IL34827A

IL34827A - Indicator strips

Info

Publication number: IL34827A
Application number: IL34827A
Authority: IL
Original assignee: Merck Patent Gmbh
Priority date: 1969-08-12
Filing date: 1970-07-01
Publication date: 1973-08-29
Also published as: ZA704440B; US3715192A; CS151032B2; IL34827A0; DE1940964A1; NL7009870A; BE754658A; FR2057766A5; SE366836B; CH550401A; GB1274617A

Description

Indicator Strips' The present invention is concerned with new and improved indicator strips.

Indicator devices which permit a rapid determination of substances dissolved in liquids are of ever increasing importance in analytical chemistry. The detection usually takes place colorimetrically and can be not only qualitative but also quantitative. However, it is precisely in the case of quantitative or semi-quantitative methods of determination that the previously known indicator devices exhibit considerable disadvantages.

Thus, for example, indicator devices are known which contain reagent papers enclosed by synthetic resin envelopes, the indicator part of which changes colour in the presence of a particular substance in the medium to be investigated. As a rule, the length of the capillary material which changes colour is a measure of the concentration of the substance to be determined in the medium being investigated, the depth of colour usually being disregarded. It is impossible, in the case of this type of indicator device, to use reagents for the indicator part which are soluble in the medium to be investigated since such reagents would become non-uniformly distributed in the impregnated layer due to the ingress of the medium and thus would bring about a non-uniform coloration of the indicator part of the device.

Furthermore, test sticks are known which comprise one or more indicator paper strips sealed between synthetic resin foils. These test sticks have the considerable disadvantage that a relatively viscous medium, such as serum, is only slowly soaked up by the indicator paper. Consequently, in the absorption of this liquid, an undesired chromatographic separation can, in some cases, occur. This chromatographic separation occurs not only in the case of the reagents contained in the indicator papers, insofar as they are soluble in the liquid to be investigated, but also in the case of the components dissolved in the liquid to be investigated. In this way, there is obtained a non-uniform coloration of the impregnated zone which can then only be related v/ith difficulty to an appropriate colour scale.

The determination is also made difficult by an air bubble which, as a rule, is formed between the indicator paper, and the covering foil, upon dipping the test stick into the medium to be tested.

We have now found that, by a special construction of such indicator devices, the above-described disadvantages can be avoided.

Thus, according to the present invention, there is provided an indicator test device which comprises at least one absorbent capillary material impregnated with one or more reagents, which test strip is enclosed between foils, at least part of which is transparent, said device having or being adapted in use to have at least part of the capillary material free of foil and at least one side of the impregnated capillary material being in connection with at least one hollow space.

Consequently, an absorbent capillary material impregnated with reagents can be positioned between two synthetic resin foils in such a manner that one foil lies in close contact v/ith the capillary material and between the capillary material and the other foil, there is provided smaller hollow spaces. However, it is also possible to arrange the synthetic resin foils in such a manner that hollow spaces are provided on both sides of the impregnated capillary material. Furthermore, two impregnated strips of the capillary material can also be arranged between two synthetic resin foils in such a manner that the hollow space is formed between the capillary materials .

The provision of a hollow space in connection with at least one side of the capillary material impregnated with reagents gives the following advantages: The impregnated capillary material becomes completely soaked with the liquid being investigated much more quickly than in the case of the previously known indicator paper test devices of this type and also takes up a definite volume of this liquid, which volume can be predetermined. Due to the rapid and complete soaking of the impregnated indicator part, there occurs neither a chromatographic separation, which would impair the coloration, nor a migration in the capillary material of reagents which are soluble in the liquid. Furthermore, the impregnated capillary material assumes a characteristic coloration or decoloration which corresponds to the content of the components in the liquid being investigated and thus permits the carrying out of a quantitative or at least semi-quantitative determination. The formation is also avoided of. an undesired air bubble between the capillary material and the synthetic resin foil upon immersion of the indicator device into the liquid to be investigated. In this way, the exactitude of the reading off of the colour change is increased and the assessment of the colour which is formed or of the decolo isation to an appropriate colour scale is considerably simplified.

