CA1147247A - Test device resistant to cross contamination between reactant areas and process for making it - Google Patents

Test device resistant to cross contamination between reactant areas and process for making it

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Publication number
CA1147247A
CA1147247A CA000350286A CA350286A CA1147247A CA 1147247 A CA1147247 A CA 1147247A CA 000350286 A CA000350286 A CA 000350286A CA 350286 A CA350286 A CA 350286A CA 1147247 A CA1147247 A CA 1147247A
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CA
Canada
Prior art keywords
reagent
hydrophobic layer
test device
affixed
reagents
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000350286A
Other languages
French (fr)
Inventor
Myron C. Rapkin
David L. Tabb
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Bayer Corp
Original Assignee
Miles Laboratories Inc
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Filing date
Publication date
Application filed by Miles Laboratories Inc filed Critical Miles Laboratories Inc
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Publication of CA1147247A publication Critical patent/CA1147247A/en
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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N31/00Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
    • G01N31/22Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/525Multi-layer analytical elements
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/805Test papers

Abstract

ABSTRACT OF THE DISCLOSURE A test device for detecting the presence of constit-uents in a liquid test sample, and method for preparing it are disclosed, The device comprises a base support member coated with a hydrophobic barrier layer onto which is affixed a plurality of spaced apart reagents respectively responsive to different constituents of the test sample. The barrier layer comprises finely divided silica particles, to the surface of which are randomly covalently bound groups having the structure -O-SiR3 wherein the R substituents, same or different, arc hydrogen, lower alkyl or aryl.

Description

~1~72~

Docket No. lL848 TEST DEVICE RESISTANT TO CROSS CONTAMINATION BFTWEFN
REACTANT AREAS AND PROCESS FOR MAKING 17' BACKGRO~ND OE THE INVENTION

Fie 1,d of the .~nvention The present invention relates to a test device for detecting the presence of a constituent in a liqu;d tcst sample and method for making it. Moreover, it relatcs to minimizing the adverse effects of misuse of the dcvicc, thereby enhancing its accuracy and dependability.
The art of analytical chemistry has bcen greatly advanced since biochemistry began emerging as a primary scientific frontier, requiring increasingly sophistic.ltc~l analytical methods and tools to solve problems, thc sol~l-tions to which were never before attempted. Likcw;se, tllc lS medical profession has lent impetus to the growth of analytical chemistry, with its desiderata of both higll precision and speed in obtaining results. This rcmarkahlc progress has been still further spurred by industrics sucl as brewing, chemical manufacturing, and others.

~7~47 To satisfy thc needs of these expanding techllologics, a myriad of analytical procedures, compositions and apl~
TatuSes have evolved, including solution chemistry -tecll-niques, automated machinery and the so-called "clip-an~-rea(l"
type reagent strips. It is to the last of these that tllc present invention is primarily directed, although suh~tantiill benefit ultimately attaches to the other procedures a~ well.
Reagent strip test devices enjoy wide use in m.lny analytical applications, especially in the chemical an.llysis of biological fluids, because of their relatively low cost, ease of utilizability and speed in obtaining results. In medicine, for example, numerous physiological functions c<ln be monitored merely by dipping reagent strips into a saml~e of body fluid, such as urine, and observing a detectahle response such as a change in color or a change in the amount of light reflected from or absorbed by the strip.
Compatible with such "dip-and-read" reagent strips havc arisen many chemistries for detecting body fluid componellts.

Many of these produce a detectable response which is qlJ.I~lti-tative or at least semi-quantitative. Thus, by measuring the response after a predetermined time, the analyst C<lll obtain not only a positive indication of the presence of a particular constituent in a test sample, but also an esti-mate of how much of the constituent is present. Such strips provide the physician with a facile diagnostic tool as well as the ability to guage the extent of disease orbodily malfunction.

1147~

Illustrative of such strips currently in use are prod-ucts available from the Ames Division of Miles Laboratories, Inc under the trademarks CLINISTIX~, MULTISTIX~, K~TOSTIX , N-MULTISTIX , DIASTIX~, DEXTROSTIX~, and others. Test devices such as these usually comprise one or more carrier matrices, such as absorbent paper, having incorporated with them a particular reagent or reactant system which manircsts a color change in the presence of a specific test samplc component. Depending on the reactant system incorporated with a particular matrix, these devices can detect the presence of glucose, ketone bodies, bilirubin, urobilinogen, occult blood, nitrite, and other substances. The specific color change and the intensity of the color observed within a specific time range after contacting the strip with the sample is indicative of the presence of a particular com-ponent and its concentration in the sample. Some of these test devices and their reactant systems are set forth in United States Patent Nos 3,123,443 (CLINISTIX~); 3,212,855 (KETOSTIX~); 39814,668, 3,164,534 and 2,981,606 (DIASTIX~);
and 3,298,789, 3,092,465, 3,164,534 and 2,981,606 (DEXTROSTIX~).
It is to those of the above-described devices having more than one reagent-bearing carrier matrix that the prcscnt invention is primarily applicable. Thus, a reagent strip can contain tests for more than one constituent in a particular liquid sample. For example, a single reagent strip could consist of a reagent-bearing carrier matrix responsive to 11~7~47 glucose in urine, and another matrix spaced from but acl-jacent the first responsive to ketones, such as ~cetoacetate.
Such a product is marketed by Ames Division under tllc ll.lll)C
KETO-DIASTIX~. Another reagent strip marketecl hy Ames Division, N-MULTISTIX~, contains eight adjacent reagellt-incorporated matrices and provides analytical measuremcnts of pll, protein, glucose, ketones, bilirubin, occult bloo~l, nitrite and urobilinogen.
Despite the obvious, time-proved advantages of sucll multiple test reagent strips as these, misuse can result in misinformation. These multiple-analysis tools comprisc complex chemical and catalytic systems, each reagent m.ltrix containing a unique reactive system, responsive to its particular analysate. Thus it is possible, if thc rcagent strip is misused, for chemicals to be transported by thc liquid sample being analyzed from one carrier matrix Oll thc strip to another. Should this happen it is possible for reagents from one carrier matrix to interfere with those of the others so contacted, causing unreliable results. Altl~orJgl it is common in the reagent strip industry to provicle detailed instructions as to how this problem is avoided, i.e., directions for properly manipulating the reagent strips, nevertheless ignorance or disregard of these instrllc-tions could permit reagents from one matrix to run over onto an adjacent one. It is to the prevention of this "runover"
problem that the present invention is primarily clirectcd.

