Frontal Polymerizations: From Chemical Perspectives to Macroscopic Properties and Applications.

The synthesis and processing of most thermoplastics and thermoset polymeric materials rely on energy-inefficient and environmentally burdensome manufacturing methods. Frontal polymerization is an attractive, scalable alternative due to its exploitation of polymerization heat that is generally wasted and unutilized. The only external energy needed for frontal polymerization is an initial thermal (or photo) stimulus that locally ignites the reaction. The subsequent reaction exothermicity provides local heating; the transport of this thermal energy to neighboring monomers in either a liquid or gel-like state results in a self-perpetuating reaction zone that provides fully cured thermosets and thermoplastics. Propagation of this polymerization front continues through the unreacted monomer media until either all reactants are consumed or sufficient heat loss stalls further reaction. Several different polymerization mechanisms support frontal processes, including free-radical, cat- or anionic, amine-cure epoxides, and ring-opening metathesis polymerization. The choice of monomer, initiator/catalyst, and additives dictates how fast the polymer front traverses the reactant medium, as well as the maximum temperature achievable. Numerous applications of frontally generated materials exist, ranging from porous substrate reinforcement to fabrication of patterned composites. In this review, we examine in detail the physical and chemical phenomena that govern frontal polymerization, as well as outline the existing applications.

Anisotropic frontal polymerization in a model resin-copper composite.

This work investigates experimentally and numerically frontal polymerization in a thermally anisotropic system with parallel copper strips embedded in 1,6-hexanediol diacrylate resin. Both experiments and multiphysics finite element analyses reveal that the front propagation in the thermally anisotropic system is orientation-dependent, leading to variations in the front shape and the front velocity due to the different front-metal strip interaction mechanisms along and across the metal strips. The parameters entering the cure kinetics model used in this work are chosen to capture the key characteristics of the polymerization front, i.e., the front temperature and velocity. Numerical parametric analyses demonstrate that the front velocity in the directions parallel and perpendicular to the metal strips increases as the system size decreases and approaches the analytical prediction for homogenized systems. A two-dimensional homogenized model for anisotropic frontal polymerization in the metal-resin system is proposed.

Rapid frontal polymerization achieved with thermally conductive metal strips.

Frontal polymerization, which involves a self-propagating polymerizing reaction front, has been considered as a rapid, energy-efficient, and environmentally friendly methodology to manufacture lightweight, high-performance thermoset polymers, and composites. Previous work has reported that the introduction of thermally conductive elements can enhance the front velocity. As follow-up research, the present work investigates this problem more systemically using both numerical and experimental approaches by investigating the front shape, front width, and heat exchange when aluminum and cooper metal strips are embedded in the resin. The study reveals that the enhancement in the front velocity is mainly due to a preheating effect associated with the conductive element. Moreover, the numerical parametric study for the system size shows that the front speed increases as the system size decreases, ultimately approaching a prediction provided by a homogenized model for polymer-metal composites.

Influence of reaction-induced convection on quorum sensing in enzyme-loaded agarose beads.

In theory, groups of enzyme-loaded particles producing an acid or base may show complex behavior including dynamical quorum sensing, the appearance of synchronized oscillations above a critical number or density of particles. Here, experiments were performed with the enzyme urease loaded into mm-sized agarose beads and placed in a solution of urea, resulting in an increase in pH. This behavior was found to be dependent upon the number of beads present in the array; however, reaction-induced convection occurred and plumes of high pH developed that extended to the walls of the reactor. The convection resulted in the motion of the mm-sized particles and conversion of the solution to high pH. Simulations in a simple model of the beads demonstrated the suppression of dynamical quorum sensing in the presence of flow.

Skin glands of an aquatic salamander vary in size and distribution and release antimicrobial secretions effective against chytrid fungal pathogens.

