WO2015101411A1 - Device and method for determining the crystallization probability of a salt in a liquid sample containing ions - Google Patents

Device and method for determining the crystallization probability of a salt in a liquid sample containing ions Download PDF

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Publication number
WO2015101411A1
WO2015101411A1 PCT/EP2014/003470 EP2014003470W WO2015101411A1 WO 2015101411 A1 WO2015101411 A1 WO 2015101411A1 EP 2014003470 W EP2014003470 W EP 2014003470W WO 2015101411 A1 WO2015101411 A1 WO 2015101411A1
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Prior art keywords
substance
reaction zone
mixture
indicator
further
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PCT/EP2014/003470
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German (de)
French (fr)
Inventor
Heinz Busch
Udo Grabowy
Norbert Laube
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NTTF Coatings GmbH
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/06Crystallising dishes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/84Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving inorganic compounds or pH
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0621Control of the sequence of chambers filled or emptied
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16Reagents, handling or storing thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087Multiple sequential chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0677Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0688Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/08Regulating or influencing the flow resistance
    • B01L2400/084Passive control of flow resistance
    • B01L2400/086Passive control of flow resistance using baffles or other fixed flow obstructions

Abstract

The invention relates to a device for determining the crystallization probability of a salt in a liquid sample containing ions, said device having at least one measuring channel (10) comprising an open end, an end sealed off from the liquid and a defined volume, and having an inlet opening (18) for the introduction of the liquid sample. The open end of the measuring channel (10) is coupled to the inlet opening (18). The measuring channel (10) comprises at least one first reaction zone (12) at the open end of the measuring channel (10) and a final reaction zone (16) at the end of the measuring channel sealed off from the liquid (10). A phase boundary (40) is formed between the neighbouring reaction zones (12, 14, 16), said boundary being permeable to the liquid sample but being formed such that the transfer of the liquid sample slows down between the neighbouring reaction zones (12, 14, 16). A first reservoir (28) comprising a substance or a mixture of substances is associated with the first reaction zone (12), such that the substance or the mixture of substances is added to the liquid sample in the first reaction zone (12). A final reservoir (32) comprising an indicator or a mixture of indicator substances is associated with the final reaction zone (16), such that the indicator or the mixture of indicator substances is added to the liquid sample in the final reaction zone (16). The substance or the mixture of substances together with the ions of the liquid sample form the salt for which the crystallization probability is to be determined. The indicator or the mixture of indicator substances indicates the salt for which the crystallization probability is to be determined.

Description

description

Apparatus and method for determining the probability of crystallization of a salt in a liquid ion-containing sample

The invention relates to an apparatus and method for determining the probability of crystallization of a salt in a liquid ion-containing sample. In particular, the invention relates to apparatus and a method for determining the probability of crystallization of calcium oxalate in a urine sample.

In many applications it is advantageous to be able to estimate the probability of a particular crystallization salt in a liquid ion-containing sample. In principle there is the possibility that concen- ration of the relevant ions in the sample to be determined and to specify the amount of potential reactant or to determine therefrom and estimate the probability of crystallization of the salt or to calculate. However, the salt formation depends in liquids with a complex composition not only by the amounts of the primary reaction partners involved, but also on the presence of other constituents and their interactions from.

One such application is the determination of the probability of crystallization of calcium oxalate in a urine sample. By the crystallization of calcium oxalate urinary stones called arise. Calcium oxalate is the essential ingredient of urinary stones. Urinary stones are formed of constituents of the urine in the body. Urinary stones are crystalline concretions with a size of a few tenths of a millimeter to several centimeters. Currently, there are no sufficiently accurate, simple and cost-effective means and methods available to determine the crystallization probability of a urine sample at a Harnsteinpatienten or a vulnerable person. One criterion for the risk of urinary stone is the so-called Bonn Risk Index. The Bonn-risk index is determined from a native urine sample with an induced crystallization test, whereby all dissolved and not dissolved organic and inorganic constituents in their native urine concentration ratios and mutual complex interactions are taken into account. This approach simulates in a urine sample which take place in the body processes of urinary stones. The the formal genesis of urolithiasis associated physicochemical processes of nucleation, crystal growth and crystal aggregation of a specific mineral phase are determined with respect to this stage from the actual interactions in the electrolyte system, the ionic strength and the resulting urine supersaturation. The urine supersaturation is the thermodynamic driving force for precipitation and crystallization processes.

