CA1101771A - Method of making reagent test device and reagent test device made according to this method - Google Patents

Method of making reagent test device and reagent test device made according to this method

Info

Publication number
CA1101771A
CA1101771A CA280,848A CA280848A CA1101771A CA 1101771 A CA1101771 A CA 1101771A CA 280848 A CA280848 A CA 280848A CA 1101771 A CA1101771 A CA 1101771A
Authority
CA
Canada
Prior art keywords
reactants
test device
carrier
reagent test
substances
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
CA280,848A
Other languages
French (fr)
Inventor
Ann-Marie Gronberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alfa Laval AB
Original Assignee
Alfa Laval AB
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from SE7606999A external-priority patent/SE423651B/en
Priority claimed from SE7613334A external-priority patent/SE402822B/en
Application filed by Alfa Laval AB filed Critical Alfa Laval AB
Application granted granted Critical
Publication of CA1101771A publication Critical patent/CA1101771A/en
Expired legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B41—PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41M—PRINTING, DUPLICATING, MARKING, OR COPYING PROCESSES; COLOUR PRINTING
    • B41M3/00—Printing processes to produce particular kinds of printed work, e.g. patterns
    • B41M3/14—Security printing
    • B41M3/142—Security printing using chemical colour-formers or chemical reactions, e.g. leuco-dye/acid, photochromes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B41—PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41M—PRINTING, DUPLICATING, MARKING, OR COPYING PROCESSES; COLOUR PRINTING
    • B41M3/00—Printing processes to produce particular kinds of printed work, e.g. patterns
    • B41M3/001—Printing processes to produce particular kinds of printed work, e.g. patterns using chemical colour-formers or chemical reactions, e.g. leuco dyes or acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
    • G01N31/22—Investigating 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
    • 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
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/521—Single-layer analytical elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00657—One-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays

Abstract

ABSTRACT OF THE DISCLOSURE

The present invention provides a method of making a reagent test device, comprising a carrier and at least two substances, supported by said carrier, to be activated upon use of the reagent test device, characterized by applying at least two liquids, each of which containing one of said sub-stances, directly to one surface of the carrier in such a way, that said substances will remain on the surface separated by a predetermined interspace along said surface, printing tech-niques known per se being used for obtaining an exact, prede-termined interspace.

Description

1~63~

The present invention relates to a method of making a reagent test device, comprising a carrier and at least two substances, supported by said carrier, to be activated upon use of the reagent test device. The invention also comprises a reagent test device, made according to this method.
Reagent test devices of the type mentioned above have hitherto been maae in several different ways. In ac-cordance with one method, one of said substances is encapsu-lated in so-called microcapsules that are suspended in a li~uid containing the other substance, whereupon the micro-capsules and the liquid are applied to a carrier in one way or other. The manufacture of such reagent test devices is rather expensive.
According to another method, a reagent test device of the type mentioned above is made by impregnating a carrier with a porous structure in two ~ones, separate from each other, with liquids containing the substances. The manufac-ture of such reagent test devices is complicated due to the difficulties to impregnate one and the same carrier with two different liquids.
The present invention has for an object to provide a method of making a reagent test device of the type men tioned abo~e, which method is simple and cheap, and which results in reagent test devices which make possible a quanti-tative analysis of high accuracy.
According to the present invention, in a method ofmaking a reagent test device of the type mentioned by way of introduction, at least two liquids, each of which containin~
one of said substances, are applied directly to one surface of the carriex in such a way, that said substances will re-main on the surface separated by a predetermined interspace -1- . ~k along said surface, printing techniques known per se being used for obtainingiu}-e~e~, predetermined interspace.
t Preferably at least one of said substances is ap-plied to the carrier in such a way, that it remains fixed to it even upon use of the reagent test device.
In accordance with one preferred embodiment of the present invention the substances in question are applied to said surface of the carrier on a plurality of locations, spaced apart with small interspaces, for example as dots and/or stripes on the surface. The locations may be mixed on the surface.
The invention is applicable for several reagent test or indicator systems. Reference is made, by way of ex-ample only, to U.S. Patents Nos. 3,092,463, 3,511,608, 3,549,328 and 3,926,732.
As mentioned above, according to one preferred em-bodiment of the invention the substances, acting when the indicator device is used, are applied to a plurality of loca-tions on the surface of the carrier with very small inter-spaces between them. This does not mean, however, that thescope of the invention is limited to cases where interspaces of microscopic orders are necessary. Even in such cases, where the distance between the substances shall be somewhat larger, e.g., about l mm, the invention applies. Such an interaction between different substances on the suxface of a reagent test device carrier is also possible where the inter-space between the substances is of this si~e, if a liquid that is to be brought into contact with the reagent test de-vice carrier has to be able to penetrate through the sub-stances to provide a diffusion means, for example for partof one of the substances on its way to the other substance.

