In vivo biocompatibility and analytical performance of intravascular amperometric oxygen sensors prepared with improved nitric oxide-releasing silicone rubber coating

The in vivo biocompatibility and analytical performance of amperometric oxygen-sensing catheters prepared with a new type of nitric oxide (NO)-releasing silicone rubber polymer (DACA/N2O2 SR) is reported. The NO-release silicone rubber coating contains diazeniumdiolated secondary amine sites covalently anchored to a dimethylsiloxane matrix. Narrow diameter (0.9 mm, o.d.) silicone rubber tubing coated with this polymer can be employed to construct functional oxygen-sensing catheters that release NO continuously at levels > 1 x 10(-10) mol/cm2-min for more than 20 h. In vivo evaluation of such sensors within the carotid and femoral arteries of swine over a 16-h time period demonstrates that sensors prepared with the new NO-release coating exhibit no significant platelet adhesion or thrombus formation, but control sensors (non-NO release) implanted within the same animals do show a high propensity for cell adhesion and bulk clot formation. Furthermore, the in vivo analytical data provided by sensors fabricated with NO-release coatings (N = 9) are shown to be statistically equivalent to PO2 levels measured in vitro on discrete samples of blood. Control sensors (N = 9) placed within the same animals yield average PO2 values that are statistically different (p < or = 0.05) (lower) from both the levels measured on discrete samples and those provided by the NO-release sensors over a 16-h in vivo monitoring period.     

Improving the thromboresistivity of chemical sensors via nitric oxide release: fabrication and in vivo evaluation of NO-releasing oxygen-sensing catheters

The development and in vivo analytical performance of a nitric oxide (NO)-releasing amperometric oxygen sensor with greatly enhanced thromboresistivity are reported. Gas permeable coatings formulated with cross-linked silicone rubber (SR) containing NO-generating compounds (diazeniumdiolates) are shown to release NO for extended periods of time (> 20 h) while reducing platelet adhesion and activation. Oxygen-sensing catheters prepared by dip-coating the NO-releasing films over the outer SR tubes of the implantable devices display similar analytical response properties in vitro (sensitivity, selectivity, response times) when compared to analogous sensors prepared without the NO release coatings. Superior analytical accuracy (relative to blood PO2 values measured in vitro) and greatly reduced thrombus formation on the outer surface of the sensors are observed in vivo (in canine model) with the NO release PO2 sensors compared to control sensors (without NO release) implanted simultaneously within the same animals. Based on these preliminary studies, the use of NO release polymers to fabricate catheter-style chemical sensors may be a potential solution to lingering biocompatibility and concomitant performance problems encountered when attempting to employ such devices for continuous intravascular measurements of blood gases and electrolytes.     

释放一氧化氮聚合物研究进展

从制备、应用、一氧化氮的释放机制及影响一氧化氮释放的因素几个方面,综述了释放一氧化氮聚合物研究进展;分析了部分释放一氧化氮聚合物的优缺点。     

Improved planar amperometric nitric oxide sensor based on platinized platinum anode. 1. Experimental results and theory when applied for monitoring NO release from diazeniumdiolate-doped polymeric films

An improved miniature amperometric nitric oxide sensor design with a planar sensing tip (ranging from 150 microm to 2 mm in diameter) is reported. The sensor is fabricated using a platinized platinum anode and a Ag/AgCl cathode housed behind a microporous poly(tetrafluoroethylene) (PTFE; Gore-tex) gas-permeable membrane. Platinization of the working platinum electrode surface dramatically improves the analytical performance of the sensor by providing approximately 10-fold higher sensitivity (0.8-1.3 pA/nM), approximately 10-fold lower detection limit (< or =1 nM), and extended (at least 3-fold) stability (>3 d) compared to sensors prepared with bare Pt electrodes. These improvements in performance arise from increasing the kinetics and lowering the required potential for the 3-electron oxidation of NO to nitrate, relative to that observed using a nonplatinized working electrode. The outer porous PTFE membrane provides complete selectivity for NO over nitrite ions (up to 10 mM nitrite). The new sensor is applied for surface measurements of NO released from diazeniumdiolate-loaded silicone rubber films (SR-DACA-6/N(2)O(2)). The effects of sensor size (for sensor dimensions of 0.15-, 1-, and 2-mm o.d.) and the distance of the sensor from the surface of the NO-emitting polymer film are investigated via experiments as well as theoretical calculations. A significant analyte trapping effect is demonstrated, the degree of which depends on the sensor size and its distance from the surface. It is further demonstrated that surface NO concentrations for fresh SR-DACA-6/N(2)O(2) loaded films are also influenced by the polymer film thickness, with thicker films generating higher surface concentrations of NO.     