Because of the chemical complexity of the urine analyzes of selected urinalysis can, however, capture only individual distinct causes of impaired urine composition. Also, risk indices, which are based on the empirical link between the concentrations of several different urinalysis may very model capture the crystallization probability. As expected, the Bonn-risk index which covers all physicochemical risk factors, because of its methodological approach a higher diagnostic sensitivity and higher specificity than laboratory diagnostic model values.

However, many Harnsteinpatienten show no distinct pathological urinary, ie they are considered idiopathic Harnsteinbildner. Here, the crystallization either result of the urine composition, the disruption is due to an analytically not accessible, but lithogenetisch significant, component, or in an unfavorable, but not detectable, concentration ratio of known urine components to each other. The investigation of the concentrations of individual urinalysis alone can not meet the analytical requirements of a modern individualized treatment of stone disease also. Previous approaches to determine the Bonn Risk Index are consuming. The Bonn-risk index can be determined in a research laboratory and / or complex devices. The known measuring methods are not feasible due to the enormous technical and scientific costs and the high investment required for use in a doctor's office or in a small laboratory.

It is an object of the invention to provide an apparatus and method for determining the crystallization probability of a particular salt of a liquid ion-containing sample for the direct or indirect quantitative or semi-quantitative detection of the presence of a particular substance or substance group in a specific concentration or a certain concentration range to provide requiring relatively little effort. This object is solved by the subject device standpoint of claim 1.

According to the invention an apparatus for determining the probability of crystallization of a salt in a liquid ion-containing sample see superiors, wherein:

the device comprises at least one measurement channel with an open end, a closed end for liquids and a volume defined,

the apparatus having an inlet opening for introducing the liquid sample,

the open end of the measuring channel is coupled to the inlet port of the measuring channel comprises two serially arranged reaction zones, at least a first reaction zone is located at the open end of the measuring channel,

a final reaction zone is located at the closed end of the measuring channel for liquids,

in each case a phase boundary is formed between the adjacent reaction zones,

the phase boundary is permeable for the liquid sample,

the phase boundary is formed such that a transition of the liquid sample is delayed between the adjacent reaction zones, the first reaction zone is associated with a first reservoir comprising a substance or substance mixture or is provided for receiving the substance or mixture of substances, so that the substance or the substance mixture of the liquid sample is added in the first reaction zone,

the last reaction zone is associated with the last reservoir, which comprises an indicator or an indicator substance mixture or is provided for receiving the indicator or indicator substance mixture, so that the indicator or the indicator substance mixture of the liquid sample in the last reaction zone is added,

the substance or mixture of substances comprising at least one component which forms of that salt with the ion of the liquid sample, the crystallization likely to be determined, and the indicator or the indicator substance mixture comprising at least one member indicating that salt whose crystallization probability determined shall be.

The device comprises at least one liquid inlet, an outlet and an intermediate reaction region. In the reaction zone run in a time sequence controlled from triggered sequential reactions. The sequential reactions are achieved in that either the reaction region of spatially separate reaction zones, into which the liquid sample is transported in succession, or the liquid sample remains in a single room, the reactants are introduced into the in time sequence. The reaction zones can thus be spatial and / or temporal zones. The spatial reaction zones may be defined by specific mechanical partition walls, but also by the use of micro-fluidic systems, and / or the selective use of centrifugal forces. In the former case, the phase boundaries are formed by the mechanical partitions. The reaction zones may be arranged linearly. The essence of the invention is that in the first reaction zone of a channel, the formation of the salt is potentially possible by a suitable reaction partner is added to the liquid ion-containing sample with the substance or mixture of substances. In the last reaction zone of the indicator or the indicator substance mixture is added, so that the crystal formation is indicated. Since both the liquid sample and the substance or the substance mixture present in each case a defined amount, conclusions about the probability of crystallization of the salt can be drawn in the liquid sample. The device may be formed as a disposable or reusable test device.

Preferably, it can be provided that the measuring channel comprises a further reaction zone at least, which is arranged between the first reaction zone and the last reaction zone, wherein said further reaction zone is associated with a further reservoir having a further substance or a further mixture of substances or for receiving the further substance or the further substance mixture is provided, so that the further substance or the further substance mixture of the liquid sample is added to the further reaction zone. In particular, the further substance or the further substance mixture is to precipitate such components in the liquid sample, which may influence the display of the indicator.

