuli-induced changes in the polymeric material
can be transformed into an optical signal. Although T-LSPR
spectroscopy was widely used for the registration of molecular
recognition events, it was only recently employed for sensing
stimuli-induced changes in polymeric materials. Lee and Perez-
Luna reported on the reversible aggregation of gold colloidal
nanoparticles linked to the surface-grafted carboxylated dextran
chains in solvents of different polarity and the associated changes
in the optical properties.134 The observed shifts in the position of
the plasmon resonance peak were assigned to changes in the
refractive index of the hydrogel and in the strength of electro-
magnetic inter-particle coupling.
An alternative T-LSPR sensing platform has been suggested135
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sensitive molecularly imprinted polymer (chemically crosslinked
P2VP) was prepared on gold islands and covered with a mono-
layer of colloidal gold nanoparticles. Swelling of this sandwich
layer upon binding of cholesterol molecules to the MRS altered
the strength of electromagnetic coupling between the islands and
nanoparticles, resulting in a strong shift of the peak position.
This approach was later extended to pH-sensitive P2VP gel
membranes (shown in Fig. 5).104 In this work, the membrane with
chemically reduced gold nanoparticles dispersed in the P2VP gel
was deposited on a substrate with gold islands (Fig. 10a). A
change in the distance between the gold nanoparticles and islands
Fig. 10 (a) Schematic illustration of an optical sensor utilizing localized
surface plasmon resonance excited in gold nanoparticles (NPs) and
islands and coupled via the pores of a pH-responsive P2VP gel
membrane. (b) UV-vis spectra of such an optical sensor acquired in water
of pH 5.5 (solid line) and 2 (dotted line), and (c) shifts of the absorption
maximum acquired from the UV-vis spectra as a function of pH.
Reprinted with permission from ref. 104, copyright (2008) Wiley-VCH.This journal is The Royal Society of Chemistry 2009enzymes) and acted as a tunable wavelength filter. The operation
principle was based on recording a reflection spectrum that was
sensitive to the swelling degree of the hydrogel.
Integrated optical sensor chips suitable for high-resolution pH
measurements have been fabricated by Kunz and coworkers.144
Compact dual-channel chirped grating coupler sensor chips were
coated with the 90 to 300 nm thick photopatterned films of pH-
responsive hydrogels (photocrosslinkable PHEMA copolymer
containing amino groups). The sensor detected changes in
a refractive index occurring upon swelling and shrinking of the
hydrogel. A resolution DpH < 1.1 104 (at pH 7.5) has beenreported.
4.3 Actuators
Cell-culture supports with the triggered release. A promising
application of responsive hydrogel thin films is related to tissue
engineering. The idea of controlling adhesion of mammalian cells
using substrates from thermoresponsive polymers dates back to
1990 when it was first reported by Okanos group.145 Since then,
several groups have studied different aspects of this process,
which has resulted in a large number of publications. Recent
reviews on the subject can be found in the papers of Kikuchi and
Okano146 and da Silva et al.147 In many studies, thermoresponsive
surfaces have been formed by 10 to 100 nm thick crosslinked
PNIPAM-based copolymer films.147 At temperatures above the
LCST, the cells adhere, spread, and proliferate on the relatively
hydrophobic PNIPAM surfaces the same way they do on the
traditional polystyrene tissue culture dishes. However, when the
temperature is lowered well below the LCST, all cultured cells
spontaneously detach due to the PNIPAM transition into the
hydrophilic state. Such temperature-responsive culture supports
have been demonstrated as useful in regenerative medicine and
tissue engineering applications. Specifically, sheets of cultured
cells along with their extracellular matrix are harvested from
the dishes and transplanted to tissue beds with minimal celldue to swelling-shrinking of the gel modulated the propagation
of plasmons on the island layer that led to a strong shift of the
UV-vis absorption peak (Fig. 10b,c).
