An Acid Test: Facile SI-ARGET-ATRP of Methacrylic Acid

Atom transfer radical polymerization (ATRP) of methacrylic acid (MAA) is challenging. Herein is reported a study of conditions for facile surface-initiated ATRP by activator regenerated electron transfer (SI-ARGET-ATRP) growth of poly-methacrylic acid (PMAA) chains from a plasma polymer surface bearing surface-immobilized -bromoisobutyryl bromide, with no deoxygenation required. Factors that affect PMAA polymer growth off the surface under ARGET-ATRP conditions are systematically investigated, such as monomer/catalyst ratio, solvent, and, most importantly, addition of salts and change of pH. While the concentrations of the copper catalyst and acid affect grafting, the most pronounced effect arises from the concentration of chloride ions. Adding 0.1 m NaCl and acidifying the reaction solution to pH 3 offers the best trade-off between reaction rate and reproducibility; yielding approximate to 60nm thick PMAA graft polymers in 1 h under ambient conditions. Using this easily scalable recipe and surface analysis, the grafted polymers are verified to be pure PMAA and the graft coatings to be homogenous across a substrate of 100 mm diameter.

Glucose Monitoring Using a Polymer Brush Modified Polypropylene Hollow Fiber-based Hydraulic Flow Sensor

Nicolas Fortin, Harm-Anton Klok

Tight regulation of blood glucose levels of diabetic patients requires durable and robust continuous glucose sensing schemes. This manuscript reports the fabrication of ultrathin, phenylboronic acid (PBA) functionalized polymer brushes that swell upon glucose binding and which were integrated as the sensing interface in a new polypropylene hollow fiber (PPHF)-based hydraulic flow glucose sensor prototype. The polymer brushes were prepared via surface-initiated atom transfer radical polymerization of sodium methacrylate followed by postpolymerization modification with 3-aminophenyl boronic acid. In a first series of experiments, the glucose-response of PBA-functionalized poly(methacrylic acid) (PMAA) brushes grafted from planar silicon surfaces was investigated by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) experiments. The QCM-D experiments revealed a more or less linear change of the frequency shift for glucose concentrations up to similar to 10 mM and demonstrated that glucose binding was completely reversible for up to seven switching cycles. The AFM experiments indicated that glucose binding was accompanied by an increase in the film thickness of the PBA functionalized PMAA brushes. The PBA functionalized PMAA brushes were subsequently grafted from the surface of PPHF membranes. The hydraulic permeability of these porous fibers depends on the thickness and swelling of the PMAA brush coating. PBA functionalized brush-coated PPHFs showed a decrease in flux upon exposure to glucose, which is consistent with swelling of the brush coating. Because they avoid the use of enzymes and do not rely on an electrochemical transduction scheme, these PPHF-based hydraulic flow sensors could represent an interesting alternative class of continuous glucose sensors.

Amer Chemical Soc2015

Synthesis of Responsive Polymer Brushes for Sensing Applications

Nicolas Bertrand Schüwer

During the past decades the field of sensors has been subject to much attention due to an increased demand for (bio)sensors and environmental monitoring. The efforts have been concentrated to create sensors which are reliable, highly sensitive and selective, small and fast responding. Surface modification by polymer coating has been proven an excellent method to introduce selectivity on actuators. Among the various techniques that allow the formation of polymer thin film, polymer brushes have gained attention along the past decades due to their unique structure and the possibility offered by controlled/"living" surface-initiated radical polymerization technique to generate polymer thin film with precisely controlled thickness, composition and architecture. Polymer brushes have found numerous applications including nonbiofouling surfaces and cell adhesive surfaces, protein binding and immobilization, chromatography supports, membrane functionalization, responsive surface, antibacterial coatings or low friction surfaces. Despite their interesting properties and the numerous reports describing the potential of polymer brush as responsive surface, their use for "real" sensing applications has receive little or no attention so far. This Thesis describes how polymer brushes can be employed as selective surface modification for sensing application. We aimed at synthesizing polymer thin film able to detect analytes of interest, with a particular focus on low detection limit and high selectivity. After a short introduction to the field of polymer brushes (Chapter 1), Chapter 2 presents a review of the work accomplished in the field of responsive polymer brushes with an emphasis on solvent responsive, thermoresponsive, pH- and ion-sensitive polymer brushes. The pH-induced swelling and collapse of surface-tethered, weak polyelectrolyte brushes is of interest not only for the development of responsive surface coatings but also for the pH controlled transport or adsorption. Chapter 3 discusses results of an extensive series of quartz crystal microbalance (QCM) experiments that aimed at further understanding the influence of brush thickness and density on the pH-responsiveness of poly(methacrylic acid) (PMAA) brushes and developing strategies that allow to engineer the pH responsiveness and dynamic response range of PMAA based brushes. It was observed that due to their high grafting density, the apparent pKa of surface-tethered PMAA differs from that of the corresponding free polymer in solution and also covers a broader pH range. The pKa of the PMAA brushes was found to depend both on brush thickness and density; thicker brushes showed a higher pKa value and brushes of higher density started to swell at higher pH. The second part of this section demonstrates the feasibility of the N-hydroxysuccinimide-mediated post-polymerization modification to engineer the pH responsiveness of the PMAA brushes. By using appropriate amine functionalized acids, it was possible to tune both the pH of maximum response as well as the dynamic response range of these PMAA based polyelectrolyte brushes. In Chapter 4, benzo-15-crown-5 functionalized polymer brushes prepared via surface-initiated atom transfer radical polymerization were used as the active layer in a potassium-selective QCM sensor. The polymer brushes allowed the selective detection of potassium ions, even in the presence of a large excess of sodium ions and the sensitivity of the sensor could be tuned by varying the brush thickness. Chapter 5 demonstrates the possibility to use peptide functionalized polymer brush, prepared via surface-initiated atom transfer radical polymerization (SI-ATRP), to probe heavy metal ions via voltammetric based methods. The polymer brush enhanced the mercury (II) ions sensitivity as compared to the bar electrode and allowed the detection of mercury down to the nanomolar concentration range. Furthermore it was demonstrated that the heavy metal recognition is a reversible and reproducible process. Post-polymerization modification reactions are widely employed to prepare functional polymer brushes. Relatively little is known, however, about the distribution of functional groups in such post-modified brushes. Using neutron reflectivity and UV-visible spectroscopy as principal tools, Chapter 6 investigates the p-nitrophenyl chloroformate (NPC) mediated post-polymerization modification of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes, prepared via surface-initiated atom transfer radical polymerization, with D-10 leucine and D-3 serine. The neutron reflectivity experiments indicate that the post-polymerization modification depends both on the brush thickness and density. Whereas, for dense brushes, post-polymerization modification with D-10 leucine is limited to the top ∼ 200 Å of the brush, independently of the brush thickness, the extent of post-modification can be significantly extended by decreasing brush density, or by using the more hydrophilic and sterically less demanding D-3 serine, which reflects the ability of this amino acid to more readily penetrate the brush. UV-vis. experiment revealed that the NPC activation is also non-uniform, but brush thickness and density dependent, which adds to brush thickness, density and the nature of the amino acid as another of a complex set of variables that determine the final distribution of functional groups in post-modified brushes.