As synthetic resin foils, there can be used all foils which have previously also been used for such purposes. The foils ought not to be porous and must be impermeable to liquids and at least one of the foils must be transparent. Examples of materials which can be used include foils of polyethylene, polypropylene, homopolymers of vinyl compounds, such as polyvinyl chloride, polyvinyl acetate and polyvinyl!dene chloride, and polyethylene glycol terephthalic acid ester, as well as appropriate · co-pqlymers. There can also be used bonded or laminated foils when an' increased rigidity is desired, as well as a sufficient degree of heat sealability of the foils.

Synthetic resin foils coated with fusible adhesives or hot-sealable lacquers can also be used.

The thickness of the foils can be between 20 and lOOOyOL, preferably between 50 and 200/x . It is not necessary for both foils to have the same thickness. On the contrary, for example, a foil in close contact with the capillary material can be very thin (for example 30/χ) , whereas the foil forming the hollow space on the other side of the capillary material is expediently considerably thicker (up to 1000 μ-) in order that it has sufficient strength' and rigidity. If desired, one or both of the foils can be self-adhesive so that a sealing together of the foils is unnecessary. The adhesive must then, of course, be 'selected in such a manner that it does not impair the detection reaction to be carried out. On the other hand, the foils enveloping the capillary material \ can be welded together by any of the conventional methods, for example, b ' pressure, heat or high frequency or also by the action of solvents and/or swelling agents. At least one of the foils must be transparent. It is often expedient to make the other foil non-transparent or even coloured since, in this way, the colour effect achieved can sometimes be increased, the exactitude of reading off of the colour change thereby being increased.

As capillary material which is impregnated with reagents, there can be used any absorbent material. Thus, there can be used all porous materials which can take up and/or absorb a liquid or a solid material. The material should have capillary properties which are due to its porous structure. Preferably, there are used fibrous materials, for example, paper, especially filter paper, but any other' material can be employed which possesses a wick-like action, for example, other celluloses, synthetic fibres, glass fibres, finely-divided granulates and natural and synthetic fibrous nets.

The capillary materials used advantageously have a thickness of about 0.05 - 3 mm., preferably of about 0.2 - 0. mm. The surface of the capillary material which is not covered with synthetic resin foils and is intended for a reaction, is preferably square in format and preferably 2 has an area of between about 10 and 50 mm . The capillary material should be uniform with regard to porosity, thickness and chemical properties.

The indicator strips according to the present invention are expediently constructed in such a manner that the hollow space extends over the whole area of the \ impregnated capillary material on at least one side. In any case, at least k % of one surface of the capillary material should he in connection with the hollow space in order that the desired effects are achieved. The hollow space or spaces can also be divided up into several smaller hollow spaces. In order that the liquid to be investigated can penetrate into the device and react with the impregnated reagents, the capillary -material must be free of foil on at least one side edge and preferably on both side edges. However, it is also possible to leave the absorbent material free of foil on all edges., an additional possibility of deaeration or escape of air from the absorbent material thereby being provided.

Insofar as, in some cases, it, is desired to provide additional possibilities of deaeration, one or both of the foils can also be provided with perforations at any desired places. In general, however, such a modification of the indicator device according to the present invention is not necessary.

It is of importance so to arrange the hollow space above the capillary material that, in relation to the r capillary material, it has a definite height. We have found that especially advantageous indicator strips are obtained when the ratio of the thickness of the capillary material to the maximum height of the hollow space present thereover or to the capillary space, considered in cross-section, is about 1:0.5 to 1:10, preferably about 1:1 to 1:2. Surprisingly, it is not the volume of the hollow space which is decisive but rather this ratio of thickness to height.

\ Of course, when several investigations are to be carried out simultaneously or when, in a test procedure, a detection is to take place simultaneously by various reactions, several different capillary materials or a capillar material impregnated with several different reagents can be incorporated in one indicator strip. In this way, the individual hollow spaces over the capillary materials can, as desired, be connected to one another or can also be separated from one another so that, in the latter case, there is obtained a multi-chamber indicator strip. This is preferred when there is a danger that ' reagents contained in the capillary material or colorations which are formed will influence one another and can thus impair the desired measurement result. Even v/hen several reactions are to be carried out independently of one another with a single test strip, this principle is of especial advantage. The separation can be achieved either by the construction of the foil or also by special separating layers. Thus, for example, the capillary material can be flanked on one or both sides by a preferably hydrophobic material, for example, a resin, wax or synthetic resin.

