Reducing the thrombogenicity of ion-selective electrode membranes through the use of a silicone-modified segmented polyurethane.

The susceptibility of segmented polyurethanes (SPUs) to in vivo oxidative cleavage and hydrolysis constitutes a drawback in the use of these materials in the fabrication of implantable devices. The introduction of poly(dimethylsiloxane) (PDMS) groups into the polymer main chain has been previously reported to enhance the stability of SPUs. Herein, we evaluated the use of BioSpan-S, a silicone-modified SPU, in the design of membranes for cation-selective electrodes. The resulting electrodes exhibited good potentiometric response with all of the tested ionophores (valinomycin, sodium ionophore X, and nonactin). The obtained selectivity coefficients meet the selectivity requirements for the determination of sodium and potassium in blood. Moreover, as reflected by SEM studies, membranes prepared with BioSpan-S showed less adhesion of platelets than membranes prepared with conventional poly(vinyl chloride) (PVC). These results lead to the conclusion that BioSpan-S would be an appropriate candidate for the fabrication of implantable ion-selective electrodes.

Development of a fully integrated analysis system for ions based on ion-selective optodes and centrifugal microfluidics.

A fully integrated, miniaturized analysis system for ions based on a centrifugal microfluidics platform and ion-selective optode membranes is described. The microfluidic architecture is composed of channels, five solution reservoirs, a measuring chamber, and a waste reservoir manufactured onto a disk-shaped substrate of poly(methyl methacrylate). Ion-selective optode membranes, composed of plasticized poly(vinyl chloride) impregnated with an ionophore, a proton chromoionophore, and a lipophilic anionic additive, were cast, with a spin-on device, onto a support layer and then immobilized on the disk. Fluid propulsion is achieved by the centrifugal force that results from spinning the disk, while a system of valves is built onto the disk to control flow. These valves operate based on fluid properties and fluid/substrate interactions and are controlled by the angular frequency of rotation. With this system, we have been able to deliver calibrant solutions, washing buffers, or "test" solutions to the measuring chamber where the optode membrane is located. An analysis system based on a potassium-selective optode has been characterized. Results indicate that optodes immobilized on the platform demonstrate theoretical responses in an absorbance mode of measurement. Samples of unknown concentration can be quantified to within 3% error by fitting the response function for a given optode membrane using an acid (for measuring the signal for a fully protonated chromoionophore), a base (for fully deprotonated chromoionophore), and two standard solutions. Further, the ability to measure ion concentrations by employing one standard solution in conjunction with acid and base and with two standards alone were studied to delineate whether the current architecture could be simplified. Finally, the efficacy of incorporating washing steps into the calibration protocol was investigated.

Flow injection analysis of sulfite ion with a potentiometric titanium phosphate-epoxy based membrane sensor.

A potentiometric sensor based on the use of titanium phosphate (TP) in epoxy matrix membrane is prepared and characterized. The sensor exhibits near-Nernstian response for many anionic species over the concentration range 10(-1)-10(-5) mol l(-1). The origin of response is explained on the basis of the conversion of titanium phosphate cation exchanger into hydrated titanium oxide anion exchanger by the effect of the high pH of the epoxy matrix. The sensitivity and selectivity of the sensor for sulfite ions are optimized by conversion of sulfite into gaseous SO(x) by acidification, and diffusion of the gas through a membrane-based gas dialyzer followed by potentiometric detection of sulfite ions formed within a flowing recipient stream. No interferences are caused by many common anions and acidic gas releasing species except sulfide and nitrite ions. Determination of sulfite ion at levels as low as 10(-4) mol l(-1) or less in the presence of nitrite and sulfide ions is performed by using a modified carrier buffer stream (10(-2) mol l(-1) MES, pH 5.0 containing sulfamic acid) and pretreatment with Pb(2+). Advantages offered by the proposed gas dialyzer/flow injection system with TP-epoxy membrane based sensor over traditional ion exchange based sensors includes long life time (>8 months), excellent stability and reproducibility ( approximately 1 mV), fast response time (<30 s), wide pH working range (pH 5-9), high sample throughput ( approximately 60 samples h(-1)), low detection limit (8x10(-6) mol l(-1)) and high thermal stability (up to 80 degrees C).

