Polymer macrogels that can undergo rapid and significant volume changes in response to an external stimulus, such as a fluctuation in blood glucose concentration, are critical for their versatility. We report here such a polymer macrogel, which is made of a highly-ordered array of poly(phenylboronic acid) microgels tethered chemically to bridging polymers (a thin hydrogel matrix). This unique microstructure makes the newly developed macrogels exhibit a rapid response rate and extraordinarily large responsive swelling ratio upon adding glucose into the bathing medium over a glucose concentration range of 0–30 mM at a physiological pH of 7.4. While the macrogels can swell (e.g., the weight of the macrogels increases by ca. 310-fold if the glucose concentration in the bathing medium increases from 0 to 30.0 mM) and reach stability shortly (reach ∼99% of the maximum change within 90 s) after increasing glucose concentration from 0 to a concentration in the 150.0 μM to 30.0 mM range, the volume changes of the macrogels can be fully reversible within the experimental error even after twenty cycles of adding/removing glucose. The macrogels in this extremely expanded state were somewhat flowable, allowing their use as injectable glucose-sensing materials. With the macrogels as carriers, in vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations, and in vivo studies revealed that these formulations may improve glucose control in streptozotocin-induced diabetic mice subcutaneously administered with the insulin-loaded macrogels.

Immobilization of sulfur in microgels is achieved via free radical polymerization of commercial poly(ethylene glycol) dimethacrylate in the solution of sulfur-terminated poly(3-oligo(ethylene oxide)4-thiophene), a copolymer prepared by the inverse vulcanization of S8 with allyl-terminated poly(3-oligo(ethylene oxide)4-thiophene). This microgelation leads to enhanced Li–S battery performance over the sulfur-terminated polymer.

We report a class of poly(anionic liquid) microgels that undergo stimuli-responsive volume phase transitions. Such a microgel is synthesized by free radical precipitation polymerization of a tetrabutylphosphonium 4-styrenesulfonate monomer and a cross-linker N,N’-methylenebisacrylamide. These microgels can not only undergo reversible volume phase transitions in response to changes in temperature in water, methanol, or water/methanol mixtures, but also undergo re-entrant swelling–shrinking–swelling transitions as the methanol content increases in water/methanol mixtures at a set temperature in our experimental temperature window of 25.0–64.0 °C. Such microgels can be post functionalized, e.g., via ion-exchange treatment with HSO3CF3 to partially transform sulfonate to the catalytic Brønsted acidic –SO3H, whilst the yielded microgels can inherit the responsive properties. With both responsive and catalytic properties simultaneously harnessed on the same object, the functionalized microgels potentially can be used as a highly efficient catalyst for the esterification reaction of palmitic acid and the transesterification reaction of tripalmitin with methanol (as model reactions) at 65.0 °C (temperature of an oil bath), and allow the catalytic activity to be modulated to a certain extent in a non-monotonous way, making it possible to boost the reactions at a relatively lower temperature (e.g., 42.0 °C), while maintaining considerable catalytic activity. These features underlie the feasible use of the microgels in biodiesel production (with waste cooking oil as a model feedstock).

Glucose-responsive polymer microgels that can undergo highly selective, reversible, and rapid volume phase transitions in response to fluctuations in blood glucose concentration have the potential to regulate insulin delivery to improve patient compliance and health. Herein, we report such a glucose-responsive polymer microgel, which is made of a representative apo-enzyme, apo-glucose oxidase (apo-GOx), interpenetrated in a chemically-crosslinked network of poly(N-isopropylacrylamide) (pNIPAM). Introduction of apo-GOx into the pNIPAM network made the newly developed semi-interpenetrating-structured microgels responsive with high selectivity to glucose over a glucose concentration range of 0–20 mM at a physiological pH value of 7.4. While the microgels could swell and reach stability shortly (<1 s) after adding glucose over a concentration range of 50.0 μM–20.0 mM, the changes in the average hydrodynamic diameter and the size distribution of the microgels could be fully reversible within experimental error even after twenty cycles of adding/removing glucose. The association rate constant was determined to be ca. 1.0 mM−1 s−1 with a ca. 10.1 s−1 dissociation rate constant, indicating a fast reversible time response to the glucose concentration change of the microgels. With the microgels as carriers, in vitro insulin release could be modulated in a pulsatile profile in response to glucose concentrations, and in vivo studies revealed that these formulations may improve glucose control in streptozotocin-induced diabetic mice subcutaneously administered with the insulin loaded microgels.