O/sub 2/ sensing properties of Zn- and Au-doped Fe/sub 2/O/sub 3/ thin films

Zn- and Au-doped iron oxide thin films have been prepared by liquid phase deposition. These films have been characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their performance as oxygen gas sensors has been measured. It has been shown that both the Zn and Au dopants increase the oxygen response of the pure iron oxide films. The XRD and SEM results show that Zn changes both the microstructure and the particles size of the sensing layer through the formation of a solid solution with iron oxide. However, the strong increase in sensitivity to oxygen of the Au-doped Fe/sub 2/O/sub 3/ film has been related to the more favorable chemisorption of oxygen on the small gold particles at the interface with the semiconductor oxide. The results show that Au-doped iron oxide sensors are most promising for oxygen gas sensing.     

多角形非晶粉/硅橡胶复合薄膜压磁性能研究

分别以FeCuNbSiB和FeSiB非晶粉为粉体与硅橡胶复合,制成具有压磁效应的复合薄膜。利用4284A阻抗分析仪对两种薄膜的压磁特性进行了研究。研究表明,非晶FeCuNbSiB粉体/硅橡胶和FeSiB粉体/硅橡胶复合薄膜均具有良好的压磁性能,对于FeCuNbSiB粉体/硅橡胶复合薄膜,在压应力<0.6MPa,频率低于200kHz的条件下,压磁效应敏感;对于FeSiB粉体/硅橡胶复合薄膜在0～1.45MPa内,薄膜的压磁效应变化幅度比较均匀;薄膜中粉体含量越高,复合薄膜的压磁效应越大,当含量为83.3%(质量分数)时,压磁性能最好;相同条件下,以FeCuNb-SiB为粉体制成的复合薄膜的压磁性能优于以FeSiB为粉体制成的薄膜的压磁性能。     

Optical chloride sensor based on dimer-monomer equilibrium of indium(III) octaethylporphyrin in polymeric film

A novel transduction chemistry for preparing optical anion-selective polymeric films that respond reversibly and selectively to chloride ion activity is demonstrated. The chloride sensors are prepared by casting thin (5-10 microm) plasticized PVC films containing indium(III) octaethylporphyrin hydroxide, along with optimized levels of a lipophilic tetraphenylborate salt, onto glass slides. When bathed in low-pH buffered solutions void of chloride, the porphyrin species spontaneously forms a hydroxide ion-bridged dimer, with the added lipophilic borate species serving as the counteranion for this complex. The maximum for the Soret absorption band of this dimeric species is shifted to 390 nm, from 410 nm for the initial monomeric porphyrin. Increases in chloride ion levels in the bathing solution results in chloride extraction and ligation to the In(III) center, and concomitant breaking of the dimer into monomeric porphyrin species, yielding a decrease in absorbance at 390 nm and an increase in optical signal at 410 nm. Under optimized conditions, optical selectivity coefficients toward chloride over a wide range of other anions (NO3-, ClO4-, SCN-, SO4(2-), F-, Br-, H2PO4-) are measured to be < 10(-3). Of all anions tested, only salicylate yields a slightly greater response than chloride. This selectivity is shown to be adequate for reversible and accurate sensing of chloride levels in diluted serum samples.     

Capillary waveguide optrodes: an approach to optical sensing in medical diagnostics

Glass capillaries with a chemically sensitive coating on the inner surface are used as optical sensors for medical diagnostics. A capillary simultaneously serves as a sample compartment, a sensor element, and an inhomogeneous optical waveguide. Various detection schemes based on absorption, fluorescence intensity, or fluorescence lifetime are described. In absorption-based capillary waveguide optrodes the absorption in the sensor layer is analyte dependent; hence light transmission along the inhomogeneous waveguiding structure formed by the capillary wall and the sensing layer is a function of the analyte concentration. Similarly, in fluorescence-based capillary optrodes the fluorescence intensity or the fluorescence lifetime of an indicator dye fixed in the sensing layer is analyte dependent; thus the specific property of fluorescent light excited in the sensing layer and thereafter guided along the inhomogeneous waveguiding structure is a function of the analyte concentration. Both schemes are experimentally demonstrated, one with carbon dioxide as the analyte and the other one with oxygen. The device combines optical sensors with the standard glass capillaries usually applied to gather blood drops from fingertips, to yield a versatile diagnostic instrument, integrating the sample compartment, the optical sensor, and the light-collecting optics into a single piece. This ensures enhanced sensor performance as well as improved handling compared with other sensors.     

