Thermoresponsive Microgels Research Articles

Patterned Thermoresponsive Microgel Surfaces to Control Cell Detachment.

The aim of this work is to examine how adhered individual cells could detach from the patterned, discontinuous thermoresponsive coating substrate and how different patterns in the form of thermoresponsive squares and gaps would affect cell detachment. Microgels prepared from copolymerization of N-isopropylacrylamide and styrene (pNIPAAmSt) were spin-coated on polyethylenimine (PEI) precoated glass coverslips to form a uniform microgel monolayer; then a surface-moisturized PMDS stamp was used to contact the microgel monolayer at room temperature. The thin layer of water on the PDMS stamp surface worked as an ink to penetrate the microgels so that any microgels in direct contact with the wet stamp surface became swollen and could be peeled away, while uncontacted microgels formed patterns. Using this method, various patterns with different thermo-island diameters and gaps could be fabricated. NIH3T3 fibroblast cells were then cultured on these patterns to study their detachment behavior. It was found that cells could detach not only from these discontinuous thermoresponsive coatings, but also from the patterned surfaces with the thermoresponsive area being as low as 20% of the cell spread area.

Dual stimuli-responsive oligo(ethylene glycol)-based microgels: insight into the role of internal structure in volume phase transitions and loading of magnetic nanoparticles to design stable thermoresponsive hybrid microgels

Design of multi-responsive biocompatible P(MEO2MA-co-OEGMA-co-MAA) microgels and their hybrid magnetic couterparts.

Confinement of thermoresponsive microgels into fibres via colloidal electrospinning: experimental and statistical analysis

Colloidal electrospinning allow confining microgels within polymer fibre. Optimization (DoE) to minimize fibre diameter gives rise to nanofibres (63 nm).

Quantitative X-ray microscopic analysis of individual thermoresponsive microgel particles in aqueous solution

The temperature dependent phase transition of individual thermoresponsive microgel particles in aqueous solution has been studied by high resolution soft X-ray transmission microscopy (STXM).

Mechanics at the glass-to-gel transition of thermoresponsive microgel suspensions.

We study the rheology of systems of thermoresponsive microgels which can transition between a repulsive glass and an attractive gel state. We find marked differences between these two colloidal solids, within the same experimental system, due to the different origins for their dynamic arrest. While the rigidity of the repulsive systems depends solely on particle volume fraction, we find that the change in linear elasticity upon introducing attractive bonds in the system scales linearly with the adhesive bond strength which can be tuned with the temperature in our experiments. And while the glasses yield reversibly and with a rate-dependent energy dissipation, bond-reorganisation in the gels is suppressed so that their rupture is irreversible and accompanied by a high, but rate-independent, dissipation. These results highlight how colloids with responsive interactions can be employed to shed new light onto solid-solid transitions.

Synthesis and Characterization of Core-Shell Thermo-Responsive Microgels with Linear Transition Behavior

Thermo-responsive microgels with core-shell structure were prepared by free radical emulsion polymerization. The core of microgels was consisted of poly (N-isopropyl acrylamide) (PNIPAM), while the shell was consisted of poly (ethylene glycol) methyl ether methacrylate (POEGMA300). In order to compare the transition behavior of the core-shell microgels with the microgels consisted of one thermo-responsive microgel, PNIPAM and POEGMA300 microgels were prepared. PNIPAM exhibits a lower critical solution temperature (LCST) of 32 °C, and the LCST of POEGMA300 is approximately 63 °C. The thermo-responsive microgel behavior was measured by dynamic light scattering (DLS). It is observed that both of PNIPAM and POEGMA300 microgels show a thermo-responsive ability. The particle size significantly drops when the temperature passes LCST. Moreover the particle size of the thermo-responsive microgels with core (PNIPAM)-shell (POEGMA300) structure shows a linear transition behavior when the temperature is between 50 °C and 70 °C.

Photothermally Induced Optical Property Changes of Poly(N-isopropylacrylamide) Microgel-Based Etalons.

