Electrochemical Sensor Array for Glucose Monitoring Fabricated by Rapid Immobilization of Active Glucose Oxidase within Photochemically Polymerized Hydrogels

Abstract

Background:Currently, monitoring blood glucose levels for diabetic patients is invasive and painful, involving pricking the finger to obtain a blood sample three to four times daily. The need for frequent tests and pain involved with testing leads to poor compliance. In order to raise compliance, we propose to create an implantable electrochemical sensor array that would monitor glucose levels continuously. Methods:Glucose sensor arrays were fabricated on gold electrodes on flexible polyimide sheets by photopolymerization of the biocompatible polymer poly(ethylene glycol) diacrylate (PEG-DA) to develop hydrogels and encapsulate the sensing elements. Using conventional silicon fabrication methods, arrays of five gold microdisk electrodes were fabricated using lift-off photolithography and sputtering techniques. A redox polymer was then attached electrostatically to the electrode, and glucose oxidase was entrapped inside the hydrogel on the array of electrodes by ultraviolet-initiated photopolymerization of PEG-DA. Results:When the array of fabricated sensors was sampled together the elements behaved like one large electrode with peak current equivalent to the sum of individual array elements. The enzyme, glucose oxidase, catalyzed the oxidation of glucose and then exchanged electrons with the redox polymer in the hydrogel. The entrapped glucose oxidase was found to respond linearly to increasing glucose concentrations (0-360 mg/dl), as determined using cyclic voltammetry. Conclusion:The fabricated microarray sensors were individually addressable and showed no cross talk between adjacent array elements as assessed using cyclic voltammetry. We have fabricated an array of glucose sensors on flexible polyimide sheets that exhibits the desired linear response in the biological range.

Redox Protein-Polymer Films for Simultaneous Determination of Ascorbic Acid and Hydrogen Peroxide

“…We recently used the redox polymer, poly[4-vinylpyridine Os(bipyridine)2Cl]-co-ethylamine (Pos-Ea) to assemble films with the polymer exchanging electrons with glucose oxidase. 24,25 Determination of concentration of ascorbic acid does not interferer with determination of hydrogen peroxide. …”

Carbon nanofiber modified with osmium based redox polymer for glucose sensing

“…The oxidation peak for polymer by itself on the electrode surface appeared at 0.39 V while the reduction peak appeared at about 0.29 V. In earlier literature, the redox polymer trapped in polyethylene glycol gel still gave similar voltammograms but the peak current was unstable after continuous scanning [31,32]. For the redox polymer modified nanofibers, scanning several times over three weeks yielded the same peak current, indicating thus a good stability of redox polymer adsorbed on CNF.…”

“…Glucose oxidase (GOX) is the most popular enzyme extensively used in fabrication of electrochemical glucose biosensor [5] as well as in other bio-catalytic systems [6,7]. Previously, osmium based redox polymer was used as a mediator entrapped together with GOX hydrogels through the UV-initiated free radical cross-linking [1,2].…”

“…There is continuous interest in low cost, stable and sensitive biosensors for glucose. Many glucose sensing platforms have been developed using glucose oxidase enzyme and various forms of redox mediators on electrodes [1][2][3][4]. Glucose oxidase (GOX) is the most popular enzyme extensively used in fabrication of electrochemical glucose biosensor [5] as well as in other bio-catalytic systems [6,7].…”

Redox polymer covalently modified multiwalled carbon nanotube based sensors for sensitive acetaminophen and ascorbic acid detection

“…Other work in the literature has involved noncovalent bonding of nanotubes with polymers including poly(aminoquinone) [19], poly(vinylimidazole) complexed with Os(4,4 -dimethylbpy) 2 Cl [20], polypyrrole [21,22], and poly(ethylene glycol) [23] to make the nanotubes biocompatible. Recently, we used biocompatible PEG-DA hydrogel networks to physically trap both the redox polymer and glucose oxidase on polyimide sheets for glucose sensor applications [24,25]. The osmium-based redox polymer replaced oxygen as a non-physiological electron acceptor in the reaction.…”