Diagnostic device

Abstract

Diagnostic agent for the detection of components contained in liquids, e.g. body fluids, comprising a felt or fleece of preponderantly polyamide fibers and impregnated with appropriate reagents.

Description

The present invention is concerned with diagnostic agents for the detection of components in liquids, especially in body fluids, comprising an absorbent carrier impregnated with reagents.

Test strips impregnated with suitable reagents have been in use for a long time for detecting components of liquids. pH indicator papers are used very widely but other reagent papers are also employed. In recent years, test papers have achieved great importance for the detection of glucose, protein, nitrite and the like in body fluids, for example in urine and blood, because they enable the physician to carry out a rapid and simple diagnosis of metabolic disturbances outside the laboratory.

For the various tests, a large number of absorbent carriers has been proposed, for example, wood, asbestos, gypsum, glass fiber felts, synthetic resin fleeces and the like, but in actual practice filter paper is used almost exclusively for the commercially available test strips. The reason for this is that, in addition to the cheapness and ease of working up of paper, the reagents on the cellulose fibers of the paper are especially reactive.

Although filter paper is usually the best carrier material, there are chemical test reactions which cannot be carried out on paper. Quite apart from test reagents which, in a state of fine division, are unstable in air and, therefore, cannot be applied to a carrier by impregnation, there are a number of test reagents which destroy paper fibers and make the paper brittle. Such reagents include, for example, strongly alkaline, strongly acidic and oxidizing substances and especially reagent mixtures with a high salt content.

Tests which are especially important for medical diagnosis but which cannot be carried out or cannot be carried out satisfactorily with the use of test strips include, for example, Legal's test for ketonic bodies and Ehrlich's test of pyrrole bodies. Legal's test requires, for a satisfactory functioning, a high concentration of a strongly alkaline buffer in the reaction solution and Ehrlich's test requires a high concentration of a weakly acidic compound, for example, oxalic acid or potassium bisulfate.

Filter papers which have been impregnated with the high salt concentrations necessary for these test admittedly show a rapid and sensitive reaction with the substrates in question but are so hard and brittle that they cannot be bent, folded or cut up without breaking and crumbling. Since not only in the production but also in the transport and use of such strips, mechanical stresses constantly occur, the usefulness of such strips is severely limited.

Attempts to make such papers mechanically more stable by laminating on to a synthetic resin film were unsuccessful because the hard paper, upon bending or folding, again separated or crumbled away from the film. Cellulose fleece strengthened with synthetic resin fibers, for example, with polyvinyl chloride or polyester fibers, also have not proved to be advantageous because they still did not possess a sufficient degree of stability.

The obvious complete replacement of cellulose by more stabel synthetic resin fibers, for example by polypropylene fibers, such as has been propsed in German Patent Specification No. 2,007,013 for a bilirubin test, also do not prove to be successful in the case of the above mentioned tests since these test strips show a sufficient mechanical stability but only showed very weak color changes which, in the lower concentration ranges, could no longer be evaluated as an indication of bilirubin.

Microscopic investigations have shown that the important difference between the cellulose fibers of paper and synthetic resin fibers is that the cellulose fibers swell during the impregnation and a part of the reagents is embedded or incorporated into the fibers, whereas in the case of synthetic resin fibers, the reagents are only deposited on the surfaces of the fibers.

After laborious and fruitless experiments with a very large variety of absorbent materials, especially with various synthetic resin fleeces, we have now, surprisingly, found, that the felts or fleeces of the instant invention differ significantly from all of the other materials tested.

The present invention provides diagnostic agents comprising an absorbent carrier which consists entirely or preponderantly of polyamides. Only these fleeces or felts based on polyamides provide the final test strips with a sufficient degree of stability, without destroying the reactivity and sensitivity of the test reagents.

It is not known why polyamides differ in this manner from other synthetic resins, for example from polyesters and polyvinyl chlorides. The difference is extremely surprising because the reagents are also not embedded or incorporated into the polyamide fibers.

As polyamides to be used according to the present invention, there can be employed not only those of the nylon type, made from dicarboxylic acids and diamines, but also those of the perlon type, made from .omega.-aminocarboxylic acids. As mixture components in mixed felts and fleeces, it is especially preferred to use polyester fibers but fibers of other synthetic resins, for example of polyvinyl chloride and the like, can also be admixed in amounts of up to 50%.

The felts and fleeces can be produced not only be wet-depositing but also by dry-depositing, the fibers can be oriented or lie at random and they can be connected thermally or by binding agents or they can be needled.

