CA1285721C - Device composed of polymers with a membrane structure and incorporated solids particles - Google Patents
Device composed of polymers with a membrane structure and incorporated solids particlesInfo
- Publication number
- CA1285721C CA1285721C CA000490609A CA490609A CA1285721C CA 1285721 C CA1285721 C CA 1285721C CA 000490609 A CA000490609 A CA 000490609A CA 490609 A CA490609 A CA 490609A CA 1285721 C CA1285721 C CA 1285721C
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- particulate matter
- polymer
- incorporated
- particles
- solids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
- G01N33/545—Synthetic resin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Manufacture Of Macromolecular Shaped Articles (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Detergent Compositions (AREA)
Abstract
Abstract of the disclosure A device is described which is composed of a waterproof, preferably two-dimensional polymer with a membrane struc-ture and incorporated solids particles, wherein these par-ticles are preferably absorbent, and wherein one partner in a chemical reaction is bonded to these particles.
Such a device can be used as an analytical reagent and in particular as a test reagent.
Such a device can be used as an analytical reagent and in particular as a test reagent.
Description
BEHRING~ERKE AKTIENGESELLSCHAFT HOE 84/3 019 Device composed of polymers ~ith a membrane structure and incorporated solids particles The invention relates to a devic~ of preferably two-dimensional shape, composed of a waterproof poLymer ~ith a membrane structure and incorpora~ed solid particles and containing at ~east one participant in a chemical reaction.
Such a device can be used as an ana~ytical reagent and particularly as a test device, preferab~y as a test strip.
The use of membrane filter-like ~aterial for the prepara-tion of test reagents, the membrane having purely the function of a paper substitute, and in which fillers including those having adsorbing properties can be incor-pora~ed, has been described in 6erman Offenlegungsschrift
Such a device can be used as an ana~ytical reagent and particularly as a test device, preferab~y as a test strip.
The use of membrane filter-like ~aterial for the prepara-tion of test reagents, the membrane having purely the function of a paper substitute, and in which fillers including those having adsorbing properties can be incor-pora~ed, has been described in 6erman Offenlegungsschrift
2,602,975, Nile~, publi~hed Augu~t 26, 1976.
German Offenlegung~schrift 1,956,214, Miles, published Nay 21, 1970, has disslosed the suspending of cellulose, crosslinked dextran3 or ion exchanger~ a3 reagent carrier in organic solutions of polymers, such a~ et:hylcellulo e or cellulose acetate, a~d thu the coating of pla~tic carrierq with the su~pen~ions. The disadvantages of ~uch a method are that the absorptive character of the reagent carriers i~ greatly reduced.
These are incorporated in a plastic film, th~ pore width of the film beiny only in~ufficiently controllable by the production proce~s. Moreover, the pore ~ for example with cellulose as the incorporated material, can be sealed when the films are dried.
~L2~
In German Offenlegungsschrift 3,007,744, Richard Luca~ u. Soehne, published January 29, 1981, test reagents Ln the orm of modified cellulose materials are suspended in organic polymer solutions, which have the functions of an adhesive, and are applied to plastic carriers.
These techniques cause great difficulties if, for example, everal zones of different solids material~ are to be prep~red, through which a development ~olvent i9 to flow successively in the sense o~ a chromatographic proce~. In thi3 casa, the zone~
must have a high absorbency and be contiguous, and the reactivity of reagen~ carrier~ contained therein must be preserved.
In German Offenlegungsschrift 2,922,856, VEB Arzneimittelwerk Dresden, published February 14, 1980, which relates to a detection of glucose, various reagent solution~ are applied in parallel on, for example, a paper strip by means of pens.
In German O~enlegungs5chrift 2,620,923, Riedel de Haen, published December 1, 1377, the pxoblem of contiguously arranging several~zones of absorbent material~ is solved in such a way that the matQrials are succe~sively filled into small glass columns.
The inadequacy of ths existing application methods i9 emphasized particularly in this last process. Since, in this case, a color zone, proportional to the substance, is to be obtained by th~
color change of a chromogenic zone when an analytical sample . . ~ ~, ., 3LZ~
flows through, the zones mu~t have a high ab~orbancy, and their density must be reproducible when preparing them.
If test rods are used for test reagents for the sor~ of purpose described, the applied layers must have a high ab~orbency and, in the solid which may be porous, pores must not be sealed by the preparation process. The~e precondition~ are no$ guaranteed when the indicated methods are used; this applies in particular to the absorptive character.
In order to regulate the absorbency of polymer films, a procedure is followed in German Offenlegungsschrift 2,910,134, Boehringer Nannheim, published September 25, 1980, in which solids particles are incorporated in polymer films during the preparation of th latter. The films are "opened" in such a way that the ~Ifilm opener"
,/
/
/
.
3L2~
content meters the absorbency. If~ however, absorbent solids particles, such as cellulose, are incorporated, it is observed that the absorbency decreases sharply in com-parison ~ith, say, the same quantity of incorporated gypsum. It must be assumed here ~hat the pores of the cellulose are at least part;ally sealed and that the f;lm-forming polymer is adhesively bonded to the surface of the cellulose~
If a cellulose, which has been modified in accordance with German Of~enlegungsschrift 3,016,618, G. Scharf, published November 5, 1981, to give a polymeric enzyme suhstra~e for peroxidase, is used as the "film opener", only a very slow reaction is detectable on immersion into a solutlon which contains hydrogen peroxide as well as psroxidase. In order to reach the reactivity of the normal cellulose preparations even approximately, the polymer content of the film-forming suspension must be lowered to such an extent that adequate mechanical strength of the layer formed is no longer ensured.
