DE1798423C3 - - Google Patents

Description

The invention relates to an analysis tape for an automatic analysis device with a carrier tape on which a number of reagent storage locations each with at least one reagent are provided.

From US-PS 30 36 894 an analysis tape is known, which consists of an upper and a lower layer is formed. These two layers are connected to one another in such a way that one behind the other on the Analysis tape yields a multitude of enclosed chambers, each between two adjacent chambers Chambers a z. B. by the application of pressure destructible partition is provided. In a foremost in the transport direction of the an.iKsierungsbandes Chamber is housed a substance to be analyzed, while in the subsequent chambers different reagents for the analysis of the substance can be accommodated.

If pressure is exerted on the foremost chamber, the dividing wall between the foremost one becomes first Kaminer and the subsequent chamber, which is a first Contains reagent, destroyed, allowing an analysis of the substance by interacting with the first Reagent takes place. Pressure is then applied to this second chamber, creating the next The partition to the adjacent chamber is destroyed and the one in the first chimney with the first reagent displaced substance enters the chamber containing the second reagent and there by additional displacement is further analyzed with this second reagent. Then again by applying Pressure the substance to be analyzed one after the other through all the different reagents Chambers passed through. In this known analysis tape, the individual reagents added one after the other to the substance to be analyzed, while those already added Reagents can no longer be separated from the substance to be analyzed. However, this affects the Freedom of movement when analyzing the substance, as the individual reagents also influence one another be able.

From US-PS 27 85 057 an analyzer is known, 'ei of the individual reaction points for the analysis of a substance in the form of strips one behind the other arranged made willow, after which the tape is cut to only a single one at a time Form sections containing reaction site, with information for treatment on the sections

ier respective response time can be applied metric tons.

From US-FS 30 36 893. 32 16 30-4. 32 60 413 and 32 61 668 known analysis devices work with a combination of three separate analysis belts for evenly depositing a part a sample to be examined on the tape containing the reagents. This facility enables Perform only a single test on multiple samples for each of three analysis tapes existing unit. To carry out other tests of a different type, the unit must be replaced by another unit be replaced that works with another analysis tape containing other reagents.

It is the object of the invention. an analysis tape for an automatic analyzer create, in conjunction with other similar analysis tapes to carry out several different tests can be used.

In an analysis tape of the type mentioned at the beginning Art this object is achieved according to the invention in that a number of between the reagent storage locations arranged, the carrier tape penetrating openings is provided, the number of Number of reagent storage locations and their dimensions correspond to the dimensions of the reagent storage locations in the plane parallel to the plane of the carrier tape are the same, and that the distances / wipe each opening and the reagent storage locations adjacent to it are the same.

An opening is expediently arranged in the middle between adjacent reagent storage locations. There can also be a number of openings between each two groups of reaction sites be provided.

This new analysis tape enables the arrangement of a large number of tapes on top of one another, whereby the relative movement of the individual tapes to one another causes the memory location of a certain tape to flow with one or more openings of the additional tapes arranged above, so that through these openings a specific reagent storage position of a specific analysis tape with a to be analyzed sample can be applied. Be such acted upon by the sample Rcagenzspeicherstclle, / .. B. can then electro-optically in the same manner, investigated by the light beams hindurchgelangcn by the respective aligned apertures of the other Analysicrungsbänder and in each case only a specific Reagcnzspeicherstelle by radiation of a particular Analysicrungsbandes. Due to the possible arrangement of a large number of analysis tapes on top of one another, the individual reagent storage locations of which are loaded with certain samples to be analyzed from a sample tape running parallel to the analysis tapes, for example, any assignment of the most varied of reagents to the samples to be investigated is possible in a simple manner so that a variety of different tests can be performed simultaneously and continuously.

Further embodiments of an analysis tape according to the invention relate to the arrangement of the reagent storage elements in the form of rows as well as the special design of the reagent storage facilities. /. Am Forms a disk attached to the tape, consisting of a porous matrix and at least one in this is formed evenly as an impregnation reagent present. The reagent can also be found in the Matnx be chemisorbed. It can also be chemisorbed in the support of the analysis tape. The invention is explained in more detail with reference to the embodiments shown in the drawing. It indicates

F i g. 1 is a perspective view of an automatic analyzer, which is equipped with a new Analysis tape works,

ίο Fig. 2 is a plan view of the one shown in FIG Facility,

3 shows the enlarged plan view of an analysis tape,

4 shows the section of a serving as a sample carrier Tape for use in the in F i g. 1 shown device,

Fig. 5 shows the greatly enlarged section of six with Analyzing tapes provided with openings. which are located at the sample entry point,

: o F i g. 6 the greatly enlarged line of six different analytical tapes provided with openings, which are located at the evaluation point. and

F i g. 7 shows the greatly enlarged section of one with one

;> Opening provided tape at the evaluation point, a multi-layer reagent-containing layer over the opening on the tape Disc is located.