A class of smart composite materials based on the assembly of conjugated polymers on responsive polymer microgels has been prepared. We have chosen poly(3-((2-(2-methoxyethoxy)ethoxy)methyl)-thiophene) as the model conjugated polymer and an ammonia-responsive microgel of phenoxazinium-functionalized poly(N-isopropylacrylamide-co-propargyl acrylate) as the model template. Under this design, the composite materials can combine the electrical conductivity of the conjugated polymers and the ammonia recognisability of the ammonia-responsive polymer microgels; the cooperation of these properties allows the reversible control of electrical conductivity by ammonia gas. Those composite materials can not only adapt to ammonia gas, but also convert changes in the concentration of ammonia into conductance, allowing the electrical detection of ammonia gas with high selectivity. This makes the composite materials different from the conductive polymer platforms reported previously, which may also respond to non-ammonia gases and the response induced by non-ammonia gases is close to that induced by ammonia gas. Using these composite materials as sensing materials for the electrical detection of ammonia gas, the detection limit can reach as low as 1.1 ppb. These features enable their use for the electrical detection of ammonia in breath.

The catalytic activity of Au nanoparticles in phenylboronic acid-containing polymer microgels can be tuned through the swelling–deswelling transition of the microgels in response to changes in glucose concentration. Upon adding glucose, the model catalytic reduction of hydrophilic 4-nitrophenol is accelerated, while the reduction of relatively more hydrophobic nitrobenzene slows down.

A cellulose-based microgel, where an individual microgel contains approximately one cellulose chain on average, is synthesized via free radical polymerization of a difunctional small-molecule N,N′-methylenebisacrylamide in cellulose solution. This microgelation leads to a low-ordered cellulose, favoring enzymatic hydrolysis of cellulose to generate glucose.

We report a type of polymer microgel that undergoes rapid, reversible, and highly sensitive volume phase transitions upon varying ammonia concentrations in milieu. Such an ammonia-responsive microgel is made by tethering of a phenoxazinium, N-(5-(3-azidopropylamino)-9H-benzo[a]-phenoxazin-9-ylidene)-N-methylmethanaminium chloride, to the network chains of poly(N-isopropylacrylamide-co-propargyl acrylate) via a copper(I)-catalyzed azide–alkene cycloaddition. Tethering of the ammonia-recognizable phenoxazinium onto the polymer network chains makes the microgels responsive to ammonia. While a fast (<0.1 s) and stable shrinkage of the microgels can be achieved upon addition of ammonia over a clinically relevant range (0.25–2.9 ppm), the microgels can convert the elevated concentrations of the solution/gas-phase ammonia into enhanced photoluminescence signals. This makes the microgels different from the phenoxazinium, or its analogs reported in previous studies, that exhibit ammonia-induced quenching of photoluminescence. With the microgels as probes, the detection limit was ca. 7.3 × 10−2 and 3.9 ppb for the solution and the gas-phase ammonia, respectively. These features enable “turn-on” photoluminescence detection of ammonia in breath.