Poly(N-isopropylacrylamide) microgel-based optical devices were designed such that they can be stimulated to change their optical properties in response to light produced by a light-emitting diode (LED). The devices were fabricated by sandwiching the synthesized microgels between two Cr/Au layers all supported on a glass coverslip with gold nanoparticles (AuNPs) deposited. Here, we found that these devices can be stimulated to change their optical properties when exposed to green LED light, which excites the AuNPs and increases the local temperature, causing the thermoresponsive microgels to decrease in diameter, resulting in a change in the devices' optical properties. We also found that the sensitivity of the devices to light was more pronounced as the environmental temperature approached the lower critical solution temperature (LCST) for the microgels, although the sensitivity of the devices to light exposure dropped off dramatically as the environmental temperature was increased above the LCST. This was a direct result of the microgels already being in their collapsed state and therefore unable to decrease in diameter any further due to light exposure. Finally, we found that the sensitivity of the devices to light exposure increased with increasing number of AuNP layers in the devices. We anticipate that these devices could be used for drug delivery applications; by using light to stimulate microgel collapse, the microgel-based devices can be stimulated to release small molecules on demand.

Differential Photoluminescent and Electrochemiluminescent Behavior for Resonance Energy Transfer Processes in Thermoresponsive Microgels.

Stimuli-responsive microgels with redox and luminescent resonance energy transfer (LRET) properties are reported. Poly(N-isopropylacrylamide) microgels are functionalized simultaneously with two models dyes: a derivative of tris(bipyridine) ruthenium complex and cyanine 5. Both moieties are chosen as a pair of luminophores with a spectral overlap for resonance energy transfer, where the ruthenium complex acts as a donor and the cyanine an acceptor. The effect of the temperature on the efficiency of the LRET of the microgels has been investigated and compared using either photoluminescence (PL) or electrochemiluminescence (ECL) as the excitation process. In PL, the synthesized microgels exhibit resonance energy transfer regardless of the swelling degree of the microgels. The transfer efficiency is a function of the donor-acceptor distance and can be tuned either by the swell-collapse phase transition or by the dye content in the microgel network. In ECL, the microgels emit light only at the wavelength of the ruthenium complex because the resonance energy transfer does not occur. Indeed, even within the microgel matrix, the cyanine dye is oxidized at the potential required for ECL generation, which impairs its emitting properties. Thus, both excitation channels (i.e., PL and ECL) show differential behavior for the resonance energy transfer processes.

A Surface-Enhanced Raman Scattering Sensor Integrated with Battery-Controlled Fluidic Device for Capture and Detection of Trace Small Molecules.

For surface-enhanced Raman scattering (SERS) sensors, one of the important issues is the development of substrates not only with high SERS-activity but also with strong ability to capture analytes. However, it is difficult to achieve the two goals simultaneously especially when detecting small molecules. Herein a compact battery-controlled nanostructure-assembled SERS system has been demonstrated for capture and detection of trace small molecule pollutants in water. In this SERS fluidic system, an electrical heating constantan wire covered with the vertically aligned ZnO nanotapers decorated with Ag-nanoparticles is inserted into a glass capillary. A mixture of thermo-responsive microgels, Au-nanorods colloids and analyte solution is then filled into the remnant space of the capillary. When the system is heated by switching on the battery, the thermo-responsive microgels shrink, which immobilizes the analyte and drives the Au-nanorod close to each other and close to the Ag-ZnO nanotapers. This process has also created high-density “hot spots” due to multi-type plasmonic couplings in three-dimensional space, amplifying the SERS signal. This integrated device has been successfully used to measure methyl parathion in lake water, showing a great potential in detection of aquatic pollutants.

Role of Steric Interactions on the Ionic Permeation Inside Charged Microgels: Theory and Simulations

In this work, we study the effect of the steric excluded-volume interactions between counterions and thermoresponsive ionic heterogeneous microgel particles. With this aim, we perform Monte Carlo simulations to calculate the microgel effective net charge and the conunterion distribution function inside and around the microgel for different degrees of swelling. These results are compared to the ones obtained solving the Ornstein–Zernike integral equations within the HNC approximation. For this purpose, the equilibrium polymer mass and charge distribution inside the microgel resulting from simulations are used as the input for the integral equations. Two different models are considered to quantify the microgel-ion steric interaction. The model that considers polymer fibers formed by spheres demonstrates to be a very reliable way to predict counterion permeation in such microgels. Finally, integral equations are solved ignoring the steric interaction as well, in order to determine to what extent this effect ...