In the F i g. 1 and 2 is an automatic analysis ιο Approximation device 10 is shown, which contains a magazine 12 for an analysis tape 14. Of simplicity for the sake of this, there is only an analysis tape in uicsen figures Γ shown, which by the probing agency 16, the hatchery 18, the outlet 20 and

; s is then moved through the dispensing point 22. Be it However, it should be noted that a large number of analysis tapes, as shown in Fig. 5 is used, each band providing the support for a plurality of similar analytical test sites. It a sample carrier in the form of a tape 24 is also provided, which is used to store liquid samples immediately before entering the sample substance to the respective examination site on the analysis

4_s band serves. The indicator 26 is automatically on the correct memory location is set on the sample carrier 24 and shows the technician exactly which point the next sample should be applied to the sample carrier. If the carrier 24 to

w Transport of a new sample storage cell to the If the transfer point continues, the indicator 26 also continues to move and remains above one unused sample storage space c. After a sample has been hand-loaded into this unused chamber

ss ben is. the indicator moves in response to a signal from Backward one step on control panel 28 to present the technician with the next unused sample storage location for entering a sample to be analyzed. The control panel 28 enables the technician.

(. ,, to store corresponding commands 30 on the control tape 32. The control commands 30 cause a Forwarding of the corresponding analysis tape to a position in the sample input point 16 for subsequent input of the sample. Such tax records

<> \ Ichic are particularly advantageous when a Plurality of tapes in the magazine 12 are present, each of which has different Rcaktionssicllcn for different Contains analysis operations.

In I "i g. 3, the Analysierungsband Γ is shown, which is provided as a film with perforations 40 and 42, so that it can be weitergcschaltet from one position to the other. In addition to the perforation holes are the reaction sites 44, 46, 48 , s 50 and 52. These can either consist of a porous material which is impregnated with suitable reagents and adhered to the tape 7, or they are part of the tape T, if this is sufficiently strong and even porous, in which the required If desired, barriers can be provided around the areas of the reagents to prevent diffusion or transfer of the reagent and / or the sample also referred to below as reaction disk, multilayer structures can be provided in which each layer is one of a series of steps Analysis process corresponds to. In this way, different reagents can be stored in different layers of the reaction disk and / or a filter layer which removes harmful substances can be inserted between such layers. Multi-layer structures significantly increase the number of analytical methods possible, which means that the device can work in a very versatile manner. The analysis tape T also contains the information 54 in the form of a magnetic coding or punched holes, which is used to identify the sample to be analyzed and the examination carried out with it. Furthermore, space can be provided next to a respective reaction point, which is used in a similar form to store the analysis data obtained at the evaluation point. The entirety of this information can then be stored in a memory that is either assigned to the evaluation point or is available separately.

In operation, the analysis tape is conveyed from the magazine 12 to the output point 22. Each belt 4c has its own drive device (not shown) which advances it one step at a time, so that it is guided successively through the various process points. At the sample input point 16, the sample to be analyzed is removed from the tape 24 4s, which is shown in FIG. 4 and contains the samples in wells 56, 58, 60, etc. By rotating an aliquot dividing device 62, the measuring tube 64 provided in this device oscillates between the sample carrier 24 and the analysis tape T. The measuring tube 64 consists of a non-wettable material, for example to reduce contamination by the sample material or turn it off. The measuring tube is lowered over the sample carrier 24 until its tip is within the liquid sample substance. A measured portion of the sample is drawn off by a vacuum system (not shown) until it completely fills the measuring tube. The filled tube is raised and the dividing device is controlled in such a way that the tip of the measuring tube is directly above the corresponding reaction point on the analysis tape. A small amount of pressure is applied to the inner end of the measuring tube, which forces its liquid contents to the reaction site. The aliquot dividing device is now ready to return to its starting point above a sample storage point of the sample carrier. This location can be the same as before

be for the transfer of at least one further precisely measured sample, or it is through a moving step of the sample carrier a new sample storage location under the measuring tube.