Amphibian skin is unique among vertebrate classes, containing a large number of multicellular exocrine glands that vary among species and have diverse functions. The secretions of skin glands contain a rich array of bioactive compounds including antimicrobial peptides (AMPs). Such compounds are important for amphibian innate immune responses and may protect some species from chytridiomycosis, a lethal skin disease caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). While the bioactivity of skin secretions against Bd has been assessed for many amphibian taxa, similar studies are lacking for Bsal, a chytrid fungus that is especially pathogenic for salamanders. We studied the skin glands and their potential functions in an aquatic salamander, the three-toed amphiuma (Amphiuma tridactylum). Skin secretions of captive adult salamanders were analyzed by RP-HPLC and tested against the growth of Bd and Bsal using in vitro assays. We found that compounds within collected skin secretions were similar between male and female salamanders and inhibited the growth of Bd and Bsal. Thus, skin secretions that protect against Bd may also provide protection against Bsal. Histological examination of the skin glands of preserved salamanders revealed the presence of enlarged granular glands concentrated within caudal body regions. A site of potential gland specialization was identified at the tail base and may indicate specialized granular glands related to courtship and communication.

The effect of a crosslinking chemical reaction on pattern formation in viscous fingering of miscible fluids in a Hele-Shaw cell.

Viscous fingering can occur in fluid motion whenever a high mobility fluid displaces a low mobility fluid in a Darcy type flow. When the mobility difference is primarily attributable to viscosity (e.g., flow between the two horizontal plates of a Hele-Shaw cell), viscous fingering (VF) occurs, which is sometimes termed the Saffman-Taylor instability. Alternatively, in the presence of differences in density in a gravity field, buoyancy-driven convection can occur. These instabilities have been studied for decades, in part because of their many applications in pollutant dispersal, ocean currents, enhanced petroleum recovery, and so on. More recent interest has emerged regarding the effects of chemical reactions on fingering instabilities. As chemical reactions change the key flow parameters (densities, viscosities, and concentrations), they may have either a destabilizing or stabilizing effect on the flow. Hence, new flow patterns can emerge; moreover, one can then hope to gain some control over flow instabilities through reaction rates, flow rates, and reaction products. We report effects of chemical reactions on VF in a Hele-Shaw cell for a reactive step-growth cross-linking polymerization system. The cross-linked reaction product results in a non-monotonic viscosity profile at the interface, which affects flow stability. Furthermore, three-dimensional internal flows influence the long-term pattern that results.

Effect of pseudo-gravitational acceleration on the dissolution rate of miscible drops.

The effect of pseudo-gravitational acceleration on the dissolution process of two phase miscible systems has been investigated at high acceleration values using a spinning drop tensiometer with three systems: 1-butanol/water, isobutyric acid/water, and triethylamine/water. We concluded that the dissolution process involves at least three different transport phenomena: diffusion, barodiffusion, and gravitational (buoyancy-driven) convection. The last two phenomena are significantly affected by the centrifugal acceleration acting at the interface between the two fluids, and the coupling with the geometry of the dissolving drop leads to a change of the mass flux during the course of the dissolution process.

Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction.

Chemical systems that remain kinetically dormant until activated have numerous applications in materials science. Herein we present a method for the control of gelation that exploits an inbuilt switch: the increase in pH after an induction period in the urease-catalyzed hydrolysis of urea was used to trigger the base-catalyzed Michael addition of a water-soluble trithiol to a polyethylene glycol diacrylate. The time to gelation (minutes to hours) was either preset through the initial concentrations or the reaction was initiated locally by a base, thus resulting in polymerization fronts that converted the mixture from a liquid into a gel (ca. 0.1 mm min(-1)). The rate of hydrolytic degradation of the hydrogel depended on the initial concentrations, thus resulting in a gel lifetime of hours to months. In this way, temporal programming of gelation was possible under mild conditions by using the output of an autocatalytic enzyme reaction to drive both the polymerization and subsequent degradation of a hydrogel.

Europium-doped aluminum oxide phosphors as indicators for frontal polymerization dynamics.