7~247 The elimination of runover has been long sought after, but until the advent of the present invention, never ade-quately attained. Applicants' discovery, which was the cul-mination of an extensive research effort based on their initial conception of how to avoid runover interference, has finally solved this elusive problem, and the results are indeed as unique as the solution.

Discu~sion of the Prior Art The patent literature is replete with accounts of myriad attempts at curtailing runover, the great bulk of the emphasis being directed to two basic concepts: the absorbence of runover liquid by bibulous layers placed beneath the reagent-bearing layers of reagent strips; and use of hydro-phobic barriers between the spaced matrices to confine the sample liquid to the matrices. The former has met with moderate success, whereas the latter has not. But more importantly, neither has completely obviatèd the problem.
Of the multi-layer type of reagent strips, only one is described in the literature as successfully curtailing the problem of runover. Thus, United States Patent No.
4,160,008, assigned to Miles Laboratories, Inc., describes a test device in which the carrier matrices containing reagent formulations are provided wlth absorbent underlayers which 7~47 are separated therefrom by sample-impervious barrier layers.
Each matrix thus forms the upper layer of a ]aminate com-posite in which the barrier layer is disposed hetween tI~e matrix and the absorbent base layer, the composite I~eing fixed to a suitable support such as a plastic strip. W]1CT1 the test device is dipped into a liquid sample, the portion of the sample which would otherwise runover from one matrix to another is largely absorbed into the underlayer Or tlle latter through the exposed sides, the barrier layer Or tlIe composite segregating the absorbed runover from the u~I~er reagent layer.
No other art appears to be directed to the al)sor~tive underlayer approach to solving the runover prohlem, althougI-other multilayered reagent strip devices are descriI~e(I in which potentially incompatible reagents for the same test are separated from each other in layers and communicate uIlon wetting by the test sample. For example, lJ.S. Patent No.
3,531,254 teaches that potentially incompatible reagents ca be impregnated into separate layers to permit extended storage periods before use. When sueh a multi-layered matrix is wetted with a test sample, these layers communicate and the reagents previously separated become mixed to give the desired analytical test.
Another example of a multi-layered carrier matrix is the one shown in U.S. Patent No. 3,802,842. Itere, a porous pad containing no reagents abuts an upper pad containing tl~e reagents for the desired test. Thus, when liquid samI)le is 7~47 applied to such a carrier matrix some of the samplc is absorbed by the non-impregnated pad, and some by thc OllC
bearing the reagents. As in the previous patent, thc laycrs of this carrier matrix communicate with one another whcn wet. Some of the liquid (and some of the reagents) pass through the upper pad into the lower pad. There is no barrier provided between the two pads.
There exist other patents which, although less pcrti--nent than the previous two, nevertheless are oL intcrcst when considering the present invention, and are mentioncd here for the convenience and information of those intcrcstcd in the present teachings. IJ.S. Patent No. 3,418,083 ~lcpicts an indicator-impregnated absorbent carrier matrix trc.ltc(l with wax, oil or similar "hydrophobic" agents. It is 5;li~
that when a sample of blood is placed on such a reagent strip, only the colorless liquid components permcate it, thc proteinaceous, colored blood components remaining on thc surface where they can be removed. Thus, it is taught, thc liquid portion bearing the analysate permeates the reagcllt pad, whereas color interferants are precluded from it.
Still another prior art reference, U.S. Patent No.
3,672,845 assigned to the present assignee, shows spraying adhesive onto a plastic or paper support member or tllc purpose of gluing on reagent-laden polymer particlcs. Yct another, U.S. Patent No. 3,992,158, teaches an uppcr, SCllli-permeable layer containing ascorbate oxidase afixed to ;
lower, reagent-laden layer.

~7'~47 Turning now to the second of the abovementioncd attc~)ts to curb runover - hydrophobic barriers between adjaccJlt tcst areas of a reagent strip - there has been a not illCOns i ~] -erable amount of patenting activity. U.S. Patent No.
3,001,915, assigned to the present assignee, descriI)cs In absorbent paper reagent strip having spaced reagent-imprc~natc-I
test areas for more than one sample component, eacIl su-l~
area being separatcd from its neighbor by a non-aI~sor~tivc barrier portion. The barrier is provided by impregnation o r the paper strip with such materials as polystyrene, rosin, paraffin and various cellulose esters. The reagent striI) is prepared, according to this reference, by impregnating a portion of a paper strip with a glucose-sensitive rcagcnt system. When dry, a solution of one o-f the above barricr materials is applied to the paper adjacent the glucosc-sensitive portion. After further drying a protein-sensitivc reagent system is applied. The process is repeated, WitI
alternate applications of reagent and barrier solutions witl drying steps in between.
Yet an earlier patent, U.S. Patent No. 2,129,754 issuc~I
September 13, 1938, describes the impregnation o riltcr paper with paraffin wax whereby specific areas are lcft unimpregnated, but surrounded by the wax. These unwaxcd spots can then be treated with indicator systems for a particular analyte.

~1~7Z~7 U.S. Patent No. 3,006,735 carries the concept of barrier material impregnated between reagent areas Or a paper strip one step further by providing succes~-ivc rcagcllt areas responsive to different degrees of water har~lncs~.
Between these reagent areas are impregnated such watcr repellent materials as oils, waxes, silicones and prilltcr~
varnish. Like the preceding two patents, this rcrcrcncc is restricted to paper or like bibulous material whcrcin reagent and barrier material alike are impregnate~l sc(~llcn-tially along its length.
Similarly, U.S. Patent Nos. 3,011,874 and 3,127,281teach the use of hydrophobic barrier materials imprcgnatc~
in part of a paper strip in order to separate onc rcagcllt area from another to avoid contamination.
A product was recently marketed by ~iken Chemical (o.
Ltd., of Tokyo, Japan which was a 4-reagent area dip-an(l-read test strip responsive to pH, protein, occult hlood alld glucose in urine. The strip comprised a long plastic support member which was a composite of a lower polystyrcrlc layer and an upper polyvinylchloride (PVC) layer. Ihc reagents were impregnated ih paper pads which werc arrixcd to the PVC side of the composite support member. Cont.lct angle measurements with this product revealed a contact ang]e of about 108 with distilled water. Sincc Applic~llts' 7'~