The analysis tape becomes the sample input point 16 passed through a hatching point 18, at which the reaction mixture within the reaction points for sufficient time is kept to bring them into the state required for analysis. the Construction site should have such dimensions that the reaction mixture for the appropriate period is located in the environment required for this. The correct breeding season is achieved by using the propulsion device a circuit with a certain speed causes the reaction mixture to increase brings the right time for the analysis to the evaluation point. At the evaluation point 20 is a Light beam focused on the reaction mixture and passed through it so that it hits a Evaluation device, for example a photoelectric cell, detects changes in light transmission responds, which are caused by changing amounts of a known component of the sample. The electrical signal obtained from this is proportional to the amount of a certain component of the sample and is converted into evaluable data, which in turn is transferred to a display field and a memory device for further use. There are also facilities for identifying each Sample provided with regard to its source and the analyzes to be carried out with it. Within the Evaluation tests can also be used to obtain analytical data that are directly transferred to the analysis tape to get a complete record for further use. Of the Evaluation point, the analysis tape is transported to the output point, where it is placed on a take-up reel wound up or placed in an output container.

In addition to the analysis described above, many other evaluation methods can be provided for the liquid sample substance remaining at the sample storage site. For example, after the described input of measured parts of the sample into the reaction point, the sample storage belt 24 can be indexed repeatedly. At a further point along the path of this sample storage belt, a probe 66 can be lowered into the liquid sample and part of this solution can be sucked into the flame of the flame photometer 68. This evaluation is carried out using the known flame photometry. Other analysis methods that work directly on the liquid sample can be integrated into the overall system and used for the complete analysis of the sample.

As already stated, the analysis tape have a plurality of the same reaction points arranged at a distance from one another, or the band carries one A multitude of different reaction sites, each of which has a pre-filled chemical analysis unit for carrying out various chemical tests In the latter case there is a set of different reaction points, the repeats itself over the entire length of the analysis tape. A measured part of the sample can be taken from of the sample storage site are transferred to each of the various reaction sites so that one Multiple examinations for a given sample

is possible. In clinical blood chemistry this is called "I ImriUanalysc".

To calibrate the ejection device, "standard samples" containing known amounts of the portion to be analyzed are passed through the evaluation point. Such standard samples can be present in prepared areas of the analysis tape that only accept a certain amount of the standard solution and are therefore suitable for calibration . The evaluation device analyzes each standard sample and then adjusts itself for deviations from the known value. Furthermore, each primary reaction point can be assigned a secondary reaction cell which, after the analysis, enables the ejection device to be corrected for the effect of the sample and certain reagents in the reaction mixture. The sample and all reagents required for the condition of the reaction mixture during analysis are entered in the primary reaction section. The secondary reaction site contains the substance to be investigated either without a reagent or one or more reagents are present in certain ("all of them, but these must not bring the reaction to completion or impair the optical analysis. This latter reaction mixture is considered to be critical incomplete blank solution ”and its analysis enables the effects of the various reagents and the other constituents of the sample substance on the optical effects to be compensated The light is split into two equal beams, one of which is passed through the primary reaction position and the other through the secondary reaction device responds to changes in light intensity caused by the passage of light through various liquid substances; each of these light rays is received independently of the other light ray. A corresponding voltage signal is generated for each light beam, which can then be evaluated by means of suitable electronic circuits. Serve this purpose, for example, differential amplifiers which produce an output P ¹ guild, which is a measure of the concentration of a known component of the analyzed substance at the reaction site. If an extremely precise analysis is to be carried out taking into account all possible influencing factors, additional reaction points can be provided on the tape which introduce such factors, the analysis of which is carried out according to the principle of light beam splitting with a number of light beams corresponding to the number of reaction points. In this way, the primary and secondary reaction sites contain the substances described, while a third reaction site can contain a standard solution, a fourth reaction site a diluted reagent and so on. In the embodiment described, the primary reaction site contains all the necessary reagents and the sample, the secondary reaction site contains the sample alone or the sample together with one or more, but not all, reagents and the third reaction site contains no reagents, while the fourth reaction site contains all reagents without sample substance contains. It can be seen that the properties of each reaction point detr accordingly. procedures to be performed and the required accuracy are different.