We develop a class of poly(phenylboronic acid) microgels, which are made of 3-aminophenylboronic acid covalently bonded to oligo(ethylene glycol)-based polymers, to demonstrate the feasibility of on-site tailoring of the glucose-responsive volume phase transition behavior of poly(phenylboronic acid) gels. Different from the poly(phenylboronic acid) gels reported previously that typically undergo a fixed type (swelling and/or shrinking) of glucose-responsive volume phase transition behavior, the presented microgels can display switchable behavior upon adding glucose: shrinking (at temperature ≤29.0 °C), unresponsive (29.0–33.0 °C), and swelling (≥33.0 °C). The underlying mechanism for such an on-site tailoring is possibly associated with a competition of glucose-induced increase in the Donnan potential (favoring swelling; due to the formation of glucose-boronates or glucose-bis-boronates) and additional cross-links (favoring shrinking; due to the formation of glucose-bis-boronates) at a particular temperature. Accompanied by this on-site tailoring, the photoluminescence of the microgels can be tuned from “turn-off” (e.g., at 25.0 °C) to “turn-on” (e.g., at 37.0 °C) upon adding glucose, which may provide a functional basis for biosensors for prospective biomedical applications.

We describe an electrochemical approach for the synthesis of polymer microgels through polymerization of the monomer in the presence of the crosslinker. This electrochemical approach means initiation by the electron transfer processes which occur at the electrodes, in that by controlling the applied potential it is possible to control the generation of free radicals and/or other reactive species. Upon applying a suitable potential above the electrochemical oxidation waves of N-isopropylacrylamide (as a model of the monomer) and N,N′-methylenebisacrylamide (as a model of the crosslinker), the polymerization and crosslinking are able to proceed to obtain nearly monodisperse polymer microgels with high yield. The apparent rate constant was determined to be 1.69 × 10−2 min−1 based on the evolution of light scattering intensity, or 1.43 × 10−2 min−1 based on the average hydrodynamic diameter. The underlying formation mechanism to reach polymer microgels instead of macrogels, even at high monomer concentrations, is possibly due to the limitation of the primary chain length such that bridging between growing microgel regions can be eliminated. The microgel size can be tuned by varying the applied potential. The reaction medium can be recycled, and reused directly without a notable impact on the next cycle of synthesis. This electrochemical approach can be extended to synthesize microgels of poly(acrylamide) or poly(acrylic acid) (as the additional models).

A solid polymer electrolyte exhibiting high ionic conductivity (reaching ca. 10−4.8 S cm−1 at 25 °C) is fabricated using ion containing polymer microgels of lithium tris(perfluorophenyl) (2,3,5,6-tetrafluoro-4-(2-(2-(vinyloxy)ethoxy)ethoxy)phenyl) borate. This solid polymer electrolyte shows great possibilities for use in large-capacity lithium ion batteries.

The simultaneous modulation and monitoring of catalysis is possible when using metal@polymer hybrid microgels by rational design. Such hybrid microgels are made of Au nanoparticles covered with a temperature and pH dual-responsive copolymer gel shell of poly(N-isopropylacrylamide-co-allylamine). The Au nanoparticle cores can act as catalysts in a model electron-transfer reaction between hexacyanoferrate(III) and borohydride ions. The introduction of a smart polymer gel shell onto the Au nanoparticles can not only allow modulation of the catalysis of the Au nanoparticle cores through varying the solution temperature, but also allow label-free in situ localized surface plasmon resonance (LSPR) monitoring of the kinetics and thermodynamics of the catalyzed chemical reaction. Unlike conventional spectroscopic methods that only reflect the overall information occurring in the reaction system, the label-free in situ LSPR monitoring gives local information occurring on the catalytic surface and therefore has the potential to advance our understanding of the catalyzed chemical reaction.

Copper has been immobilized on a chitosan-based responsive polymer microgel by simply stirring the microgel dispersion with copper sulfate. The ensuing catalyst is highly active for a model azide-alkyne [3+2]-cycloaddition reaction, and can be recycled at least 5 times; the catalytic activity can be tuned via swelling–deswelling transitions of the polymer gels.