Aussenegg and coworkers have proposed a reflectance optical
sensing principle namedmetal island coated swelling polymer over
mirror system or MICSPOMS, for short.72,136,137 The MIC-
SPOMS is an interference device in which gold particles and the
mirror act as an optical thin film resonance system with reflection
properties depending on the thickness of the hydrogel layer.
Changes in the thickness of the hydrogel layer were monitored by
the slope of the characteristic reflection minimum of the device.
Smooth, 100 nm thick layers of pH-responsive hydrogel(photocrosslinked PNVP) with immobilized enzymes were used
as biosensing elements.136
Lowe and coworkers have developed a range of hydrogel-
based holographic sensors for detecting bacterial spores,55
measuring pH,138 ionic strength,139 and the content of ethanol in
aqueous solutions,140 as well as the concentration of metal
ions,141,142 glucose,33 and metabolites of enzymatic reactions.143
Holographic diffraction gratings comprised of fringes of silver
particles were generated in 10 mm hydrogel films (mainlypoly(2-hydroxyethyl methacrylate) (PHEMA) copolymers con-
taining analyte-sensitive groups and, in one study, immobilizedSoft Matter, 2009, 5, 511524 | 521
-
Furthermore, the future research directions in the field of
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27CView OnlineLbL multilayers provide another versatile platform for tissue
engineering because the interaction between the multilayers and
cells can be tuned (from the viewpoint of adhesion, signaling, and
cytotoxicity) by changing the composition of the multilayers, by
micro-patterning, and by incorporating receptor and signaling
molecules and inorganic nanoparticles.151 Additionally, the
multilayers can be prepared easily on substrates of complex
geometry (e.g., 3D cell-culture scaffolds and tissues). The
potential of responsive LbL multilayers for creating cell-culture
substrates with the smart behavior is yet to be explored.
5 Conclusions and outlook
In this brief review, we have demonstrated the recent progress inloss.148 They can be micro-patterned to include cells of different
types and (Fig. 11) layered to create complex 3D tissue-like
structures .149,150
Fig. 11 Schematic representation of the methods for patterning cell co-cu
(a) The first cell type, hepatocytes, is seeded and cultured at 27 C, resultinggrafted islands showing a hydrophobic nature. (b) The second cell type, en
patterned co-cultures. (c) Decreasing the temperature to 20 C induces thesheet (right). Bar: 1 cm. Reprinted with permission from ref. 150, copyrigthe field of stimuli-responsive hydrogel thin films. Owing to their
unique ability to undergo large, reversible volumetric changes in
response to small amounts of external chemical and physical
stimuli, responsive hydrogels are promising materials for a broad
range of applications, from sensors to actuators. In particular,
the self-regulating properties of responsive hydrogels combined
with the energy of chemical reactions (no need for an external
power source) and a thin film structure makes them attractive for
miniaturized (bio)sensors, autonomous drug delivery systems,
microfluidic valves and flow switches, smart cell-culture
supports, regulation of the rate of electrochemical reactions, and
many other advanced applications. Many examples of such
applications can be found throughout this overview. Hydrogel
films are extremely versatile materials in terms of possible designs
(e.g., multilayers, membranes, and patterns), fabrication
methods (e.g., chemical crosslinking of reactive polymers, LbL
deposition, and block-copolymer self-assembly), and function-
alities that can be incorporated into them (e.g., functional
groups, active substances, inorganic nanoparticles, and
enzymes).152,153 They can be rendered multifunctional and mul-
tiresponsive without compromising their mechanical stability,
522 | Soft Matter, 2009, 5, 511524smart hydrogel films may include the development of coatings
for wound healing, drug delivery systems, lab-on-a-chip
systems, switchable antimicrobial and antifouling coatings,
coatings controlling (bio)catalytic activity, memory devices,
tunable/switchable optical coatings, rewritable microreliefs, and
deformable-upon-signal coatings.