In particular it can be provided that the device has a reference channel with an open end and a closed for liquids end having the same geometrical characteristics as the measurement channel and having a first end coupled to the inlet opening, the reference channel at least two successively arranged reference reaction zones comprises respondieren cor- with the reaction zones of the measuring channel, and wherein a last reference reaction zone is assigned to a last reference reservoir, which has the indicator or the indicator substance mixture or to receive the indicator or indicator substance mixture is provided so that the indicator or the indicator substance mixture of the liquid sample is added to the last reference reaction zone. In this way, a discoloration of the indicator is displayed in the last reference reaction zone that serves as a comparison.

Furthermore, it can be provided that the reference channel comprises a further reference reaction zone is at least arranged between the first reference reaction zone and the last reference reaction zone, wherein the further reference reaction zone is associated with a further reference reservoir, which further substance or has the further substance or mixture is provided for receiving the further substance or the further substance mixture so that the further substance or the further substance mixture of the liquid sample is added in the further reference reaction zone. This rule in the reference channel, apart from the induced crystal formation, the same conditions as in the measurement channel.

In particular, the device may be provided for determining the probability of crystallization of calcium oxalate in a urine sample, wherein the substance or substance mixture has a component in the first reservoir at least forming with calcium ions of the calcium oxalate urine sample. In this case, the substance or mixture of substances, for example solid dissolved salts of oxalic acid or, in particular ammonium niumoxalat having. Calcium oxalate is the essential ingredient of urinary stone so that conclusions about the risk of urinary stone can be drawn from the crystallization likelihood of calcium oxalate in the urine sample.

In the aforementioned case, the further substance or the further substance can mixture in the further reservoir comprise at least one member of the one or more insoluble phosphate compounds, such as magnesium ammonium phosphate, together with phosphate ions of the urine sample. The phosphate ion may influence the display of the indicator, which is inhibited by the formation of insoluble crystalline phosphate compounds.

In particular, the device comprises a plurality of measurement channels, with the first reservoirs of the measurement channels o- different amounts of the substance having the mixture of substances. In this way can be executed in parallel sev- eral crystallization reactions wherein the reactant is dosed differently in the various reservoirs. Preferably, the amounts of the substances or mixtures of substances in the reservoirs are metered such that in at least one of the channels, a noticeable color change of the indicator takes place.

The object underlying the invention is object method is achieved by the subject matter of the patent claim. 8

According to the invention, the method for determining the probability of crystallization of a salt in a liquid ion-containing sample to the steps of:

a) introducing a predetermined quantity of the liquid sample in a first reaction zone,

b) imparting a predetermined amount of a substance or a substance-mixture from a first reservoir to the fluid sample in the first reaction zone, wherein the substance or the substance mixture comprises at least one component which forms of that salt with the ion of the liquid sample, its crystallization probability to be determined,

Introducing the liquid sample into a final reaction zone,

Add an indicator or an indicator substance mixture of a final reservoir to the fluid sample in the last reaction zone, wherein the indicator or the indicator substance mixture comprising at least one component indicative of that salt, the crystallization likely to be determined, repeating the steps a) to d) if the indicator or the indicator substance mixture does not indicate the salt, wherein the amount of the substance or substance mixture is increased in the first reservoir, and wherein step e) is repeated as many times until the indicator or the indicator substance mixture indicates the salt, or

wherein steps a) to d) are performed in parallel in different reaction zones and the amount of the substance or mixture of substances in different first reservoirs is different doses.

According to the invention, the possible crystallization of the salt formation is simulated in the first reaction zone by a suitable reaction partner is added to the liquid ion-containing sample with the substance or mixture of substances. In the last reaction zone of the indicator or the indicator substance mixture is added, so that the crystal formation is indicated. Since both the liquid sample and the substance or the substance mixture present in each case a defined amount, NEN conclusions about the probability of crystallization of the salt in the liquid sample kön- be drawn.

In particular it can be provided that the method for determining the probability of crystallization of calcium oxalate is provided in a urine sample, wherein the substance or substance mixture has a component in the first reservoir at least forming with calcium ions of the calcium oxalate urine sample. Calcium oxalate is the essential ingredient of urinary stones, so that conclusions about the risk of urinary stone can be drawn from the crystallization likelihood of calcium oxalate in the urine sample.