Glucose-responsive polymer nanogels that can undergo a reversible and rapid volume phase transition in response to the fluctuation in blood glucose concentration have the potential to regulate the delivery of insulin mimicking pancreatic activity. We report here such a glucose-responsive polymer nanogel, which is made of concanavalin A (ConA) interpenetrated in a chemically crosslinked network of poly(N-isopropylacrylamide) (poly(NIPAM)). The introduction of ConA, a plant lectin protein, into the poly(NIPAM) network makes the newly developed semi-interpenetrating-structured nanogels responsive to glucose over a glucose concentration range of 0–20 mM at a physiological pH of 7.4. While the nanogels can swell and become stable shortly (<1 s) after adding glucose over a concentration range of 50.0 μM to 20.0 mM, the changes in the average hydrodynamic radius and the size distribution of the nanogels can be fully reversible within the experimental error even after ten cycles of adding/removing glucose. The association rate constant is determined to be ca. 1.8 mM−1 s−1, and the dissociation rate constant is ca. 7.5 s−1, indicating a fast reversible time response to the glucose concentration change of the nanogels. Moreover, in vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations.

We report a type of polymer microgel that can undergo a rapid and highly sensitive volume change upon adding H2O2. Such a H2O2-sensitive microgel is made of dextran–tyramine and horseradish peroxidase (HRP), which are interpenetrated in chemically cross-linked gel networks of poly(oligo(ethylene glycol) methacrylates). Unlike the H2O2-sensitive microgels reported in previous arts that typically involve degradation processes related to H2O2-induced cleavability of specific bonds, the proposed microgels can shrink upon adding H2O2 owing to the HRP-catalyzed coupling reaction of tyramine residues via decomposition of H2O2. While a fast (<10 s) and stable shrinkage of the microgels can be reached upon adding H2O2 over a concentration range 50.0 μM–1.0 mM, the response time can be modulated by the dispersion temperature in a nonmonotonous way over 10–38 °C. With the microgels as probes, the H2O2 detection limit was approximately 6.8 μM. In a combined use of the microgels with glucose oxidase for glucose detection, the glucose detection limit was approximately 83.1 μM.

The selective response to glucose is possible by using a poly(phenylboronic acid) microgel under a rational design. Such a microgel is made of graphene covalently immobilized in a microgel of poly(4-vinylphenylboronic acid) cross-linked with N,N′-methylenebis(acrylamide). Unlike the microgels reported in previous arts that would undergo volume phase transition in response to both glucose and other monosaccharides, the proposed microgels shrink upon adding glucose, whereas keep unchanged in the size upon adding other monosaccharides (with fructose, galactose, and mannose as models). Although the polysaccharides/glycoproteins (with dextran and Ribonuclease B as models) that contain many glycosyl residues can slightly absorb on the microgel surface and lead to a small impact on glucose-response, it can be addressed by further coating the microgel as a core with a thin nonglucose-responsive poly(N-isopropylacrylamide) gel shell. This selectively glucose-responsive volume phase transition behavior enables “turn-on” photoluminescence detection of glucose in blood serum (a model for complex biosystems).

•The 5-amino-2-fluorophenylboronic acid modified silver nanoparticles (FPBA-AgNPs) were employed for colorimetric dynamic analysis of glucose.•Highly modulating, sensitive, and selective sensing of glucose is realized via glucose-modulated assembly of the FPBA-AgNPs.•Glucose-modulated assembly of the FPBA-AgNPs occurred by the bridged binding of a glucose molecule to two FPBA-AgNPs.•The glucose level variations associated with a biological reaction were monitored by using the FPBA-AgNPs, without altering the reaction mechanism.The development of advanced nanostructures that allow dynamic quantification of glucose level can contribute to tight glucose control in diabetes management and other medical/biological fields. In this paper, we demonstrated that the assemblies of the 5-amino-2-fluorophenylboronic acid modified silver nanoparticles (FPBA-AgNPs) can be employed for highly modulating, sensitive, and selective colorimetric sensing of glucose over a physiologically important concentration range of 0–20 mM at a physiological pH of 7.4. The glucose-modulated assembly of the FPBA-AgNPs occurred by the regulable formation of interparticle linkages via the bridged binding of 1,2-cis-diols and 5,6-cis-diols (for furanose form; or 4,6-cis-diols for pyranose form), respectively, of a glucose molecule to two FPBA-AgNPs. The detection limit was 89.0 μM. The mean error of glucose detection in a macro-bio-system, blood serum of adult, was smaller than 10%. Furthermore, we show that the glucose level variations associated with a model biological reaction process can be monitored by using the FPBA-AgNPs, whilst with the reaction mechanism remaining nearly unchanged.

