Temperature-jump investigations of the kinetics of hydrogel nanoparticle volume phase transitions.

The dynamics of the deswelling and swelling processes in thermoresponsive poly-N-isopropylacrylamide (pNIPAm) hydrogel nanoparticles have been studied by using time-resolved transmittance measurements, in combination with a nanosecond laser-induced temperature-jump (T-jump) technique. A decrease in the solution transmittance associated with deswelling of the particles has been observed as the solution temperature traverses the volume phase transition temperature of the particles. Upon inducing the T-jump, the deswelling transition only occurs in a small percentage (<10%) of the particle volume, which was found to be a thin periphery layer of the particles. The particle deswelling occurs on the microsecond time scale, and as shown previously, the collapse time can be tuned via adding small amounts of hydrophobic component to the particle shell. In contrast, the reswelling of the particles was thermodynamically controlled by bath equilibration, and only small differences in particle reswelling kinetics were found due to sluggish heat dissipation (millisecond time scale) from the sample cell.     

Photothermal patterning of microgel/gold nanoparticle composite colloidal crystals

We present a new method for laser direct writing in self-assembled hydrogel microparticle colloidal crystals via photothermal excitation of co-assembled colloidal Au particles. Close-packed colloidal crystals are assembled from approximately 224 nm diameter, thermoresponsive, poly-N-isopropylacrylamide hydrogel microparticles (microgels); these crystals display sharp Bragg diffraction peaks in the mid-visible region of the spectrum due to the periodic dielectric function of the assembly. Raising the temperature of the crystal above the characteristic volume phase transition temperature of the microgel particles results in a reversible melting of the crystalline material due to the particle-based deswelling event. This transition can be used either to anneal defects from the crystalline material or to controllably and reversibly convert the assembly from the colored, crystalline state to a nondiffracting glassy material. Crystal-to-glass transitions are similarly accomplished via photothermal excitation when 16 nm diameter colloidal Au particles are co-assembled with the responsive microgels. Excitation of the colloidal Au plasmon absorption with a frequency doubled Nd:YAG laser (lambda = 532 nm) results in optically directed conversion of either glasses to crystals or crystals to glasses, depending on the initial state of the assembly and the illumination time. These results represent a fundamentally new method for the patterning of self-assembled photonic materials.     

SUPERABSORBENCY AND VOLUME PHASE TRANSITION IN CROSSLINKED POLY[[3-(METHACRYLOYLAMINO)PROPYL]-TRIMETHYLAMMONIUM CHLORIDE] HYDROGELS†

Hydrogels of poly[[3-(methacrylolylamino) propyl]tri-methyl-ammon-ium chloride] (PMAPTAC) were synthesized by polymerizing an aqueous solution of [3-(methacryloyl-amino)propyl]-trimethylammonium chloride using N,N′-mehtylenebis(acrylamide) (Bis) as crosslinker. The swelling behavior of the hydrogel was monitored as a function of temperature, pH, and solvent composition. The hydrogel exhibits ampholytic behavior. Solvent induced volume phase transition (VPT) is observed in systems such as acetone-water and ethanol-water. The swelling kinetics conform to second order kinetics.

     

Dynamic Properties of Polyampholyte Hydrogel Elucidated by Proton NMR Spin-spin Relaxation Time

1H spin-spin relaxation time（T2） measurement of polyampholyte hydrogel poly（methylacrylic acidacryloyloxyethyl trimethylammonium chloride）[P（MA-DAC）] in different pH, ionic strength and temperature was carried out to reveal the molecular mobility. Spontaneous volume transition of the polyampholyte hydrogel was also investigated by spin-spin relaxation time measurement. Meanwhile T2 and the proton component fraction were acquired to study the swelling behaviour of the hydrogel. Moreover the changes of T2 characterized the molecular mo- bility of polyampholyte hydrogel in various swelling states. And the results suggest that the mobility of the main chains and a few free side chains（the long T2） of P（MA-DAC） was dominated by the mesh size in the hydrogel net- work, depending on the swelling ratio（Q） and the mobility of the side chains（the short T2） was influenced by electrostatic interaction between different charges in polymer side chains. Finally the T2 measurements of P（MA-DAC） hydrogel in the spontaneous swelling-deswelling process demonstrated the electrostatic interaction of the charged side chains caused deswelling behavior. At the same time, the mobility state transition temperature of the charged side chains was also studied by the lH spin-spin relaxation time measurements, and the transition activation energy of the side chains is 2.72 kJ.     