EPFL2011

Functional polymer brushes via surface-initiated controlled radical polymerizations

Stefano Tugulu

The term polymer brush refers to a well defined arrangement of polymer chains, which are tethered with one end to an interface and usually the surface of a solid substrate. Due to steric repulsion the polymer chains furthermore adopt a defined, stretched chain conformation, which significantly differs from the random walk conformation of free polymer chains in solution or in conventionally solution casted polymer coatings. From a structural point of view polymer brushes can therefore be regarded as the most defined type of polymer coating that can currently be realized. Especially the combination of surface-initiated polymerizations (SIP) with modern, controlled polymerization methods thereby allows tailoring the structure of the polymer brushes almost on the molecular level. Specifically precise control over the thickness, composition, chain architecture, grafting density and via the use of lithographic techniques also over the topography of the brushes can be achieved. This high degree of control over the structural and implicated (physico-)chemical properties of the brush allows at the same time tailoring and fine tuning the interfacial properties of the brush. This thesis describes the systematic exploitation of well-defined polymer brushes as functional coatings with fine-tuned physicochemical properties to direct and control the interaction with and the response of specific biological, bioanalytical and even reactive chemical environments. In detail the use of surface-initiated atom transfer radical polymerization (SI-ATRP) for the fabrication of functional polymer brushes will be presented. These brushes were used as highly defined coatings in various applications ranging from biomedical and bioanalytical applications to biomimetic materials fabrication (Figure 1). Figure 1 Numerous synthetic approaches for the preparation of polymer brushes have been described in the literature. Chapter 2 will therefore present a summary of the most important types of surface-initiated polymerizations, focusing especially on controlled SIP methods and SI-ATRP. Chapter 3 describes a chemoselective and specific immobilization strategy to decorate intrinsically bioinert polymer brushes with proteins of interest in a defined orientation and density. Specifically the resulting substrates represent attractive candidates for the realization of protein microarrays. In view of this application protein-small molecule and protein-protein interactions as well as posttranslational modifications were analyzed within a feasibility study. Due to their well-defined structure polymer brushes represent also attractive candidates for the realization of molecularly defined cell adhesion substrates for tissue engineering or as highly defined biophysical model system to analyze cell adhesion and mechanics. Chapter 4 describes the decoration of intrinsically bioinert polymer brushes with small peptide ligands with defined density to induce integrin specific cell adhesion on the brushes. Peptide functionalized polymer brushes could be readily endothelialized and adhering cell layers have shown to preserve their homeostatic ability to respond to an applied mechanical stimulus in a physiological manner. In Chapter 5 the limitations of high density polymer brushes in biomedical applications were assessed by analyzing their stability under in vitro cell culture conditions. Intrinsically bioinert high density polymer brushes were found to degraft from glass or silicon substrates upon swelling in good solvents, which lead to deterioration of the bioinert properties of the substrate. The degrafting of the brushes might be connected to swelling induced mechanical activation of chemical bonds, which link the brushes to the substrate. Chapter 6 describes the transfer of the developed SIP approach onto flexible PDMS substrates by exploiting the formation of interpenetrating networks of ATRP-initiator siloxane and PDMS. The modification of the PDMS substrates with hydrophilic brushes effectively reduces the unspecific protein adsorption on the substrates. This approach might therefore represent an attractive and facile route for the surface modification of miniaturized PDMS devices for biomedical or bioanalytical applications. In Chapter 7 the systematic development of a reliable and robust protocol for the aqueous SI-ATRP of sodium methacrylate is presented, which gives access to poly(methacrylic acid) (PMAA) brushes with defined molecular weight and grafting density. The resulting brushes were assessed for their ability to direct the mineralization of calcium carbonate. Chapter 8 describes the use of photolithographically patterned poly(methacrylic acid) brushes as biomimetic, acidic macromolecular matrix to fabricate microstructured calcite thin films that are an exact 3D replica of the PMAA brush. The presented strategy relies on three key elements: (i) the use of photolithographic techniques to prepare microstructured PMAA brushes; (ii) the ability of PMAA brushes to stabilize amorphous calcium carbonate (ACC) and (iii) the possibility to convert the metastable ACC phase into a polycrystalline calcite film via a thermal treatment.