first learning of this product, it appears that Eiken has withdrawn this configuration from the marketplace in deference to a new product whereby the PVC layer of the composite support member has been eliminated.
Finally, U.S. Patent No. 3,964,871 me~tions the sepa-ration of indicator reagent sites by non-absorbent or hydrophobic material.
Whereas the foregoing patents represent what is be-lieved to be those most pertinent to the present invention, it should be noted that currently marketed reagent strip products for the most part comprise reagent-impregnated matrices affixed to a hydrophobic organo-plastic strip.
Thus, the multiple reagent strip known as N-MULTISTIX , marketed by the Ames Division of Miles Laboratories, con-tains eight different reagent-impregnated matrices mounted on a strip of polystyrene film. Since polystyrene is hydro-phobic, the reagent strip can be said to have hydrophobic interstices between adjacent matrices.
Despite the lip service given by prior art accounts of eliminating runover, the fact remains that there are presently no reagent strips commercially available capable of stifling this problem to anywhere near the extent achieved by the present invention. Of the patent art cited above, only that approach disclosed in U.S. Patent No. 4,160,008, 7~47 i.e., the use of an isolated absorbent underlayer, provi(Ies a real advance in the art. But even that approac]l, cer-tainly widely divorced from the present invention, canlIot approach the success at eliminating runover which the present invention achieves.
Prior art attempts using waxes, oils, silicones, etc.
have not curtailed runover to a clinically significant extent; and what modest advances that may have been ma-Ie were more than offset by serious drawbacks inherent to the~e attempts. For example, applying hydrophobic materials on]y at reagent area interstices embodies enormous technical problems, especially when compared with current techniqIJes for manufacturing dip-and-read reagent strips. ]3esi(Ies tlle obvious extra steps required by intersticial applicatio there is the danger of some of the hydrophobic material overlapping the reagent areas - thus interfering with the paramount purpose of the device. Moreover, none of these prior art substances provides a suitable surface for a~-hesion. Small wonder no runover-free commercial products are available.

But even if these shortcomings were not prohib;tivc enough, the prior art hydrophobic substances lack tIIC ~Iegree of hydrophobicity required to prevent runover. They ~o not provide a sufficient enough contact angle to achieve the ~47'~4~

required hydrophobicity, nor do they provide a suitahlc surface for binding either the absorbent matrices or thc reagents themselves, were they to be coated directly on tl~c hydrophobic surface. Only the present invention constitutcs this long sought after breakthrough.
The present invention virtually eliminatcs cross-contamination between adjacent reagent areas oF multiplc test reagent strips. These results are truly incontro-vertible, Nothing in the prior art approachcs thc dr.l-matically high degree of success in solving this problcmafforded by the presently disclosed concepts.
But the contribution of this discovery to thc statc of the art goes beyond the elimination o-f runover. Surpris-ingly, it has been found that adhesive techniqucs currcntly used for attaching reagent matrices to a polystyrenc 1)aSC
support provide even stronger adhesive bonds when thc prcscTlt invention is utilized. Moreover, it is not necessary to utilize expensive process steps such as depositing hy(lro-phobic coats between adjacent matrices. These and othcr advances in the current state of the art will beco~e cvi~lcnt in view of the present specification and claims.

1~7~47 SUMMARY OF THE INVENTION

Briefly stated, the present invention relatcx to a tcst device for detecting the presence of a constituent in a liquid test sample and method for making it It comprixcx ;l base support, a hydrophobic layer affixed to the baxc XUppOl't and a test reagent affixed to a predetermined surfacc portion of the hydrophobic layer. The hydropho~;c laycr comprises a binder material, and finely divided si]ic.l particles having randomly covalently bound to thcir xurlaccx ] groups having the structure -O-SiR3 wherein the R substituents, which can be the same or dilrcrcllt, are hydrogen, lower alkyl or aryl.

BRIEF DESCRIPTION OF THE DRAWINGS

Figures 1-9 are provided to assist in illustrating all~l describing the presently-disclosed inventive concepts.
Figure 1 is a side view of a preferred embodiment Or tl~c test device. Figure 2 depicts the contact angle xul~tclldcd by a drop of distilled water on uncoated polystyrcnc rilm, whereas Figure 3 shows a drop of distilled water on thc xalllc film when coated in accordance with the present tcachingx.

~1~7~47 Figure 4 is a graphic presentation of data obtainc~l from comparing the invention with the prior art. Iigurcs 5 ~ln~l ( graphically present performance data from assays Or occult blood and urobilinogen, respectively, in urine using thc presently disclosed device. Figures 7 and 8 prescnt d<lta from adhesive studies, and portray the performancc Or various adhesives on polystyrenc film with and w-itllout application of the present inventive conce~ts. ~inally, Figure 9 depicts the apparatus and method uscd in tcsting the adhesive propensity of polystyrene film coatcd witll tllC
presently described hydrophobic layer.

