Smart Microgels Research Articles

Nano-in-Micro Smart Hydrogel Composite for a Rapid Sensitive Immunoassay.

Immunoassays are an important tool in various bioanalytical settings, such as clinical diagnostics, biopharmaceutical analysis, environmental monitoring, and food testing. An enzyme-linked immunosorbent assay (ELISA) is usually used to amplify immunoassay signals; however, it requires labor-intensive and time-consuming procedures, which hinders its application to rapid cytokine detection. In this study, a nano-in-micro composite system, where immunosensing polystyrene beads (≈320 nm) are incorporated within a stimuli-responsive microgel matrix (≈40 µm) via microfluidics, is investigated. The intrinsic volume phase-transition change properties of the smart microgels allows an enzyme-free enhanced immunoassay, enabling instant enhancement in signal-to-noise ratios of ≈5-fold. This nano-in-micro hydrogel composite offers a simple yet highly effective method for sensitive and multiplexed cytokine analysis without complex enzyme-based signal amplification steps, greatly benefitting advanced immune medicine.

Non-ionic copolymer microgels as high-performance draw materials for forward osmosis desalination

Ionic thermo-responsive microgels have been recently developed as smart draw agents for forward osmosis (FO) desalination. Although ionic microgels are able to demonstrate high water flux, their water recovery performance is compromised due to strong hydration of ionic moieties. In this study, we design and explore various non-ionic thermo-responsive microgels as the FO draw materials. Among these microgels, the copolymer microgels of N-isopropylacrylamide and acrylamide show higher water recovery than ionic microgels, while maintaining high water flux, where the initial water flux and water recovery of the copolymer microgel with 5 wt% acrylamide reach 24.7 LMH and 78.7%. Hansen solubility parameter analysis is launched to theoretically elucidate the mechanism of non-ionic microgels as draw materials in FO operation. The prediction from solubility parameter analysis aligns well with experimental results. This work will guide us in the future development of high performance smart microgels as draw materials in FO desalination.

A Simple Device Based on Smart Hollow Microgels for Facile Detection of Trace Lead(II) Ions

A simple device, which is equipped with a non-woven fabric filter medium immobilized with ion-recognizable smart hollow microgels, is developed for facile detection of trace lead(II) ions (Pb2+ ). The ion-recognizable smart microgels are made of poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (PNB), in which the 18-crown-6 groups act as the sensors of Pb2+ and the N-isopropylacrylamide groups act as the actuators. The PNB hollow microgels can isothermally change from a shrunk state to a swollen state in response to recognizing Pb2+ in the aqueous environment due to the electrostatic repulsion among the charged 18-crown-6/Pb2+ complex groups and the enhancement of hydrophilicity of the microgels. Due to the hollow structures, the PNB microgels show remarkable isothermal swelling ratio. Thus, the flux of solution pass through the non-woven fabric filter medium decreases significantly because of the remarkable reduction in the space for liquid flowing upon recognizing Pb2+ . The Pb2+ concentration can be detected quantitatively by simply and easily measuring the change of solution flux using the proposed device, which is operated without external power supply or spectroscopic measurements. The strategy proposed in this study provides a promising method for facile detection of trace Pb2+ in aqueous environments.

Stimuli-Responsive Microgels and Microgel-Based Systems: Advances in the Exploitation of Microgel Colloidal Properties and Their Interfacial Activity.

In this paper, recent developments in the chemical design of functional microgels are summarized. A wide range of available synthetic methods allows the incorporation of various reactive groups, charges, or biological markers inside the microgel network, thus controlling the deformation and swelling degree of the resulting smart microgels. These microgels can respond to various stimuli, such as temperature, pH, light, electric field, etc. and can show unique deformation behavior at the interface. Due to their switchability and interfacial properties, these smart microgels are being extensively explored for various applications, such as antifouling coatings, cell encapsulation, catalysis, controlled drug delivery, and tissue engineering.

Role of Anionic Surfactants in the Synthesis of Smart Microgels Based on Different Acrylamides.