In this study, we present an inexpensive and practical method that allows the monitoring and visualization of front polymerization, propagation, and dynamics. Commercially available europium-doped aluminum oxide powders were combined with video imaging to visualize free-radical propagating polymer fronts. In order to demonstrate the applicability of this method, frontal copolymerization reactions of propoxylated glycerin triacrylate (EB53), pentaerythritol triacrylate (PETA), and pentaerythritol tetra-acrylate (PETEA) with 1,1-Bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane (Luperox 231®) as an initiator were studied and compared to the results obtained by IR imaging. Systems exhibiting higher filler loading, higher EB53 content, and less acrylated monomers showed a marked decrease in front velocity, while those with more acrylated monomers and higher crosslinking density showed a marked increase in front velocity. Finally, in order to show the potential of the imaging technique, we studied fronts propagating in planar and spherical geometries.

Free-Standing 3D Printing of Epoxy-Vinyl Ether Structures Using Radical-Induced Cationic Frontal Polymerization.

The application of frontal polymerization to additive manufacturing has advantages in energy consumption and speed of printing. Additionally, with frontal polymerization, it is possible to print free-standing structures that require no supports. A resin was developed using a mixture of epoxies and vinyl ether with an iodonium salt and peroxide initiating system that frontally polymerizes through radical-induced cationic frontal polymerization. The formulation, which was optimized for reactivity, physical properties, and rheology, allowed the printing of free-standing structures. Increasing ratios of vinyl ether and reactive cycloaliphatic epoxide were found to increase the front velocity. Addition of carbon nanofibers increased the front velocity more than the addition of milled carbon fibers. The resin filled with carbon nanofibers and fumed silica exhibited shear-thinning behavior and was suitable for extrusion-based printing at a weight fraction of 4 wt %. A desktop 3D printer was modified to control resin extrusion and deposition with a digital syringe dispenser. Flexural properties of molded and 3D-printed specimens showed that specimens printed in the transverse direction exhibited the lowest strength, likely due to the presence of voids, adhesion issues between filaments, and preferential carbon nanofiber alignment along the filaments. Finally, free-standing printing of single, angled filaments and helical geometries was successfully demonstrated by coordinating ultraviolet-based reaction initiation, low air pressure for resin extrusion, and printing speed to match front velocity.

Kinetic and Chemical Effects of Clays and Other Fillers in the Preparation of Epoxy-Vinyl Ether Composites Using Radical-Induced Cationic Frontal Polymerization.

Addition of fillers to formulations can generate composites with improved mechanical properties and lower the overall cost through a reduction of chemicals needed. In this study, fillers were added to resin systems consisting of epoxies and vinyl ethers that frontally polymerized through a radical-induced cationic frontal polymerization (RICFP) mechanism. Different clays, along with inert fumed silica, were added to increase the viscosity and reduce the convection, results of which did not follow many trends present in free-radical frontal polymerization. The clays were found to reduce the front velocity of RICFP systems overall compared to systems with only fumed silica. It is hypothesized that chemical effects and water content produce this reduction when clays are added to the cationic system. Mechanical and thermal properties of composites were studied, along with filler dispersion in the cured material. Drying the clays in an oven increased the front velocity. Comparing thermally insulating wood flour to thermally conducting carbon fibers, we observed that the carbon fibers resulted in an increase in front velocity, while the wood flour reduced the front velocity. Finally, it was shown that acid-treated montmorillonite K10 polymerizes RICFP systems containing vinyl ether even in the absence of an initiator, resulting in a short pot life.

pH wave-front propagation in the urea-urease reaction.

The urease-catalyzed hydrolysis of urea displays feedback that results in a switch from acid (pH ~3) to base (pH ~9) after a controllable period of time (from 10 to >5000 s). Here we show that the spatially distributed reaction can support pH wave fronts propagating with a speed of the order of 0.1-1 mm min(-1). The experimental results were reproduced qualitatively in reaction-diffusion simulations including a Michaelis-Menten expression for the urease reaction with a bell-shaped rate-pH dependence. However, this model fails to predict that at lower enzyme concentrations, the unstirred reaction does not always support fronts when the well-stirred reaction still rapidly switches to high pH.

