Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Patent
1992-10-19
1995-01-03
Warden, Robert J.
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
20415312, 204403, 422 8201, 435817, G01N 2726, G01N 27327
Patent
active
053786289
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The instant invention relates to a sensor for measuring the amount of a component in solution designed to be used in an amperometric device for measuring the concentration of said component in the solution. This sensor is in particular suitable for analysing glucose.
BACKGROUND OF THE INVENTION
Many patients with diabetes frequently have to measure their blood glucose level, or glycemia. If they detect a state of hyperglycemia they immediately have to take medication to regulate their glucose level. To simplify the daily life of these patients, numerous miniaturized glucose measuring devices which can be used by a layperson have appeared on the market.
The implantation of insulin pumps in diabetics has also been proposed. These insulin pumps have to be supplied with devices for measuring glucose that can also be implanted and which, as a function of the glycemia measured, supply information to the pump and possibly start it operating.
The majority of these devices for measuring glycemia use an enzyme specific to glucose--glucose oxidase (GOD).
As shown in the appended FIG. 1, GOD is a flavoprotein (obtained for example from moulds) which catalyses the oxidation of glucose, in this case for example blood glucose, into gluconolactone, with the formation of hydrogen peroxide H.sub.2 O.sub.2, starting from the molecular oxygen O.sub.2 present in the solution to be tested, in this case blood.
This enzyme (GOD) and oxygen have thus frequently been used in devices for measuring glucose in which the oxidation of the glucose was detected by an electrical or optical transducer.
Similarly, this enzyme (GOD) and oxygen have frequently been used in amperometric devices and their use is described in the literature.
These amperometric devices comprise on the one hand a measuring apparatus provided with at least two electrical contacts connected to an ammeter and to display means and, on the other hand, a sensor which may be disposable and which can be connected to these two electrical contacts. This sensor comprises at least two electrodes: a reference electrode and a measuring electrode. The measuring electrode comprises a metal conductor coated with an enzyme specific to the product to be detected.
The appended FIG. 2 illustrates the chemical reactions occurring on the surface of this measuring electrode. When the solution to be tested is deposited on the measuring electrode, the product to be tested (in this case glucose) reacts with the enzyme (in this case the oxidized GOD) located on the electrode to form gluconolactone while the GOD passes into the reduced state [GOD(H.sub.2).sub.(red) ]. This reduced GOD then reacts with oxygen O.sub.2 which passes into the reduced state H.sub.2 O.sub.2 and which then transfers two electrons e.sup.- towards the electrical conductor C, the potential of which is fixed and is in the region of 650 mV. The fact that it is necessary to work at elevated potentials causes additional interference problems. The oxygen thus plays the part of mediator since it permits the transfer of electrons. This transfer of electrons, which is proportional to the amount of glucose present in the solution to be tested, is then measured by the ammeter and the amount of glucose present in the solution is displayed by the display means of the measuring apparatus.
Additional research has shown that amperometric devices using non-physiological, organic, inorganic or organometallic mediators can supplant devices using oxygen as the mediator. Indeed, as shown in FIG. 2, devices using oxygen as the mediator cannot be used in solutions where the stoichiometric oxygen content is less than the concentration of the component to be measured. Otherwise, in this case, while the total amount of the component to be measured is able to react with the oxidized enzyme to form the reduced enzyme, only part of the total amount of the reduced enzyme can react with the oxygen present, in proportion to this amount of oxygen. The rest of the reduced enzyme is unable to react and the quantity of electrons transm
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Fraser David
Frenkel Erik J.
Gratzel Michael
Randin Jean-Paul
Zakeeruddin Shaik M.
Asulab S.A.
Carpenter Robert
Warden Robert J.
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