Influence of a crown ether comonomer on the temperature-induced phase transition of poly(N-isopropylacrylamide) hydrogels

Copolymerization of thermosensitive hydrogels based on poly(N-isopropylacrylamide) (PNIPA) is a possible route to enhanced storage capacity of guest molecules. This article describes the synthesis of the amphiphilic crown ether N9-propenoyl-3,6,12,15-tetraoxa-9,21-diazabicyclo[15.3.1]heneicosa-1(21),17,19-triene (CE) and its incorporation into a PNIPA hydrogel (PNIPA/CE). Mechanical measurements on the gel show that the CE units contribute to the elasticity of the network, but the swelling ratio in water is reduced compared to the unmodified system. The comonomer reduces the temperature of the volume phase transition (VPT), TVPT, and broadens the transition. Both the enthalpy and the entropy associated with the VPT decrease. Scattering measurements indicate that the local structural features on the scale of 10 A are unchanged, but the CE units form large clusters, the size of which increases with rising temperature. In the phase-separated state above TVPT these clusters are distributed on the polymer-water interface.     

In-situ atomic force microscopy (AFM) imaging: influence of AFM probe geometry on diffusion to microscopic surfaces

The effect of AFM probe geometry on diffusion to micrometer-scale reactive (electrode) interfaces is considered. A disk-shaped substrate electrode was held at a potential to reduce a species of interest (aqueous Ru(NH 3) 6 (3+)) at a diffusion-controlled rate and the current response during AFM imaging provided information on local mass transport to the interface. This approach reveals how the AFM probe influences diffusion to a reactive surface, which is of importance in more clearly delineating the conditions under which in-situ AFM can be treated as a noninvasive probe of surface processes involving mass transport (e.g., electrode reactions and crystal dissolution and growth). An assessment has been made of three types of probes: V-shaped silicon nitride contact mode probes; single beam silicon probes; and batch-fabricated scanning electrochemical-atomic force microscopy (SECM-AFM) probes. Two disk electrodes, (6.1 microm and 1.6 microm diameter) have been considered as substrates. The results indicate that conventional V-shaped contact mode probes are the most invasive and that the batch-fabricated SECM-AFM probes are the least invasive to diffusion at both of the substrates used herein. The experimental data are complemented by the development of simulations based on a simple 2D model of the AFM probe and active surface site. The importance of probe parameters such as the cantilever size, tip cone height, and cone angle is discussed, and the implications of the results for studies in other areas, such as growth and dissolution processes, are considered briefly.     

Interfacial nonradiative energy transfer in responsive core-shell hydrogel nanoparticles

Fluorescently labeled core-shell latex particles composed mainly of the thermoresponsive polymer poly-N-isopropylacrylamide (p-NIPAm) have been synthesized such that an energy transfer donor (phenanthrene) and an energy transfer acceptor (anthracene) are covalently localized in the core and shell, respectively. When the thermally induced particle deswelling is interrogated by photon correlation spectroscopy (PCS), a continuous (non-first order) phase transition is observed. Conversely, when the nonradiative energy transfer (NRET) efficiency is used to probe the collapse of these same particles, the phase transition event is observed to occur over a much smaller temperature range and approaches first-order (discontinuous) behavior. Furthermore, core-shell particles with differing shell thicknesses display identical phase transition temperatures when PCS is used to monitor the transition, while NRET measurements show a clear increase in collapse temperature as the shell thickness is increased. These apparently contradictory results are discussed in terms of a radial phase coexistence that exists in the microgel particles, which arises from a similarly radial inhomogeneity in the cross-linker concentration. The prospects for the NRET technique as a molecular-scale probe of nanostructured microgels are also discussed.     

Impact of Polymer Network Inhomogeneities on the Volume Phase Transition of Thermoresponsive Microgels

Thermoresponsive polymer gels exhibit pronounced swelling and deswelling upon changes in temperature, rendering them attractive for various applications. This transition has been studied extensively, but only little is known about how it is affected by nano‐ and micrometer‐scale inhomogeneities in the polymer gel network. In this work, droplet microfluidics is used to fabricate microgel particles of strongly varying inner homogeneity to study their volume phase behavior. These particles exhibit very similar equilibrium swelling and deswelling independent of their inner inhomogeneity, but the kinetics of their volume phase transition is markedly different: while gels with pronounced micrometer‐scale inhomogeneity show fast and affine deswelling, homogeneous gels shrink slowly and in multiple steps.     

Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels

The volume phase transition of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels depends in a complex way on the effective charge density within the polymer network. A series of monodisperse PNIPAM/AAc microgels with different content of acrylic acid were synthesized by surfactant-free emulsion polymerization employing sonication instead of a conventional stirring technique. Subsequently, the colloids were characterized by dynamic light scattering and electron microscopy. Potentiometric titrations provided the amount of carboxyl groups incorporated into the copolymer. The effective charge density was systematically controlled by the content of acrylic acid monomers, the pH value of the suspension, and the salt concentration. The hydrodynamic dimensions of the microgels have been measured by dynamic light scattering. The swelling/deswelling behavior is determined by the delicate balance between hydrophobic attraction of NIPAM and the repulsive electrostatic interactions of the carboxylate group of the acrylic acid moieties. Compared to their macroscopic counterparts the charged microgel particles show a significantly different swelling/deswelling behavior. This manifests in the occurrence of a two-step volume phase-transition process with increasing acrylic acid content. Hydrogen bonding has to be considered to understand this two step volume phase transition uniquely observed for colloidal microgels. Another interesting phenomenon presented here is the reversible formation of well-defined aggregates at low pH and under high salt conditions.     

Smart thermometer style sensor with volume readout and visualization for pH detection

A novel visual volume-type hydrogel sensor like thermometer for pH response was developed. The multifunctional stimuli-responsive fluorescent hydrogel was fabricated by employing 5, 6-dicarboxylic fluorescein crosslinked partially ammoniated polyacrylamide (PAM). The polymer hydrogel was characterized with fluorescent inverted microscope (FIM) and scanning electron microscope (SEM), as well as N₂ adsorption–desorption analysis. The polymer hydrogel emitted fluorescence and exhibited volume phase transition (VPT) in response to pH in aqueous solution. The intelligent response hydrogel was put into an elaborately altered shower-like pipette with uniform holes in which the water can pass through without the swelling hydrogel. A visual thermometer style hydrogel sensor combination of chemical reaction, separation and detection was designed. It was accurately measure the volume of hydrogel instead of the pH value when response to different pH solution by reading the graduation with naked eye. Therefore, the challenge for direct measurement of hydrogel volume was overcome. Meanwhile, a scale bar was also designed to indicate pH according to the volume. We can directly read the pH from the bar, similar to a thermometer in daily life. The volume-type sensor paves the way for VPT hydrogel sensors with convenience, visualization, low-cost, portable, smartness and ease of operation.     

Thermoresponsive behavior of poly(n-isopropylacrylamide) hydrogels containing gold nanostructures

We report the changes in the structure and thermoresponsive behavior of poly(N-isopropylacrylamide) (PNIPAm) hydrogels when gold nanostructures are synthesized in situ within the hydrogel matrix. Cross-linked PNIPAm hydrogels were synthesized using NIPAm and 0.00-3.50% (w/w versus NIPAm) of N,N'-methylenebisacrylamide (MBAm) and/or N,N'-cystaminebisacrylamide (CBAm) as cross-linking agents. The hydrogels were soaked in potassium tetrachloroaurate to introduce gold ions. The hydrogels containing Au3+ were then immersed in a sodium borohydride solution to reduce the gold ions. Infrared spectroscopy, UV-visible spectroscopy, and equilibrium swelling were used to examine the structural/physical differences between gels of different compositions; UV-visible spectroscopy and mass measurements were used to observe the kinetics and thermodynamics of the hydrogel volume phase transition. These studies revealed several differences in the physical characteristics and thermoresponsive behavior of hydrogels based on cross-linker identity and the presence or absence of gold nanostructures. Hydrogels with gold nanostructures and high CBAm and low MBAm content have equilibrium swelling masses 3-20 times their native analogues. In comparison, gold-containing hydrogels with high MBAm and low CBAm content have swelling masses that are equal to their native analogues. Additionally, the gold-containing PNIPAm hydrogels cross-linked with only CBAm have a deswelling temperature of approximately 40 degrees C, approximately 8 degrees C above the samples cross-linked with only MBAm. Varying the CBAm content and introducing gold enables tuning of the deswelling temperature.     

Unperturbed volume transition of thermosensitive poly-(N-isopropylacrylamide) microgel particles embedded in a hydrogel matrix

The thermoresponsive behavior of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in a covalently cross-linked polyacrylamide hydrogel matrix was investigated using ultraviolet-visible (UV-vis) spectroscopy, small-angle neutron scattering (SANS), and confocal laser scanning microscopy. The hydrogel synthesis was performed at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or fully collapsed PNiPAM microgel particles during the incorporation step. UV-vis spectroscopy experiments verify that the incorporation of thermosensitive microgels leads to temperature-sensitive optical properties of the composite materials. SANS measurements at different temperatures show that the thermosensitive swelling behavior of the PNiPAM microgels is fully retained in the composite material. Volume and structure criteria of the embedded microgel particles are compared to those of the free microgels in acrylamide solution. To visualize the temperature responsive behavior of larger PNiPAM particles, confocal fluorescence microscopy images of PNiPAM beads, of 40-microm size, were taken at two different temperatures. The micrographs also demonstrate the retained temperature sensitivity of the embedded microgels.     

