Microgels In Solution Research Articles

Mechanochromic Hydrogel Fibers with Multiple Fluorescent Colors.

Mechanochromic polymers can change their color in response to external force and have shown promising applications in stress sensing and failure warning. They are usually obtained as thin films or bulky specimens. The mechanochromic fibers, which can be used to make smart fabrics, have been seldom reported due to the lack of efficient fabrication techniques. In this work, a general method using photo-polymerization of microgel solution in a template tube to produce mechanochromic hydrogel fibers is reported. The obtained hydrogel fibers can generate visible and fluorescent color changes upon deformation. The diameter of the mechanochromic fibers can be easily adjusted by using different template tubes. The mechanochromic fibers can be fabricated as long as 1 m. By reducing the fiber diameter or increasing the microgel concentration, the mechanical properties of the mechanochromic fibers can be improved, leading to more obvious mechanochromic behavior. The polymethacrylate (PMA) is further used to coat the hydrogel fibers, prevent the loss of water in the fibers, and increase the storage time. The mechanochromic fibers with multiple fluorescent colors are further fabricated by utilizing different microgel solutions. This work provides an easy and effective method to fabricate mechanochromic fibers with different color change abilities.

Charge Transfer Kinetics of Redox-Active Microgels.

Polymer microgel particles decorated with redox-active functional groups are a new and promising object for electrochemical applications. However, the process of charge exchange between an electrode and a microgel particle carrying numerous redox-active centers differs fundamentally from charge exchange involving only molecular species. A single act of contact between the microgel and the electrode surface may not be enough to fully discharge the microgel, and partial charge states are to be expected. Understanding the specifics of this process is crucial for the correct analysis of the data obtained from electrochemical experiments with redox-active microgel solutions. In this study, we employed coarse-grained molecular dynamics to investigate in detail the act of charge transfer from a microgel particle to a flat electrode. The simulations take into account both the mobility of functional groups carrying the charge, which depend on the microgel architecture and the charge exchange between the groups, which can accelerate the propagation of charge within the microgel volume. A set of different microgel systems were simulated in order to reveal the impact of their characteristics: fraction of redox-active groups, microgel molecular mass, cross-linker content, cross-linking topology, and solvent quality. We have found trends in microgel composition leading to the most efficient charge transfer kinetics. The obtained results would be useful for understanding experimental results and for optimizing the design of redox-active microgel particles aimed at faster discharge rates.

Osmotic swelling behavior of surface-charged ionic microgels.

In recent years, ionic microgels have garnered much attention due to their unique properties, especially their stimulus-sensitive swelling behavior. The tunable response of these soft, permeable, compressible, charged colloidal particles is increasingly attractive for applications in medicine and biotechnologies, such as controlled drug delivery, tissue engineering, and biosensing. The ability to model and predict variation of the osmotic pressure of a single microgel with respect to changes in particle properties and environmental conditions proves vital to such applications. In this work, we apply both nonlinear Poisson-Boltzmann theory and molecular dynamics simulation to ionic microgels (macroions) in the cell model to compute density profiles of microions (counterions, coions), single-microgel osmotic pressure, and equilibrium swelling ratios of spherical microgels whose fixed charge is confined to the macroion surface. The basis of our approach is an exact theorem that relates the electrostatic component of the osmotic pressure to the microion density profiles. Close agreement between theory and simulation serves as a consistency check to validate our approach. We predict that surface-charged microgels progressively deswell with increasing microgel concentration, starting well below close packing, and with increasing salt concentration, in qualitative agreement with experiments. Comparison with previous results for microgels with fixed charge uniformly distributed over their volume demonstrates that surface-charged microgels deswell more rapidly than volume-charged microgels. We conclude that swelling behavior of ionic microgels in solution is sensitive to the distribution of fixed charge within the polymer-network gel and strongly depends on bulk concentrations of both microgels and salt ions.