7'~

In such a case it is obvious that utmost accuracy is needed regarding the interspace between said substances, such as an accuracy of one or a few hundredths of a mm.
The present invention arose as the inventor just by chance happened to get acquainted with the details of con~entional printing techniques. The inventor found that ~-a printed text or picture might consist of a plurality of minute little dots, situated in microscopic distances from each other, which distances normally cannot be detected by the naked eye. The inventor also got aware, that a printed picture in color, which the eye perceives as just being of one color, in fact can consist of a plurality of dots of different colors. Thus a picture which the eye perceives as green can consist of a plurality of blue and yellow dots.
The knowledge on conventional printing techni~ues gained by the inventor led her to realize the unique poten-tial of printing techniques to apply two or more reagent substances to the surface of a reagent test carrier, the interspace be~ween said substances being accurately predeter-mined.
Thus the reagent test device in accordance with the present invention is made according to printing tech-niques, known per se, like photogravure printing, which maans that the substances, dissol~ed in appropriate solvents, are applied to the surface of the carrier by printing rollers, provided with very small depressions or pores, with differ-ent depths.
Silk screening is also part of well-known printing techniques. This means that the substance in question is dissolved in an appropriate solvent, which is pressed out 7'7~

through a screen provided with fine meshes. The screen is placed around a rotatable roller.
There are several types of printing techniques, known per se, which are not generally called "conventional".
There are, for example, different kinds of plateless printing techniques, like direct electrostatic printing, indirect electrostatic printing and ink-jet printing, which have gained more and more importance lately.
Direct electrostatic printing means, that electro-static charges are created direct and held on specially coated paper which has a conducting layer covered by an in-sulating layer. The electrostatic charge is developed into visible image by a toner, which can be a liquid containing the desired reagent substance.
Indirect electrostatic printing is an offset pro-cess where the electrostatic charge is held on an intermedi-ate surface (such as a drum) and only the toner, containing the desired reagent substance, is transferred and fixed to the paper. This method is used in the Xerox ~ copying sys-tem.
Ink-jet printing has developed very fast lately.
There are many different systems, but they all depend on continuous or discontinuous flows of very thin liquid jets, that are directed with great accuracy in the desired direc-tion toward the carrier in question.
An~ type of reproducing graphic techniques may be used to perform the present invention.
Regarding the embodiment of the invention, accord-ing to which the substances are applied to a plurality of lGcations with very small interspaces, it should be noted that there is an advantage that a color change, due to the . .

activating of the substances as the reagent test device is being used, will be perceived as a simultaneous color change over a relatively large area. (The surrounding parts of the reagent test device carrier should preferably have the same color as said surface had before the color change.;) Such a reagent test device, for example comprising two substances, will give a more safe indication of an occurred reaction than a reagent test device with one surface covered with one of the substances only, which gradually changes its color from one part to another part, as the second substance is diffus-ing along the surface. Thus, i~ said substance is complete-ly cons~med before it has diffused over the entire surface area, whereby a color change will occur in just part of the surface area, there may arise doubt as to the reliability of the reagent test device. The possiblity of using a re-agent test device for quantitative analysis is also improved, if a color change occurs over a relatively large surface area.
The present invention will now be described more in detail, re~erence being made to the enclosed drawing.
Figs. 1 4 show schematically different embodiments of a re-agent test device, made according to the invention. Fig. 5 discloses, by way of example only, schematically the prepa-ration of an indicator device in accordance with Figs. 1-4.
Referring to Figs. 1-4, three different reagent test devices are shown, for example intended for indication of any occurrence of a certain enzyme in a liquid. The re-agent test devices comprise carriers 1, 2, 3 and 4. Two reagent substances A~ B have been printed with conventional printing technique in various patterns on these carriers.
A reagent test device of this kind may be intended for 7'7~