Composite Hydrogels for Sustained Release of Therapeutic Agents

The goal of this research is to develop a composite hydrogel system for sustained release of therapeutic agents. The hydrogel composites were prepared by embedding drug‐loaded, biodegradable poly (DL‐lactide‐co‐glycolide) (PLGA) microparticles in semicrystalline hydrogels of polyvinyl alcohol (PVA). The gels were physically cross‐linked by the formation of the crystallites. The presence of the crystallites and the composite nature of the structure were confirmed by using differential scanning calorimetry and ATR‐FTIR spectroscopy. The distribution of microparticles in the hydrogel matrix was evaluated by using confocal laser scanning microscopy with coumarin‐6 as a fluorescence marker. The numbers of particles in the hydrogel matrix increased along the scanning depth, indicating uneven distribution. The release behavior of a model therapeutic agent, hydrocortisone, was evaluated, and the hydrogel composite system provided for better control of release than the microparticles and hydrogels alone. The addition of outer layers of PVA to the original single‐layer composite further reduced the initial burst effect from the microparticles and allowed for a linear release profile for greater than 1 month.     

Probing small unilamellar EggPC vesicles on mica surface by atomic force microscopy

Sonicated small unilamellar egg yolk phosphatidylcholine (EggPC) vesicles were investigated using atomic force microscopy (AFM) imaging and force measurements. Three different topographies (convex, planar, and concave shape) of the EggPC vesicles on the mica surface were observed by tapping mode in fluid, respectively. It was found that the topography change of the vesicles could be attributed to the interaction force between the AFM tip and vesicles. Force curves between an AFM tip and an unruptured vesicle were obtained in contact mode. During approach, two breaks corresponding to the abrupt penetration of upper and lower bilayer of vesicle were exhibited in the force curve. Both breaks spanned a distance of around 4 nm close to the EggPC bilayer thickness. Based on Hertz analysis of AFM approach force curves, the Young's modulus (E) and the bending modulus (kc) for pure EggPC vesicles were measured to be (1.97 +/- 0.75) x 10(6)Pa and (0.21 +/- 0.08) x 10(-19)J, respectively. The results show that the AFM can be used to obtain good images of intact and deformed vesicles by tapping mode, as well as to probe the integrity and bilayer structure of the vesicles. AFM force curve compare favorably with other methods to measure mechanical properties of soft samples with higher spatial resolution.     

Quantitative measurement of friction between single microspheres by friction force microscopy

The sliding friction between single silica microspheres was examined by applying friction force microscopy to probe the interaction between spherical silica particles glued to a tipless atomic force microscopy (AFM) cantilever and another particle glued to a glass slide. A three-dimensional model handling the complex contact geometry between spherical particles was established to compute friction and normal forces at the sliding interface from measured deflections of the AFM cantilever. Results obtained at different loads show a linear relationship between friction and normal force, with a friction coefficient of 0.4 between silica spheres. Friction in this system occurs at multi-asperity contacts. The results show that the macroscopic friction law of Amontons can be used to model the friction behavior of micrometer-sized granular matter. For plasma-treated silica particles, increased friction as well as wear could be observed during sliding.     

Direct functionalization of cell-adhesion promoters to hydrogel microparticles synthesized by stop-flow lithography

Polyethylene glycol (PEG) hydrogel microparticles generated via stop-flow lithography can be utilized for efficient microparticle-based cell culture processes because of their high biocompatibility, the molecular diffusion capability in the gel structure, and the tunability of their shape and size. However, the typical functionalization process of PEG microparticles with cell-adhesion promoters has inevitable limitations, requiring additional linker molecules and the preconjugation of linkers to cell-adhesion promoters and microparticles. In this study, a simple and direct cell-adhesion promoter functionalization process of the PEG microparticles is presented by use of aza-Michael reaction between remnant unreacted acrylate groups in particles and amine groups in cell-adhesion promoters. On the basis of proposed process, particles are directly conjugated with poly-l -lysine (PLL), a typical cell-adhesion promoter that can electrostatically interact with cellular membranes, in a controllable manner. We demonstrate enhanced cell-adhesion capabilities of the particles along with the increased amount of conjugated PLL in the particles. Furthermore, to validate extended applicability, the particles are directly conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides, in which RGD sequence is involved in the cell-adhesion behavior of extracellular matrix proteins, including fibronectin. The introduced GRGDS peptides increase the cell-adhesion capacity of the microparticles binding to integrin proteins in cellular membranes.     

