Electrochemistry in Diabetes Management

Abstract

Diabetes devastates lives and burdens society. Hypoglycemic (low glucose) episodes cause blackouts, and severe ones are life-threatening. Periods of hyperglycemia (high glucose) cause circulatory disease, stroke, amputations, blindness, kidney failure and nerve degeneration. In this Account, we describe the founding of TheraSense, now a major part of Abbott Diabetes Care, and the development of two products that have improved the lives of people with diabetes. The first, a virtually painless microcoulometer (300 nL volume), the FreeStyle blood glucose monitoring system, was approved by the FDA and became available in 2000. In 2009, this system was used in more than one billion blood assays. The second, the enzyme-wiring based, subcutaneously-implanted FreeStyle Navigator continuous glucose monitoring system, was approved by the FDA and became available in the United States in 2008. The strips of the FreeStyle blood glucose monitoring system comprise a printed parallel plate coulometer, with a 50 microm gap between two facing printed electrodes, a carbon electrode and a Ag/AgCl electrode. The volume of blood between the facing plates is accurately controlled. The glucose is electrooxidized through catalysis by a glucose dehydrogenase (GDH) and an Os(2+/3+) redox mediator, which is reduced by the glucose-reduced enzyme and is electrooxidized on the carbon electrode. Initially the system used pyrroloquinoline quinone (PQQ)-dependent GDH but now uses flavin adenine dinucleotide (FAD)-dependent GDH. Because the facing electrodes are separated by such a small distance, shuttling of electrons by the redox couple could interfere with the coulometric assay. However, the Os(2+/3+) redox mediator is selected to have a substantially negative formal potential, between 0.0 and -0.2 V, versus that of the facing Ag/AgCl electrode. This makes the flow of a shuttling current between the two electrodes virtually impossible because the oxidized Os(3+) complex cannot be appreciably reduced at the more positively poised Ag/AgCl electrode. The FreeStyle Navigator continuous glucose monitoring system uses a subcutaneously implanted miniature plastic sensor connected to a transmitter to measure glycemia amperometrically and sends the information to a PDA-like device every minute. The sensor consists of a narrow (0.6 mm wide) plastic substrate on which carbon-working, Ag/AgCl reference, and carbon counter electrodes are printed in a stacked geometry. The active wired enzyme sensing layer covers only about 0.1 mm(2) of the working electrode and is overlaid by a flux-limiting membrane. It resides at about 5 mm depth in the subcutaneous adipose tissue and monitors glucose concentrations over the range 20-500 mg/dL. Its core component, a miniature, disposable, amperometric glucose sensor, has an electrooxidation catalyst made from a crosslinked adduct of glucose oxidase (GOx) and a GOx wiring redox hydrogel containing a polymer-bound Os(2+/3+) complex. Because of the selectivity of the catalyst for glucose, very little current flows in the ab...

Enzymatic Electrosynthesis: An Overview on the Progress in Enzyme- Electrodes for the Production of Electricity, Fuels and Chemicals

“…GOx is a well characterized and stable enzyme which catalyzes the oxidation of glucose to glucanolactone [242]. Several studies were performed to increase the electron transfer in GOx, especially based on using carbon nanotubes (CNTs) and gold nanoparticles [30,36,99,109,156,225,228,[243][244][245][246][247], by using mediators such as ferrocene derivatives [59,248,249], by coordination complexes of osmium with polymers [243,[250][251][252][253][254][255][256][257], by protein modification and engineering to achieve improved GOx properties [258][259][260] etc. Likewise, the other enzymes such as GDH, alcohol dehydrogenases were also studied from different sources and with various enhancing strategies in e-BES [14].…”

Specific ion effects on the electrochemical properties of cytochrome c

“…[1][2][3] Cytochrome c (cyt c) is an electron transport protein comprised of a heme group and a 104 amino acid residue organized into a series of five -helices and six -turns. 4 It is one of the most extensively studied redox proteins and 30 has been widely used as a model to study electron transfer in proteins.…”

Advances in carbon nanotube based electrochemical sensors for bioanalytical applications

“…However, a novel FAD-dependent glucose dehydrogenase was reported and this enzyme is very specific to glucose and uses a ferricyanide mediator (Tsujimura et al, 2006). This enzyme is currently used by Abbott ( (Heller and Feldman, 2010) and Bayer (Toghill and Compton, 2010) for in vivo glucose sensing with linearity ranging from 1 to 30 mM.…”

“…One of the main reasons is the exorbitant cost of introducing a new device to compete with existing technologies. As an example, the cost of introducing a continuous glucose monitoring system is over US100 million, which is beyond the means of a small enterprise (Heller and Feldman, 2010).…”