Finally, the process between step b) and step c) may comprise the fol- lowing further steps of:

Introducing the liquid sample into a further reaction zone, and imparting a further substance or a further mixture of substances from a further reservoir to the fluid sample in the further reaction zone, wherein the further substance or the further substance mixture comprising at least one constituent with

, Forming phosphate ions of the urine sample, one or more insoluble crystalline phosphate compounds, such as magnesium-ammonium phosphate.

Since the phosphate ion may influence the display of the indicator, this is prevented by the formation of insoluble phosphate compounds.

Further features, advantages and particular embodiments of the invention are the subject of the dependent claims. Hereinafter, preferred embodiments of the invention are explained in detail with reference to the accompanying drawings. Show it:

1 shows a schematic sectional view of an apparatus for determining the probability of crystallization of a salt in a liquid ion-containing sample according to a preferred

Embodiment of the invention.

In FIG 1 is a schematic sectional view of an apparatus for determining the probability of crystallization of a salt in a liquid ion-containing sample according to a preferred form shown is guide of the invention. In this particular example, the device comprises linearly arranged explicitly indicated reaction zones. The apparatus comprises a measuring channel 10, an inlet port 18 and a reference channel 20. The measuring conduit 10 and the reference channel 20 each have an open and a closed for liquids end. The inlet port 18 is coupled to the open ends of the measuring channel and the reference channel 10 twentieth The measurement channel 10 and the reference channel 20 have the same geometrical structure. In this specific example, the measuring channel 10 and the reference channel 20 are arranged side by side and parallel to each other. The inlet opening 18 is provided for introducing a predetermined amount of the liquid ion-containing sample so that the sample in the measuring channel 10 and in the reference channel 20 propagates. The measurement channel 10 and the reference channel 20 form two separate reaction lines.

The measurement channel 10 after the other comprises arranged reaction zones 12, 14 and 16. The reaction zones 12, 14 and 16 of the measurement channel 10 form so-with a number. In this specific example, the measuring channel 10 includes three reaction zones 12, 14 and 16. Similarly, the reference channel 20 includes three series-arranged reference reaction zones 22, 24 and 26, so that the reference reaction zones 22, 24 and 26 form a row. Each reaction zone 12, 14 and 16 of the measurement channel 10 is in each case a Messkanal- reservoir 28, 30 and 32 associated. Accordingly, each reference reaction zone is 22, 24 and 26 of the reference channel 20, respectively, a reference reservoir 34, 36 and 38 associated. However, the first reference reservoir 34 of the first reference reaction zone 22 is optional.

As reaction zones of the measurement channel 10, and the reference channel 20, for example shaped cavities are adapted These cavities may possibly be filled with a protective gas atmosphere. The reservoirs in the reaction zones of the measurement channel 10, and the reference channel 20 containing the required for the in the respective reaction zones chemicals. These chemicals can be in liquid or gel form or solid form. For example, the present in solid form chemicals are formed as powder, tablet or coating. The reaction zones are separated from each other by phase boundaries.

Between the adjacent reaction zones 12, 14 and 16 is a respective phase boundary 40. Also, between the adjacent reference reaction zones 22, 24 and 26 is in each case a phase boundary 40. The phase boundaries 40 are permeable, but form a flow resistance for the liquid sample, so that first the first reaction zone 12 and the first reference reaction zone 22 is completely filled and then the liquid sample penetrates into the second reaction zone 14 or in the second reference reaction zone 24th Accordingly, it acts between the second reaction zone 14 and the third reaction zone 1 6 and the second reference reaction zone 24 and the third reference reaction zone 26. For example, the flow resistance of the partition walls 40 is dimensioned such that for the liquid sample for a predetermined reaction time in the respective reaction zones 12 and 14 and reference reaction zones is available 22 and 24th

The phase boundaries between the reaction zones are excluded forms, for example as a check valve, rupture disc, film, membrane, mesh or blister.

The measuring channel reservoirs 28, 30 and 32, and the reference reservoirs 36 and 38 are provided for receiving substances and / or substance mixtures with the liquid sample in the respective reaction zones 12, 14 and 16 and reference reaction zones 24 and respond 26th In contrast, in the first reference reservoir 34 no substance is provided, which could react with the liquid sample. Either is located in the first reference reservoir 34 a substance that enters with the liquid sample no or at least no interfering reaction, or there is no substance in the first reference reservoir 34th

The apparatus including the measuring channel 10, the inlet port 18 and the reference channel 20 is formed for example in one piece. Pre preferably the device may be an injection molded part. In particular, the device is designed as a one-way analysis device. Preferably, the analysis device is designed as a plastic injection molded part. The analyzer can have approximately the size of a credit card.

