DE2241646A1 - STRIPS WITH A SERIES OF RADIOIMMUNOLOGICAL SAMPLES AND THE METHOD AND DEVICE FOR MANUFACTURING SUCH A STRIP - Google Patents

Description

1. Dr.re.nat. Dr. med. Friedrich Erhardt

2. Jüraen Henner

3. Prof. Dr.med. Peter C. Scriba

II. Medical Clinic of the University of Munich 8 Munich 2, Ziemssenstrasse 1

"Strips with a number of radioimmunological samples as well Method and device for producing such a strip "

For the preparation and evaluation of radioimmunological samples The technical term "radio immunoassay" has become established.

With radio-immunoassay currently performed as standard (e.g. II. Medical Clinic of the University of Munich) depends on whether a calibration or a measurement on an unknown The sample is intended to be assumed from a standard or a serum of an antigen, which is a hormone or another can be a biological substance, for example a thyroid stimulating agent Hormone (TSH). An antigen-specific first antibody becomes an antigen-specific first antibody to the antigen in a test tube pipetted in, and the approach v / is optimal time periods, e.g. for a few days, left to react with each other, i.e., "incubated". Then a corresponding to the antigen, radioactively labeled antigen, a so-called "tracer", is pipetted into the same test tube, and this approach is repeated

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incubated for several days. Finally, a. ^ - globulin-specific second antibody is pinched into the same test tube and allowing this incubation mixture to stand for about one or more hours. As an antigen, e.g. 0.3 ml TSH standard or Serum with 0.5 ml of an anti-TSH serum of a suitable concentration pipetted together, after two days of incubation with 0.1 ml

125
J radioactively labeled TSH are added, incubated for three days and finally 0.2 ml of an antiglobulin serum of suitable concentration are added and incubated, for example, for three hours, in each case at room temperature in closed vessels. If the temperature changes, the optimal incubation times change. It is also possible to change the order of the steps for obtaining the incubation mixture. Finally, in the sense of a more recent development of the radio-immunoassay, antibodies could be replaced by receptors. No second antibody would be necessary here.

The different ones in a number of test tubes In the standard method mentioned, incubation mixtures are then sedimented by centrifugation. Of the liquid supernatant is then removed by suction, and that The test tube containing the radioactive precipitate is placed in a Inserted counting tubes to measure the radioactivity.

The antigen content of the original sample is calculated from the comparison of standard with serum samples.

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This well-known radio-immunoassay procedure is cumbersome, time consuming and requires extensive manual work.

A semiautomatic immunoassay method has already been used to at least partially avoid these difficulties provided (Bottermann, Erraler and Kenner, II. Medical Clinic of the University of Munich, "Semiautomatic Method for Immunoassay of Insulin and Human Growth Hormone". In Horm.Hetab. Res. 3: 55-56, 1971). This semi-automatic process is identical to the first-mentioned process in that it is again each individual incubation mixture is prepared in its own test tube. The precipitate is here from the incubation mixture however, not by centrifugation, but separated by filtration by simultaneously removing the incubation mixture from 25 test tubes each suctioned via a suction line with a connected peristaltic or hose pump and each is pipetted onto an assigned of 25 membrane filters, each of which is placed on a filter holder connected to the suction tube is hung up. The 25 membrane filters assigned to the individual radioimmunological samples are then individually solution of their radioactivity is supplied by the sea.

The equipment required for the 25 parallel suction lines and filter holders however, it is still very large here; the radioactivity of the 25 individual membrane filters is also measured manually by placing it in a counting tube.

It is also already a fully automated radio immunoassay process with filter separation has become known (Pollard and Waldron 'Automatic Radio- · Immunoassay "in" Automation in Analytical Chemistry " , 1966, Technicon Symposium, N..Y. , Pp. 49-58, and "Interim Bulletin "from Technicon Corporation, Ardsley, New York Io5o2

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entitled Automatic Radio Immuno-Assay, 1967). In this known radio-immunoassay method, from which the invention is based, a relatively long glass paper strip is moved continuously as a filter strip over an elongated suction surface of a suction head, the contact surface of which on the glass fiber paper strip is a perforated polytetrafluoroethylene layer on a perforated base plate connected to a vacuum source is applied and its material is intended to enable sliding ability despite the negative pressure applied to the suction head. In the running direction of the filter strip, spaced one behind the other, three pipettes are arranged above the suction head, the first of which drips a moistening liquid onto the filter strip, the second pipettes fractions of various incubation mixtures onto the filter strip in a continuous flow and the third pipettes to the precision that has meanwhile moved on another wa. ^c ; ch liquid drips on. The second pipette is connected to a branching line system in which the antigen, the tracer and the two antibodies are brought together in pairs at the individual branches, with delay sections for incubating the combined currents being interposed between the individual branches. The filter strip is unwound from a supply roll, covered with a self-adhesive cover strip on its upper side after passing the suction head and automatically passed through a measuring slot of a 4p measuring head of a counter to measure the radioactivity. An alternative (according to the Technicon company) provides, instead of the one third pipette for applying washing liquid, two such pipettes connected in series, since otherwise the precipitate applied to the filter would obviously not pass through sufficiently.

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is washed.

This well-known fully automatic process already offers the Significant advantage of not having to provide the individual radioimmunological samples individually for counting, but rather on a long filter strip on which a large number of samples are applied one after the other and

automated
which enables an orderly and / or measurement of these samples one after the other in the Hesskopf. On the other hand, this known radio-immunoassay method also shows a number of serious disadvantages, including the following: First, the processing capacity of samples in the known systems is limited, in practice to about 60 samples per day. Furthermore, different samples are passed through the same pipe system and finally the same pipette without the possibility of intermediate cleaning, so that different batches of incubation mixtures can cross-influence each other and, under certain circumstances, considerable incorrect measurements can occur. In addition, undesirable compromises have to be made when the liquid supernatant is sucked off by the suction head. On the one hand, one would like to quickly and completely separate the precipitate from the namely / liquid supernatant with a suction head that is as fine-pored as possible and a high suction

Araft work, but on the other hand this comes with the requirement in contradiction that the continuously advanced filter strip must not adhere to the suction head, but in the On the contrary, it should slide over this as smoothly as possible. this

minor

leads to a relatively / porosity of the suction head, undesirable elongated shapes of this suction head and too low suction forces. While the second-mentioned semi-automatic

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still very angry. the

Processes see themselves, for example, / glass frits as for / suction heads very suitable for deicing, these separate with the known continuous process practically because a free sliding of the filter strip over a frit is not satisfactory can be guaranteed. Finally, compromises must also be made in the choice of the filter material for the filter strip be made; while, for example, cellulose acetate filters or more generally for the said semi-automatic process Membrane filters, such as those used in electrophoresis, can be used, which have a large number of fine pores in the range of 0.01-0.5 / µm, Mirden for that Known fully automatic processes, although such filter strips were also considered, but because of their high price, their relative low mechanical resistance and their only small landel length discarded and instead Filter strips made of fiberglass paper are provided, which are additionally reinforced on both sides by a rubber impregnation Need to become.

