Vasile V. Cosofret

Flexible (Kapton-based) microsensor arrays of high stability for cardiovascular applications

The design, fabrication and performance characteristics of Kapton-based planar mini and semimicro potentiometric sensors with an Ag/AgCl or a quinhydrone-based redox internal reference electrode are described. The ion-selective membranes cast from conventional and various modified PVC matrices and containing different pH-sensitive ionophores are ranked on the basis of their performances in hostile environments. The adhesive bonding strength of the different PVC membranes to the polyimide-coated Kapton substrate was quantitatively evaluated as a function of fabrication procedure and sample solution contact. The long-term stability of the electrodes was characterized by the alterations of the analytical parameters of the sensors over a period of time, as well as by determining the resistance changes of their sensing membranes.

Responses of H(+) selective solvent polymeric membrane electrodes fabricated from modified PVC membranes.

Potentiometric responses of a novel class of pH sensitive ionophores, namely several phenoxazine derivatives, were tested in different modified PVC matrices. The ionophores were compounded into liquid membranes as usual or were covalently coupled to the polymeric matrix. The general analytical performance of the membranes and other membrane characteristics (i.e., resistance and response time, as measures of membrane decomposition or structural changes) were followed in time. The transient responses of membranes with mobile ionophores in high molecular weight (HMW) and carboxylated PVC (PVC-COOH) were compared to those with immobilized ionophores. The response time of membranes with immobilized ionophores was found to be between those with mobile ionophores in HMW (fast response) and PVC-COOH (sluggish response). Accordingly, the rate of response was correlated primarily to the -COOH content of the membranes.

New neutral carrier-based H+ selective membrane electrodes

H+-selective membrane electrodes based on two neutral ion carriers of the class of phenoxazine derivatives which contain different lipophilic imino chains (9-(diethylamino)-5-octadecanoylimino-5H- benzo[a]phenoxazine and 9-(dimethylamino)-5-[4-(16-butyl-2,14-dioxo-3,15-dioxaeicosyl)phenylimino]- 5H-benzo[a]phenoxazine respectively) are described. Both ionophores, previously used as chromo-ionophores in optode construction, with added potassium tetrakis(p-chlorophenyl) borate (KTpClPB) as cation exchanger sites were embedded into a high molecular weight poly(vinyl chloride) matrix containing o-nitrophenyl octyl ether (o-NPOE) as plasticizer. Both polymeric pH electrodes exhibited near -Nernstian responses over the ranges depending on the pK of the ionophore within the membrane used as electroactive material. The selectivities and other main characteristics of the electrodes are presented.

In vivo and in vitro testing of microelectronically fabricated planar sensors designed for applications in cardiology

SummaryIon-sensitive, planar micro-electrode arrays were fabricated by photolithographic microelectronics technology on a flexible polyimide substrate. The steps of the microelectronics processing are summarized. The electrodes were tested in blood serum, whole blood and in the hamstring muscle of anesthetized rabbits. The performance characteristics of planar pH-sensors are compared with commercial glass electrodes. The close correlation of the data are encouraging for further acute and later chronic applications.

Electroanalytical and biocompatibility studies on carboxylated poly(vinyl chloride) membranes for microfabricated array sensors.

Potassium ion-selective and pH membrane electrodes based on neutral carrier ionophores for K+ (valinomycin) and H+ (TDDA and ETH 5294), respectively, immobilized in carboxylated PVC (PVC-COOH) with normal (classical) and reduced amounts of plasticizer, were investigated with respect to their general analytical performances (linear range, slope, detection limit, selectivity, internal membrane resistance), their biocompatibility and cellular responses. The analytical performance of potassium selective electrodes was not affected by reducing the plasticizer content from 66% (m/m) to about 33% (m/m) while that of pH electrodes was significantly changed at the lower plasticizer concentration level. The adhesive properties of PVC-COOH membranes to an inert substrate such as polyimide-coated Kapton are greatly improved by reducing the plasticizer content of the membrane. In addition, as was reported earlier by this group, improved biocompatibility was observed with these membranes relative to those with increased plasticizer content. A ratio of 1:1 m/m for PVC-COOH to plasticizer is recommended for the construction of planar ISEs without massive use of internal solution.