In one embodiment. those with a variety of Analyzing bands η works, each band is provided with regularly distributed reaction points, whereby Openings / between adjacent reaction sites or adjacent groups of reaction sites are provided, the dimensions of which correspond to those of the reaction cells, each of the various Analysis tapes contain deposited or impregnated reaction sites that are used to carry out various chemical analyzes are suitable. There are devices in the analysis device required for this intended for the switching of the tapes in particular in the sample input point and the evaluation point, so that a respective reaction site (or reaction site) of a first band under the aligned openings of the belts above the first belt. In this way, a sample entry to a specific tape that is necessary to perform the analysis you want Contains reagents, as well as a determination of at least one of the physical properties at the evaluation point of the liquid substance contained in the porous structure of the reaction site (or reaction site) be made.

In Fig. 5 the enlarged section of six analysis tapes 70, 72, 74, 76, 78 and 80 is shown, which are located at the sample input point 16, each tape is provided with a plurality of reagent disks which are arranged on its upper surface and between each of which a single opening is formed. Belt 70 contains reagent disks 102 and 104, belt 72 disks 106 and 108, belt 74 disks 110 and 112, belt 76 disks 114, belt 78 disks 116 and 118, and belt 80 disks 120 . In the illustrated case, the bands 70, 72 and 74 switched according to the control command of the belt 32, so that the openings 122, 124 and 126 are located directly below the tip 128 of the sensing tube 64th Before this alignment, the aliquot dividing device 62 has removed a measured portion of a liquid sample from one of the depressions in the sample storage belt 24 . It then rotates to a position shown in Figures 1 and 2 so that the tip 128 is directly over a reagent disk of one of the analyzer tapes. Such a disk can be on the uppermost or on one of the lower belts in FIG. The tip of the measuring tube is lowered and the liquid sample material passes from the tube 64 onto the corresponding disk. The liquid is preferably removed from the measuring tube by applying a slight pressure which forces the liquid out of the tube through the tip 128 . Emptying by capillary action is also possible. The gauge 64 is preferably of a non-wettable plastic material which, as to the sample entering no more liquid retains apparent from Figure 5, the sample material is applied to the disc 114, since the openings of the bands are aligned with 70.72 and 74th If an opening in the tape 76 were located below the tip 128 , the sample would be applied to the disk 120. By appropriately switching the tapes, parts of a particular sample can be applied to one or more different

709 612/83

Reaction points of the various analysis tapes are applied.

From the sample input point 16, the analysis tapes arrive at the incubation point 18, where the the substance present in the reaction site is held until it has the desired state for the analysis has reached. The breeding site should be long enough. creating the necessary dwell time will. The correct breeding season is also achieved by the drive device with different Speed, works, making for each special Different breeding seasons are possible. Also loops can be formed that lead the way of the ligament through the breeding site, whereby the The incubation period is increased without changing the drive speed. Since a large number of analysis tapes is used, the Brulvorrichtung can additionally be divided into several different zones, each generate other influences.

In Fig. 6 shows a double-beam evaluation device which evaluates the bands 130, 132, 134 and 136. Each band is alternately provided in pairs with reaction points and openings. Belt 130 supports disks 138 and 140 and has openings 142 and 144, belt 132 supports disks 146 and 148 and has openings 150 and 152. Belt 134 supports disks 154 and 156 and has openings 158 and 160 and the belt 136 supports disks 162 and 164 and has openings 166 and 168. One of the pairs of disks stores the reagents required to perform the desired analysis and the sample is added at the sample entry point. The other disk can contain a standard solution that enables calibration of the ejector device, or a sample is added that enables the formation of a "critically incomplete blank solution" in the manner described. This latter reaction mixture makes it possible to compensate for the effects of the various reagents and other components of the sample substance on the optical analysis. By properly indexing the disk 146 containing the reaction mixture and the disk 148 around the openings 142 and 144 on one or more belts between the belt to be analyzed and a source 170 of electromagnetic radiation. The radiant energy passes through a filter 172, producing light of one or more desired wavelengths. Since each analysis may require light of a different wavelength, it is convenient to place a group of filters between the source 170 and the ribbons. During the analysis, however, there is only the corresponding one filter in the optical path between the source and the panes to be analyzed, while the other filters are swiveled out of their operating position. After passing through the filter, the beam falls on the semi-silvered mirror 174, which has a semi-reflective and semi-transparent surface. One half of the radiant energy of the source 170 is reflected by the surface 176 onto the prism 178 , which has the totally reflecting surface 180. The other half of the light from the source 170 is transmitted through the surface 176 and thus falls through the mirror 174 . In this way, two parallel energy beams A and B are generated, one of which is directed through disk 146 and the other through disk 148 . Ray A falls behind