Poly(N-isopropylacrylamide) Microgel Lubricants with High Friction Sensitivity

Poly(N-isopropylacrylamide) (PNIPAM) microgels with a unique thermosensitive swelling and deswelling behavior in water may be capable of sensing the frictional heat in sliding interfaces and altering the performance of water-lubricated contacts accordingly. However, the rheological properties of PNIPAM microgels and the formation mechanism of tribofilms at the sliding interface during friction are currently unclear. In the present study, the variation in the rheological behaviors and kinetic characteristics of PNIPAM microgels during phase transformation was investigated using a temperature-controlled rheometer and molecular dynamics (MD) simulations. As the temperature increases to the lower critical solution temperature (LCST) of PNIPAM, an atypical increase in the viscosity of the microgel solution is observed due to the increased loss modulus (G″). The interaction between PNIPAM microspheres is enhanced above the LCST, as shown by MD simulations. Tribological evaluations demonstrate that PNIPAM microgels could effectively improve the tribological performance due to the formed gel layer that confines water in its porous structure and changes the friction interface from hard-on-hard to soft-on-soft contact, and the forming ability of the gel layer is related to the aggregation and deposition of PNIPAM microspheres due to the deswelling of PNIPAM microgels triggered by frictional heat.

Swelling, collapse and ordering of rod-like microgels in solution: Computer simulation studies

Polymer microgels have proven to be highly promising macromolecular objects for a wide variety of applications. In particular, the soft particles of an anisotropic (rod-like) shape are of special interest because of their potential use in tissue engineering or materials design. However, a little is known about the physical behavior of such microgels in solution, which inspired us to study them using mesoscopic computer simulations. For single networks, depending on the solvent quality, the dimensional characteristics were obtained for microgels of different molecular weight, crosslinking density and aspect ratio. In particular, the conditions for the rod-to-rod (preserving the nonspherical shape) and rod-to-sphere collapse were found. In addition, the effect of the liquid-crystalline (LC) ordering was demonstrated for the ensemble of rod-like microgels at different swelling ratios, and the influence of microgel aspect ratio on the volume fraction of the LC transition was shown.

In-line Monitoring of Microgel Synthesis: Flow versus Batch Reactor

In-line monitoring of polymerization via Raman spectroscopy is standard for batch reactors but yet to be manifested for flow reactors. When transferring the in-line Raman spectroscopy from batch to flow reactors, the aim is to maintain the measurement precision. We present a customized Raman measurement cell for in-line monitoring in a tubular flow reactor and a systematic accuracy analysis of the obtained measurement. The accuracy analysis involves comparing three calibration models and measurements of flowing solvent, monomer solution, and microgel solution. The evaluation of the measurements reveals that multimolecular analyte solutions most significantly influence the quantification accuracy. From these investigations, we derive a quality criterion for the Raman measurements based on the root mean square error, and apply the criterion to the monitoring of precipitation polymerization of poly(N-iso-propylacrylamide) (PNIPAM) microgels. The results compare the predictions from the Raman measurements of the microgel synthesis in the flow and batch reactor. Applying the quality criterion enables high-quality measurements and allows the functional detection of outliers during the synthesis. The identification and exclusion of outliers eliminate several potential errors to cause the difference in measurement results from the flow and batch reactors. This contribution serves as a guideline for transferring in-line monitoring from batch to flow reactors as the example of precipitation polymerization.

Analysis of flow and slip behavior of microgel solution inside microchannel

We conducted experiments and computations to investigate the flow of a microgel solution inside a microchannel. The model fluid was a 0.2 wt% Carbopol 941 microgel solution, which was injected into the microchannel with dimensions of 200 μm × 200 μm × 15 mm at a flow rate of 800 μL/h. We devised a new approach for visualizing the flow using the relative velocity, and used a new velocimetry method based on image processing to calculate the velocity profiles with reasonable accuracy. Our study focused on two aspects: 1) introducing a new velocimetry method based on image processing of flow visualizations, and 2) deducing a slip parameter by comparing the experiments and computations. Based on the model, we computationally explored various flow rates that could not be realized experimentally and investigated the slip behavior.

Effect of BSA loading on the properties of P (NIPAM-co-AAc) microgel

The N-isopropyl acrylamide (NIPAM) and acrylic acid (AAc) copolymer (P (NIPAM-co-AAc)) microgel was prepared through soap-free emulsion polymerization. The morphology and the transmittance of P (NIPAM-co-AAc) microgel before and after loading protein of bovine serum albumin (BSA) were observed by atomic force microscopy (AFM) and spectrophotometer, respectively. AFM image showed that the particle size of the microgel was about 900 nm in contrast with 20 nm of BSA particles. It was also found that from AFM, the P (NIPAM-co-AAc) microgel particles were uniformly dispersed with a conical shape, while the BSA-loaded microgel particles formed agglomerates and the microgel particles were distributed in a cylindrical shape, which was caused by the significant improvement of microgel particles after protein adsorption. The changes of surface properties ultimately influenced the lower critical solution temperature (LCST) of microgel solutions, leading to a decrease in the LCST of the BSA-loaded microgel solution.