It ~as therefore the object of the present invention to develop a form of preparation of solids with coupled reaction systems, which overcomes the disadvantages des-cribed.
In these forms of preparation, one constituent is to ensure the strength required for practical purposes, ~hereas a ~urther incorporated constituent contains or carr;es at least one substance which can be a part;cipant ;n a chemi-cal reaction. Within the scope of the invention, sub-stances which are intended to provide strength to the sys~
tem are meant to be membrane-forming substances, in par-ticular ~aterproof plastics with a membrane filter struc-ture.
Such a form of preparat;on preferably has a t~o-dimensional shape.
" .~
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The invent;ion therefore r~lates to a preferably two-dimen~ional device composed of solids particles (hereinafter also referred to as particulate matter) incorporated into a waterproof polymer with a membrane filter structure, and containing one or more participants in a chemical reaction, whereln at least one reactant is bonded to solids particle~.
The incorporated solids particles are preferably composed of an absorbent mater;al, such as cellulose or celluose derivatives, crosslinked dextrans, ion exchangers~ poly-10 amides, porous glasses, macroporous polymers, zeolites, kieselguhr, porous silica, kaolin or activated carbon~
The absorbency of the incorporated particles is preserved in the above process for the preparation of such a device.
These solids part;cles can here also be par~icles with a 15 non-absorbent core.
Methods for bonding partners in a chemical react;on to solids are known. These methods relate to purely adsorp-tively bonded systems such as, for example, described as early as 1916 for the adsorption of enzymes on carbon and aluminum (Weetall, H.H., Anal. Chem~ 46, 602 A (1974)).
Other materials ~h;ch can be used are alum;num oxide~
alumina or gla~s.
Methods are also known for covalently bonding chemical reactants such as~ for example, acid-base ;ndicators~
chelate formers or biologically active substances such as enzymes, antigens or antibodies, to such solids. Çor example, aminopropyl der;vatives of glasses which, by means of a large number of methods, can be reacted w;th substances wh;ch can then later function as partners in a chemical reaction, can be obtained by reaction ~ith amino-propyl-triethoxysilane.
There are also solids ;n ~hich a series of adsorbed mlcro-particles are fixed on a solid core. These m;cropart;cles can be used analogously to reaction systems incorporated in membranes.
Such reagent-carrying, non-absorbent or partially absor~
bent sol;ds part;cles can, according to the present inven-t;on, be processed to give a mechan;cally strong mater;al, the absorbency and reac~iv;ty be;ng preserved~
The products or devices described can be produced by dis-solving polymers ;n solvent systems ~hich contain low-boiling solvents for the polymer, higher-boiling s~elling agents and precipitating agents for the polymer. The essential point here is that the precipitating agents are preferentially absorbed by the solid to be incorporated.
When a solid is suspended in such a polymer solvent system and the suspension is poured out onto a substrate, a coacervate forms during the evaporation of the low-boiling polymer solvent, the coagulation starting preferentially in the vicinity of the solids particles loaded with pre-cipitation constituents. The result is that the precip;-tating polymer cannot adhes;vely bond to the sol;ds par-ticles. This gives a product in ~hich the polymer has the structure of a hollow foam, the solids particles being enveloped by the polymer.
The invention therefore relates also to a process for pre-par;ng a dev;ce as described above, ~hich comprises mixing the solids particles with a polymer solution, ~hich forms membrane filters, and producing waterproof membranes.
A process, using absorbent solids particles, is preferred ~hich comprises mixing the solids particles ~ith a polymer solution, ~hich forms membrane filters, the solvent system being selected such that the precipitating fractions of the solvent mixture preferentially penetrate into the ~2~1S~
absorbent sollds particles, and producing membranes The proportion of the ~aterproof polymer in the weight of the total preparation can amount to 3-50 9/100 9.
A process is particularly preferred in ~hich one partner in a chemicalreaction is or has been bonded to the solids particles.
This process allows the production of contiguous zones with solids materials which may d;ffer, products then being obtained ~hich are suitable for a chromatography-like throughput of fluids, it being possible for the flo~to pass successively through the contiguous zones.
Such a product can, for example, be used for the prepara-tion of a fault-free urinary sugar test. For th;s purpose, the various zones can have the following functions: zone 1 contains ion exchangers which are charged with the con-stituents of a buffer system; zone 2 contains a polymeric enzyme substrate based on o-dianisidine coupled to cellu-lose, and the enzymes requ;red for the reactions.
If a test strip prepared in this way is immersed in glucose-containing urine, interfering cons~ituen~s such as ascorbic acid are removed in ~one 1 and, at the same time~
the bonded buffer substances are released and, on flo~ing through zone 2, carry out the oxidatlon of the glucose and of the chromogen, bonded to a polymer, by per-oxidase.
Such products ~ith sufficient stability in use cannot beproduced by means of the kno~n techniques.
The process according to the invention gives products in ~hich solids particles are enclosed in ~aterproof polymers of the type of hollow foam, the absorbency of any absorbent particles being preserved and it being possible for a partner in a chemical reaction to be bonded to these . .
~X8S"~Z~
particles.
At polymer contents of bet~een 3 and 50 ~ preferably 6 and 35 9, per 100 9 of the total applied material after drying, the products have a very ~ood mechanical strength.