It has already been recognized (Pollard and Waldron, p. 55, col. 1, middle Paragraph) that compared to the known continuous radio-immunoassav process an intermittent automatic process could bring advantages. To such a one too create, it was thought to filter the sample in one place then move the filter paper into a washing position and then to dry the sample on the step-by-step advancing filter strip and to feed it to the measuring head. As a result corresponding attempts at negative outcomes,

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however, the soculation was called an intermittent Discarded operation and instead preferred the described continuous operation despite its disadvantages.

The invention is based on the task of being able to record the individual radioimmunological samples one after the other on a strip of material, as in the known, fully automatic, continuous radio immunoassay and thus to automatically feed them to the measuring head in an orderly manner, but on the other hand, mutual influencing of different samples and contour lines during the separation of the sample to avoid as much as possible on the strips and thereby gain a very high, daily possible capacity of automatically processable samples without excessive expenditure on equipment. _a

To this end, the invention creates a new method of application of the radioimmunological samples on a strip material as well as a device adapted to it and gives a new one Strip in which the individual samples are no longer continuous in the longitudinal direction as in the known automatic method are smeared together, but are available for measurement at discrete locations.

In a method for making a strip with. a series of radioimmunological samples placed one after the other on areas of strip material made of filter material are applied by combining and incubating of an antigen! an antigen-specific first, antibody ,

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- β

a radioactively labeled antigen corresponding to the antigen and a / "- globulin-specific second antibody, The incubation mixture obtained is pipetted onto an area of the strip material consisting of filter material with suction of the filtrate from the back of the filter material, rinsing with further suction of the filtrate from the back of the filter material and repeating the process after removing the filter area provided with the precipitate from the place de- "suction and supplying a subsequent one Filter area to the location of the suction, the invention provides for this purpose that in the manual described above and semi-automatic methods known way to the antigen in each case the first antibody, the radioactively labeled antigen and the second antibody is pipetted into the same reagent chamber and the respective incubation is carried out in this is, and that the strip material is intermittently guided past the location of the rear suction and thereby alternately one behind the other a filter area of the strip material sucked in on the back, at the same suction point that in the reagent chamber The incubation mixture is located and then the washing liquid is pipetted on, the filter area provided with the precipitate of the strip material separated from the suction source and advanced. and a subsequent filter area of the strip material is sucked in again at the same suction point for the start of the next cycle.

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Procedure ' ' -

In contrast to the known continuous method, the inventive / offers the possibility of preparing the individual batches of the incubation mixture in each of their own assigned rooms and thus reliably avoiding cross-influencing of different batches. It is not absolutely necessary that the individual components of the mixture always remain in the same vessel; it is eg. also possible to merge two partners from two vessels into another vessel. It is essential, however, that a separate, assigned reaction chamber remains, which, as in the known process, is not passed through by a large number of fractions one after the other.

Another advantage of this preparation of the individual batches of the incubation mixture is that the processing time of the batches does not depend on the flow data of a specific continuous flow Flow pipe system is dependent, but that, depending on the incidence of the samples, practically any number of incubation mixture approaches can be prepared not only in quick succession, but even parallel to each other, which can then be used for further Processing according to the 'method according to the invention are available.

The continuous sequence taking place Aufpipettierung of successive fractions from different batches of the incubation mixture in the known method leads to a continuously ongoing Präzipitataufbringung on the filter strip, in which the crossing points of the various product

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- praises are difficult to mark. Since after the invention the above in one and the same place the precision on the filter strips is applied, the precision concentrates everyone Sample on a specific spot form the insane area of each filter strip.

If, after the precision of a sample has been applied, it is sufficient The step size of the intermittent strip feed is σο -selected, can be made in a manufactured according to the invention Stripes distinguish the individual samples from one another in that they follow one another with a horizontal distance. The mutual distance can be selected so that only the radioactivity is measured on the measuring head provided for measuring the radioactivity a specific sample is measured. Infoloe of the different required shielding of beta or gamma measuring ovens depending on the type of radioactive marking Provide different distances between the samples. In the rule, the creaenseitiae distance of the fleckenffirmicr applied individual samples to the strip from edge to edge of the precipitate application a multiple of the diameter of the sample spot.

The diameter of the sample spot is not only determined by the application of the precipitate in the same place, but also by rinsing with washing liquid in the same place kept small. This rinsing is expediently carried out through the same pipette as the incubation mixture

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is applied, with the result that the application pipette The process sequence alone is always washed through again and thus for the inclusion of a new batch of an incubation mixture is cleaned. In this essential feature, the invention differs particularly clearly from the known Speculation of considered and then discarded intermittent radio-immunoassay operation.

Another consequence of the application of the incubation mixture and the subsequent washing at the same point is that the suction head unlike the known .continuous process only needs to have a limited length extension, practical only the same as for a single one of the 25 holders of the known semi-automatic operation. There is also the filter strip no longer needs to slide constantly over the nursing head, but rather during the application times of the incubation mixture

and then vertically lifted the filter strip firmly sucked / can be sucked onto the suction head,

can be used with highly porous suction heads without special surface

to the cmth Anlaoe

slipperiness work ', e.g. with / smoothly sanded on the surface High porosity frits, especially glass frits. aside from that a high pressure difference can be used to suck the filter strip onto the suction head if the suction force is further The feed of the filter strip is interrupted intermittently, or strongly throttled and / or to lift the strip off the suction head external lifting means used.

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In the process according to the invention, just as in the previously known continuous process, a continuous process can be carried out Use glass fiber paper strips as filter strips, as in the known case by means of a rubber strip impregnation can be made self-supporting. However, it is preferred if the filter material of the strip is supported by a support strip is. This carrier strip can have various tasks,

as

E.g./supporting sensitive filter materials to avoid them a crumbler, aids in lifting the filter material from the suction head, sealing of protruding areas, carrier of transport and regional perforations or marks or other marking information, e.g. to identify the sample, Sealing of areas of the suction head that are not covered by the filter material, ensuring that there is no tensile strength and thus one reliable step and register control of the strip in automatic operation, etc. You can easily use a carrier strip, for example from a suitable plastic, produce in great lengths and apply a continuous strip of filter material composed of several individual lengths to this. this makes possible already the use of such filter materials, for example made of cellulose nitrate, cellulose acetate or recrenated cellulose loose, which are only available in relatively short lengths and therefore in spite of overleaving filtering properties for the

did not drive the known continuous process / as oeeianet anae-

were seen. In such a case, the wedding strip can be used

wise divided into two parts ^r > a and jev; ei] s support the two edges of the filter material. However, one can also use one at least in the middle 409813/05 0 6

BAD LOCATION

richly permeable support strip, e.g. from a suitable one Use gauze material.