Nitric oxide-releasing xerogel-based fiber-optic pH sensors

A xerogel-based optical pH sensor capable of releasing low levels of nitric oxide (NO) and measuring changes in solution pH is reported. Through simple dip-coating procedures, aminoalkoxysilane-based xerogel films modified with N-diazeniumdiolate NO donor precursors and the fluorescent pH indicator seminaphthorhodamine-1 carboxylate (SNARF-1) were sequentially deposited onto optical fibers. The resulting sensors were characterized by fast and linear response to pH throughout the physiological range (pH 7.0-7.8). Real-time chemiluminescence measurements confirmed that the presence of the overlying SNARF-1-containing TMOS layer did not have an inhibitory effect on N-diazeniumdiolate formation or NO release, and the NO-releasing coatings were capable of maintaining NO fluxes >0.4 pmol/cm(2) s up to 16 h. In vitro blood compatibility studies using porcine platelets confirmed the expected thromboresistivity of the NO-releasing xerogel coatings.     

Tailoring of sol-gel films for optical sensing of oxygen in gas and aqueous phase

Sol-gel-based optical sensors for both gas-phase and dissolved oxygen have been developed. Both sensors operate on the principle of fluorescence quenching of a ruthenium complex which has been entrapped in a porous sol-gel silica film. A comprehensive investigation was carried out in order to establish optimal film-processing parameters for the two sensing environments. Both tetraethoxysilane and organically modified sol-gel precursors such as methyltriethoxysilane and ethyltriethoxysilane were used. Film hydrophobicity increases as a function of modified precursor content, and this was correlated with enhanced dissolved oxygen (DO) sensor performance. Extending the aliphatic group of the modified precursor further improved DO sensitivity. The influence of water/precursor molar ratio, R, on the sol-gel film microstructure was investigated. R value tailoring of the microstructure and film surface hydrophobicity tailoring were correlated with oxygen diffusion behavior in the films via the Stern-Volmer constants for both gas phase and DO sensing. Excellent performance characteristics were measured for both gas-phase and DO oxygen sensors. The long-term quenching stability of DO sensing films was established over a period of 6 months.     

FeCuNbSiB/硅橡胶磁性复合薄膜制备及压磁性能研究

以FeCuNbSiB粉为填料,硅橡胶为基体制备了FeCuNbSiB/硅橡胶磁性复合薄膜,并对压磁性能进行了研究.利用4294A 阻抗分析仪,在0～100MHz频率范围内研究了样品的点压磁阻抗效应.结果表明,FeCuNbSiB/硅橡胶复合薄膜具有优越的压磁性能,薄膜的阻抗随着频率的增加而减小.薄膜对微应力变化非常敏感,具有低频压磁特性.当FeCuNbSiB粉末与硅橡胶的质量比为3∶1时的磁性薄膜压磁性能最有规律,压磁稳定性最好.     

Xerogel optical sensor films for quantitative detection of nitroxyl

Xerogel sensing films were synthesized via sol-gel chemistry were used to fabricate optical nitroxyl (HNO) sensors [corrected] Selective detection of HNO in solution was achieved by monitoring the rates of manganese(III) meso-tetrakis(4-sulfonatophenyl) porphyrinate (MnIIITPPS) reductive nitrosylation in the anaerobic interior of aminoalkoxysilane-derived xerogel films. Nitroxyl permeability in sensor films deposited in round-bottom 96-well plates was enhanced via incorporation of trimethoxysilyl-terminated poly(amidoamine-organosilicon) dendrimers in the xerogel network. The selectivity of MnIIITPPS for HNO, the overall sensitivity, and the working dynamic range of the resulting sensors were characterized. The HNO-sensing microtiter plates were used to quantify pH-dependent HNO generation by the recently described HNO-donor sodium 1-(isopropylamino)diazene-1-ium-1,2-diolate (IPA/NO), and compare HNO production efficiency between IPA/NO and Angeli's salt, a traditional HNO-donor.     