Acknowledgements
The authors gratefully acknowledge the support of the US
ARMY via the grant W911NF-05-1-0339 and the Nationalwhich is secured by a 3D crosslinked network structure. The
potential of hydrogel thin films is not yet exploited and offers
virtually endless opportunities for the development of new,
exciting active materials and functional devices on their base.e and harvesting of co-cultured cell sheets using a dual patterned surface.
localization of hepatocytes onto PNIPAM-poly(n-butyl methacrylate) co-
helian cells, is seeded and cultured at 37 C, resulting in the generation ofchment of the co-cultured cell sheet. Harvested patterned co-cultured cellScience Foundation (NSF) via the grant DMR-0706209.
References
1 Y. Qiu and K. Park, Adv. Drug Deliv. Rev., 2001, 53, 321.2 A. S. Hoffman, Adv. Drug Deliv. Rev., 2002, 54, 3.3 T. Miyata, T. Uragami and K. Nakamae, Adv. Drug Deliv. Rev.,2002, 54, 79.
4 Y. Osada, J. P. Gong and Y. Tanaka, J. Macromol. Sci. - Polym.Rev., 2004, C44, 87.
5 S. Nayak and L. A. Lyon, Angew. Chem. Int. Edit., 2005, 44, 7686.6 N. A. Peppas, J. Z. Hilt, A. Khademhosseini and R. Langer, Adv.Mater., 2006, 18, 1345.
7 C. C. Lin and A. T. Metters, Adv. Drug Deliv. Rev., 2006, 58, 1379.8 J. Kopecek, Biomaterials, 2007, 28, 5185.9 J. Kopecek and J. Y. Yang, Polym. Int., 2007, 56, 1078.10 S. Chaterji, I. K. Kwon and K. Park, Prog. Polym. Sci., 2007, 32,
1083.11 R. V. Ulijn, N. Bibi, V. Jayawarna, P. D. Thornton, S. J. Todd,
R. J. Mart, A. M. Smith and J. E. Gough, Mater. Today, 2007, 10,40.
12 J. K. Oh, R. Drumright, D. J. Siegwart and K. Matyjaszewski, Prog.Polym. Sci., 2008, 33, 448.
13 P. J. Flory and J. J. Rehner, J. Chem. Phys., 1943, 11, 512.14 P. J. Flory and J. J. Rehner, J. Chem. Phys., 1943, 11, 521.15 P. J. Flory, J. Chem. Phys., 1950, 18, 108.
This journal is The Royal Society of Chemistry 2009
-
Dow
nloa
ded
by Z
hejia
ng U
nivers
ity on
17 Fe
bruary
2012
Publ
ished
on
17 N
ovem
ber 2
008
on h
ttp://
pubs
.rsc.
org
| doi:1
0.1039
/B8138
27CView Online16 P. J. Flory, Principles of Polymer Chemistry, Cornell UniversityPress, Ithaca, NY, 1953.
17 J. Ricka and T. Tanaka, Macromolecules, 1884, 17, 2916.18 A. Katchalsky, S. Lifson and H. Eisenberg, J. Polym. Sci., 1951, 7,
571.19 A. Katchalsky and I. Michaeli, J. Polym. Sci., 1955, 15, 69.20 A. R. Khokhlov, S. G. Starodubtzev and V. V. Vasilevskaya, in
Advances in Polymer Science: Responsive Gels: Volume TransitionsI, ed. K. Dusek, Springer Verlag, Berlin, 1993, vol. 109, p. 123.