For better transverse reinforcement, however, it is recommended if the support strip in predetermined longitudinal sections each with Windows is provided, which are each covered by filter material sections, da.ja the individual samples only in larger mutual Follow the intervals one after the other. This also enables the particularly economical development of the invention that between the filter material strips covering the windows in each case uncovered by filter material, Absehnitter the carrier strip are located. This offers quite a number in particular: more remarkable; Advantages, e.g. use of the relatively expensive, but especially for suitable filter materials such as cellulose η itr at, cellulose- ' acetate or regenerated cellulose only in the area where the single sample is applied ;, distant;]; Availability; dey intermediate sections the carrier strip as a carrier for other information or auxiliary transport devices, such as register holes, sample markings etc. In addition, these can be removed from the filter material uncovered areas work well as hinge points when guiding the Take advantage of the strip, as the filter material is not when it is bent is claimed. -

In the case of the strip of the known continuous process, only the application side of the fiberglass paper strip subsequent to 'the application of the precipitate with a self-

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coated with adhesive film. According to the invention is preferably one Complete preservation of the strip is provided by covering both sides with a cover strip. It is not necessarily so required that this cover strip apch the filter material uncovered areas of the support strip fully covered. An assignment with individual cover strip lengths is an option or an application of varnish or to avoid contact with the radioactive sample Laek spraying. The precipitate applied is expediently dried before the cover is applied.

The inventive method can also be used without prior Moisten the filter strip when using the suction tent sized accordingly. However, it is more advantageous as with that known continuous process a previous moistening this filter strip. However, this moistening can also occur in the area where the precipitate is applied, and even in the advance direction of the strip behind this, since the strip is in each case remains stationary on the suction head during the suction step and the liquid settles relatively quickly in the filter material can spread. The arrangement in the feed direction behind the application appears disadvantageous at first glance, offers however, the advantage of being able to keep the other side completely free for the supply of the incubation mixture.

It is possible, especially when suction is interrupted and

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Appropriate support of the filter material by means of a support strip means that the filter strip is only lifted off the suction head about the means of transport. Preferably, however, one is in time with the intermittent advancement of the strip up and down lifting device provided, which lifts the strip for its advance from the suction head and after it Feed again applies to the suction head.

In principle it is possible to use the individual approaches of the incubation mixture simply tilt from a test tube at the suction point onto the filter material. Usually one becomes an applicator pipette provide and through this the washing liquid conduct. Here you can have a number of reagent rooms with separate Approaches of incubation mixtures gradually one after the other a transfer location 'and from the transfer location located reagent space in the same incubation mixture, for Pipette the incubation mixture onto the pipette serving as the filter material and then use this pipette to direct the washing liquid.

According to an alternative, the individual partners of the incubation mixture can only be prepared proportionally to one another and carry out the dosing by adding a dosed amount of sample incubation mixture to the respective reagent compartment is removed.

If, however, the incubation mixture is auantita-

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tively prepared, you can use the whole incubation mixture take from the respective reagent compartment. For safe avoidance a mutual influencing of different incubation mixtures, it is then recommended that after removal of the incubation mixture the washing liquid is first filled into the reagent chamber from which the incubation mixture is taken and that the washing liquid is then fed from the reagent chamber through the pipette to the incubation mixture.

A particularly important further development of the invention is respectively se during a aleichen Betriebspha _(either one after the other in this or even at the same time, a number of samples on the strip under suction of the liquid the supernatant apply the filtrate and then the increment of the intermittent advancement of the strip to be chosen so that the simultaneous or at least in the same operating phase

step

Applied samples are guided into / past the suction device v / earth. The suction device can consist of individual discrete suction heads or a combination suction head, While the invention enables sample processing of more than a thousand samples per day even without this multiplication, since the operating rhythm no longer depends on the preparation of the samples, but solely on the time at which the samples were applied depends on the filter strip and its feed rate, the capacity can still be reduced by this multiplication

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further increase decisively, qeq even by an order of magnitude or more.

The strips produced according to the invention can be canned as a whole keep and measure at a suitable measuring station when the time comes. However, one can also as in the case of the known connect a measuring head immediately after the continuous process. It is particularly advantageous if you have an intermediate storage provides strip areas already provided with samples. You can then use the measuring head which can be operated continuously E.g. operate continuously in daytime and nighttime operation, since the measurement the radioactivity of the individual samples usually takes more time than the preparation of the strips according to the invention, and partially buffer the produced strip. The same would be the case with the operating speed being reversed Apparatus apply. -

Here, too, the possibility given according to the invention of having the carrier strip available as a recording medium is special essential, since the whole operation of the invention by appropriate marks or a magnetic recording track Process can be controlled fully automatically and reliably. The tensile strength of the made possible by the support strip The strip ensures reliable operation.

Further advantageous details of the invention emerge from the remaining subclaims and from the following description of exemplary embodiments of the invention based on schematic drawings.

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Show it:

Fig. 1 is a flow chart to illustrate one according to the invention possible preparation of the incubation mixture;

FIG. 2 shows, in a schematic representation, the part of an inventive part which is operationally connected to the flowchart of FIG. 1 Contraption;

FIG. 3 shows an area adjoining the device area according to FIG. 2 or connectable device area for measurement a strip according to the invention provided with samples in the device area according to FIG. 2;

Fig; 4 and 5 side view and top view of a lifting device for lifting and placing the strip according to the invention on the suction head;

Figures 6 and 7 in section along the central axis of the strip the suction head with the strip applied or lifted off by means of the lifting device according to FIGS. 4 and 5;

8 shows a cross section through the suction head of the suction device of FIGS. 6 and 7;

9a to 9g different successive operating phases

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19 of a section of the device area according to FIG. 2;

Fig. Io is a view of an alternative to Fig. 2 structure of the Area of sample application and suction of the liquid supernatant of the incubation mixture with simultaneous multiple Application and suction;

FIGS. 11a, 11b and 11c are top views of alternative embodiments a strip according to the invention with double-sided, one-sided and transport perforation; and

Fig. 12 on an enlarged scale "a plan view of another Embodiment of a strip according to the invention, partly with Filter stains placed on windows, some without.

is illustrated in Fig. 1 possibility of an inventive To prepare the incubation mixture, the antigen Io is initially located as a liquid in a test tube 12. Each a dosed sample of this antigen is prepared according to case 14 by means of a suitable. Into one of the three test tubes 14, 16 and 18 transferred. This triplicate approach 20, 22 and 24 of the antigen is also carried out via a suitable sampling device 26 an adapted amount of an antigen-specific first in accordance with the arrows in the diagram Antibody 28 from a storage vessel 3o via pipettes 32, 34 and 36 is added. The mixture approach is tripled only for the purpose of. Averaging of errors. Basically

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- 2ο -

one could start from a single vessel 14 with antibody 2o. Of course, there are also doubles or higher multiples of the original sample preparation of a starting antibody in question. The multiplication is both with union of the relevant mixture components in series operation as well as in multiple passes on a carousel.