We investigated the influence of two anionic surfactants, namely, sodium dodecyl sulfate and sodium decyl sulfate, on acrylamide-based microgels consisting of N-n-propylacrylamide. In this context, the main focus was on the influence of surfactant addition on the size of the microgels. The surfactant was added to the reaction mixture before or during the polymerization at different points in time. Microgels were characterized via photon correlation spectroscopy and atomic force microscopy. All results were compared to those for other more common acrylamide-based microgels consisting of N-isopropylacrylamide and N-isopropylmethacrylamide. A significant difference between the three microgels and a strong dependence on the surface activity of the surfactant was found.

Ultrasensitive microchip based on smart microgel for real-time online detection of trace threat analytes

Real-time online detection of trace threat analytes is critical for global sustainability, whereas the key challenge is how to efficiently convert and amplify analyte signals into simple readouts. Here we report an ultrasensitive microfluidic platform incorporated with smart microgel for real-time online detection of trace threat analytes. The microgel can swell responding to specific stimulus in flowing solution, resulting in efficient conversion of the stimulus signal into significantly amplified signal of flow-rate change; thus highly sensitive, fast, and selective detection can be achieved. We demonstrate this by incorporating ion-recognizable microgel for detecting trace Pb(2+), and connecting our platform with pipelines of tap water and wastewater for real-time online Pb(2+) detection to achieve timely pollution warning and terminating. This work provides a generalizable platform for incorporating myriad stimuli-responsive microgels to achieve ever-better performance for real-time online detection of various trace threat molecules, and may expand the scope of applications of detection techniques.

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.

In situ cross-linking of stimuli-responsive hemicellulose microgels during spray drying.

Chemical cross-linking during spray drying offers the potential for green fabrication of microgels with a rapid stimuli response and good blood compatibility and provides a platform for stimuli-responsive hemicellulose microgels (SRHMGs). The cross-linking reaction occurs rapidly in situ at elevated temperature during spray drying, enabling the production of microgels in a large scale within a few minutes. The SRHMGs with an average size range of ∼1–4 μm contain O-acetyl-galactoglucomannan as a matrix and poly(acrylic acid), aniline pentamer (AP), and iron as functional additives, which are responsive to external changes in pH, electrochemical stimuli, magnetic field, or dual-stimuli. The surface morphologies, chemical compositions, charge, pH, and mechanical properties of these smart microgels were evaluated using scanning electron microscopy, IR, zeta potential measurements, pH evaluation, and quantitative nanomechanical mapping, respectively. Different oxidation states were observed when AP was introduced, as confirmed by UV spectroscopy and cyclic voltammetry. Systematic blood compatibility evaluations revealed that the SRHMGs have good blood compatibility. This bottom-up strategy to synthesize SRHMGs enables a new route to the production of smart microgels for biomedical applications.

Enhanced activity of acetyl CoA synthetase adsorbed on smart microgel: an implication for precursor biosynthesis.

Acetyl coenzyme A (acetyl CoA) is an essential precursor molecule for synthesis of metabolites such as the polyketide-based drugs (tetracycline, mitharamycin, Zocor, etc.) fats, lipids, and cholesterol. Acetyl CoA synthetase (Acs) is one of the enzymes that catalyzes acetyl CoA synthesis, and this enzyme is essentially employed for continuous supply of the acetyl CoA for the production of these metabolites. To achieve reusable and a more robust entity of the enzyme, we carried out the immobilization of Acs on poly(N-isopropylacrylamide)-poly(ethylenimine) (PNIPAm-PEI) microgels via adsorption. Cationic PNIPAm-PEI microgel was synthesized by one-step graft copolymerization of NIPAm and N,N-methylene bis-acrylamide (MBA) from PEI. Adsorption studies of Acs on microgel indicated high binding of enzymes, with a maximum binding capacity of 286 μg/mg of microgel for Acs was achieved. The immobilized enzymes showed improved biocatalytic efficiency over free enzymes, beside this, the reaction parameters and circular dichroism (CD) spectroscopy studies indicated no significant changes in the enzyme structure after immobilization. This thoroughly characterized enzyme bioconjugate was further immobilized on an ultrathin membrane to assess the same reaction in flow through condition. Bioconjugate was covalently immobilized on a thin layer of preformed microgel support upon polyethylene terephthalate (PET) track etched membrane. The prepared membrane was used in a dead end filtration device to monitor the bioconversion efficiency and operational stability of cross-linked bioconjugate. The membrane reactor showed consistent operational stability and maintained >70% of initial activity after 7 consecutive operation cycles.