21 T. Tanaka and D. J. Fillmore, J. Chem. Phys., 1979, 70, 1214.22 L. Brannon-Peppas and N. A. Peppas, Chem. Eng. Sci., 1991, 46,
715.23 A. E. English, T. Tanaka and E. R. Edelman, Journal of Chemical
Physics, 1997, 107, 1645.24 Y. V. Lyatskaya, F. A. M. Leermakers, G. J. Fleer, E. B. Zhulina
and T. M. Birshtein, Macromolecules, 1995, 28, 3562.25 A. Nayak, H. W. Liu and G. Belfort, Angewandte Chemie-
International Edition, 2006, 45, 4094.26 R. A. Etchenique and E. J. Calvo, Analytical Chemistry, 1997, 69,
4833.27 E. S. Forzani, M. A. Perez, M. L. Teijelo and E. J. Calvo, Langmuir,
2002, 18, 9867.28 M. Tagliazucchi, D. Grumelli and E. J. Calvo, Physical Chemistry
Chemical Physics, 2006, 8, 5086.29 M. Tagliazucchi, F. J. Williams and E. J. Calvo, Journal of Physical
Chemistry B, 2007, 111, 8105.30 I. S. Lokuge and P. W. Bohn, Langmuir, 2005, 21, 1979.31 L. Y. Chu, Y. Li, J. H. Zhu and W. M. Chen, Angew. Chem. Int.
Edit., 2005, 44, 2124.32 R. Gabai, N. Sallacan, V. Chegel, T. Bourenko, E. Katz and
I. Willner, J. Phys. Chem. B, 2001, 105, 8196.33 S. Kabilan, A. J. Marshall, F. K. Sartain, M. C. Lee, A. Hussain,
X. P. Yang, J. Blyth, N. Karangu, K. James, J. Zeng, D. Smith,A. Domschke and C. R. Lowe, Biosens. Bioelectron., 2005, 20, 1602.
34 R. V. Ulijn, J. Mater. Chem., 2006, 16, 2217.35 A. Kikuchi, K. Suzuki, O. Okabayashi, H. Hoshino, K. Kataoka,
Y. Sakurai and T. Okano, Anal. Chem., 1996, 68, 823.36 J. Hiller and M. F. Rubner, Macromolecules, 2003, 36, 4078.37 A. Richter, A. Bund, M. Keller and K. F. Arndt, Sens. Actuators, B,
2004, 99, 579.38 G. Gerlach, M. Guenther, J. Sorber, G. Suchaneck, K. F. Arndt and
A. Richter, Sens. Actuators, B, 2005, 111, 555.39 M. Guenther, G. Gerlach, C. Corten, D. Kuckling, M. Mueller,
Z. Shi, J. Sorber and K. F. Arndt, Macromol. Symp., 2007, 254,314.
40 M. Guenther, D. Kuckling, C. Corten, G. Gerlach, J. Sorber,G. Suchaneck and K. F. Arndt, Sens. Actuators, B, 2007, 126, 97.