After locking the relevant single, multiple or quadruple Test tubes, here the triple test tubes 14, 16

Hours up to and including 24, there will initially be a suitable time of usually /

incubated for several days. This is aemäß in the device

or a coolable Fig. 1, optionally heated /, incubation vessel 38 shown in which the three reagent glasses to the described recorded preparatory phase I subsequent preparatory phase II to be transferred.

In the subsequent third preparatory phase III, the three test tubes 14, 16 and 18 are again out of the incubation vessel 38 moved further into a position in which three pipettes 40, 42 and 44 via a suitable sampling device 46 radioactively labeled antigen 4 8 is admixed from a further storage vessel 5o.

In the fourth preparatory phase, this approach is again implemented in

Hours to
an incubation vessel 5l / incubated for a few days. Connecting

Send in the Vorboreitunasphase V are the three test tubes

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14, 16 and 18 removed from the incubation vessel 51 again .and further pipettes 52, 54 and 56 are supplied, which in turn via an appropriate sampling device 58 a gamma-globulin-specific pipette in second antibody 6o from a storage vessel 62.

After this mixture has been incubated again in the following preparatory phase VI, here in the incubation vessel 64 and 'also only one, much shorter time of one or more Hours, the finished incubation mixture 66, which is still in the vessels 14, 16 and 18, finally arrives in the Transfer area VII of the device according to FIG. 2.

In the wording of this application, in principle the same incubation mixture in the different test tubes 14, 16 and 18 three different batches of the incubation mixture which have been prepared in the same way for statistical reasons only. Further batches of incubation mixtures, prepared in the same way, become the transfer zone VII then fed in series. According to Fig. 2 is

while the test tube 18 at a transfer point 68. The arrows 69 the test tubes are supposed to go through the various preparations conveying and further conveying transport equipment imply.

Depending on the antigen, the incubation can also be carried out at room temperature or even lower temperature (e.g. in certain cases between 4 and 37 ° C) success, which has even been shown to be beneficial with certain hormones. One expediently takes place in the incubation vessel thermostatic temperature regulation. the

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Samplers 26, 46 and 58 can be commercially available automatic pipetting machines be. The starting antigen can be either a standard or a serum to be measured. If you especially the incubation rooms provides through which the test tubes are guided one after the other, it is advisable to keep the temperature in these adjustable to set up. In the embodiment of the invention shown, the individual samples are already in the respective associated Test tube has been dosed.

It is indifferent in principle and depends on the type of available Apparatus, in which way the individual batches of the incubation mixture go through the preparatory phases I to VII, whether this is e.g. one after the other according to the diagram in FIG. takes place in parallel or in a different order. It is essential that in each case a new vessel with incubation mixture in time with the following Device at Überaabeort 68 is available.

The following device is intermittent or with operated step-by-step operation by the control and actuation unit 7o.

Bi the area of the device operated by this unit 7o a suction head 72, described in more detail in FIGS. 6 to 8, with a horizontal upper suction surface 7 5 is arranged. The suction side of the suction head 72 is connected via a solenoid valve 74 to a collecting container 76, which is located below the suction head 72 and solenoid valve 74 is arranged and above the

The level of the stored supply 78 is connected to a suction pump 8o is.

A strip material 82, which at predetermined intervals with Is occupied by existing filter material areas 84 is from a supply roll 86 via the suction head 72 either to a Take-up roller 88 or continuously guided further into the device area according to FIG. 3 according to the dash-dotted arrow 9o. Between the supply roll 86 and the suction head 72, the strip material 82 first passes a 'reading device 92, which in the Cooperation with the unit 7o based on on the strip material 82 attached-index marks controls the step-by-step feed of the strip 82 so that a new one per step Area 84 of the filter material on the suction surface 75 of the suction head 72 is performed. The edge of the strip material 82 is not covered with filter material 84. Lifting jaws can be installed on this edge 94 and 96 as well as pressure jaws 9, 8 and loo attack a lifting device in order to each of the suction surfaces 75 of the suction head 72 guided filter material region 34 either to apply to the suction surface or to be lifted from it. One alternative embodiment of such a lifting device is described in connection with FIGS. 4 and 5 in detail.

In the next step, the filter material 84 arrives from the suction head 72 to a drying device, which has two drying heads Io2 and Io4 both on the top and on the

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Underside of the area occupied by the filter material area 84 of the strip. This drying device can be air blowers, in particular hot air blowers, or else by other heating devices, preferably with circulation, are formed, for example infrared radiant heaters. Implied is in the drawing. a blower.

It can be seen that a pair of jaws 94 and 98 as well as a pair of jaws 96 and loo cooperate in front of and behind the suction head 72, in order to be able to raise and lower the strip evenly. Such a gap can be provided between the jaws, that the strip between this without much play freely under the action of a transport device, possibly only a drive of the rollers 86 and 88, can slide freely. The strip can also be in the gap between the two Drying Io2 and Io4 from its normal horizontal Move position up or down a little.

In the next step, the dried filter strip 84 arrives in a gap in a cover device made up of two cover heads Io6 and Io8, which are on the filter strip and on the carrier strip Either stick a cover strip, such as a self-adhesive film, or simply stick it underneath the filter strip spray on a fast, self-curing topcoat.

Ho is only symbolically symbolized a transport device of the strip, which either consists of two friction wheels 112 and

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114 may exist, which attack the two edges of the support strip, or with gears, pins or the like. can attack in perforations on the edge of the strip material. The location of these transport means in llo 2 is only to be understood symbolically and functionally critical, while the success of the suction head 72, drying device Io2. Io4 and covering device Io6, Io8 is essential.

From above to a point in the center of the suction surface 75 is Aligned a pipette 116 through which both incubation mixture and washing liquid according to the drop shown the filter material 84 resting on the suction head can be dripped on can. For this purpose, the pipette is connected to a sampling tube 122 via the line 118 and the hose pump 12o, which from a sampler 124 intermittently into the test tube arriving at the respective transfer point 68, currently the Test tube 18 and then the test tube 16, etc., is immersed and for this purpose the sampling tube 122 is moved up and down can.