DETAILED DESCRIPTION OF THE INVENTION

The test device of the present invention lends itscl r to the analysis of a liquid test sample for numerous con-stituents. In the case where the sample is beer, it C.lll heused to determine the sugar content; hence, the extcnt Or fermentation. It can be used to determine pll in such a~
cations as battery acid strength determination. Onc ar ca nl exceptional importance is urinalysis, wherein the ~Icvicc can be used to determine such diverse urine constituents or characteristics as albumin, ascorbic acid, bilirul~in, glucose, hydrogen ion, ketone, nitrite, occult blood, specific gravity and urobilinogen. Obviously the utility or ~7'~47 this invention embraces the analysis of many more te~t sample constituents than those enumerated herein; thus the term "constituent" relates to any solution parametcr, sllch as a solute or colligative property, for which a responsivc reagent system can be devised. Equally diverse are the types of test samples which can be analyzed, inclu(]ing beer, industrial waste, urine J blood, and swimming pool water.
The reagents of the device constitute the heart of thc analytical response provided by the device, and, in the broadest sense, include one or more reagent compositions respectively responsive to particular constituents - respollsivc i.n the sense that some detectable manifestation of the presence of the constituent takes place. The response can be in the form of the appearance of color, or its dis.ll~pearlncc.
One color may change to another. A change in the amount o r light reflected or absorbed can be utilized. The analytical arts are replete with all of these types of detectahle response, as well as others.
Thus, for example, if a response to glucose in urine is sought, the reagent composition could comprise the enzymcs glucose oxidase and peroxidase and the indicator 3,3',5,5'-tetramethylbenzidine (TMB). In the presence of glucose tilis composition becomes colored various shades of blue, depen-ling ~1~7Z47 on the glucose concentration; ergo the detectahlc rcsponsc is the appearance of blue. If the constituent is ascorl-ic acid, the composition might comprise methylene grccn alld a suitable buffer. Ascorbate ion causes such a composit,ioll to fade from a dark blue to varying lighter shades Or bluc depending on the ascorbate concentration of thc saml~lc.
The base support member provides the main structurill integrity of the test device, and it should thercrorc co~
prise a rigid or semi-rigid material. Ideally it compriscs a dimensionally stable film of material such as polystyrenc, polyolefin, polycarbonate, melamine resin or other polymcr.
Especially suitable is a biaxially oriented polystyrenc ri lm such as that manufactured by Plastic Suppliers, Inc. Or Columbus, Ohio. The preferred shape is rectangular, I~cing substantially long and narrow. Reagents, whether incor-porated into matrices or otherwise, are affixed to arcas which are generally closer to one end than the othcr, thus providing a reagent-free handle portion.
A truly unique feature of the present invention, ~nd that aspect which gives rise to the advantages of elimina-tion of cross-contamination between adjacent rcagents and enhanced bonding with adhesives, is the hydrophobic laycr applied to the base support. The layer comprises a hydro-phobic material having a high contact angle and, ir ncc-essary, a suitable binding material SUC}I as a polymersoluble in an organic solvent, for example an acrylic po]ylllcr.

~'7~

The hydrophobic material utilized in the present invention can vary in many respects, but it has been found particularly suitable to employ an alkylated fused silica, such as that known as Tullanox 500 available from Tulco, Inc. of North Billerica, Massachusetts. Tullanox 500 is described by its manufacturer as an inorganic powdered silica (particle size about 0.007 micron) of low bulk density (about three pounds per cubic foot). It has an extremely high surface area which has been modified by reaction with an organic "silicone-like" compound (although not a silicone). Surface area has been calculated theo-retically to be 325 meters2/gram (m2/g), and determined experimentally by the N2 adsorption method to be 225 m2/g.
- It is derived from a.fumed silica base which is over 99.8 percent pure SiO2. The hydrophilic hydroxyl groups inherent to the surface of such silica particles have been substituted . with trimethyl siloxyl groups. The predominant physical attributes of this material are extremely fine particle size, very high surface area and almost complete lack of cohesive attraction between particles.
Although Tullanox 500 is the preferred material for the hydrophobic layer,-it is to be understood that.the present ~ discovery is of such a pioneer nature as to extend much further in scope than merely Tullanox 500. For example, the * Trade Mark ~7~47 siloxyl groups covalently bound to the silica can satisfy the general structure -O-SiR3. The R substituents, which are all methyl in Tullanox 500, can also be hydrogen, lower alkyl, aryl, or any other group which provides the above-described advantages. By lower alkyl is meant substitutedor unsubstituted alkyl groups having 1 to about 6 carbon - atoms. Thus R can comprise methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, t-butyl, cyclobutyl and the various pentyl and hexyl isomers. The term aryl is intended to include aromatic groups, substituted or unsubstituted, phenyl or polynuclear, homocyclic OT heterocyclic. Thus, R
can comprise phenyl, tolyl, and nitrophenyl.
The hydrophobic layer also comprises a suitable binder to secure the hydrophobic material-to the base support member, and it can take on many forms. ~or example, the silica material can be suspended in a solv~nt capable of partially dissolving the base support. In the case where the support member is polystyrene and the solvent contains benzene, partial dissolution of the polystyrene upon appli-cation of the suspension leads to binding of the silica to the support by the dissolved polymer after the residual solvent has evaporated. In this case the binder is the support member material itself.

* Trade Mark ~J

Other manifestations of suitable binders are normally used coating materials such as polysiloxanes, polyacrylic resins such as poly(methylacrylic acid), poly(methylmeth-acrylate), acrylic copolymers, and others, as well as copolymers of vinyl chloride and other ethylenically un-saturated monomers.
Especially ~uitable for use as a binder is the acrylic copolymer utilized by Tulco, Inc. in the product known as Tullanox LC 410. This product comprises the finely divided Tullanox 500 particles, described 8upra, suspended in a solution of an acrylic copolymer in a iiquid hydrocarbon.
The physical properties of Tullanox LC 410, as provided by Tulco, Inc., are as follows:
weight per gallon ' 7.05 lb.

, percent total solids 16.00 grams/100 milliliters (g/ml) percent solvents (Rule 66/3) 84.00 ratio of si'lica to polymer binder (wt./wt.~ 1.0 to 0.6 clarity opaque white drying time (a) tack free 60 minutes ' (b) completely dry 8 hours This suspension is infinitely dilutable in solvents, or combinations' of solvents,'having a K.B. value of 35 or higher. K.B. value is a measure of the aromatic content, hence the solvent power, of a hydrocarbon liquid.- Kauri gum is readily soluble in butanol, but insoluble in hydrocarbons.

* Trade Mark ~7~

Thus, the K.B. value is the measure of that volume of solvent required to produce turbidity in a standard solution .
containing kauri gum dissolved in butanol. Naphtha frac-tions have a K.B. value of about 30, whereas toluene is about 105.
It has been found to be desirable to dilute Tullanox LC
410 using various solvents. Especially beneficial is to utilize a solvent which partially dissolves or etches the base support member material. In the case where the support member comprises polystyrene 9 an aromatic solvent such as benzene or toluene facilitates an excellent hydrophobic finish which simultaneously offers excellent binding of the hydrophobic layer to the base support material.
The aforementioned reagent (or rea~ents) of the presently described test device is affixed by suitable means to the hydrophobic layer. The mode by which the reagent is affixed can take on a myriad of forms ranging from absorbent paper pads impregnated with the desired reagents to directly coated or imprinted reagents. In the former case the impregnated pad has traditionally been affixed utilizing a double-faced adhesive tape known as Double Stick sold by 3M
Company.

.