S Moreover, ~hen the solids/polymer suspensions are poured out onto plast;cs carriers, ~elding oF the polymer form-1ng membrane filters to the substrate can be effected.
~y pouring out several parallel, continuous zones, test reagents can be obtained ~hich are su;table for solving the problems ln the above described systems operating in a manner similar to chromatography.
The process described above can also be used to produce de vices co~sisting of more than one layer of a membrane with incorporated solid particles. In particular, if transparent carrier materials are used, further layers with filtering, light-reflecting or ion-exchanging properties may be placed on top of the chromogenlc zone which ls on the carrier.
, -~t was surprising that solids ~hich carry reactants canbe ;ncorporated into membranes in such a ~ay that the absorbency and reactivity are preserved.
Th;s 1s not at alL self-evident, for examp~e in the case of the 1ncorporat;on of ceLlulose derivatives in~o polymer solutions ~hich form membrane filters. Systems based on certain cellulose derivatives as the polymer membrane filters give slightly absorbent products, in many cases ~ith cellulose as the filler, in usual solvent sys-tens comprisin~ acetone/alcohoLs/~ater. If-the polymer content is louered in order to preserve the absorbency, the products sho~ insuffic;ent mechanical stren~th.
~n order to ensure adequate absorption of the precip;-tat;n~ constituents by the solid, the choice of '~
..~,,, ~, polymer forming membrane filters that are structurally sufficiently different, i5 essential, in addition to a sufficient differentiation in the affinity of the solvent constituents to the solid. Hydrophobic polymers, for example especially PVC or polystyrene, are suitable where cellulose is used as ~olids particles.
Apart from surfactants which may be present as constituents of reagents used in reactions comprising biological material, i.e.
proteinaceous material, surface active substances may be added to modify the properties of the polymers. In particular, hydrophobic polymers, such as PVC used in the present invention, can be substantially modified with respect to their wetting behavior by the addition of surface-active substances which are miscible with the polymer. In khe case of PVC, this can be effected, for lS example, by adding low-molecular polyoxyethylene or trialkylmethylammonium halides.
Quite generally, ~he absorbency and wear resistance can be controlled by mutually independent measures. The pore width and a well formed membrane filter structure, on the one hand, and the absorbency of the solids particlès, on the other hand, are essential for the absorbency. The absorbency of the product can be further improved by an addition of a detergent. The detergent can be used in a quantity up to 25 g/100 g of the product.
The wear resistance naturally dependei on the proportion of incorporated ~olids in the total mass. However, the quality of the membrane filter structure, the rubber elasticity and the flexibility of the polymer and also the applied thickness and sedimentation of the solids, which may possibly take place during the evaporation step, also play a role.
Well formed memhrane filter structures can also be used, without incorporated solids, for pure transport functions in combination with devices according to the invention.
In particular, when several contiguous zones are applied, one zone can be used for defining the suction volume of a _ 9 _ sample to be analyzed. ~n this case, ~ncorporated hydro-philic sol;ds ml~ht possibly have the disadvantage that their suction capacity depends on the degree of drying, that is to say on the ~trnospheric humid;ty and the ambient temperature.
Naturally, membrane fileer zones can be processed ~ith any des~red other contiguous zones~ ~or example of paper, fibers or fabr;cs, to give systems, the appl;cation of ~hith can be of importance with;n the scope of chromatography-like processes.
The ;nvent;on is described below by reference to some non-restrictive examples.
Exam~le 1 0.25 9 of diethylamino-cellulose ~as suspended in 0.025 ml of ~ater, 0.1 ml of ethyl acetate and 1 mL of tetrahydro-furan. 0.3 9 of a 10% by ~eight PVC solution in tetra-hydrofuran Mas then added. After homogenization, the suspension ~as poured onto a ~lass plate and spread out to a thickness of 3~0 micrometers. After the drying, this 3ave a highly absorbing membrane ~;th integrated cellu-Lose material~
Example 2 Analogously to Example 1, a suspension was prepared and, l;kewise in 300 ~ thickness, applied to a O~S mm thick PYC
sheet. After drying~ the material proved to be highly absorbent and was found welded to the carrier. The welded-on membrane is ~ear-resistant in the dry state and in the moist st~te. To examine the structure, the membranes ~elded to PVC uere ;nvest;gated by electron ~icroscopy.
The images, in particular the element distribution images ~ith respect to the eleMent chlorine by means of an energy-dispersive X-ray spectrometer, confirm the presumed PVC
membrane structure.
Example 3 According to German Ausle~eschrift 3,016~61B, Example 1, a polymeric chromogen, based on celLulose as the carrier and tetramethylbenzidine as the chromogen, was prepared as an enzyme substrate for the peroxidase/hydrogen per-oxide system.
0.25 ~ of th;s polymer;c chromogen was suspended ~ith 0~05 9 of ~ater, 0.1 ml of absolute alcohol, 0 9 ml of tetrahydrofuran and 0.1 ml of a 1D% by volume solution of polyethylene glycol 400 in tetrahydrofuran, and 0.25 9 of a 7% by ~eight solution of PVC in tetrahydrofuran ~as then added, and the suspens;on was homogenized after 5 minutes.
The suspension ~as then applied in a thickness of 300 ~ to a PVC carrier by means of a knife blade. After drying, this gave a highly absorbent membrane ~elded to the carrier. On immersion into a solut;on of pH 5, which contained 0.1X by volume of hydrogen perox;de and a little peroxidase, the polymeric chromogen integrated in the mem-brane ~as oxidized, a green color being formed.