41 D. Lee, A. J. Nolte, A. L. Kunz, M. F. Rubner and R. E. Cohen, J.Am. Chem. Soc., 2006, 128, 8521.
42 K. Itano, J. Y. Choi and M. F. Rubner, Macromolecules, 2005, 38,3450.
43 A. Richter, G. Paschew, S. Klatt, J. Lienig, K. F. Arndt andH. J. P. Adler, Sensors, 2008, 8, 561.
44 D. Schmaljohann, D. Beyerlein, M. Nitschke and C. Werner,Langmuir, 2004, 20, 10107.
45 M. E. Harmon, T. A. M. Jakob, W. Knoll and C. W. Frank,Macromolecules, 2002, 35, 5999.
46 R. Toomey, D. Freidank and J. Ruhe, Macromolecules, 2004, 37,882.
47 D. Kuckling, M. E. Harmon and C. W. Frank, Macromolecules,2002, 35, 6377.
48 M. E. Harmon, D. Kuckling and C. W. Frank, Macromolecules,2003, 36, 162.
49 M. E. Harmon, D. Kuckling, P. Pareek and C. W. Frank, Langmuir,2003, 19, 10947.
50 J. S. Sharp and R. A. L. Jones, Adv. Mater., 2002, 14, 799.51 J. S. Sharp and R. A. L. Jones, Phys. Rev. E, 2002, 66.52 T. Tanaka, S. T. Sun, Y. Hirokawa, S. Katayama, J. Kucera,
Y. Hirose and T. Amiya, Nature, 1987, 325, 796.53 M. Orlov, I. Tokarev, A. Scholl, A. Doran and S. Minko,
Macromolecules, 2007, 40, 2086.54 I. Tokarev, M. Orlov, E. Katz and S. Minko, J. Phys. Chem. B, 2007,
111, 12141.55 D. Bhatta, G. Christie, B. Madrigal-Gonzalez, J. Blyth and
C. R. Lowe, Biosens. Bioelectron., 2007, 23, 520.This journal is The Royal Society of Chemistry 200956 R. Bashir, J. Z. Hilt, O. Elibol, A. Gupta and N. A. Peppas, Appl.Phys. Lett., 2002, 81, 3091.
57 L. Liang, X. D. Feng, L. Peurrung and V. Viswanathan, J. Membr.Sci., 1999, 162, 235.
58 J. Reuber, H. Reinhardt and D. Johannsmann, Langmuir, 2006, 22,3362.
59 X. J. Wang and P. W. Bohn, J. Am. Chem. Soc., 2004, 126, 6825.60 Y. V. Pan, R. A. Wesley, R. Luginbuhl, D. D. Denton and
B. D. Ratner, Biomacromolecules, 2001, 2, 32.61 P. A. Tamirisa and D. W. Hess, Macromolecules, 2006, 39, 7092.62 N. A. Bullett, R. A. Talib, R. D. Short, S. L. McArthur and
A. G. Shard, Surf. Interface Anal., 2006, 38, 1109.63 N. A. Bullett, R. A. Talib, R. D. Short, S. L. McArthur and
A. G. Shard, Surface and Interface Analysis, 2006, 38, 1109.64 R. Forch, A. N. Chifen, A. Bousquet, H. L. Khor, M. Jungblut,
L. Q. Chu, Z. Zhang, I. Osey-Mensah, E. K. Sinner and W. Knoll,Chem. Vapor Depos., 2007, 13, 280.
65 K. Chan and K. K. Gleason, Langmuir, 2005, 21, 8930.66 S. Gupta, D. Kuckling, K. Kretschmer, V. Choudhary and
H. J. Adler, J. Polym. Sci. A, 2007, 45, 669.67 H. A. von Recum, S. W. Kim, A. Kikuchi, M. Okuhara, Y. Sakurai
and T. Okano, J. Biomed. Mater. Res., 1998, 40, 631.68 D. Matsukuma, K. Yamamoto and T. Aoyagi, Langmuir, 2006, 22,
5911.69 J. M. D. Heijl and F. E. Du Prez, Polymer, 2004, 45, 6771.70 J. Hoffmann, M. Plotner, D. Kuckling and W. J. Fischer, Sens.
Actuators, A, 1999, 77, 139.71 H. C. Liu and Y. Ito, J. Biomed. Mater. Res. A, 2003, 67A, 1424.72 F. R. Aussenegg, H. Brunner, A. Leitner, C. Lobmaier,
