The partly fluorinated monomers, 2,2,2-trifluoroethyl methacrylate (3FM), 2,2,3,3,4,4,5,5-octafluoropentyl methacrylate (8FM), and 1,1,2,2-tetrahydroperfluorodecyl methacrylate (17FM) have been used in the preparation of block copolymers with methyl methacrylate (MMA), 2-methoxyethyl acrylate (MEA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA) by Atom Transfer Radical Polymerization. A kinetic study of the 3FM homopolymerization initiated with ethyl bromoisobutyrate and Cu(I)Br/N-(n-propyl)-2-pyridylmethanimine reveals a living/controlled polymerization in the range 80-110 degrees C, with apparent rate constants of 1.6 . 10(-4) s(-1) to 2.9 . 10(-4) s(-1). Various 3FM containing block copolymers with MMA are prepared by sequential monomer addition or from a PMMA macroinitiator in all cases with controlled characteristics. Block copolymers of 3FM and PEGMA resulted in block copolymers with PDI < 1.22, whereas block copolymers from 3FM and MEA have less controlled characteristics. The block copolymers based on MMA with 8FM and 17 FM have PDI's < 1.30. The glass transition temperatures of the block copolymers are dominated by the majority monomer, as the sequential monomer addition results in too short pure blocks to induce observable microphase separation. The thermal stability of the fluorinated poly((meth)acrylate)s in inert atmosphere is less than that of corresponding nonfluorinated poly((meth)acrylate)s. The presence of fluorinated blocks significantly increases the advancing water contact angle of thin films compared to films of the nonfluorinated poly((meth)acrylate)s. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 8097-8111, 2008

BACKGROUNDLowering blood glucose concentration slows or prevents the development of complications in diabetes. One of the tools to control glucose levels is continuous glucose measurements. A promising technique involves measurements from glucose sensors implanted directly in skin/subcutis. However, in vivo bioinstability and drift in sensor signals have been reported after implantation, suggestively caused by the infiltration of inflammatory cells and adhesion of proteins to sensor membranes. The aim of this study was to evaluate the in vivo biocompatibility of two electrochemical glucose sensors after implantation in the skin of pigs.METHODSIn vivo biocompatibility of in-house fabricated electrochemical glucose sensors and a commercially available continuous glucose monitoring system (CGMS, Medtronic MiniMed, Northridge, CA) implanted 1 h, 2 h, 24 h, 3 days, or 7 days was examined by histological and immunohistochemical techniques.RESULTSThe extent of inflammation increased significantly as a function of time. The inflammation ranged from an acute focal fibrinous/suppurative dermatitis to a chronic fibrinous and granulating foreign body dermatitis 7 days after implantation. Immunohistochemical stainings showed that heterophilic granulocytes, macrophages, and fibrinogen/fibrinogen fragments D and E were consistent findings. Infiltration of CD3epsilon-positive T-cells was primarily confined to day 7 of implantation. In addition, the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor-alpha played a role in the reaction to sensors.CONCLUSIONThe reported in vivo bioinstability of sensors is likely to be caused by protein and cellular biofouling on the sensor membrane. Furthermore, the consistent finding of fibrinogen and fibrinogen fragments D and E at the sensor-tissue interface seems to play an important role in the pathogenesis as it possibly maintains the inflammation by promoting the recruitment of inflammatory cells to the implantation site.

Background: Continuous glucose measurements provide improved glycemic control and may prevent hypoglycemia and long-term complications of diabetes. One of the most promising techniques is the short-term implantation of electrochemical glucose sensors in subcutis. However, the inflammatory reaction to these sensors may lead to bioinstability of sensor measurements. The purpose of the present investigation was to examine factors contributing to the observed subcutaneous inflammatory reaction to an enzyme-based electrochemical glucose sensor for continuous glucose measurements. The sensor biocompatibility was assessed in vitro and in vivo. Methods: A toxicological assessment was performed on sensor materials and leachables, and the endotoxin content of sensors was determined by a Limulus amoebocyte lysate (LAL) test. Moreover, as a consequence of permanent penetration of the skin by the sensor the role of bacterial migration to the tissue was investigated. In vivo biocompatibility was investigated through histological examination of implanted sensor membranes for 3 days in pigs. Additionally, the effect of needle size and type (normal vs. inserter needle) on tissue trauma at sensor insertion was evaluated, and the healing of subcutis was assessed histologically from 3 to 14 days after removal of sensors. Results: The toxicological assessment and the LAL test showed no concerns in a 3-day implantation scenario, and bacterial migration to the subcutis could not be detected. The histological examination showed that a reduction in needle size reduced the extent of inflammation to very low levels, and that the different sensor membranes showed similar extent and type of inflammation. Additionally, the extent of subcutaneous tissue reaction after removal of sensors declined gradually over time and returned to near-normal levels after 2 weeks. Conclusion: The electrochemical enzyme-based glucose sensor for continuous glucose measurements in subcutis is acceptable from a biocompatibility point of view. Reducing the inserter needle in size reduces the trauma induced at sensor implantation to neglible levels. Furthermore, the tissue reaction to the sensor returns to near-normal 2 weeks after the sensor has been removed following a 3-day implantation period.