Absence of crystals in the phase behavior of hollow microgels.

Solutions of microgels have been widely used as model systems to gain insight into atomic condensed matter and complex fluids. We explore the thermodynamic phase behavior of hollow microgels, which are distinguished from conventional colloids by a central cavity. Small-angle neutron and x-ray scattering are used to probe hollow microgels in crowded environments. These measurements reveal an interplay among deswelling, interpenetration, and faceting and an unusual absence of crystals. Monte Carlo simulations of model systems confirm that, due to the cavity, solutions of hollow microgels more readily form a supercooled liquid than for microgels with a cross-linked core.

Effect of Experimental Variables on the Physicochemical Characteristics of Multi-Responsive Cellulose Based Polymer Microgels

Temperature and pH responsive macromolecular colloidal materials have widespread applications. pH/thermo-responsive benzyl modified cellulose based microgels (BMC-PNIPAAm-PAAc) were synthesized by copolymerization of benzyl modified cellulose with poly(N-isopropylacrylamide) [PNIPAAm], and acrylic acid (AAc) by emulsion polymerization. In order to enhance the copolymerization ability of cellulose, its hydroxyl groups were modified by treating with benzyl chloride. Microgels were characterized using Fourier transform infrared spectroscopy (FTIR), UV–Vis spectrsocopy, rheology, dynamic light scattering (DLS), flow viscometry, and density measurements. FTIR was used to investigate the various functional groups in the microgels. The influence of experimental conditions such as chemical composition and temperature/pH of microgel solutions on the sol–gel behavior of microgels was studied through rheology, light scattering, viscometry and densimetry. The shear stress and gel viscosity was measured under various shear rates and temperatures. By increasing the shear rate, a decrease in viscosity was observed. The microgels behaved as viscoelastic solids over a wide frequency range as the loss modulus was found to be smaller than the storage modulus. Temperature-dependent spectral changes of the microgels were also investigated by UV‒Vis spectroscopy at various temperatures. The relative viscosity of the synthesized microgels was also studied at various pH/temperature using concentration based times of flow Ostwald’s viscometry. Similarly, the specific volume of the gel particles was traced from the solution density The results revealed that various colloidal and physicochemical parameters of the polymer gels could be easily adjusted by changing various experimental variables, suggesting their potential use as drug delivery carriers.

Investigation of acid pre-flushing and pH-sensitive microgel injection in fractured carbonate rocks for conformance control purposes

Waterflooding in fractured reservoirs is a challenging task due to the presence of high conductive flow pathways such as fractures. Much of the injected water passes through fractures without sweeping the oil in the low permeable area, which results in an early breakthrough. Implementing deep conformance control techniques can be a remedy for this early water breakthrough. pH-sensitive microgel injection is a conformance control method in which the dependency of microgel viscosity to pH guarantees easy injection of these microgels into formations at low pH environments. Because of the geochemical reactions among rock minerals, microgels, and a pre-flushing acid, the microgel pH increases; therefore, these microgels swell and block high conductive fractures. In this study, a designed visual cell containing rock samples is implemented to observe rock–microgel interactions during a pH-sensitive microgel flooding into a fractured carbonate medium. First, the dependency of fracture aperture changes to the acid pre-flush flow rate is examined. Then, we investigate the effect of pH-sensitive microgel concentration on its resistance to block fractures during post-water flooding by studying the gel failure mechanisms (e.g., adhesive separation, cohesive failure). Finally, the effect of an initial aperture of fracture is examined on microgel washout when water injection is resumed. The results showed that both decreasing the acid flow rate and lowering the initial aperture could increase the rate of aperture changes. Moreover, the microgel solution with a concentration of 1 wt% showed the highest resistance (98.2 psi/ft) against post-water injection. Additionally, this microgel concentration had the highest permeability reduction factor. Meanwhile, the smaller initial aperture of fracture contributed to a higher microgel resistance.

