US-20260126393-A1 - METHOD FOR DETERMINING THE LITHIUM CONTENT IN A BIOLOGICAL FLUID

US20260126393A1US 20260126393 A1US20260126393 A1US 20260126393A1US-20260126393-A1

Abstract

Method for determining an amount of lithium contained in a biological fluid, said method comprising the steps consisting in adding, to a biological fluid sample of known volume, a given volume of a discriminating solution, the effect of which is to obtain a biological fluid solution buffered at a pH of between 6 and 8 and to bring about precipitation of at least a portion of the cations contained in the biological fluid sample except for the lithium ions. The method further comprises the steps consisting in depositing a given volume of biological fluid solution on an active layer ( 2 ) of an optode ( 1 ), said active layer comprising a chemical transducer of which at least one optical property is modified in the presence of lithium ions in the biological fluid solution, in measuring at least one characteristic of at least one light wave emitted or reflected by the active layer of the optode and in determining, from the at least one measured characteristic and from calibration data, an amount of lithium contained in the biological fluid.

Inventors

Bruno Wacogne
Charles-Louis AZZOPARDI
Bernard Gauthier-Manuel
Karine CHARRIERE

Assignees

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
UNIVERSITE DE FRANCHE-COMTE
CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE BESANCON
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

Dates

Publication Date: 20260507
Application Date: 20231002
Priority Date: 20221004

Claims (10)

1 . A method for determining an amount of lithium contained in a biological fluid, comprising: adding, into a sample of biological fluid of known volume, a given volume of a discriminating solution having the effect of: obtaining a solution of biological fluid buffered at a pH comprised between 6 and 8, and thereby causing a precipitation of at least a part of the mono- and di-cations contained in the sample of biological fluid with the exception of lithium ions; depositing a given volume of solution of biological fluid on an active layer of an optode, wherein said active layer comprises a chemical transducer of which at least one optical property is modified in the presence of lithium ions in the solution of biological fluid; measuring at least one characteristic of at least one light wave emitted or reflected by the active layer of the optode; and determining, from at least one characteristic measured and from calibration data, a quantity of lithium contained in the biological fluid.
2 . The method according to claim 1 , comprising, prior to the step of adding the discriminating solution, a step of filtering the solution of biological fluid on a porous membrane having a cut-off threshold of less than or equal to 50 μm.
3 . The method according to claim 1 , wherein the discriminating solution is a buffer solution not comprising magnesium and calcium and/or sodium and potassium cations.
4 . The method according to claim 1 , wherein the discriminating solution is a buffer solution comprising no di-cations and/or mono-cations except for hydronium ions.
5 . The method according to claim 1 , wherein the buffer solution is a pH 7 buffer solution of tris(hydroxymethyl)aminomethane:HCl.
6 . The method according to claim 1 , wherein the discriminating solution is an aqueous solution comprising oxalate ions at a concentration greater than 1 mM.
7 . The method according to claim 1 , wherein the at least one characteristic of the at least one light wave emitted or reflected by the active layer of the optode comprises a hue value of the active layer.
8 . The method according to claim 1 , further comprising a step of processing the at least one measured characteristic of the at least one light wave emitted or reflected by the active layer of the optode: wherein the at least one characteristic measured comprises a set of colorimetric values in a colorimetric space, comprising: a change of coordinate frame, within the colorimetric space, carried out on the two dimensions of the colorimetric space, denoted by XY, then a projection on the Y axis of the colorimetric space of the measured colorimetric values.
9 . An optode for implementing the method according to claim 1 , wherein said optode comprises: a white support made of chemically inert material; an active layer resting on the support, said active layer comprising a chemical transducer arranged so that at least one optical property is modified in the presence of a specific ionic species; and a black layer made of chemically inert material comprising at least one opening forming a well arranged to receive a solution to be analyzed and intended to be in contact with the active layer.
10 . The optode according to claim 9 , wherein: the active layer comprises an ionophore and a chromophore, and the chemically inert material is poly(methyl methacrylate) (PMMA).