Investigation of cell behaviors on thermo-responsive PNIPAM microgel films

The use of poly(N-isopropylacrylamide) (PNIPAM) as building blocks for engineering responsive coatings and their potential use as switchable substrates such as biosensors have attracted great attention in recent years. However, few studies have been conducted regarding the cell behaviors and the related mechanism on thermos-responsive surfaces consisting of PNIPAM microgel particles. In this work, monodisperse PNIPAM microgels were synthesized and used to prepare PINPAM microgel films. Uniform microgel surfaces can be fabricated by drop-coating with the precoating of a polyethylenimine (PEI) layer. Cell experiments indicate that unlike PNIPAM polymer brushes reported with controllable detachment ability, HepG2, which is a human liver carcinoma cell line, remains adherent on the microgel films upon cooling. Surface plasmon resonance (SPR) experiments show an irreversible adsorption of serum proteins on the microgel surface upon cooling, whose adsorption is a prerequisite of cell adhesion during cell culture. This fact may account for the irreversible adhesion of HepG2 cells.

Biodegradable colloidal microgels with tunable thermosensitive volume phase transitions for controllable drug delivery

In this study, we present gelatin-based thermoresponsive colloidal microgels that enable the controlled release of drugs by volume phase transition. The microgel was fabricated by physically entrapping poly(N-isopropylacrylamide-co-acrylamide) chains as a minor component within three-dimensional gelatin networks crosslinked by genipin. We demonstrate that our gelatin-based thermoresponsive microgel exhibits a tunable deswelling to temperature increase, which positively correlated to the release of bovine serum albumin (BSA) as a function of poly(N-isopropylacrylamide-co-acrylamide) concentration. The microgel was enzymatically degradable by collagenase treatment. The extent of BSA release and biodegradability were tuned by controlling the crosslinking degree of the gelatin matrix. Meeting a great need for design and synthesis of auto-degenerating smart microgels that enable the controlled release of therapeutic proteins in responsive to external stimuli, our gelatin-based microgels that satisfy both thermoresponsivity and biodegradability have a great potential in tissue engineering applications as a soft microdevice element for drug delivery.

Enhanced Pulsatile Drug Release from Injectable Magnetic Hydrogels with Embedded Thermosensitive Microgels.

Nanocomposite in situ-gelling hydrogels containing both superparamagnetic iron oxide nanoparticles (SPIONs) and thermoresponsive microgels are demonstrated to facilitate pulsatile, high-low release of a model drug (4 kDa fluorescein-labeled dextran). The materials can be injected through a minimally invasive route, facilitate a ∼4-fold enhancement of release when pulsed on relative to the off state, and, in contrast to previous gel-based systems, can maintain pulsatile release properties over multiple cycles and multiple days instead of only hours. Optimal pulsatile release is achieved when the microgel transition temperature is engineered to lie just above the (physiological) incubation temperature. Coupled with the demonstrated degradability of the nanocomposites and the cytocompatibility of all nanocomposite components, we anticipate these nanocomposites have potential to facilitate physiologically relevant, controlled pulsatile drug delivery.

Core/Shell Microgels Decouple the pH and Temperature Responsivities of Microgel Films

We investigate the impact of pH on the swelling properties of thermoresponsive microgel layer-by-layer films. Microgels were synthesized from N-isopropylacrylamide and/or N-isopropylmethacrylamide. At pH 3, films composed of traditional (core) microgels, where acrylic acid has been copolymerized throughout the microgel network, have sharp temperature responsivities as observed by increases in the intensity of scattered light. This is contrasted by results at pH 7.4, where responsivity is diminished, likely as a result of deprotonated carboxylic acid groups, which changes the osmotic pressure within the component microgels. To probe this phenomenon further, core/shell microgels were synthesized such that the acidic comonomer was isolated to the shell and the core was purely temperature-responsive. Films assembled from such core/shell microgels exhibited pH-independent temperature responsivities. Temperature controlled in-liquid atomic force microscopy was used to directly measure the thickness of microgel films at pH 3 and 7.4 at ∼26 and 50 °C. Film thickness measurements were predominately in agreement with light scattering data, where decreases in film thickness corresponded with increases in scattered light intensity. Thus, we find that spatially separating the responsivities within multiresponsive microgels can result in more predictive power over the responsivity of microgel assemblies.