* Trade Mark One of the surprising features of the present discovery is the increased affinity of this adhesive means for the hydrophobic layer as compared to the affinity of this same adhesive means for the preferred base support material, p~lystyrene, without the hydrophobic layer. Figures 7 and 8 portray this increased affinity graphically. Figure 7 shows the amount of force required to remove two samples of Double Stick tape from polystyrene strips coated with Tullanox LC 410. The data for two of the samples are shown, and as can be seen, almost identical results were obtained, in excess of 0.8 pounds of force being required in each case. As shown in Figure 8, removal of two samples of Double Stick tape from uncoated polystyrene required only about 0.5 pounds of force. The coating of the present invention dramatically enhanced the adhesive attraction of *Double Stick adhesive for the support member. The experi-ments depicted by Figures 7 and 8 will be discussed further in the Examples, infra.
A preferred embodiment of the present invention, wherein many of the features discussed above are incor-porated, is shown in Figure 1. Thus, base support member 1 comprising biaxially oriented polystyrene film is coated with a thin fllm of Tullanox L~ 410, which dries to form hydrophobic layer 2. The coating is achieved using a doctor * Trade Mark ~7~7 blade or other suitable means known in the coating or printing art. A presently preferred method for applying the hydrophobic layer to the support member comprises the use of rotogravure printing techniques, techniques which are thoroughly known in the printing art. Specifically, the hydrophobic solution of Tullanox LC 410 is pumped into the fountain of a rotogravure press from which it is transferred to the printing cylinder. A film of polystyrene support material is passed through the press and the Tullanox solution is transferred to the film.
When the coating has been sufficiently dried, such as under ambient conditions or in an air oven at elevated temperature, the desired reagent-impregnated matrices 4 can be affixed to the layer 2 in spaced relation using a suitable adhesive as at 3. As is stated ~upra, the preferred adhe-sive is Double Stick tape. The preferred reagent matrices 4 comprise rectangular pieces of filter paper which are impregnated with solutions of reagent systems respectively responsive to particular analytes, dried, and mounted to the hydrophobic layer i.
Although not the only criterion for successful elimina-tion of runover, the concept of contact angle nevertheless plays a role of great significance. By definition, the term "contact angle", as it relates to a solid-liquid interface, * Trade Mark ~ ~7~7 means the angle subtended by the solid surface and a plane tangent to the surface of a liquid drop at the point of contact between the solid and the liquid. Figures 2 and 3 depict distilled water drops 5 and 6, respectively, resting on horizontal surfaces, and the contact angles are desig-nated ~1' and ~2' respectively. The greater the contact angle caused by the particular solid surface; the greater the hydrophobicity of that surface. Likewise, the greater the hydrophobicity of the surface separating two reagent matrices of a test device such as in Figure l; the less likely is the occurrence of runover between such matrices.
Figure 3 portrays a sheet 1 of biaxially oriented poly-styrene film (Plastic Suppliers, Inc.) which has been coated with Tullanox LC 410 and dried to provide a hydrophobic layer in accordance with the present invention. The contact angle ~2) between that surface 2 and a drop of distilled water 6 is about 135. By comparison, uncoated polystyrene 1 in Figure 2 effects a contact angle (~1) of only about 50~.

EXAMPI,ES

The following Examples are provided to further illu-minate the inventive aspects of the present discovery, and to further exemplify preferred embodiments. As such, they * Trade Mark ~72~7 are intended as being merely illustrative, and are not to be construed as limiting the scope of the claims appended hereto, F~ampZe I - Preparation of a PoZystyrene Support Member An experiment was conducted to prepare a polystyrene support member having an exceedingly high degree of hydro-phobicity. Accordingly, sheets of biaxially oriented poly-styrene obtained from Plastic Suppliers, Inc. were coated with varying dilutions of Tullanox LC 410. The lullanox formulation was diluted with varying amounts of a solvent mixture comprising 65~ petroleum ether, acetone, and toluene.
The Tullanox LC 410, which contains 16~ by weight total solids, was-diluted with enough solvent mixture to make four suspensions containing 3.2, 2.4, 1.6 and 0.8 grams of Tullanox 500 particles per 100 grams of suspension. Four sets of coated polystyrene were prepared, using a 10 mil doctor blade, and these were designated A, B, C and D, respectively. The following table synopsizes these formu-lations. The films cast in this manner were subsequently dried for three minutes using a laboratory fan operated heat gun.

* Trade Mark 7'~47 Component A B C
Tullanox LC 410 1.0 g 0.75 g 0.50 g 0.25 g Petroleum Ether 3.4 ml 3.65 ml 3.90 ml 4.15 ml Toluene 0.3 ml 0.3 ml 0.3 ml 0.3 ml AcetOne 0.3 ml 0.3 ml 0.3 ml 0.3 ml Tullanox 500 (grams per 100 grams of solu-tion applied) 3.2 2.4 1.6 0.8 After drying, the coated sheets were held at an angle of 45 and ten microliter drops of water were placed on each treated sheet. All of sheets A, B, and C shed all of the water placed upon them. Sheet D, the one with the 0.8%
solids, did not shed all its water but was observed to be extremely hydrophobic nonetheless.

E~amp~e II - Contact AngZe Determinations In order to examine the relative hydrophobicit~ of uncoated polystyrene film compared with coated version B of Example I, an experiment was performed to measure the contact angles produced by each. Photographs were taken of drops of distilled water on horizontally oriented poly-styrene sheets, one coated as in Example IB, the other uncoated. The photographs were taken along the plane of the film, i.e. side views, and the resultant images were developed * Trade Mark ~ ~7~7 as ne~atives, and mounted on slides suitable for screen pro-jection. Screen projection enabled considerable magnifi-cation, thus simplifying contact angle measurement, as well as permitting great accuracy of measurement. Figures 2 and 3 simulate the resultant photographs, Figure 2 representing the uncoated polystyrene sheet, and Figure 3 the coated sheet B of Example I
The measurements were performed in triplicate for each sheet, and the results are set forth in the following table.

Polystyrene Sheet Contact Angle Example I, B 133 135 134 Uncoated 53 49 53 E~ampZe III - Preparation of Test Devices A laboratory experiment was performed wherein a test device was prepared having multiple reagent-impregnated matrices, each responsive to a different urine constituent.
The object of this experiment was to demonstrate the con-cepts of the present invention, whereby the occurrence of runover from one matrix to another following immersion in and removai from a test sample such as urine is dramatically curtailed. The reagent matrices of this device approximate those of the commercially available product known as N-MULTISTIX.