In the case of a multi-chamber indicator strip, capillary material and separation layers can, if desired, be arranged repeatedly alternatingly. Such indicator strips can be produced especially readily when the thickness of these separation layers exceeds the thickness of the capillary material by the desired height of the hollow space above the capillary material. The ratio of the thickness of the absorbent capillary material to the thickness of the hydrophobic separation layers is preferably about 1 :0.5 to 1:10, more preferably about 1:1 to 1:2. Thus., the separation layers function, as it were, as distance pieces since the covering foils can then be directly sealed or stuck on to the separation layers projecting above the capillary material, the layers in this case preferabljr be-ing of a synthetic resin. The separation layers can be as wide as desired and thus can be adapted to the intended use of the indicator strip.

It is also possible to impregnate two strips of the capillary material with different substances, especially substances which are incompatible with one another, and" then to incorporate these into one indicator strip in such a manner that a common hollow space is formed in the middle. The capillary materials then each lie with one surface close to the foils, whereas the other surfaces then face the common hollow space present in the middle; in such a case, both foils are expediently transparent.

In the accompanying drawings, there are illustrated a number of preferred embodiments of the indicator ' strip according to the present invention. However, for ease of illustration, these drawings are not to scale.

Figures 1 - 6 and 8 - 13 are longitudinal sections ' through indicator devices according to the present invention and Figs.7a, 7b and 1 + — 16 illustrate various features of the new indicator devices. In the accompanying drawings, (1) indicates the capillary material, (2) is one of the foils, (3) is the covering foil, (i+) indicates the hollow space above the capillary material (1), while (5) indicates projections, protrusions, lobes, peaks or the like in the foil (3).

\ V In Figure 1, the capillary material (1) is sealed or stuck on one side to the foil (2), while the covering foil (3) forms the hollow space (i+) over the capillary material (1). The foils (2) and (3) are welded together on two opposite sides of the capillary material.

Figure '2 is substantially the same as Figure 1.

Hov/ever, foil (3) is provided with a small step which holds the capillary material (1) in position. In this case, the capillary material (1) is not fixed to the foil (2).

. In Figure.3, the foil (3) is provided with projections (5) which subdivide the hollow space (k) into a number of small spaces when the projections (5) come into contact with the capillary material (1).

In Figure i+, there is illustrated another possibility for the subdivision of the hollow space' (k) into several small hollow spaces: the covering foil (3) is arched in a serpentine-like manner. It can touch the capillary material (1) or can lie firmly thereagainst or can also leave intermediate spaces between (1) and (3) so that a continuous hollow space is formed.

In Figure 5, an embodiment is illustrated in which the capillary material (1) is not sealed in -between the foils but, for protection, is covered on one side with the foil (2), whereas' the foil (3) forms the necessary hollow space (i+) . According to this embodiment, all four edges of the capillary material are free of foil.

Figure 6 corresponds substantially to the embodiment of Figure 5 with. the difference that, in this case, the foil (3) is formed in such a manner that the hollow space (k) is subdivided by the projections (5) into individual smaller hollow spaces when the projections (5) come into contact with the capillary* material (1).

Figures 7a and 7b illustrate cross-sections through indicator strips according to the present invention. Prom these two drawings, it can be seen that here the foil (3) is arched in serpentine-like manner parallel to the longitudinal edges of the indicator strips. In the case of these embodiments, it is expedient to leave free the lower edges of the capillary material on the narrow edges of the indicator strips, the absorption action of the individual hollow cylinders formed above the capillary material thereby being increased.

In Figure 7a, the capillary material (1) is sealed on to the foil (2) and on to the projections (5) of the foil (3), whereas according to Figure 7b, the capillary material (1) only lies upon the foil (2) and is sealed between the foils (2) and (3)· Figure 8 shows an embodiment of the indicator strips according to the present invention in which a hollow space (1+) is provided on both sides of the. capillary material (1). The foils (2) and (3) are welded together on two opposite sides of the capillary material (1). In principle, the hollow spaces (k) can have different volumes but, as a rule, for the sake of. simplicity, symmetrical arrangements are used.

