FR2530962A1 - MEMBRANE FOR CONTROLLING THE PERMEATION OF GLUCOSE THROUGH IT - Google Patents

Abstract

THE INVENTION RELATES TO A MEMBRANE FOR ADJUSTING THE PERMEATION OF GLUCOSE THROUGH IT, INTENDED TO BE FIXED ON A GLUCOSE PROBE OF THE ENZYME ELECTRODE TYPE. IT ALLOWS A HIGH CONCENTRATION OF GLUCOSE IN A SAMPLE TO BE MEASURED WITHOUT THE NEED TO DILUTE OR SUPPLY IT WITH OXYGEN.

Description

The present invention relates to a membrane for adjusting the

  permeation of glucose through it, which is intended to be attached to a

  glucose probe of the enzyme electrode type.

  A glucose probe is known for assaying glucose in a sample using a

  membrane in which glucose oxidase (

  hereinafter referred to as GOD) was fixed to oxidise the

  glucose by dissolved oxygen in the sample.

  The principle of glucose assay in the glucose probe above is based on the following reaction GOD glucose + 2 + H 20 "gluconic acid + H 202 That is, the concentration of glucose in the liquid sample (eg blood sample) is determined indirectly by measuring the concentration of oxygen in the sample or the concentration of hydrogen peroxide formed by the oxidation of glucose by dissolved oxygen in the sample in the presence As the above formula makes clear, the upper limit of the determinable glucose concentration is set by the amount of dissolved oxygen in the sample, and it was impossible to determine glucose at a higher concentration than corresponding to the highest concentration of dissolved oxygen when using the conventional glucose probe in which a fixed GOD membrane is tightly adhered to an oxygen probe membrane Therefore, in the case of the glucose assay present at a higher concentration in a sample, for example, a blood sample taken from a patient with diabetes mellitus or other diseases, it was necessary to oxygen outside the blood sample or dilute the blood sample, which is inconvenient. Consequently, the development of a glucose probe capable of reacting to a high concentration of glucose in a liquid sample, in particular a blood sample, and to inform

  on this one was highly desired.

  The present invention relates to a membrane for regulating the permeation of glucose therethrough for attachment to an enzyme-type glucose probe; by placing such a membrane to regulate the permeation of glucose therethrough (hereinafter referred to as the membrane of the invention) in the conventional glucose probe, it is possible to determine a high concentration of

  glucose in a sample without subjecting the sample

  The present membrane is a hydrophobic membrane whose surface is pierced with pores of 100 microns in diameter and 10 000 / cm 2 in diameter, and consists of a hydrophobic material which allows the permeation of the dissolved oxygen in the sample through it.

  film with a porosity of 25 to 60% with micro-

  pores of less than 0.5 micron polytetrafluoroethylene, polyethylene, polypropylene or polyvinylidene fluoride. The pore size can be chosen at will in the range of 10 to 100 microns in average diameter depending on the material and the thickness of the membrane, and / or the concentration range of glucose in the sample. penetrate through a membrane with pores less than 10 microns in average diameter, and membranes with pore sizes larger than 100 microns can not regulate glucose permeation through them.

  pore form is preferably really

  It is not particularly limited to this form. The number of pores on the surface of the membrane of the invention is 10 to 10,000 / cm 2, and it can be selected as a function of the concentration of glucose in the body. sample, to be more important in the case of a low glucose concentration and lower in the case of a higher concentration.

  high in glucose in the sample.

  It is preferable that the distance between the pores is uniform from the point of view of the

  accuracy of measurement and reaction time.

  The membrane of the invention is naturally permeable to oxygen, and it has become permeable to glucose in proportion to the pores practiced on

its surface.

  Accordingly, when the membrane of the invention is disposed in front of the membrane in front of which GOD has been attached (hereinafter referred to as the "fixed GOD membrane") of the well-known electrode type glucose probe. an enzyme with a Clark or modified Clark type oxygen electrode, the probe thus obtained can measure the high concentration of glucose in the sample without having to be diluted or supplied with

additional oxygen.

  In addition, more than two membranes of the invention

  can be installed in the glucose sensor

  after laminating them or glued to it.

  The following nonlimiting example is given

  as an illustration of the invention.

Example

  Each of the two membranes A and B according to the invention is prepared by piercing in two polypropylene films (DURAGUARDG No. 2500, manufactured by Polyplastics Co) with pores of 100 microns in diameter spaced 0.5 mm apart (membrane A ) or 1.0 mm (membrane B) The membrane thus prepared is placed in a well-known glucose probe equipped with a Clark type oxygen electrode. Then, using the probe thus obtained, the output signal of the probe when the probe is applied to a series of physiological aqueous salt solutions in which a quantity

known glucose has been dissolved.

  The attached figure gives the results obtained. In the appended drawing, the figure shows the relationship between the known concentration of glucose in the physiological aqueous saline solution (abscissa> and the output signal of the glucose probe (on the ordinate), without the membrane of the invention (curve III) and with the membrane of the invention

(curves I or II).

  Comparative Example The output signal of the same probe as in the example is determined (without the membranes of the invention A and B being put in place) by introducing the probe into the same series of physiological aqueous salt solutions in which dissolved a known amount of glucose The results

  are also given by the figure.

  As shown in the figure, the output signal of the probe shows that there is excellent correspondence with the concentration of glucose in the physiological aqueous saline solution in the concentration range of 0 to 700 mg / dl in both cases. use of the membranes of the invention A and B, while the output signal of the conventional glucose probe has lost the correspondence in the range greater than 300 mg / dl.

  In particular, it has been found that the concentration

  Glucose in physiological saline solution could be determined by applying the membrane of the invention to a well-known glucose probe equipped with a Clark type oxygen electrode.

Claims (2)

  Membrane for controlling the permeation of glucose therethrough comprising a hydrophobic membrane having pores of 10 to 100 microns in diameter from 10 to 10,000 pores / cm 2 surface of this membrane.   2 membrane according to claim 1, characterized in that the hydrophobic membrane is a film with a porosity of 25 to 60% consisting of polytetrafluoroethylene, polyethylene,   polypropylene or vinylydene polyfluoride.