Pattern formation in the iodate-sulfite-thiosulfate reaction-diffusion system.

Sodium polyacrylate-induced pH pattern formation and starch-induced iodine pattern formation were investigated in the iodate-sulfite-thiosulfate (IST) reaction in a one-side fed disc gel reactor (OSFR). As binding agents of the autocatalyst of hydrogen ions or iodide ions, different content of sodium polyacrylate or starch has induced various types of pattern formation. We observed pH pulses, striped patterns, mixed spots and stripes, and hexagonal spots upon increasing the content of sodium polyacrylate and observed iodine pulses, branched patterns, and labyrinthine patterns upon increasing the starch content in the system. Coexistence of a pH front and an iodine front was also studied in a batch IST reaction-diffusion system. Both pH and iodine front instabilities were observed in the presence of sodium polyacrylate, i.e., cellular fronts and transient Turing structures resulting from the decrease in diffusion coefficients of activators. The mechanism of multiple feedback may explain the different patterns in the IST reaction-diffusion system.

Critical Role of Layer Thickness in Frontal Polymerization.

Thermal frontal polymerization (FP) is a chemical process during which a cold monomer-initiator mixture is converted into a hot polymer as a polymerization front propagates in the system due to the interplay between heat diffusion and the exothermicity of the reaction. The theoretical description of FP generally focuses on one-dimensional (1D) reaction-diffusion (RD) models where the effect of heat losses is encoded into an effective parameter in the heat equation. We show here the limits of such 1D models to describe FP under nonadiabatic conditions. To do so, the propagation of a polymerization front is analyzed both analytically and numerically in a rectangular two-dimensional (2D) layer. The layer thickness is shown to control the dynamics of the front and to determine its very existence. We find that for given heat losses, a minimum thickness is required for front propagation as recently observed in FP experiments of 2D thin films on wood. Moreover, when the thickness exceeds a critical value, the front is observed to survive independently of the rate of heat losses. This result cannot be predicted with 1D models where front extinction is always possible. A scaling analysis is proposed to highlight the physical interpretation of such a front survival. The influence of dimensionality on thermal instabilities is also analyzed, with a focus on the differences with the 1D predictions.

Generation of 3D Spheroids Using a Thiol-Acrylate Hydrogel Scaffold to Study Endocrine Response in ER+ Breast Cancer.

Culturing cancer cells in a three-dimensional (3D) environment better recapitulates in vivo conditions by mimicking cell-to-cell interactions and mass transfer limitations of metabolites, oxygen, and drugs. Recent drug studies have suggested that a high rate of preclinical and clinical failures results from mass transfer limitations associated with drug entry into solid tumors that 2D model systems cannot predict. Droplet microfluidic devices offer a promising alternative to grow 3D spheroids from a small number of cells to reduce intratumor heterogeneity, which is lacking in other approaches. Spheroids were generated by encapsulating cells in novel thiol-acrylate (TA) hydrogel scaffold droplets followed by on-chip isolation of single droplets in a 990- or 450-member trapping array. The TA hydrogel rapidly (∼35 min) polymerized on-chip to provide an initial scaffold to support spheroid development followed by a time-dependent degradation. Two trapping arrays were fabricated with 150 or 300 µm diameter traps to investigate the effect of droplet size and cell seeding density on spheroid formation and growth. Both trapping arrays were capable of ∼99% droplet trapping efficiency with ∼90% and 55% cellular encapsulation in trapping arrays containing 300 and 150 µm traps, respectively. The oil phase was replaced with media ∼1 h after droplet trapping to initiate long-term spheroid culturing. The growth and viability of MCF-7 3D spheroids were confirmed for 7 days under continuous media flow using a customized gravity-driven system to eliminate the need for syringe pumps. It was found that a minimum of 10 or more encapsulated cells are needed to generate a growing spheroid while fewer than 10 parent cells produced stagnant 3D spheroids. As a proof of concept, a drug susceptibility study was performed treating the spheroids with fulvestrant followed by interrogating the spheroids for proliferation in the presence of estrogen. Following fulvestrant exposure, the spheroids showed significantly less proliferation in the presence of estrogen, confirming drug efficacy.