Phototactic poly(N-isopropyl acrylamide) microgels with photoresponsive property

Smart functional microgels hold great potential in a variety of applications, especially in drug transportation. However, current drug carriers based on physiological internal stimuli cannot efficiently orientate to designated locations. Therefore, it is necessary to introduce the self-propelled particles to the drug release of the microgels. In order to study self-propulsion of microgels induced by light, it is also a challenge to prepare micronsized microgels so that they can be observed directly under optical microscopes. In this work, phototactic microgels with photoresponsive properties are prepared. The microgel particles can be observed by confocal laser scanning microscopy. The photoresponsive properties of microgels are fully investigated by various instruments. Light can also regulate the state of the microgel solution, making it switch between turbidity and clarity. The phototaxis of particles irradiated by UV light was studied, which may be used for microgels enrichment and drug transportation and release.

Novel cellulose-gelatin composite films made from self-dispersed microgels: Structure and properties

A series of epichlorohydrin-couple-linked cellulose-gelatin composite films (ECGF) was fabricated in NaOH/urea aqueous solution using a process involving homogenous blending, coupling, dialysis, self-dispersion, microgel solution casting, and evaporation. Their structure and properties were characterized with elemental analysis, Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), scanning electron microscope (SEM), atomic force microscopy (AFM), ultraviolet–visible (UV–vis) spectroscopy, water vapor permeability, and mechanical testing. The results showed that the self-dispersed cellulose-gelatin microgels were successfully prepared and the coupling interactions existed in the inter- and intra-molecules of the corresponding composite films during the fabrication process. The water vapor permeability of the ECGF films was improved when the protein content was higher than 30 wt% in composite films at 75% relative humidity. Interestingly, compared with the cellulose/protein composite films prepared via phase separation method, ECGF films exhibited more homogeneous surface and compact cross-section structures, as well as presented higher light transmittance at 400 nm of about 88% and relative lower swelling ratio. Moreover, ECGF films displayed higher tensile strength compared with that of water-soluble cellulose derivatives/protein composite films in dry and wet states.

In Situ Synthesis of CuS Nanoparticle-Doped Poly(N-isopropylacrylamide)-Based Microgels for Near-Infrared Triggered Photothermal Therapy

Poly(N-isopropylacrylamide)-co-(acrylic acid) (pNIPAm-co-AAc) microgels incorporated with CuS nanoparticles (CuSNPs) were synthesized and employed for near-infrared (NIR) triggered photothermal killing of cancer cells. Cu2+ was enriched in the microgels through deprotonation of the pNIPAm-co-AAc microgels at high solution pH. CuSNPs were subsequently generated within the pNIPAm-co-AAc microgels upon exposure to heat and S2–. The solution of hybrid microgels showed an absorption peak in the NIR region (∼1000 nm). After demonstrating that the hybrid microgels were not cytotoxic, we showed that NIR excitation of the hybrid microgels could be used to kill HeLa cells. Almost 90% of the HeLa cells were killed when incubated with 400 μg/mL of the hybrid microgels and exposed to 808 nm laser light with a power density of 2 W/cm2 for 10 min. While these materials show promise for photothermal therapy, they can also be incorporated into a hydrogel matrix that can be triggered to release small molecule drugs upon ex...

Single Microgels in Core-Shell Equilibrium: A Novel Method for Limited Volume Studies.

The interactions of cationic surfactant dodecyltrimethylammonium bromide and cationic protein cytochrome c with anionic polyacrylate microgels have been investigated in microscopic liquid droplets by means of a micropipette technique at ionic strength 0.01 M and pH 8. Experiments on single microgels in solutions of limited amounts of the surfactant provide the first evidence of microgels in a stable biphasic core-shell state with the surfactant partitioned to the shell. Under the same conditions, the protein is found to distribute uniformly in the microgels. Quantitative data in the form of swelling and binding isotherms are presented and compared with literature data for macrogels and with predictions of a recent gel theory. Theory is found to be in semiquantitative agreement with the experiments. The importance of polyion-mediated attractions between the protein molecules is analyzed theoretically and proposed to explain the continuous but highly cooperative binding isotherms.