Figure 9 illustrates an indicator strip in which two, possibly different, strips of capillary material (1) are laid on the foils (2) or (3), respectively, while between the two capillary materials, a common hollow space is formed. On two opposite 'sides of the capillary material (1), the foils (2) ahd (3) are joined together, for example, by sticking or welding. In this case, it is expedient for both foils (2) and (3) to be transparent.

In Figures 10 and 11, there are illustrated indicator strips v/hich contain several strips of capillary material (1), the construction otherwise being substantially the same as in Figures 1 and 2.

Figures 12 and Ί 3 illustrate indicator strips in which the capillary material (1) lies between hydrophobic separating layers (6). Capillary material (1) and the hydrophobic material (6) are sealed on to the foil (2).' The height of the separating layers (6) determines the height of the hollow space (-+) . The foil (3) is sealed on to the separating layers (6). A, sealing together of the foils (2) and (3) can be omitted in the case of this embodiment, in which the impregnated capillary material (1) is especially well protected.

Figure 12+ is a perspective side view of an embodiment which corresponds substantially to Figure 5. Figure 1 demonstrates the free edges (7) and (8) of the capillary material (1 ) .

Figure 5 illustrates, in the embodiments a to h, various possibilities of shaping the foil (3). In principle, all forms can be chosen which permit a subdivision of the hollow space into various smaller spaces. In this case, it is not necessary for the foil (3) to have the same form over the whole of the surface above the capillary material (1). On the contrary, many possibilities of variation are possible, as well as numerous different types of transition from one stage to another. The projections, protrusions, lobes, peaks, rasters o the like can thus he arranged regularly or irregularly and can lie against the capillary material (1) or also terminate above the hollow space (k) .

Figure 16 is a partially cut-away view of an indicator strip according to the present invention showing by way of example, two further possibilities of forming the inner surface of the foil (3).

As a rule, the foil (2) is transparent, whereas the foil (3) is opaque or coloured. Insofar as a hollow space is only provided on one side, the reading off then takes place on the side remote from this hollow space.

The necessary forming of the foil (3) can take place according to all known methods, for example, by stamping or deep drawing. However, synthetic resins, powder or granulate can be sintered on to the foil. Other small particles which are suitable for this purpose, for example, glass splinters or particulate minerals, can be used to alter the inner surface of the foil (3) by melting on o by spraying on.

The new indicator strips according to the present invention can be used successfully everywhere where a qualitative or also quantitative determination is to be carried out of substances dissolved or suspended in a liquid medium to be investigated. The manner of use does not differ from that of known indicator devices. As a rule, the indicator strips are dipped into the liquid to be investigated and the colorations brought about after a certain period of time are assessed or compared with a colour scale. The rapidity and the precise reproducibility which can be achieved with the indicator strips according to the present invention represent a considerable advance in this field.

In the production, the impregnated capillary material, preferably paper, is cut up into the desired breadth and, depending upon the embodiment selected, placed between the foils. In many cases, it has proved to be especially favourable to seal or stick the strip-shaped capillary material on to a foil before the impregnation. When a capillary material connected in this manner with a foil is impregnated, then, in general, the crinkling or rolling' up of the impregnated paper after drying and in the further working up is avoided. The thus obtained welded synthetic resin strips are then cut transversely so that indicator strips are obtained which are open on the edges on the narrow sides. The indicator' strips have, as a rule, a breadth of about 3 - 1 0 mm., preferably of 5 - 7 mm., and a length of about 3Q - 00 mm., preferably of 50 -70 mm. Other dimensions are, of course, also possible.

The following Examples are given for the purpose of illustrating the present invention: -Example 1 . , Copper test strip.