A pipette 126 is still in the sampling tube above the Arranged in each case arrived at the transfer point reagent vessel, which via an automatic pipetting device 128 or alternatively a Peristaltic pump is connected to a storage vessel 13o with washing liquid.

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In the feed direction (arrow 13o) of the strip material 82 behind the transfer pipette 116, but in the immediate vicinity thereof, there is a second pipette 132 laterally somewhat opposite the center of the suction surface 74 of the suction head 72 arranged offset and via a further hose pump 134 and a corresponding hose line 136 with a vessel 138 with moistening liquid 14o, for example distilled water or alcohol, connected.

The operation of this portion of the apparatus shown in FIG results from the successive operating phases of FIGS. 9a to 9g, “calibrate a section in each case Fig. 2 show in different operating states.

In FIG. 9 a it is assumed that the hold-down jaws 98 and 100 on the filter area 84 of the strip material 82 hold down the suction surface 75 of the suction head 72, either the filter material protruding beyond the suction surface and this protrudes completely or the edge region of the strip material 82 acts in a sealing manner outside the filter material.

The solenoid valve 74 is in this case according to the arrow 142 switched on, so that full suction force is applied to suction head 72 as indicated by arrow 144. The hold-down position of the hold-down jaws 68 and loo are also indicated by arrows.

In this state, the reagent vessel 18 with the in-

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Cubation mixture 66 arranged at the transfer point 68, and others Test tubes 14 and 16, which are also with other approaches of incubation mixture, in the case of FIG. 1 with similar approaches, are filled, are ready to move up.

In this state, rinsing liquid is first applied to the filter material area through the line 132 according to the arrow 146 74 applied by corresponding actuation of the peristaltic pump 134 shown in FIG. 2. The automatic pipetting device 128 stops while the sampling tube 126 is disengaged from the incubation mixture 16 of the test tube 18.

In the next phase according to FIG. 9b, the position remains unchanged the hold-down jaws 98 and loo of the lifting device and with unchanged setting of the solenoid valve according to the arrow the sampling tube 126 is immersed in the reagent vessel 18 and the incubation mixture 66 by, corresponding operation of the Peristaltic pump I2o is completely pumped out according to the arrow 148 shown and onto the center via the transfer pipette 116 according to arrow 15o of the filter material area 84 is pumped out. Fig. 9b is an intermediate phase with a small residue of incubation mixture 66 drawn. The transfer tube 126 is expedient as a hollow needle educated. As can be seen from arrow 144, the liquid supernatant becomes the incubation mixture, followed by the moistening liquid, sucked down through the suction head, while the precipitate remains on the filter material as a deposit.

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In the next phase according to FIG. 9c, the operating state of the hold-down jaws 98 and loo and of the solenoid valve 74 are still unchanged. The peristaltic pump 12o is also still in operation according to the arrow 148. The difference, however, is that after the remainder 66 of the incubation mixture has been pumped off according to the state of FIG. : gt- * f ^r illt. You can either continue pumping out at the same time as refilling the washing liquid or, if it is better with regard to the cleaning effect, first refill the test tube with washing liquid and pump it out again and repeat this process one or more times as required The test tube 18 as well as the transfer line 118 and the transfer pipette 116 were washed through-flow.

After this phase, the two hose pumps are shown in FIG. 9d

according to the

148 and 154 put out of service again. Furthermore, / in the ratio arrow 156 reversed to arrow 142, the solenoid valve is switched over so that suction force is no longer applied to suction head 72. Finally, the lifting jaws 94 and 96 are raised in accordance with the reversed arrows 158 to remove the support strip from the suction surface 7 to lift off 5 according to the drawing.

409813/0506

The next phase according to FIG. 9e differs from the previous one Phase only in that now, according to the arrow I6o, the transport device shown in FIG llo is put into operation to the strip material by a Step forward and place a new, unprecipitated filter area 84 v / ead back over the suction surface 74 "of the suction head · 72. The exact compliance with the required Step size and possibly also the cross register setting is taken care of by the reader 92. The one applied to the filter area that was transported further Precipitate is produced by the hot air blower that is put into operation Io2, Io4 dried.

In "Fig. 9f it is shown how the filter material between the two covering heads, with otherwise unchanged operating conditions Io6 and Io8, here according to the two opposing arrows - shown merged, covered with cover strips v / earth.

It should be noted that the phases of FIGS. 9e and 9f do not occur the'Phase of Fig: 9d need to follow, but in another Step can be done at the same time with the phase of Fig. 9a.

813/0506

Finally, the phase in FIG. 9g shows that the reagent vessel 18 has moved on empty, while the reagent vessel 16 has moved up to the transfer point 68. By the way, that is The solenoid valve is switched on again according to the arrow 142 and the two hold-down jaws 98 and loo have a new filter material area 84 again applied to the suction surface 7 5 of the suction head 72 which is sucking again according to arrow 144, so that now the moistening process according to FIG. 9a immediately again can connect.

From the various line connections of the 7o in

in the
2 it can be seen that this / desired successive step-by-step synchronism both the transport device llo and the covering device Io6, Io8, the heating devices Io2, Io4, the suction pump 8o, the flagnetventil 74, the lifting device 94, 96, 98, loo, the Peristaltic pumps 12o and 134 as well as the automatic pipetting device 128 or, in the alternative drawing in FIGS. 9a to 9d, the peristaltic pump 152 is actuated.

In FIGS. 6 and 7, the suction head 72 is in more detail shown. It has the shape of a conventional glass frit with a ground suction surface 75 of the frit insert 16o within an enlarged head 162 with a round cross-section, the to * a glass stem 164 is connected to the solenoid valve 74 'leads. The diameter of the suction surface 75 only needs v / ie to be about 1 to 3 cm in the case of conventional frits, for example 2 cm. The outside diameter D of the suction head, the diameter A

409813/0506

_ O 1 _

the suction surface and the uniform taper on the suction pipe 162 with a smaller inner diameter d as well as the circular Cross-section of the suction head can be seen from FIG.

It's noted that at the location of the glass frit shown
a commercially available plastic frit or a suction filter can also occur. The diameter A is only twice the wall thickness of the suction head smaller than the diameter D, while the diameter d can be significantly smaller.

In Figs. 6 and 7 is above the suction head 72 is a for
Lifting device of FIG. 2, alternative preferred lifting device shown in detail in connection with FIGS. In the case of FIG. 6, the lifting device is in contact with the suction surface 75 of the suction head 72 in accordance with the operating phase according to FIG. 9a, while the lifting device in the illustration in FIG The strip material 82 is shown in a straight line in FIG. 6 and is shown bent slightly upwards in FIG. 7 as a result of its elevation.