~o Exa~ple 4 Diazotized p-aminobenzyl-GelLulose ~as prepared accord;ng to Ger~an Offenlegun~sschrift 1,~56~Z14, Example 19.
Sod;um acetate ~as added in smaLL portions, with vigorous stirring, at 0C to the solution containing hydrochloric acid~ until the pH value was about 4.5. The same volume of a 5% by volume solution of N,N-dimethylaniline in N,N-dimethylformamide, ~hich xas cooled beforehand to 0C, ~as then added and the mixture ~as stirred for 30 minutes in an ice bath. After filtration with suction, the cellulose product ~as then extensively ~ashed ~ith ~ater.
The material proved to be a polymeric, non-bleeding acidl base indicator uhich changes from yellow to red on addition of acid.
~35~
~y ~eans of 250 ~J thick steel stenci l sho~;ng a St~
Andre~ls cro~s, the dried m3terial ~as appl;ed ~n accord-ance ~lth E~ample 1 to a yello~-pigmented adhesive PVC
label. After dryingO ac;d-containing ~ater produc~d a red 5 ~ rn i ng c ross .
Example 5 For using the polymeric acid/base indicator trom E~ample 4 for the determination of pH values, a wh;te-p;gmented PVC
carrier ~as coated, by ~eans of a coatins apparatus, ~ith seven parallel, 3 ~m ~ide strips at a mutual ~pacing of 4 mm. The interm~diate ~ones ~ere coated ~;th PVC colors of 3 mm w;dth, the PVC colors beiny adapted in graduated steps of 0.2 pH to thc ch3nge colors of the indicator ;n , the region from 4.6 to 3.4.
After dry;ng, the carrier was cut into s~r;ps, perpen-diçular to the çolor zones.
Th;s non-bleeding ind;cator test strip has advanta~es over ~he ex;st;ng products in pH ~llocation. Due to the closely - adjo;nin~ color zones of sim;lar color ~tructure and sur-face structureO the subjectively achievab~e accuracy of allocat;on ;s ~mproved over exist;ng te~t strips.
Examp~e ~
0.1 g of a cellulose preparation, on which Congo Red (Colour Index 22120) had been ab~orbed by substanti~e d~eins, was suspended in a mixture of 0.3 g of 10~ by weight PVC in tetrahydrofuran, 0.6 ml of tetrahydrofuran and 0.2 ml of alcohol and applied in a thickness of 400 ~ to a carrier of rigid PYC.
After the evaporation of the solventR, this ga~e a highly absorbent and largely wear-resistant coating which can be used a~ an acid/base indicator which i5 substantially secure against bleeding.
German Offenlegung~schrift 1,956,214, Miles, published Nay 21, 1970, has disslosed the suspending of cellulose, crosslinked dextran3 or ion exchanger~ a3 reagent carrier in organic solutions of polymers, such a~ et:hylcellulo e or cellulose acetate, a~d thu the coating of pla~tic carrierq with the su~pen~ions. The disadvantages of ~uch a method are that the absorptive character of the reagent carriers i~ greatly reduced.
These are incorporated in a plastic film, th~ pore width of the film beiny only in~ufficiently controllable by the production proce~s. Moreover, the pore ~ for example with cellulose as the incorporated material, can be sealed when the films are dried.
~L2~
In German Offenlegungsschrift 3,007,744, Richard Luca~ u. Soehne, published January 29, 1981, test reagents Ln the orm of modified cellulose materials are suspended in organic polymer solutions, which have the functions of an adhesive, and are applied to plastic carriers.
These techniques cause great difficulties if, for example, everal zones of different solids material~ are to be prep~red, through which a development ~olvent i9 to flow successively in the sense o~ a chromatographic proce~. In thi3 casa, the zone~
must have a high absorbency and be contiguous, and the reactivity of reagen~ carrier~ contained therein must be preserved.
In German Offenlegungsschrift 2,922,856, VEB Arzneimittelwerk Dresden, published February 14, 1980, which relates to a detection of glucose, various reagent solution~ are applied in parallel on, for example, a paper strip by means of pens.
In German O~enlegungs5chrift 2,620,923, Riedel de Haen, published December 1, 1377, the pxoblem of contiguously arranging several~zones of absorbent material~ is solved in such a way that the matQrials are succe~sively filled into small glass columns.
The inadequacy of ths existing application methods i9 emphasized particularly in this last process. Since, in this case, a color zone, proportional to the substance, is to be obtained by th~
color change of a chromogenic zone when an analytical sample . . ~ ~, ., 3LZ~
flows through, the zones mu~t have a high ab~orbancy, and their density must be reproducible when preparing them.
If test rods are used for test reagents for the sor~ of purpose described, the applied layers must have a high ab~orbency and, in the solid which may be porous, pores must not be sealed by the preparation process. The~e precondition~ are no$ guaranteed when the indicated methods are used; this applies in particular to the absorptive character.
In order to regulate the absorbency of polymer films, a procedure is followed in German Offenlegungsschrift 2,910,134, Boehringer Nannheim, published September 25, 1980, in which solids particles are incorporated in polymer films during the preparation of th latter. The films are "opened" in such a way that the ~Ifilm opener"
,/
/
/
.