Through the inlet opening 18, a certain amount of the liquid sample is entered into the device. The liquid sample initially distributed in the first reaction zone 12 of the measurement channel 10 and the first reference reaction zone 22 of the reference channel 20. To the liquid sample is introduced into the first reaction zone 12 of the measurement channel 10, a defined quantity of a substance or substance mixture from the first added reservoir 28th It can be the substance or mixture of substances in solid, liquid or gaseous form. By the reaction of ions in the liquid sample with the substance or mixture of substances that this salt may arise, the crystallization likely to be determined. Also, existing salt crystals can already continue to grow. The liquid sample that enters the first reference reaction zone 22 of the reference channel 20, remains unchanged and serves as a reference. Subsequently, the liquid sample from the first reaction zone 12 into the second reaction zone 14 of the measuring channel penetrates 10. At the same time, the unchanged liquid sample from the first reference reaction zone 22 enters the second reference reaction zone 24 of the reference channel 20. From the second reservoir 30 and the second reference reservoir 36 substances and / or mixtures of substances are added, the precipitate possible interfering components.

Finally, the liquid sample from the second reaction zone 14 penetrates 10. At the same time in the third reaction zone 16 of the measuring channel enters the liquid sample from the second reference reaction zone 24 in the third reference reaction zone 26 of the reference channel 20. From the third reservoir 32 and the third reference reservoir 38 is a color indicator or color indicator substance mixture added. The color indicator or the color indicator substance mixture reacts by a color change on one hand, the crystals of the constituent salts to be determined ingredient. If the crystal formation or the crystal growth occurs, it is this or directly displayed by the color of the color indicator. Alternatively, the crystal formation or the crystal growth can be shown indirectly by a color indicator which reacts selectively to at least one of the substances constituting the crystals to be determined.

If in the liquid sample by the added is in the first reaction zone 12 from the first reservoir 28 substance has no or insufficient crystal formation has been initiated, the amount or dose of the substance or the substance mixture is increased in the first reservoir 28 in a re-test. This is repeated until crystal formation is de- tektiert.

In particular, there is the possibility that the device comprises a plurality of channels 10, an inlet port 18 and a reference channel 20, wherein different amounts of the substance or mixture of substances are defined in the first reservoirs 28 of the measuring channels 10th In this case, the liquid sample is introduced simultaneously into a plurality of measurement channels 10, wherein in each measurement channel 10, another dose of the substance or the substance mixture of the liquid sample is added. This can be determined at what dose the color of the indicator used. Alternatively, several devices may be provided, each comprising only a measuring channel 10, wherein each device has a different amount of the substance or mixture of substances in the first reservoir 28th Furthermore, a plurality of devices each having a plurality of measuring channels 10 and a reference channel 20 may be provided, each device having a different group of various amounts of the substance or mixture of substances in the first reservoirs 28th The reference channel 20 causes the crystal formation is detected more clearly, as is performed in parallel to the analysis in the measurement channel 10, a reference analysis in the reference channel twentieth The color difference between the sample in the third reaction zone 16 of the measurement channel 10 and in the third reference reaction zone 26 of the reference channel 20 is clearly visible as a color comparison between the sample in the third reaction zone 16 of the measurement channel 10, and for example, a color chart. In reference channel 20, the liquid sample is added to any substance or any mixture of substances, which causes the crystallization of the salt to be determined. Otherwise Messrs see in the reference channel 20 identical conditions. The resulting indicator color in the third reference reaction zone 26 as a reference.

The color and the color change can be detected automatically by means of a device, such as a spectrometer, using a color wedge, or with the naked eye.

The liquid samples to be tested may be all kinds of watery solutions, particularly waste water of all kinds, solutions in chemical reactors and piping systems, as well as all types of pERSonal perflüssigkeiten of humans and animals, in particular urine.

Basically, the growth of all organic and inorganic crystal formations are specifically triggered in such liquid samples, provided that these crystal formations gen under the chosen Untersuchungsbedingun- are stable. Examples crystal formations are called from the mineral classes of phosphates, sulfates, nitrates, sulfides, carbonates, silicates and oxalates.

Hereinafter, the determination of the probability of crystallization of calcium oxalate is described in detail in a urine sample.