BACKGROUND:Subcutaneously-implanted glucose sensors for continuous glucose monitoring have the potential to replace serial blood glucose measurements. The objective of the present study was to test whether continuous glucose measurements could be obtained with glucose sensors implanted in the subcutis of pigs. Moreover, the in vivo biocompatibility of the sensors was evaluated since an inflammatory reaction may lead to drift in sensor-signaling.MATERIALS AND METHODS:Two types of glucose sensor were implanted for 3 days in the subcutis of hyperglycemic pigs. The plasma glucose concentration was correlated to the sensor outputs, and tissue was sampled for histological evaluation.RESULTS:There was a good correlation between the interstitial fluid and blood glucose levels. However, there was a statistical significantly difference in linearity from days 0 and 1 to day 2 (p<0.001) and variations in the sensitivity and background current of individual sensors were observed over time. The tissue reaction caused by the sensors was a mild focal subacute fibrinous dermatitis.CONCLUSION:Continuous glucose measurement can be achieved by glucose sensors implanted in the subcutis of pigs. The observed drift in sensor signals over time may have been caused by heterophils, macrophages and/or fibrinogen at the tissue-sensor interface.

The symmetric triblock copolymer Pluronic P85 with EO25PO40EO25 has been studied by small-angle neutron scattering (SANS) at 50 and 60°C at concentrations of 0.25–10 wt.% in D2O. The data are analyzed by a model based on Monte Carlo simulations. The micelles are modeled as having a spherical core of poly(propylene oxide) (PPO) with some water surrounded by a corona of the poly(ethylene oxide) (PEO) block. The latter are non-interacting and obey Gaussian statistics, but are expelled from the core region. The analysis shows that the micelles are fairly concentration and temperature independent at the conditions studied. The micelles are slightly polydisperse in the aggregation number and have aggregation numbers in the range 40–50. The core contains about 40% water and has a radius of about 40 Å. The corona extends out to about 80–100 Å and has a fairly low volume fraction of polymer, typically less than 10%.

We have explored the effects of solvent, adsorber concentration, and environment on the formation of high-coverage monolayers of alkylsiloxanes on silicon oxide surfaces from alkylsiloxane solutions. Specifically, we have varied the solvent polarity and the concentration of octadecyltrichlorosilane (OTS) used for the deposition process. We found that for a wide range of concentrations (25 muM to 2.5 mM) and normal laboratory air humidity (RH 45-85%) OTS dissolved in heptane causes the formation of a full-coverage self-assembled monolayer on hydrophilic silicon oxide. The resulting self-assembled layers were studied by atomic force microscopy, ellipsometry, and X-ray reflectometry. Deposition of OTS from dodecane solutions resulted in multilayered films. In contrast, the use of heptane as solvent (in which the solubility of water is at intermediate level between toluene and dodecane) caused the formation of high-quality monolayers. We found consistent and reproducible results for the effect of solvents (dodecane and heptane) and conditions on the formation of OTS layers on Si/SiO2 surfaces. The substrates, which are covered by a full monolayer, function as well-defined ultraflat hydrophobic surfaces for other experiments.

Using in situ surface X-ray diffraction, the thermal stability of a self-assembled monolayer (SAM) of decanethiol, sandwiched between a Au(111) substrate and a van der Waals bound capping layer of PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride), is measured. While the bare SAM on Au(111) undergoes a melting transition at 100 °C, this transition temperature is raised to 115 °C if the SAM is capped by PTCDA. Possible mechanisms and implications of this capping-layer-mediated melting point enhancement are discussed.