T. Schalkhammer and F. Pittner, Sens. Actuators, B, 1995, 29,204.
73 M. Nitschke, S. Zschoche, A. Baier, F. Simon and C. Werner, Surf.Coat. Tech., 2004, 185, 120.
74 J. Sorber, G. Steiner, V. Schulz, M. Guenther, G. Gerlach, R. Salzerand K. F. Arndt, Anal. Chem., 2008, 80, 2957.
75 R. C. Hayward, B. F. Chmelka and E. J. Kramer,Adv. Mater., 2005,17, 2591.
76 I. Tokarev, M. Orlov and S. Minko, Adv. Mater., 2006, 18, 2458.77 R. Gottlieb, C. Kaiser, U. Gohs and K. F. Arndt,Macromol. Symp.,
2007, 254, 361.78 T. Schmidt, J. I. Monch and K. F. Arndt, Macromol. Mater. Eng.,
2006, 291, 755.79 J. Hegewald, T. Schmidt, U. Gohs, M. Gunther, R. Reichelt,
B. Stiller and K. F. Arndt, Langmuir, 2005, 21, 6073.80 V. R. Tirumala, R. Divan, L. E. Ocola and D. C. Mancini, J. Vac.
Sci. Technol. B, 2005, 23, 3124.81 B. Harnish, J. T. Robinson, Z. C. Pei, O. Ramstrom andM. D. Yan,
Chem. Mater., 2005, 17, 4092.82 S. A. Sukhishvili, Curr. Opin. Colloid Interface Sci., 2005, 10, 37.83 B. G. De Geest, N. N. Sanders, G. B. Sukhorukov, J. Demeester and
S. C. De Smedt, Chem. Soc. Rev., 2007, 36, 636.84 Y. Kanekiyo, Y. Ono, K. Inoue, M. Sano and S. Shinkai, J. Chem.
Soc. Perk. T. 2, 1999, 557.85 J. H. Dai, A. W. Jensen, D. K. Mohanty, J. Erndt and
M. L. Bruening, Langmuir, 2001, 17, 931.86 J. F. Quinn, A. P. R. Johnston, G. K. Such, A. N. Zelikin and
F. Caruso, Chem. Soc. Rev., 2007, 36, 707.87 J. F. Quinn and F. Caruso, Langmuir, 2004, 20, 20.88 E. Kharlampieva, V. Kozlovskaya, J. Tyutina and S. A. Sukhishvili,
Macromolecules, 2005, 38, 10523.89 J. D. Mendelsohn, C. J. Barrett, V. V. Chan, A. J. Pal, A. M. Mayes
and M. F. Rubner, Langmuir, 2000, 16, 5017.90 A. Fery, B. Scholer, T. Cassagneau and F. Caruso, Langmuir, 2001,
17, 3779.91 S. T. Dubas and J. B. Schlenoff, Macromolecules, 2001, 34, 3736.92 S. A. Sukhishvili and S. Granick, J. Am. Chem. Soc., 2000, 122,
9550.93 M. K. Park, S. X. Deng and R. C. Advincula, J. Am. Chem. Soc.,
2004, 126, 13723.94 E. H. Kang, X. K. Liu, J. Q. Sun and J. C. Shen, Langmuir, 2006, 22,
7894.95 T. Serizawa, D. Matsukuma, K. Nanameki, M. Uemura, F. Kurusu
and M. Akashi, Macromolecules, 2004, 37, 6531.96 E. Kharlampieva, I. Erel-Unal and S. A. Sukhishvili, Langmuir,
2007, 23, 175.Soft Matter, 2009, 5, 511524 | 523
-
97 A. Nykanen, M. Nuopponen, A. Laukkanen, S. P. Hirvonen,M. Rytela, O. Turunen, H. Tenhu, R. Mezzenga, O. Ikkala andJ. Ruokolainen, Macromolecules, 2007, 40, 5827.
98 T. M. Fulghum, N. C. Estillore, C. D. Vo, S. P. Armes andR. C. Advincula, Macromolecules, 2008, 41, 429.
99 C. M. Nolan, M. J. Serpe and L. A. Lyon, Biomacromolecules, 2004,5, 1940.
100 M. J. Serpe, K. A. Yarmey, C. M. Nolan and L. A. Lyon,Biomacromolecules, 2005, 6, 408.
101 G. Q. Jiang, A. Baba, H. Ikarashi, R. S. Xu, J. Locklin,K. R. Kashif, K. Shinbo, K. Kato, F. Kaneko and R. Advincula,J. Phys. Chem. C, 2007, 111, 18687.
102 C. Jiang, S. Markutsya, Y. Pikus and V. V. Tsukruk, Naturematerials, 2004, 3, 721.
103 C. Y. Jiang and V. V. Tsukruk, Soft Matter, 2005,