The lifting device designated as a whole by 17o is - corresponding to the double arrow 172 in FIG
moves vertically up and down. How to-be seen from Fig. 5 _f engages the plunger 174 to a lateral extension 176
the lifting device. This lateral extension consists of

AO9813 / 0506

a block extending along the strip of material 82 178, of which there is an upper web 18o and 182 and a lower web 184 each both in front of and behind the suction head and 186 extend across and across and below the strip material 82, respectively.

The two lower webs 184 and 186 each carry a rail and 19o, which each engage under one of the two edges of the strip material 82 so that they are not in the way of the narrower Filter material area 84 are. A hold-down web 192 and 194 is arranged in pairs above opposite one another. the Rail 188 and hold-down web 192 as well as the 'rail 19o and hold-down web 194 each form a guide slot 196 of a relatively small width, through which, however, the Strip material 82 together with the filter material area 84 can glciten without great friction. You can see that the two pairs made of hold-down web and rail, each opening in the direction of entry and in the direction of exit of the strip, rounded in a funnel-shaped manner to ensure that the strip enters and exits without interference. The function of the two rails 188 and 19o corresponds to that of the lifting jaws 94 and 96 according to FIG. 2 and the function of the hold-down webs 192 and 194 that of the hold-down jaws 98 and loo.

It is essential that in both of the lifting devices described never on the filter material area 84, but always only on the outer edge of the support strip 82 is attacked.

4098Ί3 / 0506

The further processing of the strip produced according to FIG applied at certain mutual distances and, after drying, covered both on the top and on the underside Sampling takes place according to FIG. 3.

Under certain circumstances, the supply roll 88 of FIG. 2 can be dispensed with and the further processing takes place immediately according to the dashed arrow 9o. Instead, however, can also from "the supply roll 88, it is not necessary that this is used in the same place. You can also be transferred to the measuring station "of FIG. 3.

The strip material 82 with the filter material regions 84, the have now taken samples and are covered on both sides, are first of all again by the roller 88 for positioning Serving reading device 2oo ′ corresponding to reading device 92 of Fig. 2 and then through a measuring slot 2o2 of a 4P measuring

led that
head 2o4 / to measure the radioactivity of each between

two scintillation crystals 2o6, about NaJ mono-

crystals used to measure gamma radiation, guided sample, the

the two large blocks 2o8 indicate the necessary shielding a single sample 21o on a filter area 84. The rectangular boxes 212 are intended to represent photomultipliers. Naturally other measuring heads are also possible.

After measuring the sample, it is moved one step further, until the next sample 212, on the next one

409 813/0506

Filter material area 84, fully indented into the measuring slot 2o2 is.

A friction wheel drive is again symbolically indicated by 214, which in turn can be replaced by a gear drive and the like. The diameter strip eventually becomes on the roll 116 is wound up.

With 118 is a second control unit for operating the transport device 114, the measuring head 2o4 and the reader 2oo. Of the last two devices, the same applies the lines marked with arrows processes the signals. A clerk or printer I2o finally holds the won Measurement results of the individual samples.

The measuring device of FIG. 3 can be operated fully automatically and for this purpose the corresponding markings and Control indices on the strip material automatically convey the necessary signals.

While the described device already allows the processing of more than a thousand samples per day or the processing of about Goo samples in ten hours, according to the alternative of FIG Reach capacity.

In accordance with the arrangement of FIG. 2, these are here

40981 3/0506

Solenoid valve 74 on the suction head 72, the collecting vessel 76 and a Suction pump 8ö provided.

The strip material is also dispensed from a supply roll 86 and taken up by a take-up reel 88.

The difference consists in the following modifications:

First of all, there is not already one with areas of filter material on the supply roll 88 provided strip material wound up,

229
but only a carrier strip / which is subsequently covered with individual filter leaves 232 step by step via the magazine 23o.

A positioning device 234 connects to the magazine 23o, which, like the reading head 92, either reads register marks read the strip and send corresponding signals to a positioning device, possibly the transport device or the Drive one of the rollers 86 or 88, can give or act actively aligning itself on the strip.

The suction head 72 that follows thereafter does not consist of one individual frit, but from a series connection of four frits 236, 238, 24o and 242, which are the details in Connection with FIGS. 6 and 7 described structure can have and with mutual spacing corresponding to the distance to be generated between samples on the strip one behind the other.

Λ 0 9 813/0506

are net. All of these individual suction heads are connected to a single suction line 244 leading to the solenoid valve 74.

Alternatively, you could think of a single elongated one Provide suction head connected to suction line 244.

above each suction head 236, 238, 24o and 242 is one of four similar pipettes 246, 248, 25o and 252 arranged. Each of these pipettes 246 to 252 corresponds to the pipette 116, by making each of these pipettes a completely independent system is assigned to the intermittent 'supply of incubation mixture. It will also turn through each of these pipettes 246, 248, 25o and 252, each time before a new batch of incubation mixture is supplied, washing liquid is also followed up, as is it in connection with the arrangement shown in single operation of the previous figures is shown.

An additional pipette, not shown, of the type “pipette” 132 for dripping on moistening liquid can also be used be provided. However, you can also use the moistening liquid just like passing the washing liquid through the respective pipette for applying the incubation mixture, if this is necessary Delay is not critical. The same naturally applies to the simple arrangement of the previous figures.

4098 13/0506

With a drying station 254 is referred to, which is here only on one side acts on the application side of the precipitate on the strip and the rest of the drying device Io2, Io4 Can correspond to simple arrangement.

This is followed by a station 256 / at which a self-adhesive cover film 262 or 264 from a supply roll 258 or 26o is placed on the top and bottom of the strip 27o by means of the pressure rollers 266 and 268. It can be seen that the stripe through this ^ ^^ nze. Device is guided as a whole horizontally.

The longitudinal extension of the individual stations is not in 'Fig. Io shown proportionally. It is essential that the step size of the operation, which is also carried out intermittently here, covers the belt in one step over all four suction heads 236, 238, 24o and passes away, so that, after the application of precipitate by a of the pipettes 246, 248, 25o and 252 on the strips 27o in the next step again fresh filter material areas at the same time comes to rest for all four individual suction heads.

For lifting the strips 27o from the four individual suction heads 236 to 242 are a pair of rails 272 which engage the edge of the strip where there is no filter material. the renewed contact with the individual suction heads is carried out by the transport mechanism itself, which then tightens the strip again pulls.

409813/0506

Λη the location of the take-up roller 88 can also be the zigzag memory 28o, from its underside, if necessary, the strip 27o at 282v is removed and at the appropriate time can be fed to a measuring station according to FIG.

It is advisable to choose the width W of the zigzag memory 28o so that an integral multiple of the number of Samples, which are simultaneously applied to the strip in the device, are arranged in a side length can. If, for example, this width W is the step width of the device according to FIG be deposited simultaneously on a straight section of the strip.