Passage through the disc 146 and that they wear Volume 132 and the openings 158 and 166 of volumes 134 and 136 on the prism 182, which di < has totally reflective surface 184, which the loan

* reflected perpendicular to the direction of the light beam B Simultaneously with the beam A passed through the disk 146, the beam B is passed through the disk 148 on the belt 132 and through the openings 160 and 16t of the belts (34 and 136. Towards a motoi ( not shown) driven rotating shutter 186. which is provided with a totally reflective surface 188 and an opening 190, is arranged in such a way that its plane bisects the intersection angle of rays A and E. The opening 190 is formed by two semicircles

, of different radii on one closure half as well as through opposite one another with respect to the center point Diameter parts formed. The totally reflective surface 188 has the same dimensions and is on the side facing the Photoverviclfacher 192

> of the lock provided. It is in the path of the light beam A in such a way that it is reflected onto the photomultiplier 192 during a half-turn of the shutter. The opening 190 is arranged in such a way that the beam B is along the line 194

. totalreflekticrl is, while the beam A is reflected on the (hotoverv.lfacher. During the other half-turn of the shutter 186 the light beam β passes through the opening 190 to the photomultiplier. At the same time, the beam A also passes through the opening, but perpendicular to the Direction of beam B. In this way, beams A and B fall independently of one another on the thermal multiplier and generate independent electrical signals, the difference between which makes it possible to determine the amount of a constituent in the sample

The analysis tape is with a load-bearing underlay, for example ius paper. Cellulose acetate or polyethylene terephthalate. This base is preferably colorless and very transparent for the radiant energy needed to analyze the on the tape existing reaction site is used. However, there are also substances such as paper that can are evenly translucent, with sufficient residue so that they are not used during

whereby

The actual position of the reaction points on the analysis tape is not critical. However, if many "! ^ΫίΓηυη 8 ^ε " provided analysis bands are to be

^{g 'he} _Ä ^ ^{We Will et} · ^{so Süil ej} ne one another arrangement of the reaction sites performed

^{So that the tapes into} g ^it official at the J ^{elle And the} billing right Ξι, H ^W c ^{rd, can s} · ^{How kan} "a one Reagent Eeordni? ^ *" ^ ^A reaction site at L ^clauses' _D ^{Ie, to tHe Kontr} ° is "used analysis, ^React J ™ hasten few" is separated gen that the A ^g "from the nearest T ^'Öffnu can f ^{band fOI} south ^end" "are ordered at £ JZ ^at ° ^rdnun g ^th e reaction sites only in the longitudinal direction of the Analysierungsbandes also aTeord ^ ^meh o ^Reakti onsstellen side by side BandÄ! ^Γ Βεΐ / ^{ίηεπΐ ported} de nto? ^e o ⁿⁿ u ^{each row of} reaction sites of SETn lh ^I L ^Re i ^{hey through an} opening row isolated entert eden & ^Mlte * "" ^each reaction Steep and

SSn wflVT ™ ^{g on one of a multitude of} h! ^{It was felt} that the direction of the analysis

• ** t:

t

17 9b

Il

ribbon run.

The reaction point can be realized in many forms. In its simplest form, the supporting base of the analysis tape is porous or at least can be impregnated with the necessary reagents so that these can be stored within a particular area of the hand. This area is preferably surrounded by a hydrophobic barrier, which consists for example of paraffin wax, whereby the transfer and diffusion of the liquid sample substance and / or the reagents from the reaction point is prevented. If the supporting base is not porous or is not suitable for accepting and storing applied reagents, a reaction cell for storing the analytical reagents is provided on one of its surfaces. In one embodiment, a layer can be poured over the entire surface of the supporting base. For example, the reagents can be stored at the reaction sites in a uniform coating, the gel is permeable to the constituents of the sample. Suitable (icle and gel-forming substances are hydroxymethyl cellulose, hydroxyethyl cellulose, silica gel, polyvinyl alcohol, gelatin, polyacrylamides and agar-agar. The reagents are mixed with the viscous gel in water, applied as a coating to the base and then dried. Except gels or gel-forming substances also other porous materials such as paper, impregnated with the necessary reagents and then glued to the supporting base Corresponding to the disks described in connection with Fig. ^R ) and b. The properties of the reagent-containing disks will generally depend on the reagents and the operational steps required to perform the desired analysis. As in the case of the tape described above, the disk can consist of a porous substance or a substance which can be impregnated with the reagents. In the present context, the term "porous" refers to the known porous substances such as B. paper, as well as the above-mentioned gels or gel-forming substances. The reagent disk can thus consist of a cellulose paper in which the necessary reagents for carrying out the desired analysis are present in one step as an impregnation. The discs are then punched out of the paper treated in this way and firmly glued to the base. For more complicated procedures, several layers of different composition (i.e. with different stored reagents can be glued together and allow the successive analysis of a respective liquid sample, with each layer containing its own reagents or performing its own special function, which corresponds to a step of the respective analysis method chosen. In addition, adjacent reagent layers within the formed disk can be separated from one another by an intermediate filter layer, whereby harmful substances are removed as the liquid reaction mixture passes from one layer to the other.