Electrostatic Self‐Assembly of Au Nanoparticles onto Thermosensitive Magnetic Core‐Shell Microgels for Thermally Tunable and Magnetically Recyclable Catalysis

A facile route to fabricate a nanocomposite of Fe3O4@poly[N-isopropylacrylamide (NIPAM)-co-2-(dimethylamino)ethyl methacrylate (DMAEMA)]@Au (Fe3O4@PND@Au) is developed for magnetically recyclable and thermally tunable catalysis. The negatively charged Au nanoparticles with an average diameter of 10 nm are homogeneously loaded onto positively charged thermoresponsive magnetic core-shell microgels of Fe3O4@poly(NIPAM-co-DMAEMA) (Fe3O4@PND) through electrostatic self-assembly. This type of attachment offers perspectives for using charged polymeric shell on a broad variety of nanoparticles to immobilize the opposite-charged nanoparticles. The thermosensitive PND shell with swollen or collapsed properties can be as a retractable Au carrier, thereby tuning the aggregation or dispersion of Au nanoparticles, which leads to an increase or decrease of catalytic activity. Therefore, the catalytic activity of Fe3O4@PND@Au can be modulated by the volume transition of thermosensitive microgel shells. Importantly, the mode of tuning the aggregation or dispersion of Au nanoparticles using a thermosensitive carrier offers a novel strategy to adjust and control the catalytic activity, which is completely different with the traditional regulation mode of controlling the diffusion of reactants toward the catalytic Au core using the thermosensitive poly(N-isopropylacrylamide) network as a nanogate. Concurrent with the thermally tunable catalysis, the magnetic susceptibility of magnetic cores enables the Fe3O4@PND@Au nanocomposites to be capable of serving as smart nanoreactors for thermally tunable and magnetically recyclable catalysis.

A new route towards colloidal molecules with externally tunable interaction sites.

We describe a route towards self-assembled colloidal molecules, where thermoresponsive microgels serve as discrete, externally tunable interaction sites. The ability of poly(N-isopropylacrylamide) (PNIPAM) and poly(N-isopropylmethacrylamide) (PNIPMAM) microgels to adsorb to the oil/water (O/W) interface and create Pickering-stabilized mini-emulsions was first tested using the controlled addition of sub-micron-sized polydimethylsiloxane (PDMS) oil droplets to a microgel suspension. The use of a mixture of PNIPAM and PNIPMAM microgels differing in size and fluorescent labeling then resulted in the formation of thermosensitive patchy particles, where the patches can be visualised using fluorescence confocal laser scanning microscopy. The size of the assembled decorated droplets and the number of adsorbed microgels was further reduced using an in situ synthesis approach, where the oil droplets are directly synthesised in the presence of microgels. This results in the formation of highly monodisperse microgel-decorated PDMS oil droplets with a small number of microgels adsorbed to the droplet interface. We demonstrate that we can use temperature to change the interaction potential between these interaction sites and thus trigger a reversible association of the individual decorated droplets at temperatures above the volume phase transition temperature TVPT of the microgels. Finally, we investigated the temporal evolution of the decorated droplets and found that small and well-defined clusters of microgels form in the early stages of the process primarily through the action of capillary forces. These clusters mimic colloidal molecules with a small number of discrete and thermosensitive binding sites.

Volume phase transition mechanism of poly[oligo(ethylene glycol)methacrylate] based thermo-responsive microgels with poly(ionic liquid) cross-linkers.