A strategy involving free radical copolymerization of a difunctional oligomer and a small-molecule crosslinker to give sub-10 nm nanogels is proposed. These nanogels can adapt to surrounding temperatures and regulate the release of a preloaded model anticancer drug 5-fluorouracil.

The development of embeddable and remotely interrogatable nanomaterials that allow dynamic quantification of intracellular glucose levels can contribute to a better understanding of physiology. We develop a fluorescent hybrid nanogel glucometer (FNG) that is applicable for intracellular glucometry. Such a FNG (<200 nm) is comprised of ZnO quantum dots covalently bonded onto a loosely-crosslinked gel network of poly(acrylamide), which is interpenetrated in another relatively highly-crosslinked gel network of poly(N-isopropylacrylamide-co-2-acrylamidomethyl-5-fluorophenylboronic acid). This newly developed double-network-structured FNG can adapt to surrounding media of varying glucose levels, and convert the disruptions in homeostasis of glucose level with high reversibility, sensitivity, and selectivity into fluorescence signals at a fast time response. We demonstrate that the FNG can enter the model B16F10 cells and employ the signal transduction ability for fluorescent intracellular glucometry. Furthermore, we show that intracellular glucose level variations associated with a model biological reaction process can be monitored with a high glucose resolution by using the FNG embedded in cells, whilst the reaction mechanism remains nearly unchanged.

Noninvasive monitoring of glucose in tears is highly desirable in tight glucose control. The polymerized crystalline colloidal array (PCCA) that can be incorporated into contact lens represents one of the most promising materials for noninvasive monitoring of glucose in tears. However, low sensitivity and slow time response of the PCCA reported in previous arts has limited its clinical utility. This paper presents a new PCCA, denoted as NIR–PCCA, comprising a CCA of glucose-responsive sub-micrometered poly(styrene-co-acrylamide-co-3-acrylamidophenylboronic acid) microgels embedded within a slightly positive charged hydrogel matrix of poly(acrylamide-co-2-(dimethylamino)ethyl acrylate). This newly designed NIR–PCCA can reflect near-infrared (NIR) light, whose intensity (at 1722 nm) would decrease evidently with increasing glucose concentration over the physiologically relevant range in tears. The lowest glucose concentration reliably detectable was as low as ca. 6.1 μg/dL. The characteristic response time τsensing was 22.1±0.2 s when adding glucose to 7.5 mg/dL, and the higher the glucose concentration is, the faster the time response. Such a rationally designed NIR–PCCA is well suited for ratiometric NIR sensing of tear glucose under physiological conditions, thereby likely to bring this promising glucose-sensing material to the forefront of analytical devices for diabetes.

Responsive catalytic hybrid nanogels with Au nanoparticle cores and a polyvinylpyrrolidone (PVP) based gel shell are prepared through a novel one-pot approach. The embedded Au nanoparticles demonstrate both a pH-modulated catalytic activity and anti-aggregation properties upon recycling.