If the strip is also formed as it will be explained in detail in Figs. 11a to c and 12, that is Filter material areas only at certain distances from each other can follow, the kink between the filter material areas as a special hinge point alone in one the support strips carrying the filter material are provided.

It has already been mentioned in the introduction that water-permeable material, e.g. gauze, can serve, so that in this case the carrier strip the filtration at any point on the strip.

^ 09813/0506

However, the formation of the carrier strip according to FIG. 12 from water-impermeable and inextensible material 300 is preferred, in that windows 3o2 are cut out at predetermined intervals D, for example of 100 mm. In the exemplary embodiment that has Window a width of 20 mm.

A filter material 3o4 with a diameter of 26 mm is placed on each of these windows, so that in the case of the Circular cross-section of the windows and the filter leaves a round a running overlap margin of 3 mm is created.

It can be seen that the filter laminae 3o4 each leave an edge zone 3o6 and 3o8 free on both sides, under which a support device can act next to the suction heads.

This edge zone is shown in dashed lines to indicate that A magnetic strip as a recording medium can also extend along it, possibly also on both sides. At the same time or alternatively, transport holes 3Io can be provided for the engagement of toothed transport wheels. To hint at this As an alternative, only individual such perforations are shown here.

In addition, the space in the center of the carrier strip can be 3oo with Register marks 312 and 314 may be provided, which are shown here in pairs, offset from the longitudinal center line of the strip and of which the middle is approximately to the longitudinal register

■ 409813 / 0-506

- 4ο -

control and the side can be used for cross register control.

FIGS. 11a to 11c show similar strips in which each in turn filter spots 3o4 with a circular cross-section are arranged in the central region of a support strip 3oo, with between the filter spots here symmetrically to the edge, however, index marks 316 arranged asymmetrically to the filter spots are provided.

The three embodiments shown differ in that in the case of the embodiment according to FIG no edge perforation is provided so that the strips can be transported by friction wheels, while in the case the "embodiment of FIG. 11b is a relatively rapidly successive one Edge perforation 318 on one strip edge and, in the case of the embodiment according to FIG. 11a, even two such Edge perforations are provided, namely on both strip edges. These perforations are used to engage the corresponding Transport wheels.

The application of the filter spots 3o4 to the carrier strip can be achieved by means of a rubber coating or some other adhesive connection, if necessary by pressing on a self-adhesive edge strip. However, you can also use the filters under certain circumstances simply press it onto the carrier strip and later

4098 13/0506

Only finally fix it by applying the cover strip. A discrete sample 305, which is covered by the cover strips, is indicated on a filter spot.

The shape of the filter spots does not have to be round either; it can also be square or rectangular with extension the longitudinal direction of the rectangle across or along the strip. Other forms are of course also possible. The circular one However, shape is when pipetting on because of the central symmetry of this process and the maximum material savings achieved particularly useful. The rectangular shape, on the other hand, offers larger mounting surfaces for round windows. However, you can also choose the window shape rectangular or square or otherwise.

32o

Provide the areas / on the carrier strip between the filter stains to apply various marks, such as holes according to the drawn register marks, reflective or transparent, colored, black or white prints. It also comes any kind of suitable filter material in question ^ likes it in paper form, be a plastic filter or a membrane filter.

The width of the carrier strip of the embodiment according to FIG. 12 is 35 mm. It must be noted, however, that the dimensions given can vary to a relatively wide extent.

The carrier strip itself can, for example, be a suitable one Be plastic film. If the filter stain is made of cellulose acetate

409813/0506

stands and thereby a pore size in the range from o, ol to

Has

, 5,

has, preferably of 0.45 .mu.m, / has the filter spot at one practical embodiment a thickness of 120 ".

It should be noted that the space between the filter spots, which now has a length of 72 in the embodiment of FIG Notes on the type of individual samples for their identification and more detailed description can be provided. One can In this room, therefore, the corresponding inscription feathers provide, for example, by placing a specific highlighted Labeling area with special color-accepting Capability.

The distance between the individual sample spots is, for example, approx. mm rreselected. It depends on whether it is soft or hard ^ radiation or 0 radiation has to be measured and abacschirnt. He should be at least one cm in real cases. The pert of approx. 80 mm is the commercially available dimensions of aeeionet scintillation crystals adapted.

Borosilicate, fiber diameter, is also used as a filter material 0.75 to 1.49 µm, infraae.

- Requests -

409813/0506

Claims (1)