The urine parameters corresponding to the reagent matrices are pH, albumin, bilirubin, urobilinogen, nitrite, occult blood, glucose and ketone.

* Trade Mark 7t'~7 A sheet of biaxially oriented polystyrene film manu-factured by Monsanto Company (essentially the same as the Plastic Suppliers, Inc. material descrlbed 6upra) was coated with a solution of Tullanox LC 410. A casting block capable of leaving a wet film of 5 mil thickness was used for this purpose. The Tullanox formulation obtained from the manu-facturer, Tulco, Inc., was diluted with varying amounts of a solvent comprising 65 petroleum ether, acetone, and toluene as in Example I. The Tullanox LC 410 contains 16% by weight total solids, and was diluted with enough solvent mixture to make three suspensions containing 1.6, 2.4 and 3.2 grams of *
Tullanox 500 particles per 100 grams of suspension (g%).
This resulted in three sheets of plastic, each containing a different amount of Tullanox methylated silica.
After drying, the reagents were applied to the coated polystyrene using ribbons of filter paper which had been impregnated with appropriate reagents for the particular urine constituent to be measured. To accomplish this, a layer of Double Stick adhesive tape was applied to one side of each of the impregnated ribbons, and the exposed adhesive side of the ribbon/tape composite was then applied to the hydrophobic coated polystyrene, along the-lengthwise dimen-sion, in spaced parallel stripes. Eight paper ribbons, responsive to each of pH, protein, glucose, ketone, bili-rubin, occult blood, nitrite, and urobilinogen, respectively, * Trade Mark 1~72~7 were applied to the coated polystyrene in reverse orcler beginning from the edge of the polystyrene sheet. 'I'hc reagent formulations were all based on standard chemistries available in the art.
After applying the reagent-impregnated ribbons to tl~e polystyrene support member, the laminate was then sliccd along the width dimension to produce test strips measur;ng 4 inches by 0.2 inches. These crude, laboratory-made test devices were then used to evaluate the reduction in runovcr attributable to the hydrophobic coating.

E~ample IV - Comparison of the ~est Devi~e ~ith Other Devicen Capab~e of Measuring the Same Urine Parameters The devices of Example III were used for comparison with similar devices prepared in similar fashion, and with devices presently commercially available.
One set of reagent strips was prepared for use in this comparison exactly as those of Example III except the hydro-phobic coating was omitted. The strips were identical to those of Example III in every other aspect.
Another set of reagent strips was prepared in thc same fashion except that, in addition to omitting the hyclro~llol)ic layer, absorbent underlayers were provided to certain reagent matrices. These were prepared in the manner set ~72~7 forth in U.S. Patent No. 4,160,008, mentioned ~upra, and made a part hereof. The reagent matrices pro-vided with absorbent underlayers were pH, protein, bili-.
rubin, occult blood and nitrite. These underlayers were separated from their respective reagent matrices by barrierlayers of Double Stick tape. Accordingly., these strips were the same as in Example III, with two important exceptions:
there was no hydrophobic layer affixed to the support member, and there were absorbent underlayers beneath five of the eight reagent matrices.
In addition, the devices of Example III were compared with commercially available products known as Ghemstrip 8 (Boehringer Mannheim GmbH), and Kapignost Total Screen and Rapignost Organoprofil (Behringwerke AG).
The test devices were dipped in urine samples con-taining 100 milligrams/deciliter (mg%) protein, 250 mg~
glucose, 0 mg~ ascorbate, and having.a specific gravity of 1.007 and a pH of 8.5. .

. The study to evaluate runover was performed by multiple personne.l, each of whom performed an evaluation of each reagent area. The data was recorded and averaged, and standard deviations calculated.

* Trade ~ark ~7Z47 The technique utilized in this study encouraged thcoccurrence of runover. The method was deliberately viola-tive of instructions accompanying commercially availahle multiple reagent test devices. Thus, the study was con-S ducted by dipping each reagent strip in urine and, uponremoval, immediately inverting it to the handle down position, and holding it in that position while examining the reagcnt matrices. This technique is explicitly proscribed in thc directions for use accompanying similar commercially avail;lhle products, because of the probability of cross-contamination of reagents. The data obtained from this experiment t}-~s reflects runover occurrence at its worst.
The readings recorded in the following table comprise -observations of aberrant color formation in the various reagent matrices. In each case, the observer examined cach reagent matrix and estimated the percentage of its surfacc which appeared to be aberrantly colored from the occurrcncc - of runover. No data is reported for the urobilinogen matrices (with exceptions as indicated in the table), because when the strips were held in their inverted position (handle down) the urobilinogen m~trix was uppermost, and therefore unaffected by runover.
The results of this experiment are tabulated below:

7~A~7 a) K D
cnLt) ~O ~ :~
,1 . . . h ~ h h O ~O~ ~1 .. ,~ C
~1 .-t `D r-l ~r~ . .r~ ~1 ~1 ,D .D

O ~::
~ O
.D t~ ' o ~ 00 ~ Lr~
. . ~ O
O~ O O O
~ ~ 0 X
U ~

~:: . ~:
. .,1 Ic ~1) O ,D
J o~ o Ln U~ ~O :1 Ul h . . . O u~ O O h ~1 o ~ ~ . .,~
~ ~ ~ ~ O ~ 5 o~ ~1 O
Z ~r-( . ~ ~ 1 ¢ ,D h~
~C
. .
~0 ~ ~ .~ .~
' ~ S Ul 00 0 V) ~ ~ L~ C) 0 O . . . O . ~ .
P~ ~ ~ ~ ~ Oot~ ~ O ~ O
C) ~ ~ S~
~ ~ ~ .
O E-Z U~
~:Z ' O ~
O O O
~ a) ~1 a~ z u~
O O o U~ U~ oo.,~ t_ U~ O~
t~ ~ V . . .. . ~ . ~ . ~
r~ ~ ~ ~ ~ O ~ O
O ~1 5 .-1 :5 t~
O S:l. U U
O O
¢ ~
o U~ ~ ~K
¢ ~ ,~ ~ I~ ~n oo ~ ~ . ~ . ~
C~ ~ ~ . . ~ ~ ~ ~ ~ 'D
O O~ O O O O ~D
O ~ ~
Z Z ~ a~
1 ~1 h . . . ~. ~ . ~_~
U~ ~ ~ ~ ~ ~ O~ ~ ~rl U~ .~1 ~C> ' ~`I
O ~
o"