Thermo-dynamic volume phase transition mechanisms of poly[oligo(ethylene glycol)methacrylate] (POEGMA) based microgels with poly(ionic liquid) (PIL) cross-linking moieties are investigated in detail on the basis of temperature-dependent Fourier transform infrared (FTIR) spectroscopy. The original FTIR data are further analysed by two-dimensional correlation spectroscopy (2Dcos) with the perturbation correlation moving window (PCMW) technique. It is observed that the content of hydrophilic PIL cross-linking structure strongly affects the temperature induced volume phase transition mechanism of microgels in which the less cross-linked microgel exhibits a sharp volume phase transition process while the highly cross-linked microgel presents a broad transition behavior. Peculiarly, the dehydration of C-H groups acts as the driving force for the whole phase transition process within the less cross-linked microgel network and cooperative response of chemical groups is identified. It is deduced that the hydrophilic PIL moieties develop polymer-water-polymer interactions with C=O groups as C=O···D2O-PIL hydrogen bonds emerge in the less cross-linked system. As regards the highly cross-linked microgel system, the phase transition process is driven by the disruption of hydrogen bonds between C=O groups and water molecules while the response of C-H groups becomes insensitive. PIL moieties passively dehydrate following the dehydration of C-H groups on oligo(ethylene glycol) side chains and no hydrogen bond between C=O group and IL-D2O association appears during the phase transition process.

Functionalized thermo-responsive microgels for high performance forward osmosis desalination

Stimuli-responsive hydrogels were recently proposed for energy-saving forward osmosis (FO) process. However, their low water flux and dewatering ability for reuse make them less attractive for industrial desalination process. In this work, the co-polymer microgels of N-isopropylacrylamide and acrylic acid with different mixing ratios were synthesized using surfactant-free emulsion polymerization to produce submicron-size hydrogels with high surface area and fast swelling-deswelling response. The microgels were employed as draw agents in a laboratory scale FO desalination system. The microgel-based FO process performed a high water flux up to 23.8 LMH and high water recovery ability of 72.4%. In addition, we explored a new conductivity measurement method to online analyze water flux of the FO system. This on-line conductivity analysis approach appeared to be an accurate and efficient method for evaluating microgel-based FO desalination performance. Our experimental data revealed that the stimuli-responsive microgel was an efficient draw agent for FO desalination.

Design of smart oligo(ethylene glycol)-based biocompatible hybrid microgels loaded with magnetic nanoparticles.

This article reports a rational strategy for preparing smart oligo(ethylene glycol)-based hybrid microgels loaded with high content of homogeneously distributed preformed magnetic nanoparticles (NPs) (up to 33 wt%). The strategy is based on the synthesis of biocompatible multiresponsive microgels by precipitation copolymerization of di(ethylene glycol) methyl ether methacrylate, oligo(ethylene glycol) methyl ether methacrylate, methacrylic acid, and oligo(ethylene glycol)diac-rylate. An aqueous dispersion of preformed magnetic NPs is straightforwardly loaded into the microgels. Robust monodisperse thermoresponsive magnetic microgels are produced, exhibiting a constant value of the volume phase transition temperature whatever the NPs content. The homogeneous microstructure of the initial stimuli-responsive biocompatible microgels plays a crucial role for the design of unique well-defined ethylene glycol-based thermoresponsive hybrid microgels.

Self-assembled two-dimensional thermoresponsive microgel arrays for cell growth/detachment control.

Monodisperse poly(N-isopropylacrylamide-styrene) (PNIPAAmSt) microgels with different St/NIPAAm ratios have been synthesized via a one-step surfactant-free emulsion polymerization process. The resulting microgel dispersions were used to fabricate 2D arrays on the surface of silicon wafers/glass coverslips through dip coating. The thermal responsiveness of the PNIPAAmSt microgel arrays was examined by spectroscopic ellipsometry and the results unraveled that the thermoresponsive behavior of the arrays was highly consistent with the microgels dispersed in the bulk, showing high dependence on the content of styrene. The structure of the films varied from nonclose-packed 2D arrays to close-packed 2D arrays, depending on both properties of the microgels and array fabrication conditions. When the weight ratio of styrene was below 40%, the microgel arrays demonstrated effective control for cell growth and detachment across their volume phase transition temperatures (around 28 °C). The extent of swelling of the microgels was the key factor to determine whether the cells could detach from the film easily. For the rather close-packed 2D arrays prepared by the same kind of PNIPAAmSt microgels, the gaps between microgel particles showed no obvious effect on the rate of cell detachment.