硅橡胶富氧膜材料研究进展

介绍了气体膜分离原理和常见的高分子富氧膜材料的透气分离性能,针对硅橡胶富氧膜材料近些年的改性研究进行了综述和分析,指出在高乙烯基含量硅橡胶中加入起到促进传递作用的金属钴络合物、氟元素以及小分子液晶等,能显著改善富氧膜的选择透过性。而利用超临界CO2对硅橡胶富氧膜进行溶胀改性以及在富氧膜材料中添加铁氧体制备所谓的富氧"磁化膜",有望成为未来富氧膜开发研究的一个新方向。     

Nitric oxide-releasing sol-gel particle/polyurethane glucose biosensors

A hybrid sol-gel/polyurethane glucose biosensor that releases nitric oxide is developed and characterized. The biosensor consists of a platinum electrode coated with four polymeric membranes including the following: (1) sol-gel with immobilized glucose oxidase (GOx); (2) polyurethane to protect the enzyme; (3) NO donor-modified sol-gel particle-doped polyurethane; and (4) polyurethane. This configuration was developed due to the drastic reduction in sensitivity observed for NO donor-modified sol-gel film-based glucose sensors. For the hybrid sol-gel/polyurethane biosensor, sol-gel particles are first modified with the NO donor and then incorporated into a polyurethane layer that is coated onto the preimmobilized GOx electrode. In this manner, the GOx layer is not exposed to the harsh conditions necessary to impart NO release ability to the biosensor, and only a minimal decrease in sensitivity due to the NO release is observed. The glucose response of the NO-releasing glucose biosensor and its NO generation profiles are reported. In addition, the stability of the sol-gel particles in the supporting polyurethane membrane is discussed.     

Sol-gel synthesized Sr4Al14O25:Eu2+/Dy3+ blue–green phosphorous as oxygen sensing materials

In this study, we utilized newly synthesized Sr₄Al₁₄O₂₅:Eu²⁺/Dy³⁺ blue–green phosphors along with silver nanoparticles (AgNPs) for fabrication of oxygen sensitive materials. To the best of our knowledge oxygen sensing mechanism of the offered design is totally different from the previously published works. One-component silicone: poly (1-trimethylsilyl-1-propyne), two component phenyl bearing silicone, plasticized polymethylmethacrylate, and ethylcellulose (EC) were tested as matrix materials. Electrospun fibers, porous and smooth thin films were produced by electrospinning or knife coating technique. Oxygen induced luminescence of the phosphors at 544 nm was followed as the analytical signal. Utilization of silver nanoparticles in silicone along with phosphors resulted with a 7.14 fold enhancement in the signal intensity and significant spectral response towards oxygen competing with the signals of the oxygen sensors utilizing metalloporphyrins or ruthenium complexes. We observed high sensitivity and stability, increased surface area and an enhancement in all sensor dynamics. Linearity of the calibration plots was superior for the pO₂ range of 0.0–20.0% with respect to the previously reported ones. When stored at the ambient air of the laboratory there was no significant drift in signal intensity after 12 months. Our sensitivity and stability tests are still in progress.     

Synthesis and characterization of cross-linked silicone thin films by pulsed laser ablation deposition (PLAD)

Stable, uniform and cross-linked silicone films have been synthesized by pulsed laser ablation deposition (PLAD) for the first time. A KrF excimer (248 nm) laser was used in the synthesis. The effect of incident energy density on the deposited film chemistry was examined in depth. The surface analysis showed that at low energy densities (100–150 mJ/cm²), smooth, hydrophobic films similar in structure to the starting cross-linked silicone elastomer were obtained. Beyond 200 mJ/cm², hydrophilic films with oxygen contents much higher than the starting polymer were obtained. These films also exhibited a more particulate texture suggesting ablation of particles and/or polymeric clusters from the silicone target. The results demonstrate that the PLAD process may prove valuable for the preparation of cross-linked silicone thin films with tailored properties. Received: 27 June 2001 / Accepted: 17 July 2001     

Effect of Polymer Loading on Drug Release from Film-Coated Ibuprofen Pellets Prepared by Extrusion-Spheronization