3L2~
content meters the absorbency. If~ however, absorbent solids particles, such as cellulose, are incorporated, it is observed that the absorbency decreases sharply in com-parison ~ith, say, the same quantity of incorporated gypsum. It must be assumed here ~hat the pores of the cellulose are at least part;ally sealed and that the f;lm-forming polymer is adhesively bonded to the surface of the cellulose~
If a cellulose, which has been modified in accordance with German Of~enlegungsschrift 3,016,618, G. Scharf, published November 5, 1981, to give a polymeric enzyme suhstra~e for peroxidase, is used as the "film opener", only a very slow reaction is detectable on immersion into a solutlon which contains hydrogen peroxide as well as psroxidase. In order to reach the reactivity of the normal cellulose preparations even approximately, the polymer content of the film-forming suspension must be lowered to such an extent that adequate mechanical strength of the layer formed is no longer ensured.
It ~as therefore the object of the present invention to develop a form of preparation of solids with coupled reaction systems, which overcomes the disadvantages des-cribed.
In these forms of preparation, one constituent is to ensure the strength required for practical purposes, ~hereas a ~urther incorporated constituent contains or carr;es at least one substance which can be a part;cipant ;n a chemi-cal reaction. Within the scope of the invention, sub-stances which are intended to provide strength to the sys~
tem are meant to be membrane-forming substances, in par-ticular ~aterproof plastics with a membrane filter struc-ture.
Such a form of preparat;on preferably has a t~o-dimensional shape.
" .~
f ~ .
~85~2~
The invent;ion therefore r~lates to a preferably two-dimen~ional device composed of solids particles (hereinafter also referred to as particulate matter) incorporated into a waterproof polymer with a membrane filter structure, and containing one or more participants in a chemical reaction, whereln at least one reactant is bonded to solids particle~.
The incorporated solids particles are preferably composed of an absorbent mater;al, such as cellulose or celluose derivatives, crosslinked dextrans, ion exchangers~ poly-10 amides, porous glasses, macroporous polymers, zeolites, kieselguhr, porous silica, kaolin or activated carbon~
The absorbency of the incorporated particles is preserved in the above process for the preparation of such a device.
These solids part;cles can here also be par~icles with a 15 non-absorbent core.
Methods for bonding partners in a chemical react;on to solids are known. These methods relate to purely adsorp-tively bonded systems such as, for example, described as early as 1916 for the adsorption of enzymes on carbon and aluminum (Weetall, H.H., Anal. Chem~ 46, 602 A (1974)).
Other materials ~h;ch can be used are alum;num oxide~
alumina or gla~s.
Methods are also known for covalently bonding chemical reactants such as~ for example, acid-base ;ndicators~
chelate formers or biologically active substances such as enzymes, antigens or antibodies, to such solids. Çor example, aminopropyl der;vatives of glasses which, by means of a large number of methods, can be reacted w;th substances wh;ch can then later function as partners in a chemical reaction, can be obtained by reaction ~ith amino-propyl-triethoxysilane.
There are also solids ;n ~hich a series of adsorbed mlcro-particles are fixed on a solid core. These m;cropart;cles can be used analogously to reaction systems incorporated in membranes.
Such reagent-carrying, non-absorbent or partially absor~
bent sol;ds part;cles can, according to the present inven-t;on, be processed to give a mechan;cally strong mater;al, the absorbency and reac~iv;ty be;ng preserved~
The products or devices described can be produced by dis-solving polymers ;n solvent systems ~hich contain low-boiling solvents for the polymer, higher-boiling s~elling agents and precipitating agents for the polymer. The essential point here is that the precipitating agents are preferentially absorbed by the solid to be incorporated.
When a solid is suspended in such a polymer solvent system and the suspension is poured out onto a substrate, a coacervate forms during the evaporation of the low-boiling polymer solvent, the coagulation starting preferentially in the vicinity of the solids particles loaded with pre-cipitation constituents. The result is that the precip;-tating polymer cannot adhes;vely bond to the sol;ds par-ticles. This gives a product in ~hich the polymer has the structure of a hollow foam, the solids particles being enveloped by the polymer.
The invention therefore relates also to a process for pre-par;ng a dev;ce as described above, ~hich comprises mixing the solids particles with a polymer solution, ~hich forms membrane filters, and producing waterproof membranes.
A process, using absorbent solids particles, is preferred ~hich comprises mixing the solids particles ~ith a polymer solution, ~hich forms membrane filters, the solvent system being selected such that the precipitating fractions of the solvent mixture preferentially penetrate into the ~2~1S~
absorbent sollds particles, and producing membranes The proportion of the ~aterproof polymer in the weight of the total preparation can amount to 3-50 9/100 9.
A process is particularly preferred in ~hich one partner in a chemicalreaction is or has been bonded to the solids particles.
This process allows the production of contiguous zones with solids materials which may d;ffer, products then being obtained ~hich are suitable for a chromatography-like throughput of fluids, it being possible for the flo~to pass successively through the contiguous zones.
Such a product can, for example, be used for the prepara-tion of a fault-free urinary sugar test. For th;s purpose, the various zones can have the following functions: zone 1 contains ion exchangers which are charged with the con-stituents of a buffer system; zone 2 contains a polymeric enzyme substrate based on o-dianisidine coupled to cellu-lose, and the enzymes requ;red for the reactions.
If a test strip prepared in this way is immersed in glucose-containing urine, interfering cons~ituen~s such as ascorbic acid are removed in ~one 1 and, at the same time~
the bonded buffer substances are released and, on flo~ing through zone 2, carry out the oxidatlon of the glucose and of the chromogen, bonded to a polymer, by per-oxidase.