dipping into a sample of said liquid, removing it from same to let a thin liquid layer remain on the carrier. One of the substances on the carrier, for example substance A, may then be brought to diffuse through the thin liquid layer, toward the other substance, i.e., substance B. The enzyme to be indicated in the liquid may react with substance A, or catalyze a chemical reaction caused by substance A. Thus substance A is completely or partly consumed during its way toward substance B dependent on the concentration of said en~yme in the liquid. If substance A is completely consumed by the enzyme in the liquid, no reaction can occur between substance A and B. If part of substance A reached substance B, these will react, substance A and B being of such a nature that the color will change. Such a reaction will cause the human eye to notice a color change over the total surface area, onto which substances A and B are applied.
The intensity of this color change is dependent on the con-centration of the enzyme to be quantitatively estimated in the liquid. Substances A and B of course can interact in any other way. For example, they may react with each other in a first stage, giving rise to an intermediate substance without any color change. Then in a second stage this intermediate compound may react with any enzyme present to bring about a color change, Alternatively, there may occur a first color change as the intermediate substance is formed, and a second color change when the intermediate sub-stance reacts with the enzyme. Such a system would make it possible to decide safely if a reagent test device has al-ready been used, even if the enzyme reaction would not occur due to the non-existence of the enzyme, In Fig. 4 a reagent test device for the indication of any catalase enzyme present in a liquid is shown. The reagent test device comprises a carrier 4 and substances A, B and C applied to it with con~entional printing technique.
Substance ~ contains a peroxidase enzyme and a dye like o-tolidine. Substance B contains the enzyme glucose oxidase and substance C glucose. Enz~mes peroxidase and glucose oxidase are both chemically fixed to cellulose par-ticles, which are fixed to the carrier by means of any suit-able binding agent using printing technique. After the application of substances A and B the enzymes are immobile in relationship to each other and to carrier 4.
The reagent test device just described will operate in the following way when brought into contact with liquid to be tested.
(1) The glucose in substance C is dissolved by the liquid and is spread over carrier 4.
(2) In the vicinity of substance B enzyme glucose oxidase catalyses the reaction between glucose and oxygen, whereby hydrogen peroxide is obtained as a reaction product,
(3) The hydrogen peroxide diffuses through the liquid provided in the a~æas between substances A
and B, to the locations of substance A.
(4) At the locations of substance A the dye o~tolidine is oxidized by hydrogen peroxide in the presencenof enzyme peroxidase, and a blue color is obtained.
~5) If there is any enzyme catalase present in the liquid, the hydrogen peroxide is decomposed completely or partly. CatalaSe in a high concentration in the liquid will decompose the hydrogen peroxide completely before it has had time to diffuse to the locations of substance A, and no blue color is obtain~d.¦
A small concentration of catalase will decompose the - ' hydrogen peroxide partly, and part of the hydrogen peroxide will diffuse to the loaations of substance A to cause a blue color. Thus, due to the concentration of enzyme catalase in the liquid a more or less intensive color change is obtained on the reagent test device. t The reagent test devices disclosed in Figs. 1-4 are prepared by printing techniques, as mentioned above. Reference is made to Fig. 5, which shows the principle of conventional printing. A sheet 5 is fed in the direction of the arrown With two printing rollers 6 and 7 two different liquids, containing substances A and B, are printed on the sheet. As already mentioned there are many types of rollers, well known to those versed in the art, so no detailed description is needed.
Of course, it is necessary to adjust the viscosity of the liquids, containing the substances in question, dependent 20 on the printing technique chosen.
Example r 10 grams or particulate CMC (carboxi methyl cellulose) were activa~d in the way well known to those skilled in the art. -Glucose oxidase (Boehringe~) and peroxidase (Sigma Co) were immobilized on different samples of the activated CMC, also according to well known methods. The mixtures for printi~ were prepared in the following way: ~
Glucose oxidase/CMC
2.5 grams of wet GO/CMC were stirred in 20 mls of -30 distilled water with the air of a magnetic stirrer 0.085 grams of colloidal CMC were added to adjust the viscosity of the mixture.
~' ~ i .. .".,. ~

L7~731 Peroxidase/CMC
2.5 grams of wet PO/CMC wer stirred in 20 mls of distilled water with the aid of a magnetic stirrer. 0.085 grams of colloidal CMC were added to adjust the viscosity of the mixture.
0.033 grams of o-tolidine were added by stirring to the mixture.
The two mixtures thus obtained were printed by silk screening as distinct parallel lines, according to the system GO-PO-GO-PO etc, on a filter paper, that had been immersed in a 10% gluclose solution in water and had been dried at 35C.

j:

,~", ~,!,

Claims (13)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A method of making a reagent test device including a carrier and at least two reactants (A,B) supported by said carrier, said reactants being capable of interacting with a con-stituent of a sample to produce a detectable response, said method being characterized by applying at least two liquids, each containing one of said reactants, directly to one surface of the carrier to cause the reactants (A,B) to remain on said one surface while separated exactly by a predetermined interspace along said surface, said liquids being applied by printing the same on said surface to obtain said predetermined interspace.
2. Method according to claim 1 characterized by apply-ing at least one of said reactants (A,B) to the surface of said carrier in such a way that it remains fixed to it even upon use of the reagent test device.
3. Method according to claim 1 characterized by apply-ing said reactants (A,B) to said surface on a plurality of loca-tions with small interspaces between them.
4. Method according to claim 3 characterized by apply-ing said locations mixed on said surface.
5. Method according to claim 3 or 4 characterized by applying at least one of the reactants (A,B) as dots on said surface.
6. Method according to claim 3 or 4 characterized by applying at least one of the reactants (A,B) as stripes on said surface.
7. Method according to claim 1, 2 or 3 characterized by applying said reactants (A,B) by photogravure printing.
8. Method according to claim 1, 2 or 3 characterized by applying said reactants (A,B) by silk-screening.
9. Method according to claim 1, 2 or 3 characterized by applying said reactants (A,B) by ink-jet printing.
10. A reagent test device comprising a carrier and at least two reactants (A,B) supported on the same surface of said carrier, said reactants (A,B) to be activated upon use of the test device, characterized by the fact that said substances (A,B) are printed separately on said surface and thus separated from each other exactly by a predetermined interspace along said sur-face.
11. A device according to claim 10, characterized by the fact that at least one of said reactants (A,B) remains fixed to said carrier even upon use of the reagent test device.
12. A device according to claim 10 characterized by the fact that said reactants (A,B) are applied to said surface on a plurality of locations with small interspaces between them.
13. A device according to claim 12, characterized in that said locations are mixed on said surface.
CA280,848A 1976-06-18 1977-06-17 Method of making reagent test device and reagent test device made according to this method Expired CA1101771A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
SE7606999-6 1976-06-18
SE7606999A SE423651B (en) 1976-06-18 1976-06-18 PROCEDURE FOR PREPARING AN INDICATOR OF THE TYPE THAT INCLUDES A CARRIER AND TWO OF THESE SUPPORTED SUBSTANCES INTENDED TO BE ACTIVATED DOWN THE INDICATOR SHOULD BE USED
SE7613334-7 1976-11-29
SE7613334A SE402822B (en) 1976-11-29 1976-11-29 INDICATOR INCLUDING A CARRIER AND AT LEAST TWO OF THESE CARRIED UP SUBSTANCES INTENDED TO BE ACTIVATED IN THE USE OF THE INDICATOR

Publications (1)

Publication Number Publication Date
CA1101771A true CA1101771A (en) 1981-05-26

Family

ID=26656724

Family Applications (1)

Application Number Title Priority Date Filing Date
CA280,848A Expired CA1101771A (en) 1976-06-18 1977-06-17 Method of making reagent test device and reagent test device made according to this method

Country Status (18)

Country Link
JP (1) JPS5313485A (en)
AR (1) AR217076A1 (en)
AU (1) AU506896B2 (en)
BR (1) BR7703799A (en)
CA (1) CA1101771A (en)
CH (1) CH629306A5 (en)
DD (1) DD130280A5 (en)
DE (1) DE2727347A1 (en)
DK (1) DK269177A (en)
ES (1) ES459894A1 (en)
FR (1) FR2355290A1 (en)
GB (1) GB1526708A (en)
HU (1) HU176739B (en)
IE (1) IE44940B1 (en)
IL (1) IL52322A (en)
IT (1) IT1143673B (en)
LU (1) LU77564A1 (en)
NL (1) NL7706718A (en)

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US5378638A (en) * 1990-08-02 1995-01-03 Boehringer Mannheim Gmbh Analysis element and process for its manufacture
US5424220A (en) * 1992-01-31 1995-06-13 Boehringer Mannheim Gmbh Analysis element and method for determination of an analyte in a liquid sample
US6465190B1 (en) 1999-10-22 2002-10-15 Ngk Insulators, Ltd. Method for producing DNA chip
US6776960B2 (en) 1999-10-22 2004-08-17 Ngk Insulators, Ltd. Method for producing DNA chip

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BR7703799A (en) 1978-04-18
DE2727347A1 (en) 1977-12-22
IL52322A (en) 1980-10-26
HU176739B (en) 1981-05-28
AR217076A1 (en) 1980-02-29
DK269177A (en) 1977-12-19
IE44940B1 (en) 1982-05-19
DE2727347C2 (en) 1987-02-05
CH629306A5 (en) 1982-04-15
IE44940L (en) 1977-12-18
JPS6136181B2 (en) 1986-08-16
AU506896B2 (en) 1980-01-24
LU77564A1 (en) 1977-09-21
ES459894A1 (en) 1978-10-01
AU2622377A (en) 1979-01-04
FR2355290B1 (en) 1980-12-05
JPS5313485A (en) 1978-02-07
GB1526708A (en) 1978-09-27
DD130280A5 (en) 1978-03-15
NL7706718A (en) 1977-12-20
IL52322A0 (en) 1977-08-31
IT1143673B (en) 1986-10-22
FR2355290A1 (en) 1978-01-13

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