Tripodal ionophore with sulfate recognition properties for anion-selective electrodes.

Ionophore topology has a profound effect on the behavior of ion-selective electrodes. This is demonstrated with a new class of ionophores that incorporates aminochromenone moieties linked through urea spacers to different scaffolds that preorganize the ionophore binding cleft into tripodal topologies. Tris(2-aminoethylamine) and cis-1,3,5-tris(aminomethyl)cyclohexane were employed as the scaffolds. The two differ in their rigidity and in the size of ionophore cavity that they create. The electrodes based on the ionophore that incorporates the tris(2-aminoethylamine) scaffold show anti-Hofmeister behavior with an improved selectivity for sulfate. In contrast, the ionophore with the cis-1,3,5-tris(aminomethyl)cyclohexane scaffold exhibits a more Hofmeister-like response.

A selective optical sensor based on [9]mercuracarborand-3, a new type of ionophore with a chloride complexing cavity.

A highly selective optical sensor for chloride, based on the multidentate Lewis acid ionophore [9]mercuracarborand-3, is described herein. This sensor is constructed by embedding the mercuracarborand ionophore, a suitable pH-sensitive lipophilic dye, and lipophilic cationic sites in a plasticized polymeric membrane. The multiple complementary interactions offered by the preorganized complexing cavity of [9]mercuracarborand-3 is shown to control the anion selectivity pattern of the optical film. The film exhibits a significantly enhanced selectivity for chloride over a variety of lipophilic anions such as perchlorate, nitrate, salicylate, and thiocyanate. Furthermore, the optical selectivity coefficients obtained for chloride over other biologically relevant anions are shown to meet the selectivity requirements for the determination of chloride in physiological fluids, unlike previously reported chloride optical sensors. In addition, the optical film responds to chloride reversibly over a wide dynamic range (16 microM-136 mM) with fast response and recovery times.

Mercuracarborand "anti-crown ether"-based chloride-sensitive liquid/polymeric membrane electrodes.

Highly sensitive and selective chloride liquid/polymeric membrane electrodes are described that employ [9]-mercuracarborand-3 (MC3), a neutral preorganized macrocyclic Lewis acid, as the anion carrier. MC3-based chloride-sensitive membrane electrodes, doped with different mole percentages of cationic additives (5, 10, and 60 mol % tridodecylmethylammonium chloride) relative to the amount of the carrier, exhibit enhanced potentiometric selectivity for chloride over other anions, including more lipophilic anions such as perchlorate, nitrate, and thiocyanate. In addition, the selectivity coefficients obtained are shown to meet the requirement for clinical applications. The obtained selectivity pattern is shown to correlate very well with 199Hg NMR titrations of MC3 with various anions, performed in organic solvents. Optimized membrane electrodes show a near-Nernstian response toward chloride over a wide concentration range and have micromolar detection limits. MC3-based chloride sensors show a fast response time (in the order of few seconds), as well as short recovery time. The developed mercuracarborand-based sensors do not practically respond to pH changes over the pH range of 2.5-7.0. Response characteristics (e.g., detection limit, linear range, response slope, and selectivity) of the [9]mercuracarborand-3 based chloride sensors remain essentially the same over a period of approximately 2 months, reflecting remarkable stability and well-defined chemistry of the macrocyclic Lewis acid ionophore.

Green fluorescent protein in the design of a living biosensing system for L-arabinose.

Analysis of monosaccharides is typically performed using analytical systems that involve a separation step followed by a detection step. The separation step is usually necessary because of the high degree of structural similarity between different monosaccharides. A novel sensing system for monosaccharides is described here in which living bacteria were designed to detect a model monosaccharide, L-arabinose, without the need for a separation step. In such sensing systems, analytes are detected by employing the selective recognition properties found in certain bacterial proteins. These systems are designed so that a reporter protein is expressed by the bacteria in response to the analyte. The concentration of the analyte can be related to the signal generated by the reporter protein. In the sensing system described here, the green fluorescent protein (GFP) was used as the reporter protein. L-Arabinose concentrations can be determined by monitoring the fluorescence emitted by the bacteria at 509 nm after excitation of GFP at 395 nm. The system can detect L-arabinose at concentrations as low as 5 x 10(-7) M and is selective over D-arabinose, the stereoisomer of the analyte, as well as over a variety of pentose and hexose sugars.