Effect of Pore-Forming Agent Type on Swelling Properties of Macroporous Poly(N-[3-(dimethylaminopropyl)]-methacrylamide-co-acrylamide) Hydrogels

Macroporous poly(N-[3-(dimethylaminopropyl)]methacrylamide-co-acrylamide) [P(DMAPMA-co-AAm)] hydrogels were prepared by free-radical crosslinking copolymerization of corresponding monomers in water using two different pore-forming agents such as hydroxypropyl celluose (HPC) and poly(ethylene glycol) (PEG). The effect of these pore-forming agents on the volume phase transition temperature (VPT-T), interior morphology and swelling/deswelling kinetics of the P(DMAPMA-co-AAm) hydrogels was investigated. Scanning electron micrographs revealed that the interior network structure of the hydrogel matrix became more porous due to the presence of HPC or PEG pore-forming agents. The more porous matrix provided numerous water channels for water diffusion in or out of the matrix and, therefore, an improved response rate to the external stimuli. Particularly, due to its unique macroporous structure, the PEG-modified hydrogel showed a tremendously faster response to the external temperature changes during deswelling process and the swelling process at 22°C.     

Enhanced mechanical stability of microtubules polymerized with a slowly hydrolyzable nucleotide analogue

Atomic force microscopy (AFM) has been used to investigate the local mechanical and structural properties of microtubules polymerized using guanylyl-alpha-beta-methylene diphosphonate (GMPCPP), a slowly hydrolyzable analogue of guanosine triphosphate. Using a combination of AFM imaging and local force spectroscopy, GMPCPP-polymerized microtubules have been qualitatively and quantitatively compared to paclitaxel-stabilized microtubules. GMPCPP-polymerized microtubules qualitatively display a greater resistance to destruction by the AFM probe tip during imaging and during deformation measurements and maintain structural details after indentation. In addition, using force spectroscopy taken during the indentation and collapse of individual microtubules with the AFM probe tip, an effective spring constant of the microtubule wall (kMT) for both types of microtubules was determined. The average kMT of GMPCPP-polymerized microtubules, 0.172 N/m, is more than twice that of paclitaxel-stabilized microtubules. These results complement previously reported measurements of bending experiments on GMPCPP-polymerized and paclitaxel-stabilized microtubules.     

Changes in the interaction characteristics of polyelectrolyte complex covered silica surfaces

The adsorption of polyelectrolyte complexes, PEC, made from the cationic poly (diallyldimethylammonium) chloride (PDADMAC) and the anionic maleic acid-co-propene copolymer (MA-P) on a Si-wafer surface has been studied. The application of highly diluted colloidally dispersed PEC solutions led to the deposition of single PEC particles onto the surface of the Si-wafer. The interaction forces of the heterogeneously covered surface were monitored by direct force measurements with an atomic force microscope (AFM) in the force volume mode. On the surface of a single PEC particle drastic changes in the interaction forces were found in comparison with the unmodified Si-wafer: in all force vs. distance curves a strong increase of the adhesion was measured that can be attributed to the formation of electrostatic bonds between the negatively charged Si₃N₄-tip and the cationic excess charge of the PEC. Additionally, the behavior during approach of both surfaces has been distinct: at pH 6.1 we see a long range electrostatic attraction between the tip and the PEC particle. The attraction becomes even stronger at pH 4.1, because of an increased positive net charge. Generally, a heterogeneous surface with a wide variety of interaction features can be created by the adsorption of PEC particles.     

Rapid deswelling of sodium alginate/poly(N-isopropylacrylamide) semi-interpenetrating polymer network hydrogels in response to temperature and pH changes

In this study, temperature-/pH-responsive semi-interpenetrating polymer network (semi-IPN) hydrogels based on linear sodium alginate (SA) and cross-linked poly(N-isopropylacrylamide) (PNIPAAm) were prepared. The semi-IPN hydrogels reached an equilibrium deswelling state within 6 h in response to temperature or pH stimuli. Compared with the conventional PNIPAAm hydrogel, their dewelling rate in response to temperature was improved significantly, owing to the formation of a porous structure within the hydrogels in the presence of ionized SA during the polymerization process. Moreover, the deswelling process could be well described with a first-order kinetics equation and it is possible to design any hydrogel with the desired deswelling behavior through the control of the SA content in the semi-IPN hydrogels.