Description

TECHNICAL FIELD The present invention relates to the field of determining the amount of lithium contained in biological or body fluids by means of an optode. More particularly, the present invention relates to the monitoring of lithium levels at home by persons who suffer from mood disorders and who receive a lithium treatment such as, but not limited to, bipolar disorder or in combination with other treatments for resistant depressive disorders. PRIOR ART The product sold by FISIC under the trade name “Medimate Multireader” is known in the prior art. This device can be used by a user for measuring their level of lithium in the body. The measurement is accurate because same is based on electrophoresis. However, the analysis requires the collection of a blood sample from the user, which is an invasive procedure. The use of an optode for the determination of the level of lithium in biological fluids is also known in the prior art. The document of Albero et al., “Novel flow-through bulk optode for spectrophotometric determination of lithium in pharmaceuticals and saliva”, Sensors and Actuators B, 145, (2010) 133-138 describes the determination of the concentration of lithium in saliva by means of an optode using spectrophotometry. A further goal of the invention is to propose a method for determining the level of lithium in a biological fluid: making it possible to determine the level of lithium at a concentration of less than 5 mM, and/ormaking it possible to determine the level of lithium in the saliva, and/orat low cost, and/orsimple to implement, and/orallowing the user to carry out the process themselves and at home. PRESENTATION OF THE INVENTION To this end, a method for determining a quantity of lithium contained in a biological fluid is proposed. The method comprises the steps consisting of: obtaining, from a sample of biological fluid of known volume, a solution of biological fluid buffered at a pH comprised between 6 and 8, denoted as step A,adding, to the solution of biological fluid, a given volume of a discriminating solution having the effect of leading to the precipitation of at least a part of the cations contained in the solution of biological fluid with the exception of lithium ions, denoted as step B,depositing a volume, preferably a given volume, of solution of biological fluid on an active layer of an optode; said active layer comprises a chemical transducer of which at least one chemical property is modified in the presence of lithium ions in the solution of biological fluid, denoted as step C,measuring at least one characteristic of one light wave emitted or reflected by the active layer of the optode, preferably by the chemical transducer,determining, from at least one characteristic measured and from calibration data, a quantity of lithium contained in the biological fluid. The solution of biological fluid may be any liquid or viscous solution, preferably aqueous, containing lithium ions. Steps A, B can be implemented in any chronological order. Preferably, step C is implemented subsequently to steps A and B. Preferably, steps A and B form a one and same step consisting in adding, to a sample of biological fluid of known volume, a given volume of a discriminating solution having the effect of: obtaining a solution of biological fluid buffered at a pH comprised between 6 and 8, andprecipitating at least part of the cations contained in the sample of biological fluid with the exception of lithium ions. Preferably, the discriminating solution has the effect of precipitating the di-cations contained in the solution of biological fluid, more particularly magnesium and calcium ions. Preferably, the discriminating solution precipitates the mono-cations contained in the solution of biological fluid, with the exception of lithium ions, more particularly potassium and sodium ions. Preferably, the discriminating solution precipitates all cations, with the exception of lithium ions, contained in the solution of biological fluid. Preferably, obtaining a solution of biological fluid buffered at a pH comprised between 6 and 8 has the effect of dispensing with the influence of at least part of the cations contained in the solution of biological fluid, preferably the di-cations, preferably the calcium and magnesium ions, and the mono-cations, with the exception of lithium ions, contained in the solution of biological fluid, preferably potassium and sodium ions, on the uptake of lithium by the active layer of the optode. Preferably, the biological fluid may be blood or saliva. In the context of monitoring the level of lithium at home by the user themselves, saliva is preferably the preferred biological fluid. Preferably, the method does not comprise any invasive step of collecting the sample of biological fluid. The manufacturing method comprises a step of obtaining a biological fluid. The term “given” can be defined as determined or known. Preferably, the at least one optical property is modified compa