X-ray and neutron scattering from macroscopically rough surfaces and interfaces is considered and a new method of analysis based on the variation of the shape of the total reflection edge in the reflectivity profile is proposed. It was shown that in the limit that the correlation length and the height of the surface roughness are larger than the wavelength (at least 100 times bigger) of the incoming beam, the total reflection edge in the reflection profile becomes rounded. This technique allows direct analysis of the variation of the reflectivity profile in terms of the structure of the surface profile in the particular case where the height variation of the surface texture is smooth and small compare to the surface correlation length (surface profile with slow variation)

Using a combination of self assembly, Langmuir-Blodgett and Langmuir-Schaeffer techniques, we have produced a multilayered film of dimyristoylphosphatidylcholine ( DMPC) intended for use as a biomembrane mimic. Neutron reflectivity measurements have revealed that the upper two layers of phospholipid are separated from the silicon substrate and the lower layers by a hydration region approximately 30 A thick. This layer limits the tethering effect of the substrate such that the phospholipid molecules within the upper bilayer have significant freedom. This freedom is evidenced by the fact that the upper bilayer shows a transition to the P-beta' ripple phase. This phase could not be observed if the phospholipid molecules were significantly constrained by the substrate.

The phase behavior of a supported dimyristoylphosphatidylcholine (DMPC) bilayer system has been investigated using neutron reflectivity. The bilayer is fabricated by a combination of Langmuir-Blodgett, Langmuir-Schaeffer, and self-assembly techniques, and while robustly associated with the substrate, the bilayer remains separated from it by a substantial layer of water, due to a Helfrich type entropic repulsion. The reflectivity data have been analyzed using a quasi-molecular model, similar to that used by Wiener and White (Wiener et al. Biophys. J. 1992, 61, 434-447) allowing easy comparison of the bilayer structure with other systems such as vesicles. The area per molecule (APM) and bilayer thickness in the gel phase are found to be identical to those in DMPC vesicles. In going from the gel phase to the fluid phase, the bilayer thickness decreases and the APM increases due to chain melting. This suggests that the bilayer is minimally constrained, since the bilayer structure seems to be determined by the packing requirements of the phospholipids rather than any influence of the substrate. The hydrating layer is thicker than in vesicles, and we suggest that this may be due to differences in the confinement regime. That is, a bilayer in a multilamellar vesicle is constrained on both sides, whereas the bilayer studied here is confined on one side only. Nevertheless, the thickness of the intervening water layer decreases across the main transition in the same way as is seen in multilamellar systems.

Neutron reflectometry has been employed to measure the surface induced ordering of a triblock copolymer comprised of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic, P85) in aqueous solution far above the critical micelle concentration at the hydrophilic surface of quartz. In the bulk micellar liquid phase, the data are consistent with a micellar layering at the solid-liquid interface, as indicated by free-form analysis and subsequent detailed modeling which includes Monte Carlo simulations of hard spheres at a hard wall. Treating the micelles as either solid spheres or solid spheres with tethered Gaussian chains interacting as hard spheres, important parameters can be obtained from fitting the reflectivity data such as the interaction and core radius of the micelles, the volume fraction, and the surface polymer density at the solid-solution interface as a function of temperature and concentration. The dependence of these variables was found to be similar to the bulk solution behavior, signifying that the micelles behave like a hard-sphere liquid (as in the bulk) at a hard structureless wall. The behavior is mainly a result of the hydrophilic nature of the poly(ethylene oxide) chains surrounding the micelles as well as the hydrophilic surface. Further support for the bulklike behavior was seen by the appearance of Bragg-like peaks occurring in the reflectivity as the prolate ellipsoidal phase and the body-centered cubic micellar crystal phase were entered.

Previously, we have shown from neutron reflectometry that the surface-induced ordering of triblock copolymer micelles in aqueous solution at the hydrophilic surface of quartz can be modeled as solid spheres with and without tethered Gaussian chains at a structureless hard wall. In this article, we present a detailed account of the necessary steps for obtaining the density profile of the ordering of micelles at a hard wall from specular reflectivity data. A numerical expression for the density of hard spheres at a hard wall, which is equivalent to the center distribution of the hard spheres, is obtained from Monte Carlo simulations valid in the hard-sphere volume fraction range from 0.05 to 0.4789. By convoluting the center distribution of the hard spheres with the projected scattering length density of the solid sphere with or without tethered chains, a five parameter expression is obtained from which we can fit the neutron reflectivity profiles. The presented model is generally applicable to other systems interacting through a hard-sphere potential close to a nonattractive planar surface.

We study the electrochemical roughening of a silicon electrode surface during the hydrogen evolution reaction in a fluoride electrolyte using neutron reflection. We demonstrate that as the roughening process modifies the morphology of the silicon surface we can follow the changes by observing the changes in the shape of the total reflection feature. We assume that the change in the morphology of the surface is due to the diffusion of hydrogen in the silicon electrode. This assumption allow us to model the changes in the reflected intensity at two different angles and find the diffusion exponent for the diffusion of hydrogen in the silicon lattice.