Z 4~ ~ ..
~ O C~
C:) ~ ~ ~10 0 0 ~ O O
¢ ~d ~ o a) CY Z ~ I
,~ ,~
~1 U ~r~ U~ X* X* X
, ~ . 0 :0 ,0 ~0 . ,DC~
H O ~ O ~ ~ H ~
1_1 p, H~. cd ~ ~1 H ~1 H ~1 . p~ ~J 5- J~ O
o o ~ 3 ~ U
h t~ h O Sl~ O
~ 3 - ~ ~ ~1 ~ 1 ~ o ,~
P~ ~ ~ r~ a ~ o p~o\o ~o\o U~
h t~ h ~ X O OX O O r~ X r 1X ~ X ~ ~ t~ O ~ h ~

7'24~

It should be borne ln mind by the reader, while ex-amining the data in the above Table, that the positioning of -reagent matrices for Chemstrip 8 and the two Rapignost devices is different from that of Example III and the varia-tions thereof prepared for the present example. Accordingly,because of the difference of positioning of the respective reagent matrices on the commercial strips, the manifestations of runover are different from those of the remaining strips.

This is because different reagents are dissolved by the sample drops and transported to neighboring matrices.

Accordingly,- although the data presented in the Table and plotted in Figure 4 are extremely useful in assessing the efficacy of the present invention, nevertheless the abso-luteness of the data is somewhat detracted rom by the above considerations.

The average readings for some of the reagent stripstested were themselves averaged and plotted versus contact angle of the base support member between reagent areas in Figure 4. The data for strips prepared as in Example III
without hydrophobic coating or underpads correspond to point 10, Chemstrip 8 to point 8, Rapignost Total Screen to point 7 and a strip of the present invention (Example III, 2.4 g%

solids) to point 9.

* Trade Mark ~ ' ' .
, ~ .

7~7 The graph shows a remarkable diminution in the inci-dence of runover directly attributable to the presently claimed concepts. Moreover, the data in the graph was obtained under the most adverse of conditions, adverse to the extent that laboratory-prepared uncoated strips showed an average runover incidence of almost 74~j whereas the same laboratory-prepared strips with the hydrophobic layer of the present invention reduced this figure to a mere 19%.
Currently available commercial products tested showed an average runover incidence of about 47 to 50%.

Examp~e V - Effect of Hydrophobic Coating on Reagent ~rea Performance An experiment was performed to determine whether the use of the hydrophobic coating of the present invention has an adverse effect upon standard analytical reagents.
Specifically, test strïps were prepared in accordance with Example III having reagent matrices responsive to occult blood and urobilinogen. The hydrophobic coating corresponded * * . .
to Tullanox LC 410 diluted to 2.4 g% Tullanox 500. Another set of strips was prepared in identical fashion except that no hydrophobic layer was applied to ~he polystyrene support membe~. Strips from each set were used to detect the levels * Trade Mark ~7'~7 of occult blood and urobilinogen in urine samples. The results given by the strips were then plotted versus the actual concentrations of these urine constituents.
The data obtained from this experiment is plotted in Figures 5 and 6, the former showing occult blood data, the latter urobilinogen. As can be seen from these graphs, the strips of the present invention ~designated "coated") demonstrated almost identical correlation of observed values to color block values as did identical strips with no hydro-phobic layer (designated "uncoated"). Thus, the presentlyclaimed concepts had no adverse effect on the performance of the occult blood and urobilinogen reagent systems studied.

E~amp~e VI - Effects of the Hydrophobic ~ayer on Adhesive Strength Because of the desirability of applying the concepts of the present invention to current reagent strip technology, whereby reagent matrices are secured to support members using adhesive means such as Double Stick Type 415 tape, an experiment was conducted to explore the bonding strength between that adhesive means and the hydrophobic layer applied to polystyrene. Hence, polystyrene sheets were coated with Tullanox LC 410~ The resultant dried films were compared with uncoated polystyrene by measuring their re-spective bonding strengths with Double Stick tape.

* Trade Mark ~ ~7'~47 The coated polystyrene film was prepared in accordance with Example I, B. The same polystyrene used in Example I, without coating, was used for the comparison. Adhesive bonding strength, or adhesion, was measured using a tensile tester known as an Instron Table Model TM Universal Measuring Instrument, obtainable from the Instron Corporation, Canton, ~lassachusetts. This test is illustrated in Figure 9, wherein the instrument has upper jaws 25 and lower jaws 26 to which opposite ends of a sample material can be attached.
The instrument is capable of applying force to these jaws such that they move away from one another at a constant pre-determined rate of speed. The amount of resistance caused by the sample between the jaws is measured on a graph whereby force is plotted versus unit time. Figures 7 and 8 are representations of the chart readings which were ob-tained in this experiment, and these will be further identified below.
The sample was prepared by applying one of the adhesive sides of Type 415 Double Stick double-faced adhesive tape to filter paper such as that used for reagent matrices on commercially available reagent strips (Eaton-Dikeman No.
204). The filter paper/ adhesive composite was then cut into strips measuring 5 by 0.2 inches. Thus one side of the adhesive tape was bound to the paper, the other adhesive side still being covered by the easily removable protective paper. A two inch portion of the protective paper was * Trade Mark ~ 7~7 removed, thus exposing two inches of adhesive on each fiveinch strip of paper/adhesive laminate. Two of these strips were then secured to a piece of polystyrene sheet, care being taken to apply only slight pressure in affixing the paper/adhesive strip to the plastic. A platen was then positioned over the prepared sample covering both of the strips and a ten pound weight placed on top of it for one minute. This latter procedure assures uniform application of the adhesive to both coated and uncoated polystyrene.
Immediately following the one minute weighting period, the polystyrene sheet was sliced between the adhesive strips, thereby yielding two samples of polystyrene each with its own paper/adhesive composite adhered to it. These samples were then tested with the Instron machine.
The samples were secured in the jaws of the machine as illustrated in Figure 9. The unsecured end of the paper/
adhesive composite 23, comprising paper layer 24 and Double Stick layer 22, was fastened in upper jaw 25. The tape was then bent as shown and the lower end of the polystyrene sheet 21 was secured in lower jaws 26 of the Instron instru-ment. In operation of the instrument, the jaws 25 and 26 were moved away from one another as described above.