Such products ~ith sufficient stability in use cannot beproduced by means of the kno~n techniques.
The process according to the invention gives products in ~hich solids particles are enclosed in ~aterproof polymers of the type of hollow foam, the absorbency of any absorbent particles being preserved and it being possible for a partner in a chemical reaction to be bonded to these . .
~X8S"~Z~
particles.
At polymer contents of bet~een 3 and 50 ~ preferably 6 and 35 9, per 100 9 of the total applied material after drying, the products have a very ~ood mechanical strength.
S Moreover, ~hen the solids/polymer suspensions are poured out onto plast;cs carriers, ~elding oF the polymer form-1ng membrane filters to the substrate can be effected.
~y pouring out several parallel, continuous zones, test reagents can be obtained ~hich are su;table for solving the problems ln the above described systems operating in a manner similar to chromatography.
The process described above can also be used to produce de vices co~sisting of more than one layer of a membrane with incorporated solid particles. In particular, if transparent carrier materials are used, further layers with filtering, light-reflecting or ion-exchanging properties may be placed on top of the chromogenlc zone which ls on the carrier.
, -~t was surprising that solids ~hich carry reactants canbe ;ncorporated into membranes in such a ~ay that the absorbency and reactivity are preserved.
Th;s 1s not at alL self-evident, for examp~e in the case of the 1ncorporat;on of ceLlulose derivatives in~o polymer solutions ~hich form membrane filters. Systems based on certain cellulose derivatives as the polymer membrane filters give slightly absorbent products, in many cases ~ith cellulose as the filler, in usual solvent sys-tens comprisin~ acetone/alcohoLs/~ater. If-the polymer content is louered in order to preserve the absorbency, the products sho~ insuffic;ent mechanical stren~th.
~n order to ensure adequate absorption of the precip;-tat;n~ constituents by the solid, the choice of '~
..~,,, ~, polymer forming membrane filters that are structurally sufficiently different, i5 essential, in addition to a sufficient differentiation in the affinity of the solvent constituents to the solid. Hydrophobic polymers, for example especially PVC or polystyrene, are suitable where cellulose is used as ~olids particles.
Apart from surfactants which may be present as constituents of reagents used in reactions comprising biological material, i.e.
proteinaceous material, surface active substances may be added to modify the properties of the polymers. In particular, hydrophobic polymers, such as PVC used in the present invention, can be substantially modified with respect to their wetting behavior by the addition of surface-active substances which are miscible with the polymer. In khe case of PVC, this can be effected, for lS example, by adding low-molecular polyoxyethylene or trialkylmethylammonium halides.
Quite generally, ~he absorbency and wear resistance can be controlled by mutually independent measures. The pore width and a well formed membrane filter structure, on the one hand, and the absorbency of the solids particlès, on the other hand, are essential for the absorbency. The absorbency of the product can be further improved by an addition of a detergent. The detergent can be used in a quantity up to 25 g/100 g of the product.
The wear resistance naturally dependei on the proportion of incorporated ~olids in the total mass. However, the quality of the membrane filter structure, the rubber elasticity and the flexibility of the polymer and also the applied thickness and sedimentation of the solids, which may possibly take place during the evaporation step, also play a role.
Well formed memhrane filter structures can also be used, without incorporated solids, for pure transport functions in combination with devices according to the invention.
In particular, when several contiguous zones are applied, one zone can be used for defining the suction volume of a _ 9 _ sample to be analyzed. ~n this case, ~ncorporated hydro-philic sol;ds ml~ht possibly have the disadvantage that their suction capacity depends on the degree of drying, that is to say on the ~trnospheric humid;ty and the ambient temperature.
Naturally, membrane fileer zones can be processed ~ith any des~red other contiguous zones~ ~or example of paper, fibers or fabr;cs, to give systems, the appl;cation of ~hith can be of importance with;n the scope of chromatography-like processes.
The ;nvent;on is described below by reference to some non-restrictive examples.
Exam~le 1 0.25 9 of diethylamino-cellulose ~as suspended in 0.025 ml of ~ater, 0.1 ml of ethyl acetate and 1 mL of tetrahydro-furan. 0.3 9 of a 10% by ~eight PVC solution in tetra-hydrofuran Mas then added. After homogenization, the suspension ~as poured onto a ~lass plate and spread out to a thickness of 3~0 micrometers. After the drying, this 3ave a highly absorbing membrane ~;th integrated cellu-Lose material~
Example 2 Analogously to Example 1, a suspension was prepared and, l;kewise in 300 ~ thickness, applied to a O~S mm thick PYC
sheet. After drying~ the material proved to be highly absorbent and was found welded to the carrier. The welded-on membrane is ~ear-resistant in the dry state and in the moist st~te. To examine the structure, the membranes ~elded to PVC uere ;nvest;gated by electron ~icroscopy.
The images, in particular the element distribution images ~ith respect to the eleMent chlorine by means of an energy-dispersive X-ray spectrometer, confirm the presumed PVC
membrane structure.
Example 3 According to German Ausle~eschrift 3,016~61B, Example 1, a polymeric chromogen, based on celLulose as the carrier and tetramethylbenzidine as the chromogen, was prepared as an enzyme substrate for the peroxidase/hydrogen per-oxide system.