Injectable and microporous scaffold of densely-packed, growth factor-encapsulating chitosan microgels

In this work, an emulsion crosslinking method was developed to produce chitosan-genipin microgels which acted as an injectable and microporous scaffold. Chitosan was characterized with respect to pH by light scattering and aqueous titration. Microgels were characterized with swelling, light scattering, and rheometry of densely-packed microgel solutions. The results suggest that as chitosan becomes increasingly deprotonated above the pKa, repulsive forces diminish and intermolecular attractions cause pH-responsive chain aggregation; leading to microgel–microgel aggregation as well. The microgels with the most chitosan and least cross-linker showed the highest yield stress and a storage modulus of 16kPa when condensed as a microgel paste at pH 7.4. Two oppositely-charged growth factors could be encapsulated into the microgels and endothelial cells were able to proliferate into the 3D microgel scaffold. This work motivates further research on the applications of the chitosan microgel scaffold as an injectable and microporous scaffold in regenerative medicine.

Synthesis of MMP sensor microgel for spatial and temporal monitoring of MMP activities

Event Abstract Back to Event Synthesis of MMP sensor microgel for spatial and temporal monitoring of MMP activities Della S. Shin1, Emi Y. Tokuda1 and Kristi S. Anseth1, 2, 3 1 University of Colorado, Department of Chemical and Biological Engineering, United States 2 BioFrontiers Institute, United States 3 Howard Hughes Medical Institute, United States Statement of Purpose: Matrix Metalloproteinase (MMPs) are a group of endopeptidases that are known to be involved in various cellular processes related to migration, such as invasion by cancer cells through remodeling of their surrounding matrix [1]. Here, we developed a method to monitor MMP activity in real time at the site of action using a microgel sensor which contains covalently coupled MMP degradable peptides with FRET fluorophore-quencher pairs at each end. With this sensor, it is possible to measure MMP activity in the range of 10 ng/ml to 50 µg/ml in real time over 100 min and analyze spatially detailed MMP activity of melanoma cancer cells. For 4-dimensional monitoring of MMPs inside the artificial extracellular matrix (ECM) (3-D space and time), the size of the microgels was selected to be over 10 µm to efficiently evade uptake by the cells and prevent rapid diffusion into the artificial ECM. This MMP activity monitoring microgel sensor can potentially serve as a platform for not only studying cancer cells, but also for monitoring cell-ECM interaction and migration inside various ECM mimicking scaffolds for tissue regeneration. Methods: A quenched fluorigenic peptide(Dabcyl-GGPQG↓IWGQK-Fluorescein-AhxC) was prepared as reported previously [2]. Briefly, a fluorophore, fluorescein and a quencher, dabcyl were both covalently functionalized at the end of MMP degradable peptide substrate, GPQG↑IWGQ (where ↑ denotes the cleavage site). Microgels were prepared using an 8-arm poly (ethylene glycol) (20 mM PEG) end functionalized with norbornene, crosslinked by dithiothreitol (36 mM DTT) through a photo-initiated (10 mM lithium acylphosphinate (LAP)) polymerization. The sensor peptide was conjugated as a pendant group (4 mM). As a control, fluorescence change was monitored in response to various collagenase solutions with an automated Operetta confocal microscopy assay. Microgel solutions were exposed to each target collagenase concentration, and the fluorescence was taken automatically every 5 minutes. For 3-D monitoring of collagenase activity, microgels were encapsulated in a matrix-mimicking hydrogel. Imaging from the bottom to top of this hydrogel gave spatial information related to the collagenase activity. Results: Microgels were synthesized and their size was characterized based on their fluorescence image. The averaged diameter of the synthesized microgels was 40 ± 5 μm or 28 ± 5 μm each when the starting monomer was 5kDa-4-arm or 10kDa 8-arm PEG-norbornene, respectively. Figure 1. (a) Fluorescence microscope image and schematic illustration of the MMP sensitive microgel before and after addition of collagenase solution which contains MMPs. (b) Fluorescence change (F/F0) after addition of various concentration of collagenase solution. Next, the fluorescence changes in the microgels was monitored during exposure to various concentration of a collagenase solution. Before exposure to the collagenase solution, the fluoresein in the microgel was quenched by dabcyl and showed only low background levels. After cleavage by MMP, the quencher molecules diffused out from the microgel, and the microgel showed higher fluorescence as shown in Figure 1-(a). This fluorescence change was dependent on the concentration of collagenase in the solution and the time of exposure to collagenase solution (Fig 1-(b)). Current research is underway to examine local changes in MMP-activity in the presence of cell-laden hydrogels. This work was supported in part by the the Howard Hughes Medical Institute and grants from the National Institutes of Health (5R21EB018505-02).