Construction of a smart microgel glutathione peroxidase mimic based on supramolecular self-assembly.

In an effort to construct smart artificial glutathione peroxidase (GPx) featuring high catalytic activity in an efficient preparation process, an artificial microgel GPx (PPAM-ADA-Te) has been prepared using a supramolecular host-guest self-assembly technique. Herein, 6,6'-telluro-bis(6-deoxy-β-cyclodextrin) (CD-Te-CD) was selected as a tellurium-containing host molecule, which also served as the crosslinker for the scaffold of the supramolecular microgel. And an adamantane-containing block copolymer (PPAM-ADA) was designed and synthesized as a guest building block copolymer. Subsequently, PPAM-ADA-Te was constructed through the self-assembly of CD-Te-CD and PPAM-ADA. The formation of this self-assembled construct was confirmed by dynamic light scattering, NMR, SEM and TEM. Notably, PPAM-ADA-Te not only exhibits a significant temperature responsive catalytic activity, but also features the characteristic saturation kinetics behaviour similar to that of a natural enzyme catalyst. We demonstrate in this paper that both the hydrophobic microenvironment and the crosslinker in this supramolecular microgel network played significant roles in enhancing and altering the temperature responsive catalytic behaviour. The successful construction of PPAM-ADA-Te not only provides a novel method for the preparation of microgel artificial GPx with high catalytic activity but also provides properties suitable for the future development of intelligent antioxidant drugs.

Preparation of Cu(II)-Imprinted Smart Microgels for Selective Separation of Copper Ions

In this study, we demonstrate a new kind of surface imprinted smart polymer by using methacrylic acid (MAA) as function monomer, attapulgite as the support material, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, and 2, 2’-azobisisobutyronitrile (AIBN) as initiator to prepare Cu(II)-imprinted microgels. The results showed that the prepared imprinted microgels have a high affinity for Cu2+ over Ca2+ and Mg2+, and the adsorption equilibrium data fitted Freundlich isotherm model well. In addition, Cu(II)-imprinted smart microgels had pH sensitivity to control the selection recognition property. Besides, It is suggested that the Cu(II)-imprinted microgels was a material that was efficient, low-cost, and could be reused five times with about 15% regeneration loss.

Microgel-Based Adaptive Hybrid Capsules with Tunable Shell Permeability

In the present work, we demonstrate the preparation of adaptive hybrid capsules with microgel/SiO2 composite walls. During the first stage of the capsule synthesis process, microgel particles stabilize the oil droplets in water and become self-assembled on the oil/water interface. At the second stage, microgels are subsequently glued by the sol–gel reaction of a silica precursor-hyperbranched polyethoxysiloxane (PEOS) which occurs at the oil/water interface. Consequently, hybrid capsules consisting of silica shell with embedded microgels are obtained. Responsive microgels present in the capsule wall act as transportation channels for different encapsulated materials. The use of smart microgels allows us to design capsules with controlled size, morphology, and wall permeability able to operate in both water and organic solvents.

Control of colloidal interactions between microgels with stimulus‐responsive properties

ABSTRACTMicrogels can switch their chemical/physical properties with external stimulus, and the colloidal behavior of microgels is strongly affected by interparticle interactions. In this article, we introduce smart microgels, focusing on Janus microgels and oscillating microgels developed by our group. Janus microgels show anisotropic shape and chemical/physical properties, and thus the structures of their flocs are also anisotropic. Oscillating microgels show autonomous swelling/deswelling and dispersing/flocculating oscillations through synchronization with chemical reactions. The interparticle interactions of these microgels are discussed. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3021–3026

Encapsulated nanodiamonds in smart microgels toward self-assembled diamond nanoarrays

We report on the successful attempt to synthesize thermoresponsive nanodiamonds hybrid microgels through a straightforward method. Resulting microgels exhibit smart properties, as the reversible collapsing of the structures when raising the temperature, with embedded nanodiamonds. Thanks to the colloidal and smart properties of the microgels, nanoscaled 2D self-assembled arrays of nanodiamonds with varying inter-particle distances were realized, without any lithographic processes, as an illustration of the promising properties of these novel diamond-based microgels. Such assemblies can constitute a first step toward a bottom–up elaboration of innovative diamond-based devices.

