Chemistry: analytical and immunological testing – Nitrogen containing – Urea or blood urea nitrogen
Patent
1997-04-17
2000-09-05
Snay, Jeffrey
Chemistry: analytical and immunological testing
Nitrogen containing
Urea or blood urea nitrogen
436150, 436174, 435 12, G01N 2706
Patent
active
061141763
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a method and a device for measuring the concentration of urea or a similar substance in a composite solution. The concentration of urea is difficult to measure directly, and therefor, urea is catalytically decomposed by urease and the differential conductivity is measured.
The solution is preferably a medical solution but can also be a biological solution such as plasma. The invention relates particularly to the measurement of the concentration of urea in connection with dialysis.
STATE OF THE ART
The present invention is based on the technique which is disclosed in EP-A2-0 437 789. This patent document discloses a system for measuring of for instance the urea concentration in a complex solution by decomposing urea into ammonium ions catalyzed by urease. It is difficult to measure the urea directly and it must first be converted into ammonium ions. The change in the conductivity due to the contribution of the ammonium ions is measured by means of a conductivity meter.
In DE-C1-39 00 119 a urea sensor of similar type is described. A capillary is positioned in a tube, through which blood passes. By means of the capillary, plasma is drawn out of the blood and is allowed to pass a urease column. The difference in conductivity before and after the urease column is measured and the difference is correlated to the urea content. In order to keep the temperature constant in the measuring apparatus the dialysis fluid is circulated in a closed loop around the urease column and the two conductivity measurement cells.
Document JP-60-165551 discloses a similar arrangement, where an ion exchange column is used to remove electrolytes by means of anion-cation-exchange. In this way, the accuracy of the measured values are considerably improved since the relative change in the conductivity becomes larger due to the fact that the initial conductivity is lower or almost zero. Furthermore a buffer is added.
Document U.S. Pat. No. 3,930,957 describes a urea sensor, where an organic buffer solution is added. As an example a solution of 0,05 M Tris(hydroxymethyl)aminomethane can be used, which is adjusted to a pH-value of about 6-7 by addition of glycine.
DISCLOSURE OF INVENTION
The object of the present invention is to provide a method and a device for measuring the concentration of urea, or a similar substance, in a composite solution by heterogenous catalytic reaction of urea with urease in a reactor column for decomposing thereof, and measuring the differencial conductivity between reacted solution and unreacted solution for providing an indication of the concentration of urea in said solution. According to the invention, carbon dioxide is added to the solution, which comprises hydrogen carbonate ions, before the reaction in the reactor column. The carbon dioxide, together with the hydrogen carbonate ions form a buffer maintaining the pH-value of the solution within predetermined limits. At the same time, the carbon dioxide contributes to making the relationship between the differential conductivity and the concentration of urea linear over a large range. The addition of carbon dioxide also results in that each urea molecule is decomposed into four ions, each contributing to the increase of conductivity.
The carbon dioxide is added in gas form, and preferably in such an amount that the solution is substantially saturated with carbon dioxide. In order to further increase the solubility of carbon dioxide gas in the solution, the pressure of the solution can be raised and/or the temperature of the solution can be lowered. In this way it is assured that a sufficient amount of carbon dioxide is dissolved in the solution for making the relationship linear over as large a range as possible.
The differential conductivity between reacted and unreacted solution can be measured by a single conductivity cell. The unreacted and reacted solutions can be switched to the single conductivity cell in sequence. In this way the two measurements are as equal as possible independently o
REFERENCES:
patent: 3930957 (1976-01-01), Cummings et al.
patent: 4311789 (1982-01-01), Nylen et al.
patent: 4465770 (1984-08-01), Modrovich
patent: 5244811 (1993-09-01), Matthews
patent: 5382525 (1995-01-01), Spencer
patent: 5698083 (1997-12-01), Glass
Patent Abstracts of Japan, vol. 10, No. 9, P-420, abstract of JP, A, 60-165551 (Yokokawa Hokushin Denki K.K.), Aug. 28, 1985.
Edgson Raymond
Goodman-Jones Arfon
Olde Bo
Olsson Lars-Fride
Gambro AB
Snay Jeffrey
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