An approximately 6 mm. wide filter paper strip with a thickness of about 320 or 370u (Schleicher & Schull No.231 or 1 50 CV) is, at a distance of about 6 mm. from one edge, sealed on to an approximately 60 mm. wide transparent foil strip (thickness about 1 00^ ) and continuously . impregnated with a solution of the follov/ing constitution: 0.2 g. cuproln 1 g. ^hydroxylamine' hydrochloride 50' ml. methanol 50 ml. benzene The paper is subsequently dried by means of hot air or infra-red light. An opaque foil, also with a width of about 60 mm. and a thickness of about 00/ , which has a 7000. high bulge, as illustrated in Figure 1 of the accompany ing drawings, is sealed on with the help of a pair of rollers (heatable and coolable rollers) . The' bulge extends in a breadth of about 6 mm. at a distance of 5 - 12 mm., from one edge. The middle of the bulge lies approximately over the middle of the impregnated capillary material. The sealed foil band is rolled up and the rolls are cut transversely to the running direction of the foil strip to give test strips with a length of 60 mm. and a breadth of about 6 mm. The capillary material is thus free on the cut edges. Example 2. · Nitrite test strip.

An approximately 50 cm. wide raw paper roll with a thickness of the capillary material of about 30 (Schleicher & Schull No.2316) is impregnated with a solution of the following constitution: 0.1 . naphthyl-1 -amine 0.85 g. sulphanilic acid g. tartaric acid 00 ml. water After drying, it is cut up into approximately 6 mm. wide rolls. The rolls thus obtained are continuously rolled off on to a transparent foil with a thickness of whereby simultaneously an opaque covering foil with a thickness of 1 00/^ is also rolled off and is sealed on to the transparent foil. The latter is provided with' a bulge of the type illustrated in Figure 2 of the accompanying drawings, the height of which is about 0 /J- and the breadth of which is about mm. The covering foil is applied in such a manner that the middle of the bulge lies approximately over. the middle of the capillary material. The capillary material is laid on the transparent foil in such a manner that one edge is about - 6 mm. from an edge of the foil.

The projections provided on the bulges of the covering foil corresponding to Figure 2 retain the capillary material securely in the desired position. After cutting the thus obtained rolls transversely to the running direction, there are obtained test strips of about 60 mm. length and 6 mm. breadth. The side edges of the capillary material are thus free.

Example 3. ■ Nickel test paper.

An approximately 50 cm. wide raw paper roll (Schleicher & Schull N0.li.5i , thickness 330 - 350/*- ) , laminated with a thin (i+0 - 100,". ) polyvinyl chloride foil, is impregnated with a solution of the. following constitution: 0.5 g. dimethylglyoxime 2 g. sodium acetate 100 ml. methanol and subsequently dried. The roll obtained is cut up into 6 mm. wide paper rolls and subsequently stuck on to a stamped foil strip which has a bulge of the type illustrated in Figure 5 of the accompanying drawings. The bulge is about deep and about k mm. wide so that, for the adhesion of the deep drawn foil on to the capillary material, 1 mm. is available above and below. The foil band thus obtained is cut transversely so that there are obtained test strips with a length of about 60 mm. and a width of 6 mm. In the case of this embodiment, all four edges of the capillary material are free. / Example k.

Chloride test strip .

An approximately 6 mm. wide paper strip (Schleicher & Schull Νο.6θ-+^ thickness about 220 μ. ) is sealed on to" the transparent foil band described in Example 1. Subsequently, it is impregnated v/ith a 0,3% aqueous- solution of potassium chromate. and then dried. The thus impregnated paper, is thereafter impregnated with a .0.5% aqueous solution of silver nitrate, homogeneously distributed silver chromate thereby being formed in and on the raw paper. Subsequently, it is sealed with the covering foil described in Example 1 using the method described in that Example. After cutting transversely to the running direction, there are obtained indicator strips analogous to those illustrated in Figure 1 of the accompanying drawings.

Example 5« Choline-esterase test strips.

In a manner analogous to that described in Example 1, there is produced an indicator strip, using an impregnation solution of the following constitution: 00 mg. phenol red 100 mg. naphtholphthalein and g. acetyl-choline hydrochloride are dissolved in 100 'ml. methanol and subsequently the pH of the solution is adjusted to 6.0 by the addition of a solution of sodium hydroxide. The impregnation can be carried out before or after the application of the filter paper to the transparent foil. The strips obtained have a length of 60 mm. and a width of 6 mm. The strips can be used for the determination of choline-esterase.