Design of ionophore-free H+-selective solvent polymeric membranes for further biomedical applications

Abstract Ionophore-free H + -selective solvent polymeric membrane electrodes based on aminated poly(vinyl chloride) (PVC-NH 2 ) are studied. Among the large number of amino-PVC derivatives, the electrodes fabricated from piperazine-modified PVC show the best analytical performances. The new pH electrodes exhibit a Nernstian response between pH 4 and pH 12, and their selectivity coefficients toward biologically interesting cations match the corresponding values of H + electrodes based on TDDA or ETH 5294. The new membrane material offers additional prospects for ion-selective electrode fabrication with technologies used in microelectronic device development.

Anion effects on Donnan failure of aminated-poly(vinyl chloride)-based and neutral-carrier-based pH sensors

Abstract Aminated poly(vinyl chloride)s (PVCs) and neutral carriers can produce nearly ideal pH sensors. However, they can show Donnan exclusion failure in low pH bathing solutions. These pH-sensitive PVC membranes illustrate a new dimension, not found for other mobile neutral-carrier-based sensors, i.e., Donnan failure produces fixed positive sites that create a nearly ideal anion sensor. The modification of Donnan theory is derived and illustrated using carrier-based and aminated-PVC-based sensors.

Development of a diamine biosensor

An amperometric diamine sensor is developed for clinical applications in diagnosis of bacterial vaginosis (BV). The sensor is based on crosslinked putrescine oxidase (PUO) which catalyzes the conversion of diamines (mainly putrescine and cadaverine) to products including hydrogen peroxide. The hydrogen peroxide is detected anodically at platinum electrode polarized at 0.5 V versus Ag/AgCl. Platinum-plated gold electrodes used as a substrate for the sensor construction, are batch-fabricated on a flexible polyimide foil (Kapton(R), DuPont). A three-electrode cell configuration is used in all amperometric measurements. The sensor construction is based on three layers: an inner layer to reject the interference effect of oxidizable molecules, an outer diffusion controlling layer, and in addition, an enzyme middle layer. The enzyme layer was immobilized by crosslinking PUO with bovine serum albumin (BSA) using glutaraldehyde (GA). An optimization study of the enzyme solution composition was carried out. With the optimized enzyme layer, the biosensor showed a very high sensitivity and fast response time of ca. 20 s. The sensor has a linear dynamic range from (0.5-300 muM) for putrescine that covers the expected biological levels of the analyte. Details on sensor fabrication and characterization are given in the present work.

Aliphatic polyurethane as a matrix for pH sensors: effects of native sites and added proton carrier on electrical and potentiometric properties

The potentiometric and impedance characteristics of polymeric membranes, based on aliphatic polyurethane (Tecoflex) as a matrix, are described and interpreted by theory and experiments for H(+) and alkali metal ion-sensitive sensors. Both dummy plasticized membranes and proton carrier-loaded membranes can show pH response. The pH response of dummy membranes is due to protonated natural negative sites in the polyurethane matrix. The electrodes with added proton carrier show improved rejection of Li(+), Na(+), and K(+) responses and give useful analytical responses. Optimal performance requires control of negative site concentration by addition of lipophilic salt (e.g. tetraphenylborate derivatives). Impedance analyses show surface-rate semicircles and, depending on the bathing electrolyte solution, appearance of a diffusional Warburg impedance. In addition to these time-dependence surface region effects, changes in the bulk membrane resistance with soaking time can be well correlated with equilibrium water content of plasticized membranes.

Ion-selective microchemical sensors with reduced preconditioning time. Membrane biostability studies and applications in blood analysis

Abstract Progress on solution of two general problems regarding the use of in vivo planar microchemical sensors is reported. These are issues of short term and long term response stability. Reduction of preconditioning time (hydration period), i.e., the time needed by the planar microchemical sensors based on Kapton® substrate to achieve the optimal analytical performances, has been achieved. By storing the electrodes in containers with humid atmospheres (100% humidity) their short time responses, e.g. measured potential, when placed in samples to be analyzed, are practically constant after one minute of immersion. The electrode sensitivity, potential reproducibility and membrane resistance of both pH and K+ sensors were evaluated and compared before and after placing them in whole blood samples for specified periods of time. Blood serum samples were successfully assayed and the results compared with those obtained with a pH glass electrode and a blood gas analyzer, respectively. The long term stability o...