Many factors are capable of influencing the mechanism of drug release from pellets prepared by extrusion-spheronization. This study was designed to elucidate the effect of polymer type and loading and the effect of processing variables on the rate and mechanism of drug release from ibuprofen pellets coated using aqueous polymeric dispersions. Qualitative and quantitative assessment of the success of the film coating process and the quality of the resultant films is made using scanning electron microscopy and in-vitro dissolution testing. The importance of plasticizer in polymeric film formation is also discussed. Uncoated pellets containing 60, 70 and 80% ibuprofen were coated with aqueous polymeric dispersions of polymethacrylates, ethylcellulose and silicone elastomer films. The high drug loading of these pellets adds special interest to this study. Drug release from uncoated pellets appears to follow first-order kinetics. The application of a polymeric membrane to uncoated cores has the effect of retarding drug release. There appears to be a critical coating level below which core coverage by the polymer is incomplete, drug release is diffusion controlled and first-order release kinetics are observed. Above a defined polymer level, drug release appears to be membrane controlled and zero-order kinetics are observed. The presence of plasticizer in the polymeric film imparts a hydrophilic component to an otherwise hydrophobic membrane. This enhances the penetration of aqueous solvent into the pellet core during in-vitro dissolution testing, increasing the rate of drug release. Scanning electron micrographs reveal the nature of these hydrophilic pores, beneath which a fine tortuous skeletal network of drug-depleted core is exposed.     

Material properties of Au-Pd thin alloy films

Thin films of Au-Pd of varying composition were formed by electron beam physical vapor deposition. They were characterized and their application as optical hydrogen sensors was studied. In addition, parameters of sensing performance such as Pd deficiency during deposition, grain size, compositional homogeneity, and the appearance of a natural buffer layer, were examined. Following deposition, Au-Pd films exhibited high atomic intermixing, and a PdO_x buffer layer formed spontaneously. This layer makes it possible to increase film thickness, which improves the intensity of the detecting signal. Accordingly, the suggested deposition method may optimize recent efforts to use Au20 wt.%-Pd thin alloy film in optical hydrogen sensors.     

Hydrophilic modification of silicone elastomer films: Thermal,mechanical and theophylline permeability properties

The improvement of the hydrophilicity of silicone rubber (SR) is sought in many biomedical applications. In the present work, we have prepared neat films coming from condensation-type SR, modified either through blending or end-linking reaction with low molecular weight poly(ethylene glycol) (PEG). The films were studied with respect to their water uptake capacity, stability of embedment of ethylenoxy moieties, and mechanical and thermal properties. Subsequently, we prepared drug-loaded films with theophylline, a relatively hydrophilic model drug, and studied the release performance of these systems. Results on neat films showed that blending increases significantly the overall water uptake of the films and, at the same time, has a limited detrimental effect on their mechanical properties. On the other hand, end-linked films loaded with theophylline exhibited better rate-controlling properties in vitro, due to better dispersion of the sorbed water.     

Fiber-optic luminescent sensors with composite oxygen-sensitive layers and anti-biofouling coatings.

Anti-biofouling polymers containing phosphorylcholine (PC)-substituted methacrylate units have been prepared by copolymerization with dodecyl methacrylate and used to coat luminescent oxygen sensors. Nanometer-sized coatings of such materials are shown to reduce significantly the adhesion of marine bacteria (more than 70%) and thrombocytes (more than 90%) to the surface of tris-(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)-doped silicone layers. A thorough analytical characterization of both the PC-coated and the uncoated dyed films has demonstrated that the anti-biofouling layers do not alter dramatically the performance of the fiber-optic oxygen sensors in aqueous media and are mechanically stable for more than one year of continuous immersion. The slope of the linear calibration plots in the 0-8 mg L(-1) oxygen concentration range (ca. 1.0 L mg(-1)) decreases 8-11% after applying the 50-nm protective layer with no change in the sensor precision (1.1-1.9% RSD, n = 6). The response time of the 200-microm O2-sensitive layers (1.5-6 min) increases up to 2-fold, depending on the nature of the PC polymer used, but the temperature effect on the sensor response (0.020 L mg(-1) degrees C(-1)) remains essentially unchanged. Oxygen detection limits as low as 0.04 mg L(-1) have been measured with the coated optodes. The novel biofouling-resistant optosensors have been successfully validated against a commercial oxygen electrode and are shown to respond faster than the electrochemical device for large oxygen concentration changes. The biomimetic coatings will be particularly useful for drift-free long-term operation of environmental optosensors and in vivo fiber-optic oxygen analyzers.