Through the inlet opening 18, a certain amount of urine is inputted into the apparatus. It can be used both a native urine sample and a physically or chemically pretreated urine sample. The urine sample is first dispersed in the first reaction zone 12 of the measurement channel 10 and the first reference reaction zone 22 of the reference channel twentieth

For the urine sample, a defined quantity of the substance or substance mixture from the first reservoir 28 is added in the first reaction zone 12 of the measuring channel 0th The substance or the substance mixture contains at least one constituent, which forms together with the calcium ions of the calcium oxalate urine sample. The substance or the substance mixture may be in solid, liquid or gaseous form. The substance or mixture of substances, for example, solid or dissolved salts of oxalic acid, ammonium oxalate in particular have. When the device comprises a plurality of measurement channels 10, the amount of the substance or substance mixture in the first reservoir 28 will vary within the device. In the apparatus with only one measurement channel 10, several devices with different amounts of substance or substance mixture in the first reservoir 28 are used. The amounts of the substance or mixture of substances in the first reservoir 28 are dimensioned such that in at least one measuring channel 10 or in at least one measurement, a precipitation of calcium oxalate is induced. By the addition of a suitable chemical buffer the pH of the urine sample to a predetermined range of values ​​can be set. The crystallization likelihood of calcium oxalate can be punched on the basis of the volume of the urine sample and the amount of sub- or mixture of substances to be determined. Calcium is an essential component of urinary stone. The urine sample passes into the first reference reaction zone 22 of the reference channel 20, remains unchanged and serves as a reference. At a calcium selective color reaction, the presence of phosphate ions can be disturbing, because the formation of sparingly soluble calcium possibility umphosphatsalze indicator under specific high pH-values ​​in the solution is. By a controlled crystallization of magnesium ammonium phosphate in advance of the calcium selective color reaction of this disturbance torque is effectively prevented. The crystallization of magnesium ammonium phosphate can be triggered controlled by adding an appropriate amount of a soluble magnesium compound, especially magnesium oxide or magnesium chloride. This takes place in the second reaction zone 14 of the measurement channel 10, and in the second reference reaction zone 24 of the reference channel 20. The soluble magnesium compounds such as magnesium oxide or magnesium chloride, are located in the second reservoir 30 and in the second reference reservoir 36 and in the second reaction zone 14 of the measurement channel 20 added to the urine sample 10 or in the second reference reaction zone 24 of the reference channel.

Finally, a urine sample from the second reaction zone 14 enters the third reaction zone 16 of the measuring channel 10th At the same time the urine sample from the second reference reaction zone 24 penetrates the third reference reaction zone 26 of the reference channel twentieth a color indicator or color indicator substance mixture is added from the third reservoir 32, and the third reference reservoir 38th The color indicator or the color indicator substance mixture reacts by a color change on the calcium oxalate. If the formation or growth of calcium oxalate occurs, this or this either displayed directly by the color change of the color indicator or indirectly reacts with a color indicator selectively on at least one of the substances that build up the calcium oxalate crystals.

Since both the urine sample and the substance or the substance mixture, for example, the solid or dissolved salts of oxalic acid, in particular ammonium oxalate, are present in each case defined quantities, back can conclusions are drawn on the crystallization probability of calcium oxalate in the urine sample. And the Bonn Risk Index can be determined from it, or at least estimated. The Bonn-Risk Index describes the risk of urinary stone. Furthermore, the formation of crystals can be triggered that do not occur naturally in urinary stones. The crystallization of toxins, drugs and their metabolites can be triggered.

Changes in the probability of crystallization of the urine sample can be attributed to changes in its composition. Crystallization probability can be promoted by known and unknown ingredients in the urine sample to be tested or inhibited. Changes in the crystallization probability can point punch on the existence of variable concentrations of unknown sub. In the body fluids, especially in urine, the Kris tallisationstest can also as an indirect detection of toxins, drugs and their metabolites are used. In body fluids B can etermination Kris tallisations- probability as indirect evidence yet unb ekannter Sub punch serve. Bes TEHT a mathematical relationship between the concentration of a very complex to be determined Subs dance and the crystallization tendency of this substance-containing solution crystallization test can be used as a simplified method of analysis.