Immobilization of sulfur in microgels is achieved via free radical polymerization of commercial poly(ethylene glycol) dimethacrylate in the solution of sulfur-terminated poly(3-oligo(ethylene oxide)4-thiophene), a copolymer prepared by the inverse vulcanization of S8 with allyl-terminated poly(3-oligo(ethylene oxide)4-thiophene). This microgelation leads to enhanced Li–S battery performance over the sulfur-terminated polymer.

The simultaneous modulation and monitoring of catalysis is possible when using metal@polymer hybrid microgels by rational design. Such hybrid microgels are made of Au nanoparticles covered with a temperature and pH dual-responsive copolymer gel shell of poly(N-isopropylacrylamide-co-allylamine). The Au nanoparticle cores can act as catalysts in a model electron-transfer reaction between hexacyanoferrate(III) and borohydride ions. The introduction of a smart polymer gel shell onto the Au nanoparticles can not only allow modulation of the catalysis of the Au nanoparticle cores through varying the solution temperature, but also allow label-free in situ localized surface plasmon resonance (LSPR) monitoring of the kinetics and thermodynamics of the catalyzed chemical reaction. Unlike conventional spectroscopic methods that only reflect the overall information occurring in the reaction system, the label-free in situ LSPR monitoring gives local information occurring on the catalytic surface and therefore has the potential to advance our understanding of the catalyzed chemical reaction.

Responsive catalytic hybrid nanogels with Au nanoparticle cores and a polyvinylpyrrolidone (PVP) based gel shell are prepared through a novel one-pot approach. The embedded Au nanoparticles demonstrate both a pH-modulated catalytic activity and anti-aggregation properties upon recycling.

A strategy involving free radical copolymerization of a difunctional oligomer and a small-molecule crosslinker to give sub-10 nm nanogels is proposed. These nanogels can adapt to surrounding temperatures and regulate the release of a preloaded model anticancer drug 5-fluorouracil.

Copper has been immobilized on a chitosan-based responsive polymer microgel by simply stirring the microgel dispersion with copper sulfate. The ensuing catalyst is highly active for a model azide-alkyne [3+2]-cycloaddition reaction, and can be recycled at least 5 times; the catalytic activity can be tuned via swelling–deswelling transitions of the polymer gels.

The catalytic activity of Au nanoparticles in phenylboronic acid-containing polymer microgels can be tuned through the swelling–deswelling transition of the microgels in response to changes in glucose concentration. Upon adding glucose, the model catalytic reduction of hydrophilic 4-nitrophenol is accelerated, while the reduction of relatively more hydrophobic nitrobenzene slows down.

A cellulose-based microgel, where an individual microgel contains approximately one cellulose chain on average, is synthesized via free radical polymerization of a difunctional small-molecule N,N′-methylenebisacrylamide in cellulose solution. This microgelation leads to a low-ordered cellulose, favoring enzymatic hydrolysis of cellulose to generate glucose.

The development of embeddable and remotely interrogatable nanomaterials that allow dynamic quantification of intracellular glucose levels can contribute to a better understanding of physiology. We develop a fluorescent hybrid nanogel glucometer (FNG) that is applicable for intracellular glucometry. Such a FNG (<200 nm) is comprised of ZnO quantum dots covalently bonded onto a loosely-crosslinked gel network of poly(acrylamide), which is interpenetrated in another relatively highly-crosslinked gel network of poly(N-isopropylacrylamide-co-2-acrylamidomethyl-5-fluorophenylboronic acid). This newly developed double-network-structured FNG can adapt to surrounding media of varying glucose levels, and convert the disruptions in homeostasis of glucose level with high reversibility, sensitivity, and selectivity into fluorescence signals at a fast time response. We demonstrate that the FNG can enter the model B16F10 cells and employ the signal transduction ability for fluorescent intracellular glucometry. Furthermore, we show that intracellular glucose level variations associated with a model biological reaction process can be monitored with a high glucose resolution by using the FNG embedded in cells, whilst the reaction mechanism remains nearly unchanged.