Unusual temperature-induced swelling of ionizable poly(N-isopropylacrylamide)-based microgels: experimental and theoretical insights into its molecular origin.

In the traditional view of temperature-driven volume phase transitions in PNIPAM-based microgel solutions, a monotonic and sharp decrease in the particle size occurs upon heating the solution to above the volume phase transition temperature (VPTT). However, at sufficiently high microgel concentrations and under low salt conditions, our dynamic light scattering experiments reveal an unexpected non-monotonic evolution of the particle size when increasing the solution temperature. These findings show that poly(N-isopropylacrylamide-co-methacrylic acid) (P(NIPAM-co-MAA)) microgels swell upon heating the solution in the temperature range where NIPAM is water-soluble (i.e., below the VPPT). Further heating the microgel solution leads to microgel collapse as typically observed at temperatures above the VPTT. This novel behavior depends on the particle and salt concentration. We have observed the expected monotonic temperature-response of P(NIPAm-co-MAA) microgel solutions at low particle density and high salt concentration. To gain insights into the molecular origin of the unusual behavior of these microgel solutions, we have combined nuclear magnetic resonance studies and molecular-level theoretical calculations of the system. A delicate balance between inter-particle steric compressions and intra-microgel physical interactions and chemical equilibria determines the size of these microgels. Both steric compression, due to finite density, and hydrogen bond formation in the interior of the microgels favors a more compact particle. On the contrary, at the pH of the experiments the acid-base equilibrium constrains the polymer charge to increase, which favors particle swelling due to intra-microgel electrostatic repulsions. This interplay between physical interactions and chemical equilibria occurring at the nanometer length-scale determines the unusual thermal-induced swelling of P(NIPAM-co-MAA) microgels.

Dynamic Light Scattering Investigation of Pnipam-Co-Maa Microgel Solution

Abstract The paper presents results of a study of the effect of the environment temperature and pH on the size of particles based on poly N (isopropylacrylamide) chain. The tested substance was the copolymer PNIPAM-co-MAA. The particle size measurements were performed by dynamic light scattering. It was found that the copolymer tested reacts specifically to temperature increase by shrinking more than two times. Important for stabilization of the structure are the chemical groups -COOH present in methacrylic acid that undergoes dissociation. Gradual increase in temperature results in a decrease in the dissociation constant, in binding of protons and thus causes shrinkage of the entire particle. It was also shown that PNIPAM-co-MAA in high concentrations undergoes crystallization.

Swelling Mechanism Investigation of Microgel with Double-Cross-Linking Structures

Microgel is a novel conformance control technology that can be injected into high permeability zones and transport into deep area through pore throats. It can efficiently plug large pores to force injection water diversion to achieve conformance control. In this paper, we synthesized the microgel with a double-cross-linking structure of non-labile and labile characteristics. Then, a polarizing microscope, laser particle analyzer, Brookfield DV-III, and atomic force microscopy (AFM) were used to investigate the swelling mechanism of the microgel in high-saline water (total dissolved solids is from 30 to 100 g/L) at 65 °C. Results show that the swelling ability of the double-cross-linking structure microgel is not sensitive to salinity and the solution viscosity can increase to a certain degree with the maximum value of 18 mPa s. The decomposition of labile cross-linker results in a loose and explosive structure, which seems like a “mushroom cloud”. Because of the high-density cross-linking sites provided by the non-labile cross-linker, the integrity of the spherical feature of the microgel was reserved after aging for 70 days. On the basis of the viscosity increase of microgel solution during the swelling process, a concept to develop a novel water shutoff agent is proposed. That is, the conventional cross-linkers, such as formaldehyde, methenamine, or phenolic or chromic salt, can be added to microgel solution during the injecting process. Thus, the cross-linker can have the potential to cross-link with the groups that released during the swelling process to form a bulk gel system, which can further improve the water shutoff performance.