LIST OF REFERENCE NUMBERS

10 measuring channel

12 first reaction zone

14 second reaction zone

16 third reaction zone

18 inlet port

20 reference channel

22 first reference reaction zone

24 second reference reaction zone

26 third reference-reaction zone

28 first reservoir

30 second reservoir

32 third reservoir

34 first reference reservoir

36 second reference reservoir

38 third reference reservoir

40 phase boundary

Claims

claims
1. Apparatus for determining the probability of crystallization of a salt in a liquid ion-containing sample, wherein:
- the apparatus comprises at least one measurement channel (10) having an open end, a closed end for liquids and a volume defined,
the apparatus having an inlet port (1 8) for introducing the liquid sample,
- the open end of the measuring channel (0) with the inlet port
(18) is coupled,
of the measurement channel (10) comprises at least two consecutively arranged reaction zones (12, 14, 16),
a first reaction zone (12) at the open end of the measuring channel (10) is arranged,
a final reaction zone (16) at the closed end of the measuring channel for liquids (10) is arranged in each case a phase boundary (40) between the adjacent reaction zones (12, 14, 16) is formed,
- the phase boundary (40) is permeable for the liquid sample, the phase boundary (40) is formed such that a transition of the liquid sample between the adjacent reaction zones (12, 14, 16) is delayed,
the first reaction zone (12) a first reservoir (28) is conces- assigns comprising a substance or substance mixture or is provided for receiving the substance or mixture of substances, so that the substance or the substance mixture of the liquid sample (in the first reaction zone 12) is added,
- the last reaction zone (16) is associated with a final reservoir (32) having an indicator or an indicator substance or mixture is provided for receiving the indicator or indicator substance mixture, so that the indicator or the indicator -substance mixture of the liquid sample is added in the last reaction zone (16), the substance or mixture of substances comprising at least one component that forms salt with the ion of the liquid sample, the crystallization likely to be determined, and
the indicator or the indicator substance mixture comprising at least one member indicating that salt, the crystallization likely to be determined.
Device according to claim 1,
characterized, in that
of the measurement channel (10) at least one further reaction zone (14) includes fully between the first reaction zone (12) and the last reaction zone (16) is arranged, said further reaction zone (14) a further reservoir (30) is assigned, having a further substance or another substance or mixture is provided for receiving the further substance or the further substance mixture so that the further substance or the further substance mixture of the liquid sample is added to the further reaction zone (14).
Device according to claim 1 or 2,
characterized, in that
the apparatus comprises a reference channel (20) having an open end and a closed for liquids end having the same geometrical characteristics as the measuring channel (10) and having a first end with the inlet opening (18) is coupled, wherein the reference channel (20) at least two successively arranged reference reaction zones (22, 24, 26), with the reaction zones (12, 14, 16) of the measuring channel (10) correspond, and wherein a last reference reaction zone (26) a final reference reservoir ( 38 is assigned) having the indicator or the indicator substance mixture or is provided for receiving the indicator or indicator substance mixture, so that the indicator or the indicator substance mixture of the liquid sample in the last reference-reaction zone (26) is added.
Device according to claim 3, when dependent on claim 2, characterized in that
the reference channel (20) at least one further reference comprises reaction zone (24) between the first reference reaction zone (22) and the last reference reaction zone (26) is arranged, wherein the further reference reaction zone (24) a further reference reservior (36) is associated, comprising the further substance or the further substance mixture or is provided for receiving the further substance or the further substance mixture so that the further substance or the further substance mixture of the liquid sample (in the further reference reaction zone 24 ) is added.
Device according to one of the preceding claims,
characterized, in that
the device is provided for determining the probability of crystallization of calcium oxalate in a urine sample, wherein the substance or the substance mixture in the first reservoir (28) comprises at least one component which forms with calcium ions of the calcium oxalate Urinprob.
6. Apparatus according to claim 5, when dependent on claim 2, characterized in that
the further substance or the further substance mixture in the further reservoir (30) comprises at least one member of the one or more insoluble phosphate compounds, such as magnesium ammonium phosphate, together with phosphate ions of the urine sample.
7. Device according to one of the preceding claims,
characterized, in that
the device having a plurality measuring channels (10), wherein the first reservoir (28) of the measuring channels (10) have different amounts of the substance or mixture of substances.
8. A method for determining the probability of crystallization of a salt in a liquid ion-containing sample, said method comprising the steps of:
a) introducing a predetermined quantity of the liquid sample in a first reaction zone (12),
b) imparting a predetermined amount of a substance or substance mixture of a first reservoir (28) to the fluid sample in the first reaction zone (12), wherein the substance or the substance mixture comprises at least one ingredient with the ions of the liquid sample forms of that salt, the crystallization likely to be determined,
c) introducing the liquid sample (in a final reaction zone 16),
d) imparting an indicator or an indicator substance mixture of a final reservoir (32) to the fluid sample in the last reaction zone (16), wherein the indicator or the indicator substance mixture comprising at least one loading stand portion that indicates salt whose crystallization likelihood is to be determined, and
e) repeating steps a) to d) if the indicator or the indicator substance mixture does not indicate the salt, wherein the amount of the substance or mixture of substances in the first reservoir (28) is increased, and wherein step e) whenever is repeated until the indicator or the indicator substance mixture indicates the salt, or f) wherein steps a) to d) in different reaction zones
(12, 16) are executed in parallel and the amount of the substance or mixture of substances in different first reservoirs (28) is different doses.
The method of claim 8,
characterized, in that
the method for determining the probability of crystallization of calcium oxalate is provided in a urine sample, wherein the substance or the substance mixture in the first reservoir (28) comprises at least one component which forms with calcium ions of the calcium oxalate urine sample.
10. The method of claim 9,
characterized, in that
the method, between step b) and step c) comprises the further steps of:
Introducing the liquid sample into a further reaction zone
(14), and
Add another substance or a further mixture of substances from a further reservoir (30) to the fluid sample in the further reaction zone (14), wherein the further substance or the further substance mixture comprising at least one constituent with phosphate ions to the urine sample, one or more forming insoluble crystalline phosphate compounds, such as magnesium ammonium phosphate.
PCT/EP2014/003470 2013-12-31 2014-12-24 Device and method for determining the crystallization probability of a salt in a liquid sample containing ions WO2015101411A1 (en)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4473530A (en) * 1980-09-24 1984-09-25 Villa Real Antony Euclid C Compact sanitary urinalysis unit
US6391644B1 (en) * 1998-11-04 2002-05-21 Dan Gottlieb Image analysis of urine
US6448088B1 (en) * 1998-03-07 2002-09-10 Robert A. Levine Method and apparatus for detecting insoluable constituents in a quiescent urine sample
EP1685388A2 (en) * 2003-11-19 2006-08-02 Raumedic Ag Device and method for analysing a liquid sample
US20120156112A1 (en) * 2009-04-13 2012-06-21 Micronics, Inc. Microfluidic clinical analyzer
US20130280725A1 (en) * 2012-04-20 2013-10-24 California Institute Of Technology Fluidic devices for biospecimen preservation
US20130287630A1 (en) * 2010-09-29 2013-10-31 Siemens Healthcare Diagnostics Inc. Hydrophilic coating for nonporous surfaces and microfluidic devices including same