0.25 ~ of th;s polymer;c chromogen was suspended ~ith 0~05 9 of ~ater, 0.1 ml of absolute alcohol, 0 9 ml of tetrahydrofuran and 0.1 ml of a 1D% by volume solution of polyethylene glycol 400 in tetrahydrofuran, and 0.25 9 of a 7% by ~eight solution of PVC in tetrahydrofuran ~as then added, and the suspens;on was homogenized after 5 minutes.
The suspension ~as then applied in a thickness of 300 ~ to a PVC carrier by means of a knife blade. After drying, this gave a highly absorbent membrane ~elded to the carrier. On immersion into a solut;on of pH 5, which contained 0.1X by volume of hydrogen perox;de and a little peroxidase, the polymeric chromogen integrated in the mem-brane ~as oxidized, a green color being formed.
~o Exa~ple 4 Diazotized p-aminobenzyl-GelLulose ~as prepared accord;ng to Ger~an Offenlegun~sschrift 1,~56~Z14, Example 19.
Sod;um acetate ~as added in smaLL portions, with vigorous stirring, at 0C to the solution containing hydrochloric acid~ until the pH value was about 4.5. The same volume of a 5% by volume solution of N,N-dimethylaniline in N,N-dimethylformamide, ~hich xas cooled beforehand to 0C, ~as then added and the mixture ~as stirred for 30 minutes in an ice bath. After filtration with suction, the cellulose product ~as then extensively ~ashed ~ith ~ater.
The material proved to be a polymeric, non-bleeding acidl base indicator uhich changes from yellow to red on addition of acid.
~35~
~y ~eans of 250 ~J thick steel stenci l sho~;ng a St~
Andre~ls cro~s, the dried m3terial ~as appl;ed ~n accord-ance ~lth E~ample 1 to a yello~-pigmented adhesive PVC
label. After dryingO ac;d-containing ~ater produc~d a red 5 ~ rn i ng c ross .
Example 5 For using the polymeric acid/base indicator trom E~ample 4 for the determination of pH values, a wh;te-p;gmented PVC
carrier ~as coated, by ~eans of a coatins apparatus, ~ith seven parallel, 3 ~m ~ide strips at a mutual ~pacing of 4 mm. The interm~diate ~ones ~ere coated ~;th PVC colors of 3 mm w;dth, the PVC colors beiny adapted in graduated steps of 0.2 pH to thc ch3nge colors of the indicator ;n , the region from 4.6 to 3.4.
After dry;ng, the carrier was cut into s~r;ps, perpen-diçular to the çolor zones.
Th;s non-bleeding ind;cator test strip has advanta~es over ~he ex;st;ng products in pH ~llocation. Due to the closely - adjo;nin~ color zones of sim;lar color ~tructure and sur-face structureO the subjectively achievab~e accuracy of allocat;on ;s ~mproved over exist;ng te~t strips.
Examp~e ~
0.1 g of a cellulose preparation, on which Congo Red (Colour Index 22120) had been ab~orbed by substanti~e d~eins, was suspended in a mixture of 0.3 g of 10~ by weight PVC in tetrahydrofuran, 0.6 ml of tetrahydrofuran and 0.2 ml of alcohol and applied in a thickness of 400 ~ to a carrier of rigid PYC.
After the evaporation of the solventR, this ga~e a highly absorbent and largely wear-resistant coating which can be used a~ an acid/base indicator which i5 substantially secure against bleeding.
Claims (9)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A device composed of particulate matter incorporated into a waterproof polymer with a membrane filter structure, said particulate matter being composed of or comprising an absorbent material and containing one or more reactants in a chemical reaction and, wherein at least one reactant is bonded to said particulate matter.
2. The device as claimed in claim 1 containing a detergent.
3. The device as claimed in claim 1 or 2, in a two-dimensional form.
4. The device as claimed in claim 1 or 2, wherein the proportion of the waterproof polymer is 3 to 5 g per 100 g of device.
5. The device as claimed in claim 1 or 2, wherein the proportion of the waterproof polymer is 6 to 35 g per 100 g of device.
6. The device as claimed in claim 1 or 2, wherein the proportion of particulate matter is 50 to 97 g per 100 g of device.
12 ?. The device as claimed in claim 1 or 2, wherein the proportion of particulate matter is 65 to 94 g per 100 g of device.