Electrochemical assay of proteinase inhibitors using polycation-sensitive membrane electrode detection.

A simple and sensitive electrochemical method suitable for real time detection of trypsin-like proteinase inhibitors is described. The method is based on utilizing a protamine (a polycationic substrate for trypsin-like proteinases)-sensitive membrane electrode to monitor, potentiometrically, the initial rate of protamine decomposition upon the addition of a proteinase-antiproteinase test solution. In the presence of proteinase inhibitors, the initial rate of change in electromotive force is dependent on the concentration of proteinase inhibitor in the sample solution. The feasibility of this new assay method is demonstrated by detecting four inhibitors of trypsin-like proteinases: alpha1-antiproteinase inhibitor, alpha2-macroglobulin, aprotinin, and soybean inhibitor, using trypsin as the indicator proteinase. The efficacy of inhibition by each species, as expressed by I50 values (concentration of the inhibitor that induces 50% of the maximum proteinase inhibition), is shown to correlate well with literature values for the association constant of the proteinase-antiproteinase complex (k[assoc]). The proposed electrochemical assay for aprotinin is examined further using trypsin, plasmin, and kallikrein as the proteinase indicator reagents. It is found that the trypsin-aprotinin system offers the highest sensitivity and lowest detection limit for aprotinin detection. Application of the proposed method for measuring aprotinin in pretreated plasma samples is also reported.

Potentiometric anion selectivity of polymer membranes doped with palladium organophosphine complex.

The potentiometric anion selectivity of polymer membrane-based electrodes formulated with a palladium organophosphine complex (benzylbis(triphenylphosphine)palladium(II) chloride) as the membrane active component is examined. The electrode is shown to exhibit a non-Hofmeister selectivity pattern with a significantly enhanced response toward nitrite over the concentration range of 10 microM-10 mM (log-linear range) and a detection limit 5.0 microM. The effect of lipophilic anionic (tetraphenylborate derivatives) and cationic (tetraalkylammonium) site additives within the membrane on the anion selectivity is examined in detail. Addition of both cationic and anionic sites is shown to improve potentiometric anion selectivity, suggesting that the palladium complex may operate simultaneously as a neutral and charged carrier-type ionophore within the polymer membrane phase. Using optimal membrane formulations (with added 20-30 mol % cationic sites), the sensors prepared with the palladium complex do not exhibit proton/hydroxide response in the range of pH 3.5-12, a potential advantage over previously reported nitrite electrodes prepared with Co(III) corrins and porphyrin complexes.

PVC Membrane electrodes for manual and flow-injection determination of tetraphenylborate: Applications to separate and sequential titrations of some metal ions.

Three novel poly (vinyl chloride) matrix membrane electrodes, highly sensitive and selective for tetraphenylborate anion (TPB), are developed and electrochemically evaluated. They are based on the use of iron(II) bathophenanthroline, nickel(II) bathophenanthroline-and nitron-TPB ion-pair complexes as electroactive materials with dioctylphthalate (DOP) and 2-nitrophenyl phenyl ether (NPPE) as plasticizing solvent mediators. The electrodes exhibit stable and rapid near-Nernstian response for 10(-2)-10(-6)M TPB over the pH range 4-10. Use of these electrodes for direct potentiometric determination and potentiometric titration of as low as 1 mug of TPB/ml and 0.6 mg of TPB/ml give results with average recoveries of 99.3% (mean standard deviation 0.5%) and 99.4% (mean standard deviation 0.2%), respectively. Incorporation of nitron-TPB PVC sensor in a flow-through sandwich cell provides an efficient flow-injection detector for determining TPB with an input rate of at least 60 samples/hr. The limit of detection is 1.6 mug TPB/ml in a 20-mul sample. The electrodes are also used to monitor separate and sequential titrations of some metal ions with TPB. Alkaline earth and transition-metal ions upon reaction with polyethylene glycol and ethylenediamine, respectively, form cationic complexes readily titrated with TPB. Optimum conditions are outlined for sequential titrations of various combinations of metallic species.