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3240159A1 (en) * 1982-10-29 1984-05-03 Schneider Hans Joachim Prof Dr Diagnostic composition and test method for detecting crystallisation effects in biological systems
US7556776B2 (en) * 2005-09-08 2009-07-07 President And Fellows Of Harvard College Microfluidic manipulation of fluids and reactions
US9180453B2 (en) * 2008-08-15 2015-11-10 University Of Washington Method and apparatus for the discretization and manipulation of sample volumes
US20110301535A1 (en) * 2008-10-10 2011-12-08 The Regents Of The University Of Michigan Microfluidic control systems
DE102009050175A1 (en) * 2009-10-21 2011-04-28 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Biochip associated examination apparatus and corresponding method of operation

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4473530A (en) * 1980-09-24 1984-09-25 Villa Real Antony Euclid C Compact sanitary urinalysis unit
US6448088B1 (en) * 1998-03-07 2002-09-10 Robert A. Levine Method and apparatus for detecting insoluable constituents in a quiescent urine sample
US6391644B1 (en) * 1998-11-04 2002-05-21 Dan Gottlieb Image analysis of urine
EP1685388A2 (en) * 2003-11-19 2006-08-02 Raumedic Ag Device and method for analysing a liquid sample
US20120156112A1 (en) * 2009-04-13 2012-06-21 Micronics, Inc. Microfluidic clinical analyzer
US20130287630A1 (en) * 2010-09-29 2013-10-31 Siemens Healthcare Diagnostics Inc. Hydrophilic coating for nonporous surfaces and microfluidic devices including same
US20130280725A1 (en) * 2012-04-20 2013-10-24 California Institute Of Technology Fluidic devices for biospecimen preservation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None

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