The felt or fleece selected depends essentially upon the nature of the reagents to be used for the impregnation thereof. From the large number of commercially available felts and fleeces the best one can easily be determined by a few simple preliminary experiments.

Thus, in the case of impregnation with acidic salts, for example with potassium bisulfate in the case of the urobilinogen test, it is recommended to use a mixed felt or fleece containing polyester fibers. On the other hand, in the case of basic salts, such as are used for the ketonic body test, pure polyamide felt or fleece has proved to be the best. In special cases, a mixed felt or fleece of polyamide fibers and cellulose fibers can also be used.

The thickness and weight per unit area of the felt or fleece used can be varied. However, very thin or light felts and fleeces take up very little reagent and thus have a poorer reactivity. Thick or voluminous felts and fleeces, on the other hand, take up large amounts of reagents and it is thus more difficult to work them up. Here again, the most suitable felt or fleece for any particular case can be easily determined by a few simple preliminary experiments.

The felt or fleece can be impregnated in conventional manner. However, in order to improve wettability, it is sometimes desirable either to add a wetting agent to the impregnation solution or first to impregnate the felt or fleece with a wetting agent.

The impregnated felt or fleece is then dried in the usual manner. If desired, it can be cut up into narrow strips and used directly or, as still smaller pieces, can either be stuck on to a handle of synthetic resin or, according to German Patent Specification No. 1,546,307, can be sealed between synthetic resin films or, according to German Patent Specification No. P 21 18 455.4, can be sealed between a synthetic resin film and a synthetic resin mesh.

The following Examples are given for the purpose of illustrating the present invention, the properties of the fleeces and felts used in the following Examples being summarized in Table 4 given hereinafter.

EXAMPLE 1

Urobilinogen Test

The materials set out in the following Table 1 were impregnated with an aqueous solution containing, per 100 ml, 20 g potassium bisulfate and 0.2 g p-dimethylaminobenzaldehyde. The properties of the impregnated test strips, as well as their reactions with urobilinogen-containing urine, were also set out in the following Table 1.

TABLE 1 ______________________________________ material and stability reaction material number ______________________________________ filter paper (1)* very brittle good becomes grey uniform polyester fleece (9) stable weak non-uniform polyester-polyamide very good fleece (8) stable uniform ______________________________________ *The material numbers are described in Table 4, infra.

EXAMPLE 2.

Ketonic Body Test

The materials set out in the following Table 2 were impregnated with Solution I, dried, impregnated with Solution II and again dried.

______________________________________ Solution I trisodium phosphate dodecahydrate 21.0 g disodium hydrogen phosphate dihydrate 11.2 g glycocoll 18.7 g distilled water ad 100.0 ml Solution II sodium nitroferricyanide dihydrate 0.9 g polyvinylpyrrolidone-vinyl acetate copolymer (50% solution in ethanol) 6.5 ml organic phosphate ester of anionic surface-active agent (10% solution 1.7 ml in ethanol) dimethyl sulfoxide 38.0 ml ethanol 18.5 ml distilled water ad 100.0 ml ______________________________________

The properties of the impregnated test strips and the reactions with urine containing increasing amounts of acetoacetate or of acetone were also set out in the following Table 2.

TABLE 2 ______________________________________ material and stability reaction material number ______________________________________ filter paper (1) very brittle very good uniform polyester fleece (9) stable weak non-uniform polyamide fleece (5) stable good uniform ______________________________________

EXAMPLE 3

Ketone Body Test

The materials set out in the following Table 3 were impregnated with Solution I, dried, again impregnated with Solution II and again dried.

______________________________________ Solution I tetrasodium ethylenediamine- tetraacetate 38.5 g glycocoll 18.7 g distilled water ad 100.0 ml Solution II sodium nitroferricyanide dihydrate 1.0 g dimethyl formamide 40.0 ml methanol ad 100.0 ml ______________________________________

The following Table 3 also shows the mechanical properties and the reactions of the test strips with urine which contains increasing amounts of acetoacetate or of acetone.