8. The device as claimed in claim 2, containing up to 25 g of a detergent per 100 g of device.
9. A process for preparing a device composed of particulate matter incorporated into a waterproof polymer with a membrane filter structure, said particulate matter being composed of or comprising an absorbent material, and containing one or more reactants in a chemical reaction and, wherein at least one reactant is bonded to said particulate matter comprising the steps of mixing said particulate matter with a polymer solution, which forms said membrane filter structure, the solvent system being selected such that the precipitating fractions of the solvent mixture preferentially penetrate into said particulate matter and then precipitating the mixture to form a membrane filter.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3433563.3 | 1984-09-13 | ||
| DE19843433563 DE3433563A1 (en) | 1984-09-13 | 1984-09-13 | DEVICE MADE OF POLYMERS WITH MEMBRANE STRUCTURE AND STORED SOLID PARTICLES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1285721C true CA1285721C (en) | 1991-07-09 |
Family
ID=6245262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000490609A Expired - Lifetime CA1285721C (en) | 1984-09-13 | 1985-09-12 | Device composed of polymers with a membrane structure and incorporated solids particles |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0175195B1 (en) |
| JP (1) | JPH0672877B2 (en) |
| AT (1) | ATE70129T1 (en) |
| AU (1) | AU592771B2 (en) |
| CA (1) | CA1285721C (en) |
| DE (2) | DE3433563A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3637421C1 (en) * | 1986-11-03 | 1987-10-29 | Nerbe Plus Ges Fuer Medizinisc | Reaction vessel for the blood coagulation reaction |
| CA2025476A1 (en) * | 1989-09-27 | 1991-03-28 | Shan F. Ching | Hydrophilic laminated porous membranes and methods of preparing same |
| CA2025474A1 (en) * | 1989-09-27 | 1991-03-28 | Donald I. Stimpson | Hydrophilic laminated porous membranes and methods of preparing same |
| CA2025475A1 (en) * | 1989-09-27 | 1991-03-28 | Donald I. Stimpson | Hydrophilic laminated porous membranes and methods of preparing same |
| GB9822436D0 (en) * | 1998-10-14 | 1998-12-09 | Cambridge Combinatorial Ltd | Sintered/co-sintered materials |
| EP1502957B1 (en) * | 2003-07-11 | 2008-08-27 | F. Hoffmann-La Roche Ag | Castable diffusion membrane for enzyme-based sensor application |
| CA2473069C (en) | 2003-07-11 | 2014-03-18 | F. Hoffmann-La Roche Ag | Castable diffusion membrane for enzyme-based sensor application |
| US8022013B2 (en) | 2003-08-29 | 2011-09-20 | Illumina, Inc. | Method of forming and using solid-phase support |
| CN112592586B (en) * | 2020-12-14 | 2022-11-22 | 上海长伟锦磁工程塑料有限公司 | High-brightness black scratch-resistant spraying-free nylon material and preparation method thereof |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1001238B (en) * | 1954-07-01 | 1957-01-24 | Rohm & Haas | Selectively permeable cationic film |
| DE1045648B (en) * | 1957-03-26 | 1958-12-04 | Nat Aluminate Corp | Process for the production of selectively ion-permeable membranes |
| DE1955935A1 (en) * | 1968-11-06 | 1970-09-17 | Kurashiki Rayon Co | Flexible porous adsorbent material and process for its manufacture |
| US3993451A (en) * | 1970-07-28 | 1976-11-23 | Miles Laboratories, Inc. | Test for a given constituent in a liquid |
| IN141704B (en) * | 1975-01-28 | 1977-04-09 | Miles Lab | |
| DE2705734C3 (en) * | 1977-02-11 | 1982-04-22 | Akzo Gmbh, 5600 Wuppertal | Dialysis membrane for hemodialysis |
| DE2705735C3 (en) * | 1977-02-11 | 1982-05-19 | Akzo Gmbh, 5600 Wuppertal | Dialysis membrane for hemodialysis |
| DE2739008A1 (en) * | 1977-08-30 | 1979-03-15 | Behringwerke Ag | Indicator sheet for use with liquids, esp. blood and urine - having coating of hydrophilic swellable polymer particles, preventing indicator running |
| NL184440C (en) * | 1978-05-17 | 1989-07-17 | Battelle Memorial Institute | TEST SAMPLE FOR ANALYZING Dissolved Substances. |
| HU177369B (en) * | 1978-09-08 | 1981-09-28 | Radelkis Electrokemiai | Industrial molecule-selective sensing device and method for producing same |
| DE2910134A1 (en) * | 1979-03-15 | 1980-09-25 | Boehringer Mannheim Gmbh | DIAGNOSTIC AGENT FOR DETECTING COMPONENTS OF BODY LIQUIDS |
| JPS568549A (en) * | 1979-07-02 | 1981-01-28 | Fuji Photo Film Co Ltd | Multilayer chemical analyzing material |
| DE3050157A1 (en) * | 1979-12-28 | 1982-03-25 | Albany Int Corp | SORBENT-LOADED TEXTILE YARNS AND FILMS AND METHODS OF FABRICATING SAME |
| JPS59102388A (en) * | 1982-12-03 | 1984-06-13 | Fuji Photo Film Co Ltd | Biological reaction layer and its preparation |
| US4849311A (en) * | 1986-09-24 | 1989-07-18 | Toa Nenryo Kogyo Kabushiki Kaisha | Immobilized electrolyte membrane |
-
1984
- 1984-09-13 DE DE19843433563 patent/DE3433563A1/en not_active Withdrawn
-
1985
- 1985-08-31 AT AT85111004T patent/ATE70129T1/en not_active IP Right Cessation
- 1985-08-31 EP EP85111004A patent/EP0175195B1/en not_active Expired - Lifetime
- 1985-08-31 DE DE8585111004T patent/DE3584807D1/en not_active Expired - Lifetime
- 1985-09-12 CA CA000490609A patent/CA1285721C/en not_active Expired - Lifetime
- 1985-09-12 AU AU47413/85A patent/AU592771B2/en not_active Expired
- 1985-09-12 JP JP60200711A patent/JPH0672877B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE3433563A1 (en) | 1986-03-20 |
| AU592771B2 (en) | 1990-01-25 |
| JPS6172027A (en) | 1986-04-14 |
| EP0175195B1 (en) | 1991-12-04 |
| DE3584807D1 (en) | 1992-01-16 |
| ATE70129T1 (en) | 1991-12-15 |
| EP0175195A3 (en) | 1988-10-05 |
| JPH0672877B2 (en) | 1994-09-14 |
| EP0175195A2 (en) | 1986-03-26 |
| AU4741385A (en) | 1986-03-20 |
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