* Trade Mark 7'~7 Figure 7 depicts the results obtained with polystyrene coated with Tullanox LC 410, whereas Figure 8 shows the data yielded from the same experiment except that uncoated poly-styrene was used. The data of Figures 7 and 8 clearly show the enhanced adhesion between Double Stick tape and a poly-styrene sheet bearing the hydrophobic layer of the present invention. The force required to separate the paper/adhesive composite from the coated support member was about 0.8 pounds (Fig. 7) whereas the uncoated required only about 0.5 pounds (Fig. 8).

Prior art attempts at applying hydrophobic coatings such as wax, oil and silicones resulted in failure because the coating would not adhere sufficiently to adhesives for mounting carrier matrices. The foregoing Example demon-strates that this problem does not exist when the presently-described concepts are utilized. In fact, the adhesivepropensity of polystyrene for Double Stick adhesive tape is actually dramatically increased.

While the examples illustrate the advantages of the invention with respect to those forms in which the reagents are affixed to the hydrophobic layer via incorporation in absorbent matrices, it is understood that the advantage of greatly reduced runover is also inherent in those forms of the invention wherein the reagents are affixed to the hydro-phobic layer by other means, for example printing or coating directly onto said layer.

* Trade Mark .~ s

Claims (19)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:-
1. A test device for determining the presence of a constituent in a liquid test sample comprising a base support member, a hydrophobic layer affixed to said support member and a reagent affixed to said hydrophobic layer, said reagent being capable of producing a detectable response in the pre-sence of said constituent;
said hydrophobic layer comprising (a) finely divided silica particles having covalently affixed to the surfaces thereof groups having the structure -O-SiR3 wherein said R substituents, same or different, are hydrogen, lower alkyl, or aryl, and (b) a suitable binder.
2. The test device of claim 1 wherein said R substi-tuents are all lower alkyl.
3. The test device of claim 1 wherein said R substi-tuents are all methyl.
4. The test device of claim 1, 2 or 3 wherein said reagent is incorporated with a hydrophilic carrier matrix.
5. The test device of claim 1, 2 or 3 wherein said reagent is incorporated with a paper carrier matrix.
6. The test device of claim 1, 2 or 3 wherein said binder is an acrylic polymer.
7. The test device of claim 1, 2 or 3 wherein said base support is a polystyrene film.
8. The test device of claim 1 wherein said base support member is a polystyrene film, said R substituents in said hydrophobic layer are substantially all lower alkyl, said binder is an acrylic polymer, and said reagent is in-corporated with a hydrophilic carrier matrix.
9. The test device of claim 8 wherein said hydrophilic carrier matrix comprises paper.
10. The test device of claim 1, 2 or 3 wherein the device is capable of determining the presence of two or more sample constituents, said device comprising a separate re-agent for each of said constituents, said reagents being affixed to said hydrophobic layer in spaced relation to each other.
11. The test device of claim 8 or 9 wherein the de-vice is capable of determining the presence of two or more sample constituents, said device comprising a separate re-agent for each of said constituents, said reagents being affixed to said hydrophobic layer in spaced relation to each other.
12. The test device of claim 1, 2 or 3 wherein the device is capable of determining the presence of two or more sample constituents, said device comprising a separate re-agent for each of said constituents, said reagents being affixed to said hydrophobic layer in spaced relation to each other and said device comprising reagents responsive respec-tively to occult blood, hydrogen ion, bilirubin, urobilino-gen, ketone, nitrite, albumin and glucose.
13. The test device of claim 8 or 9 wherein the de-vice is capable of determining the presence of two or more sample constituents, said device comprising a separate re-agent for each of said constituents, said reagents being affixed to said hydrophobic layer in spaced relation to each other and said device comprising reagents responsive respec-tively to occult blood, hydrogen ion, bilirubin, urobilino-gen, ketone, nitrite, albumin and glucose.
14. The test device of claim 1, 2 or 3 wherein the device is capable of determining the presence of two or more sample constituents, said device comprising a separate re-agent for each of said constituents, said reagents being affixed to said hydrophobic layer in spaced relation to each other and said device comprising reagents responsive respec-tively to albumin, ascorbic acid, bilirubin, glucose, hydro-gen ion, ketone, nitrite, occult blood, specific gravity, urobilinogen or combinations thereof.
15. The test device of claim 8 or 9 wherein the de-vice is capable of determining the presence of two or more sample constituents, said device comprising a separate re-agent for each of said constituents, said reagents being affixed to said hydrophobic layer in spaced relation to each other and said device comprising reagents responsive respec-tively to albumin, ascorbic acid, bilirubin, glucose, hydro-gen ion, ketone, nitrite, occult blood, specific gravity, urobilinogen or combinations thereof.
16. A method for eliminating the occurrence of run-over in a test device for determining the presence of a constituent in a test sample, the method comprising the steps of preparing a hydrophobic coating material comprising (a) finely divided silica particles having affixed thereto groups having the structure -O-SiR3, wherein the R substi-tuents, same or different, are hydrogen, lower alkyl or aryl, and (b) a suitable binder, affixing said hydrophobic coating to a base support member to form a hydrophobic layer on said support member, and affixing to said hydrophobic layer a reagent capable of producing a detectable response in the presence of said constituent.
17. The method of claim 16 wherein said reagent is incorporated with a hydrophilic carrier matrix which is affixed to said hydrophobic layer.
18. The method of claim 16 wherein said reagent is incorporated with a paper carrier matrix which is affixed to said hydrophobic layer.
19. The method of claim 16 which includes the addi-tional steps of affixing to the hydrophobic layer additional reagents respectively responsive to other constituents of a test sample, said reagents being affixed to the hydrophobic layer in spaced relation to each other.
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AU5777080A (en) 1981-01-08
US4301115A (en) 1981-11-17
FI801968A (en) 1980-12-23
FI74151C (en) 1987-12-10
DK266180A (en) 1980-12-23
AU531540B2 (en) 1983-08-25
NO154476C (en) 1986-09-24
ATE6697T1 (en) 1984-03-15
EP0021261B1 (en) 1984-03-14
NO154476B (en) 1986-06-16
NO801670L (en) 1980-12-23
FI74151B (en) 1987-08-31
DK160447C (en) 1991-08-19
BR8003869A (en) 1981-01-13
JPH024859B2 (en) 1990-01-30
AR221539A1 (en) 1981-02-13

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