TABLE 3 ______________________________________ material and properties reaction material number ______________________________________ filter paper (1) very brittle very good cellulose-cottonwool very brittle still good fleece (2) regenerated cellulose- polyvinyl chloride rather brittle good fleece (3) regenerated cellulose- polyamide fleece (4) scarcely brittle very good polyamide fleece (5) stable very good polyamide fleece (6) stable good polyamide fleece (7) stable still good polyester-polyamide fleece (8) stable good polyester fleece (9) stable weak polyester fleece (10) stable weak ______________________________________

The following Table 4 gives the properties and description of the various carrier materials used in the above Examples:

TABLE 4 __________________________________________________________________________ material material type producer synthetic working up thickness wt. per No. (in Western resin mon- in mm. unit Germany) omers and area in average g/m.sup.2 mol. wt. __________________________________________________________________________ 1 filter paper 23SL Schleicher -- random, with 0.45 230 & Schull wet tear strength agent 2 cellulose- Paratex Lohmann -- longitudinally 0.2 190 cottonwool III/50 KG laid with fleece (7:3) binding agent 3 regenerated VS 446 Binzer vinyl random, with 0.5 100 cellulose- chloride binding agent polyvinyl M.W. about chloride 100,000 fleece (95:5) 4 regenerated (sample) Binzer .epsilon.-capro- random, with 1.0 150 cellulose- lactam binding agent polyamide M.W. about fleece (1:1) 22,000 5 polyamide V 27835 C. Freu- .epsilon.-capro- longitudinally 0.35 100 fleece (sample) denberg lactam and transverse- M.W. about ly laid, therm- 20,000 ally strength- ened 6 polyamide N 933c C. Freu- .epsilon.-capro- longitudinally 0.5 95 fleece (sample) denberg lactam and transverse- M.W. about ly laid, therm- 20,000 ally strength- ened 7 polyamide FT 2114 C. Freu- .epsilon.-capro- longitudinally 0.25 80 fleece denberg lactam and transversely M.W. about laid, thermally 20,000 strengthened 8 polyester- Suprotex Kalle terephthalic longitudinally 1.5 300 polyamide acid-ethylene and transversely fleece glycol M.W. laid, thermally (1:1) about 18,000 strengthened, adipic acid- needled, without hexamethylene- binding agent diamine, M.W. about 20,000 9 polyester E 5209 Kalle terephthalic needled, therm- 0.35 250 fleece (sample) acid-ethylene ally strengthened glycol M.W. about 18,000 10 polyester H 1015 C. Freu- terephthalic longitudinally 0.25 170 fleece denberg acid-ethylene and transversely glycol M.W. laid, thermally about 18,000 strengthened __________________________________________________________________________

It will be understood that the specification and examples are illustrative but not limitative of the present invention and that other embodiments within the spirit and scope of the invention will suggest themselves to those skilled in the art.

Claims

We claim:

1. Diagnostic device for the detection of components contained in liquids, which diagnostic device comprises an absorbent carrier comprising felt or fleece preponderantly consisting of polyamide fibers, wherein said carrier is impregnated with appropriate reagents.

2. Diagnostic device as claimed in claim 1 wherein said absorbent carrier contains up to 50 percent by weight of fibers other than polyamide fibers.

3. Diagnostic device as claimed in claim 2 wherein said other fiber is at least one member of the group consisting of polyester fibers, polyvinylchloride fibers and cellulose fibers.

4. Diagnostic device as claimed in claim 1 in which the felt or fleece fibers are oriented directionally.

5. Diagnostic device as claimed in claim 1 in which the felt or fleece fibers are randomly disposed.

6. Diagnostic device as claimed in claim 1 wherein the fibers of the felt or fleece are bonded thermally or by means of bonding agents.

7. Diagnostic device as claimed in claim 1 wherein said felt or fleece is a needled felt or fleece.

8. Diagnostic device as claimed in claim 1 wherein said carrier is impregnated with a wetting agent.

9. Diagnostic device as claimed in claim 1 wherein the reagents are strongly alkaline phosphate buffer, sodium nitroferricyanide and glycocoll, for carrying out Legal's test for ketonic bodies.

10. Diagnostic device as claimed in claim 1 wherein the reagents are potassium bisulfate and p-dimethylaminobenzaldehyde, for carrying out Ehrlich's test for urobilinogen.

11. Diagnostic device as claimed in claim 1 wherein said absorbent composition is in the form of a narrow strip adhered to a synthetic resin backing extending therefrom.

12. Diagnostic device as claimed in claim 1 wherein said absorbent carrier is sealed between two synthetic resin films.

13. Diagnostic device as claimed in claim 1 wherein said absorbent carrier is sealed between a synthetic resin film and a synthetic resin mesh.

14. Diagnostic device as claimed in claim 9 wherein said absorbent carrier consists essentially of pure polyamide felt or fleece.

15. Diagnostic device as claimed in claim 10 wherein said absorbent carrier is a mixed felt or fleece also containing polyester fibers.

16. Diagnostic device as claimed in claim 1 wherein the polyamide is of the nylon type.

17. Diagnostic device as claimed in claim 1 wherein the polyamide is of the perlon type.