45

60 As already described, the reagent disks are punched out of the treated carrier and glued to the supporting base, suitable adhesives are adhesives such as polyvinyl acetate adhesive, rubber solution, silicone adhesives and other adhesives. If the adhesive interferes with the optical analysis, the reagent disk is placed over an opening in the arialysis tape. G in F i. 7 shows a tape 200 in which a reagent disk 202 consisting of several layers is arranged over an opening 204 . The disk 202 has a first reagent layer 206, a second layer 208 and a third reagent layer 210. The layer 208 can also be designed as a filtering layer and serve to remove undesired substances when the liquid sample passes from the layer 206 to the layer 210 . Layer 210 contains a dye that produces a color that indicates the concentration of the constituent of the liquid sample to be analyzed. The optical analysis is disturbed by the adhesive connection of the disk 202 and the tape 200 at the locations 212. Therefore, the analysis is performed by reflecting the radiant energy from source 214 on surface 216 onto photomultiplier 218 .

In addition to the impregnation of a porous substance with one or more reagents, a preferred embodiment provides for the chemisorption of the deposited reagent in the carrier, specifically for reaction sites within the analysis band. for even layers or for reagent disks. Chemisorption is a physical phenomenon in which an electron cloud is transferred between the absorbed and the absorbing substance during absorption. In the present description, however, the term "chemisorption" refers not only to the strong chemical attraction as a result of the electron transfer, but also to the actual reaction of the applied substance with the carrier, so that a functional component in the areas of the reagent deposition is chemically attached to the carrier is bound. The process of chemisorption, examples are given for the still, is of extreme importance as it prevents "ringing" when a solution of a body fluid or other sample later the reaction site is added during analysis. Ring formation is understood as the uneven distribution of the reagent or the reagent with the sample after a solvent for the reagent has been applied to a reaction site. As the solvent spreads, it washes away the reagent where it was initially applied. The ring formation is caused by the uneven distribution of the substance with an area of lower concentration in the middle and an area of greater concentration on the periphery, where the solvent contained the reagent and then evaporated. This uneven distribution affects the measurements and causes errors in the optical analysis. As already described, chemisorption avoids this undesirable physical phenomenon in that the reagent is chemically bound in its place. Furthermore, a three-band structure, as described in US Pat. Nos. 3,036,893, 32 16 804 32 60 413 and 22 61668, is completely unnecessary. While in these patents there: the top band is used to evenly apply a liquid sample to the bottom band, which is there:

Jf

.-wfc-

f ₉₄₇

adheres to deposited reagent, the ilusMge ΙΊ exert on the j / eiunulene by chemisorption. the reagent containing reactioi ^ Mole Je \ new Naiulev direct be applied, i> hn.r Ju- ..- KihghtLlungeiu. beltiivh ten / u must, the diiiU- < entails the optical \ iuil \ se •, doors would

The following examples serve the more healing Ii remediation of the new volume you MmI U-dig.licli - \ u <.tuhrungsbeispiele / ur Manufacture of Ueitkiion-vMcllcn