Claims

1. •Λ' What we claim is :-1. Indicator strip comprising at least one capillary-material impregnated with one or more reagents, which strip is enclosed between foils, at least part of.which is transparent, said strip having or being adapted in use to have at least part of the capillary material free of foil and at least one side of the impregnated capillary material being in connection with at least one hollow space.

2. Indicator strip according to claim 1, wherein the hollow space extends over at least 0% of one surface of the impregnated absorbent capillary material.

3. Indicator strip according to claim 1 or 2, wherein the impregnated absorbent capillary( material lies, on one side, in close contact with one foil, w.hereas the other foil is so shaped that a hollow space is formed over the absorbent capillary material.

4. k. · Indicator strip according to any of the preceding claims, wherein the hollow space is subdivided into several smaller hollow spaces.

5. Indicator strip accordin to any of the preceding claims, wherein the hollow space is partially filled by projections projecting from the inner side of the foil forming said hollow space.

6. Indicator strip according to claim 5, wherein at . most 60% of the volume of the hollow space is filled by the projections projecting from the inner side of the foil.

7. Indicator strip according to any of the preceding claims, wherein at least one edge of the absorbent capillary material is free of foil.

8. Indicator strip according to claim 7, wherein tv/o opposite edges of the absorbent capillary material are free of foil.

9. Indicator strip according to claim 7 , wherein all the edges of the absorbent capillary material are free of foil.

10. * Indicator strip according to any of the preceding claims,- wherein the ratio of the thickness of the absorbent capillary material to the maximum height of the hollow space is, on average, about 1 : 0.5 to 1 : 10.

11. 1 1 . Indicator strip according to claim 10, wherein the ratio of the thickness of the absorbent capillary material to the maximum height of the hollow space is, on average, 1 : 1 to 1 : 2.,

12. 1 2. Indicator strip according to any of the preceding claims, wherein the absorbent capillary material has a thickness of 0.05 to 3 mm..

13. 3. Indicator strip according to claim 12, wherein the absorbent capillary material has a thickness of 0.2 -0.i+ mm.

14. Indicator strip according to any of the preceding claims, wherein filter paper is used as the capillary material.

15. Indicator strip according to any of . the preceding claims, wherein it has a length of about 30 - 100 mm.

16. Indicator strip according to claim 15 , wherein it has a length of about 50 - 70 mm.

17. Indicator strip according to any of the preceding claims, wherein it has a width of about 3 - 0 mm.

18. 1 8 . Indicator strip according to claim 17, wherein it has a width of 5 - 7 nun.

19. Indicator strip according to any of the preceding claims, wherein the capillary material has a surface area 2 of about 10 - 50 mm and is of square , format .

20. . Indicator strip according to any of the preceding claims, wherein it contains several pieces of capillary material which are spaced apart from one another.

21. Indicator strip according to any of the preceding claims, wherein it contains capillary material which has been impregnated after application to a foil. ■ · ■

22. . Indicator strip. according to any of the preceding claims,, wherein the capillary material is arranged between hydrophobic separation layers.

23. Indicator strip according to claim 22 , wherein the ratio of the thickness of the absorbent capillary material to the thickness of the hydrophobic* separation layers is about 1 : 0.5 to 1 : 1 0 .

24. 2k» Indicator strip according to claim 23 » wherein the ratio of the thickness of the absorbent capillary material to the thickness of the hydrophobic separation layers is about 1 : 1 to 1 : 2 .

25. . Indicator strip according to any of claims 22 - 2k, wherein one of the foils is sealed or stuck on to the separation layers.

26. Indicator strip according to any of the preceding claims, wherein one or both of the foils is transparent.

27. . Indicator strip according to any of the preceding claims, wherein the foils have a thickness of 20 - 1 000 .c.

28. Indicator strip according to' claim 27 , wherein the

29. Indicator strip according to any of the preceding claims, wherein the foils have different thicknesses .

30. Indicator strip according to claim 29, wherein the foil forming the hollow space is thicker than the- other foil.

31. Indicator strip according to claim 30,. wherein the foil forming the hollow space has a thickness of up to lOOO Lc , whereas the other foil has a thickness of about

32. Indicator strip according to claim 1 , substantially as hereinbefore described and exemplified. P. 0. Box 116.9, Tel-Aviv Attorneys for Applicant