Multifunctionality in metal@microgel colloidal nanocomposites

The integration of metal nanoparticles within crosslinked polymeric microgels, in a well-defined core–shell structure, offers unique possibilities in various fields due to the potential to introduce multiple functionalities by tailoring the properties of the inorganic and the organic components. This Highlight describes recent developments related to hybrid nanocomposites comprising a metal core and a smart microgel shell. Different synthesis approaches for the preparation of such hybrid systems are described, including not only surface-initiated polymerization, but also in situ chemical reactions for core optimization and functionality addition. The main properties derived from the multifunctionality of these nanocomposites are also addressed and potential applications in the fields of catalysis and sensing are presented.

Microgel‐Stabilized Smart Emulsions for Biocatalysis

Emulsions stabilized by stimuli-responsive microgels were used to perform enzyme catalysis. Many substrates are poorly water-soluble, while enzymes naturally require aqueous environments, thus resulting in a two-phase aqueous-organic system. Smart microgels allow an enzyme-catalyzed reaction to be performed in an emulsion that can be broken under controlled conditions to separate the reaction product and to recycle the enzyme (E) and the microgel.

Tuning drug release from smart microgel–hydrogel composites via cross-linking

Soft nanocomposite hydrogels consisting of thermoresponsive microgels physically entrapped or covalently cross-linked to a non-thermoresponsive hydrogel are synthesized and tested for their capacity to facilitate long-term drug release of a small molecule drug. Copolymer microgels based on N-isopropylacrylamide and acrylic acid were synthesized that exhibited ionic affinity for binding to bupivacaine, a cationic local anesthetic. These microgels were subsequently physically entrapped within an in situ-gelling carbohydrate-based hydrogel network cross-linked via hydrazide–aldehyde chemistry; alternately, hydrazide-functionalized microgels were prepared that covalently cross-linked to the bulk hydrogel phase. Both the overall rate of drug release and the magnitude of the burst release were significantly decreased when microgels were restricted from undergoing a phase transition between the preparation temperature of the nanocomposite (25°C) and the test temperature (37°C), whether deswelling was inhibited by increasing the cross-link density within the microgel itself or by cross-linking the microgel to the bulk hydrogel network. This result facilitates facile tuning of soft nanocomposite drug delivery systems to achieve targeted drug release kinetics.

Non NIPAM Based Smart Microgels: Systematic Variation of the Volume Phase Transition Temperature by Copolymerization

Abstract Thermoresponsive copolymer microgels based on N-n-propylacrylamide (NNPAM) and N-isopropylmethacrylamide (NIPMAM) with varying compositions were synthesized via precipitation polymerization. Photon correlation spectroscopy (PCS) and turbidity measurements were used to investigate their volume phase transition. A linear correlation between the nominal composition and the volume phase transition temperature (VPTT) was observed. Furthermore, the hydrodynamic radii of the particles exhibit a linear dependency on the nominal composition. The presented system is suitable for the synthesis of thermoresponsive microgels with a well defined VPTT or size and gives access to tune these two crucial parameters in a systematic and controlled way by simply choosing the right composition of the monomer feed. Additionally, the first derivatives of the swelling curves obtained from turbidity measurements were analyzed in detail, allowing a quantitative comparison of the phase transition of different microgels.

Tuning Smart Microgel Swelling and Responsive Behavior through Strong and Weak Polyelectrolyte Pair Assembly

The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.

Novel thermo- and pH-responsive hydroxypropyl cellulose- and poly (l-glutamic acid)-based microgels for oral insulin controlled release

Novel smart microgel particles made of poly (l-glutamic acid-2-hydroxylethyl methacrylate) (PGH) and hydroxypropyl cellulose-acrylic acid (HPC-AA) have been successfully prepared via emulsion polymerization. The dynamic light scattering measurement reveals that the average hydrodynamic radius 〈Rh〉 and hydrodynamic radius distributions f (Rh) of the microgel particles depend on the temperature and pH value thus the microgel particles exhibit both pH- and temperature-sensitivity. In vitro release study shows that the amount of insulin released from microgels in the gastric juice (at pH 1.2) is significantly less than that in the intestinal fluid (at pH 6.8). These results indicate that the resultant microgels are of potential for use in intelligent oral drug delivery systems.