H e i s ρ ι e I I

The following procedure describes the preparation of a reagent-containing disc for the quantitative measurement of Iioicui in a koi liquid. Cellulose paper is first washed with acetone and then immersed for one minute or until saturation in a copper sulphate bath containing one part of saturated copper sulphate solution to three to seven times distilled water. Then the paper is immersed in a sodium hydroxide bath for about 1 minute or until the complex blue color has fully developed. Finally, the paper is immersed in a sodium potassium tar bath and then washed in distilled water. After drying, circular disks are punched out of the paper and affixed to a catheter terephthalate pad. This process results in a reagent-containing disk in which the biuret complex is uniformly chemisorbed within the porous matrix of the cellulose paper. This method is preferably carried out in the manner described above. If the sequence of the steps is changed, the complex is still chemisorbed within the porous structure. however, the paper is not as uniform and therefore not of as high quality as in the order of the steps given. In order to improve the uniformity even further, the porous matrix, that is to say the cellulose paper mentioned, can also be provided with acetone before the treatment with the reagents mentioned. Thereby, harmful substances such as I ^r cti removed from the paper, so that the alkali cellulose formed can unite the hydroxide with the cupric sulfate. The tartrate is a common stabilizing agent in CuSOj serum reaction analysis. Quantitative results were achieved when using the tapes and reagents-containing discs described above with 5 to 10 microliters of serum (either undiluted or diluted with distilled water), the reaction mixture being kept on the disc for 2 to 5 minutes at 40 C at the incubation site and was then transported to the evaluation point, where light of 540 nm wavelength was passed on and through the discs containing the reaction mixture.

As already described, the disks can be designed as a single porous layer impregnated with the necessary reagents (as in the previous example) or each disk forms a multilayer structure in which each layer has its own special configuration corresponding to at least one step. sio'.mg> a procedure. The actual size of the disk containing the reagents depends on the particular diary and the procedure to be carried out for the treatment. The introductory example serves to explain a single-layer disk in which the reagent is within the IXiIiA ₁ -I! Matrix chemisorbed in the example refers to the manufacture of a multi-layer disc.

Example Il

The following procedure describes the manufacture of a multi-layer reagent-containing disc for the quantitative measurement of the serum glutamine oxalic acid transaminase (SGOT) in the blood. A derr Known to those skilled in the art under the name "substrate";

ι- reagent is prepared by adding 33.5 grams of dibasi potassium phosphate and 1.0 gram monobasic potassium phosphate to 800 milliliters of distilled water to be added. After the potassium phosphai is carefully dissolved, the solution becomes 7.05

μ grams of L-astartic acid, 1.0 grams of alpha-ketoglutaric acid and 1.0 milligrams of tetrasodium ethylenediaminetetraacetic acid were added. The pH of the solution is adjusted to 7.4 and the solution is diluted to one liter. A porous matrix, in the present

. ■■ .. the case of cellulose paper, is completely with the substrate solution saturated and then dried or, preferably, first dehydrated with ethanol and then itift-dried. The substrate is then covered with a cellophane dialysis membrane connected, what about moist starch as

·> Binder is used. It should be noted that others Aqueous adhesives such as sugar and flour are also used to bind the dialysis membrane to the substrate layer are suitable. A third layer is made by dissolving Ponceau-L dye in water to saturation

:· will. The porous matrix to be impregnated, for example Nylon paper or silica gel, is saturated with the solution, removed from the dye bath, about 3 (1 Immersed in ethanol for seconds to about 1 minute, immersed in ethyl ether to remove the ethanol and

• s quickly after removal from the ether bath air dried. If a paper made of polyamide fibers is used, the Ponceau 1 dye is applied to a Buffered pH between 2 and 4.5 to obtain full color during analysis. Polyamide fiber

; Paper and silica gel chemisorb the dye on their surface in such a way that the harmful effects of ring formation are avoided. To impregnate the silica gel into the paper, a treatment with an alkali hydroxide is carried out, for example

j; with sodium hydroxide or potassium hydroxide, so that Sodium silicate is formed. The cellulose paper is immersed in the sodium silicate solution, which causes some of the Paper is converted into alkali cellulose saturated with sodium silicate. The treated paper is then turned into

■ immersed in an acid bath, which dissolves the sodium silicate in Silica gel converts back, which now evenly within the porous matrix of the cellulose paper is deposited. The paper is air dried and washed with distilled water to remove excess

- ■ <to remove acid and the pH to about 4.5 decrease (i.e. to the pH of the blood serum). The paper is buffered in a saturated solution of Dipped Ponceau L dye and then quickly air dried. Because the dye chemisorbs on the silica is. does not occur when the ProbeiiMoffc is added Ring formation. The chemisorbed dye layer is applied to the free surface of the dialysis membrane an aqueous adhesive similar to that used to join the first two layers attached. Rs note that Ponceau · L dye is found in Solution is sensitive to light. somewhat unemp-imdhcher as a solid material. Exposure should therefore be carefully avoided in order to