Reaction-diffusion hydrogels from urease enzyme particles for patterned coatings.

The reaction and diffusion of small molecules is used to initiate the formation of protective polymeric layers, or biofilms, that attach cells to surfaces. Here, inspired by biofilm formation, we present a general method for the growth of hydrogels from urease enzyme-particles by combining production of ammonia with a pH-regulated polymerization reaction in solution. We show through experiments and simulations how the propagating basic front and thiol-acrylate polymerization were continuously maintained by the localized urease reaction in the presence of urea, resulting in hydrogel layers around the enzyme particles at surfaces, interfaces or in motion. The hydrogels adhere the enzyme-particles to surfaces and have a tunable growth rate of the order of 10 µm min-1 that depends on the size and spatial distribution of particles. This approach can be exploited to create enzyme-hydrogels or chemically patterned coatings for applications in biocatalytic flow reactors.

Development of a Flow-free Gradient Generator Using a Self-Adhesive Thiol-acrylate Microfluidic Resin/Hydrogel (TAMR/H) Hybrid System.

Microfluidic gradient generators have been used to study cellular migration, growth, and drug response in numerous biological systems. One type of device combines a hydrogel and polydimethylsiloxane (PDMS) to generate "flow-free" gradients; however, their requirements for either negative flow or external clamps to maintain fluid-tight seals between the two layers have restricted their utility among broader applications. In this work, a two-layer, flow-free microfluidic gradient generator was developed using thiol-ene chemistry. Both rigid thiol-acrylate microfluidic resin (TAMR) and diffusive thiol-acrylate hydrogel (H) layers were synthesized from commercially available monomers at room temperature and pressure using a base-catalyzed Michael addition. The device consisted of three parallel microfluidic channels negatively imprinted in TAMR layered on top of the thiol-acrylate hydrogel to facilitate orthogonal diffusion of chemicals to the direction of flow. Upon contact, these two layers formed fluid-tight channels without any external pressure due to a strong adhesive interaction between the two layers. The diffusion of molecules through the TAMR/H system was confirmed both experimentally (using fluorescent microscopy) and computationally (using COMSOL). The performance of the TAMR/H system was compared to a conventional PDMS/agarose device with a similar geometry by studying the chemorepulsive response of a motile strain of GFP-expressing Escherichia coli. Population-based analysis confirmed a similar migratory response of both wild-type and mutant E. coli in both of the microfluidic devices. This confirmed that the TAMR/H hybrid system is a viable alternative to traditional PDMS-based microfluidic gradient generators and can be used for several different applications.

Frontal Polymerization of a Thin Film on a Wood Substrate.

Frontal polymerization has been explored as a technique to form two-dimensional thin films (<0.5 mm) on wood. We used trimethylolpropane triacrylate with a thermal free-radical initiator. The viscosity of the resin was adjusted by incorporating fumed silica within the formulation. As filler materials, either calcium carbonate or graphene nanoplatelets was used to evaluate the effect of filler type and content on front propagation. We observed that resin viscosity and film thickness critically affected the qualitative and quantitative propagation of the thermal front resulting in the formation of the coating. A workable coating was formed at a viscosity of 0.6 Pa·s, which was obtained when 3 phr (parts per hundred resin) of fumed silica was used in the resin formulation. Wet film thickness for this resin system was also found to have a limiting value, and full propagation of the front to result in a conformal coating required at least 15 mil (1 mil = 25 µm) of wet film thickness. Filler materials affected film propagation as a function of particle size and thermal properties. While 15 phr calcium carbonate could be incorporated with the resin, only 5 phr graphene nanoplatelets could be loaded within the matrix to ensure complete propagation of the front. Interestingly, for graphene fronts, velocity and temperature reduced systematically as a function of filler content. Filler type and content affected porosity and roughness of the coating, which was quantified by computerized tomography to understand the relationship between porosity and adhesion of the coated film with the wood substrate.