to increase the layer and to avoid light decay of the photosensitive dye. Circular disks are punched out of this southern leaf and glued onto a conveyor belt. In operation, the serum is added to the substrate layer in an amount sufficient to distribute it evenly over this layer, but not to saturation. The tape is conveyed into a breeding zone in which the serum in the substrate ^{layer is kept at 40 °} C. and the SGOT reacts with the substrate for about 15 minutes to form oxaloacetic acid. Upon removal from the breeding zone, distilled water is added to the substrate layer to saturate that layer, causing the oxaloacetic acid in and through the dialysis membrane to diffuse into the dye-containing layer. It should be noted that large molecules such as proteins can not diffuse through the dialysis membrane una therefore colorimetric effect of the dye does not interfere. The oxaloacetic acid that has passed through the dialysis membrane is exposed to an incubation process for approx. 10 minutes together with the Ponceau L dye in order to enable full color development. After these incubation steps, the tape is led to the evaluation point, where the optical density of the third layer is measured by reflecting light with a wavelength of 455 nm. Since the

concentration of SGOT in the sample proportional to optical density is at this wavelength, quantitative measurements can be carried out with this method will.

It was found that the alkali cellulose is an excellent chemisorption substrate for any alkaline Reagent is while polyamide fibers and preferably silica gel are used with acidic reagents.

There can be many forms of mass transfer to move the reaction mixture from the top Layer of a multilayer reaction site can be applied to a lower layer: While the Adding distilled water has been described as a form of mass transfer, too other forms such as B. electrophoresis, osmosis, etc. possible. It should also be noted that each analytical method is suitable for the tapes described. While the tapes described especially for routine blood chemistry such as glucose, blood urea nitrogen, albumin, bilirubin, Whole protein, SGOT, etc. are suitable, numerous other analytical tests that are included in carried out at regular intervals in any chemical environment will.

For this purpose 3 sheets of drawings

Claims (15)

Patent claims: 1. Analysis tape for an automatic analysis device, with a carrier tape, on which a number of reagent storage locations are provided, each with at least one reagent, characterized in that a number of between the reagent storage locations (102,104) arranged, the carrier tape (70) penetrating openings (122) is provided, the number of which Number of reagent storage locations and their dimensions corresponds to the dimensions of the reagent storage locations in the plane parallel to the plane of the carrier tape are the same, and that the distances are the same between each opening and the reagent storage locations adjacent to it. 2. Analysis tape according to claim 1, characterized in that in each case one opening (122) in located midway between adjacent reagent storage locations (102,104). 3. Analysis tape according to claim 1, characterized in that a number of openings between two groups of reagent storage locations are provided. 4. Analysis tape according to claim 1, characterized in that over the width of the carrier tape a number of different reagent storage locations is provided in the form of a first row, the is separated from the next row by a row of openings in the middle between the first and the next row. 5. Analysis tape according to one of claims I to 4, characterized in that each reagent storage serial (104) of a reagent-containing disk attached to the carrier tape (70) consists of a porous matrix and at least one in this evenly as an impregnation present reagent is formed. 6. Analysis tape according to one of claims 1 to 4, characterized in that each reagent storage location (104) of a porous matrix and at least one reagent chemisorbed by this consists. 7. analysis tape according to claim 5, characterized in that the reagent within the porous matrix of the supporting base (70) is chemisorbed. 8. analysis tape according to claim 6, characterized in that the reagent within the porous matrix of a reaction disk (104) is chemisorbed, which is attached to the carrier tape (70). 9. analysis tape according to claim 8, characterized in that the reaction disk (202) from a number of layers (2O6,208,210) is formed. 10. Analysis tape according to claim 9, characterized in that in the lowermost layer (210) a do indicating the concentration of a sample to be analyzed in the form of a certain color Dye is chemisorbed. 11. Analysis tape according to claim 9 or 10, characterized in that at least one layer (208) consists of a filter layer and / or a dialysis layer is formed. H", 12. Analysis tape according to claim 9 or 10, characterized in that one consists of a dialysis layer and / or a layer (208) consisting of a filter layer, a layer containing a reagent (206) from a layer (210) containing a dye. 13. Analysis tape according to one of claims 8 to 12, characterized in that one Reaction disk (202) is arranged over an opening (204) in the carrier tape (200). 14. Analysis tape according to one of claims 6 to 13, characterized in that the porous Matrix consists of cellulose paper and silica gel evenly distributed in a carrier matrix. 15. Analysis tape according to one of claims 6 to 13, characterized in that the porous Matrix consists of polyamide paper and silica gel evenly distributed in a carrier matrix.