Claims (1) strips with a number of radioimmunolonic samples, one after the other on areas consisting of 'filter material a strip material are applied, characterized in that the individual samples (3o5) with successive mutual spacing. 2. The strip of claim 1, wherein the strip material is reinforced with a second material, which draws σ e k e η η that the filter material (84; 232; 3o4) is supported by a support strip (82; 229; 3oo). 3. Strip according to claim 2, characterized by a support strip which is wide-meshed at least in the central zone and a continuous strip of filter material applied at least in this central zone. 4. Strip according to claim 2 or 3 , characterized in that. that a continuous strip of filter material is composed of several individual lengths. 5. A strip according to claim 2, characterized in that the support strip (3oo) is provided with windows (3o2) at predetermined Länasabstands, each of which is covered by filter material sections (3o4). 4098 13/0506 6. Strip according to claim 5, characterized geke.nnzeichn e t that between the filter material sections (3o4) covering the windows (3o2) each uncovered by filter material Sections (32o) of the Traa strip (3oo) are located. 7. Strips according to Ansoruch 6, thereby oekennzeichn e t that the filter material (3o4) uncovered sections (32o) of the strip with marks (312,314; 316) for the longitudinal register control the longitudinal advance of the strip (27o) and / or for the identification of the individual radioimmunological samples are provided. I * 8. Strip according to one of claims 1 to 7, characterized in that the support strip (82; 229; 3oo) consists of sealing material. 9. Strip according to one of claims 2 to 8, characterized in that the support strip (82; 229; 3oo) consists of stretch-resistant material. 10. Strip according to one of claims IbLs 9, characterized in that the filter material (84; 232; 3o4) made from cellulose nitrate, cellulose acetate or regenerated cellulose consists. 11. Strips according to Claim Io, characterized in that that the pore size of the filter material (82, -229; 3oo) between o. oil and o. 5 .mu.m, preferably o. 45 .mu.m. 4098 13/0506 12. Strips after one of the cracks 5 to 11, thereby characterized in that the window (3o2) has a round cross-section to have. 13. Strip according to claim 12, characterized net that the filter material sections are square, isdTtedd.- ' gen or round (3o4) cross-section. -. 14. Strip according to one of claims 2 to 13, characterized in that ^{a transorto perforation (31o; 318) is formed along min ^ c r} : tsns of a pandes of the support strip (3oo). 15. Strip according to one of Claims 2 to 14, characterized by a magnetic recording duration (at 3o6 or 3o8), in advance on the ribbon (3oo). 16. Strip according to one of Ansorüche 1 to 15 with a Cover layer on the side carrying the samples, g e k e η η ■ "-drawn by an additional cover layer on the back, whereby the respective cover layer is preferred only. in the Area of the respective radioimmunological sample spotted is upset. 17. Strip according to claim 16, characterized in that both cover layers of adhesive films (262, 264) are. .40 9813/0506 18. Strip according to claim 16, characterized in that it draws e k e η η that at least one top layer is a lacquer layer. / 19 /. Method of making a strip with a
Series of radioimmunological samples, one after the other
of a strip material consisting of filter material regions are applied by combining and incubating an antigen, an antigen-specific first antibody, a radioactively labeled agent corresponding to the antigen and a
• ^ f-alobulin-specific second antibody, pioetting of the
Incubationsaemiaches obtained on an area of the strip material consisting of filter material with suction of the filtrate from the back of the filter material, rinsing with further suction of the filtrate from the back of the filter material and repeating the previous procedure after removing the filter area provided with the precipitate from the place of the suction sauna and adding it
a subsequent filter area to the place of Absauoung, characterized in that in per se known
Way to the antigen in each case the first / \ ntikörpor, the radioactively marked antine and the second antibody in the same
The reagent chamber is added by a pipette and the respective incubation is also carried out in this, and that the strip material is intermittently guided past the location of the back-up vacuuming and that a filter area of the strip material is alternately located on the back, at the next location
Incubationsciemix located in the reacience space and then the / ►0981 3/0506 Wash liquid is ninetted on, eggs provided with the precision The filter area of the strip material is separated from the absorbent media and advanced and a subsequent filter area of the strip material for the beginning of the next cycle on the same suction location is sucked again. 20. The method of claim 19, wherein the filter material the strip material before the incubation mixture is pipetted on ■ is moistened, characterized that the moistening at the same location as the incubation mixture is spinetted is made. 21. The method according to claim 19, wherein the filter material of the strip material before spinetting the incubation mixture is moistened, characterized in that the moistening in the direction of advance of the strip material behind the suction point where the incubation mixture is pipetted is made. 22. The method according to any one of claims 19 to 21, characterized in that a number of reagent chambers with separate batches of incubation mixtures is gradually fed one after the other to a Ube'raabeort, and that from the The reagent room located at the point of delivery jextfeils incubation mixture in the same, for pipetting on the incubation mixture transferred to the filter material serving pipette and then the washing liquid is passed through this pipette in each case. 409813/0506 23. The method according to Ansoruch 22, characterized in that in each case the nanze incubation mixture
is removed from the respective reagent compartment. 24. The method according to claim 23, characterized in that the washing liquid in each case initially
is filled in the reagent chamber to which the incubation mixture
was removed, and that the washing liquid from dem.Reagenzräum then fed through the pipette to the incubation mixture
will. 25. The method according to claim 22, characterized in that g e 'k * e η η draws that in each case a dosed sample menu of incubation mixture is taken from the respective reagent compartment. 26. The method according to one of the claims 19 to 25, thereby
characterized in that in the same work phase a greater number of approaches or preferably a large number of the
Incubation mixture at a corresponding number of filter material locations following one another in the longitudinal direction of the strip material
is pipetted that at all these filter material points
the filter material is sucked in from the back so that washing liquid is also pipetted on at all these points, and that all filter areas of the strip material provided with the respective precipitate are separated from the suction drum in the same subsequent work phase and pushed forward so far that the same suction locations for the beainn of the next cycle 409813/0 506 the fresh filter material is available. 27. The method according to claim 26, characterized in that the different approaches of incubation cream-simultaneously pipetted on and / or sucked on at the same time. 28. Method according to claim 26 or 27, characterized in that the different, with the respective Precipitate-provided filter material areas oleichzeitlg be removed from their respective place of reception. 29. The method according to any one of claims 19 to 28, in which on the side of the filter material provided with the precipitate a top layer is applied, thereby q e k e η η-draws that a cover layer is also applied to the back of the filter material provided with the precipitate will. - 30. The method according to claim 29 / characterized that a cover strip is glued on as a cover layer in each case in a manner known per se. 31. The method of claim 3o, characterized in that to form the covering layer a lacquer aufqetraaen to the filter material, preferably sprayed or aufqespritzt _f. '*' 4098 13/0506 32 / device for carrying out the method according to a of claims 19 to 31 with a feed device for a Strips of consecutive strips made of filter material Areas, reagent rooms for bringing together and for incubating the antiqens, the radioactively marked .Antiqens and the two antibodies from different antigen samples into a series of batches of the incubation mixture which can be inserted one after the other into the same pipette directed onto the strip from above are, a Sauqkopf, which comes to the bottom of the filter material strip on the lower side facing away from the pipette, so / ie a supply of washing liquid to an adjacent to the Sauqkopf Area of the filter material, characterized q e k e η η, that for the reception of the antiaene, the radioactive labeled Antiqens and the two antibodies of each approach of the Incubationsaemisches - each have a common Reaaenzaefnß (14; 16; 18) a number of the different approaches of the incubation mixture assigned changed reagent vessels (14, 16,18 ...) it is provided that an intermittent drive (llo) is provided for the feed device of the strip (27o) is that during the pipetting of the incubation mixture and the feeding of the washing liquid keeps the strip still above the sauce head (72), and that the washing liquid flows through the same PiDette (116; 246, 248,25ο, 252) v / ie the incubation mixture is feedable. 33. Vorrichtunq according to claim 32 for carrying out the method according to claim 2o or 21 with a second pipette for bringing on a moistening liquid, thus q e k e η η - 409813/0506 characterized in that the additional pipette (132) of the Inkubationsaemisches by the first pipette (116; 246,248,25o, 252) laterally beside or in the feed direction of the strip (27o) behind the location of the Aufpioettierens is arranged. 34. Apparatus according to claim 32 or 33, characterized by a connection between Sauakoof (72) and Saugauelle (8o) in the cycle of the intermittent advance of the strip (27o) opening and closing shut-off valve (74). 35. Device according to Qinem of claims 32 to 34, characterized by a lifting device that goes up and down in time with the intermittent advance of the strip (94,96,98, loo; 17o; l72), which lifts the strip (27o) for its advance from the suction head (72) ″ and after its advance leat on the suction head again. 36. Device according to Claim 35, characterized in that the lifting device is a DoDpelschiene (188,19ο; 272) which supports the two side edges (3o6, 3o8) of the strip (27o). 37. Apparatus according to claim 36, characterized in that α e k e nn, that over the double rail (188,19ο) along each rail a hold-down stea (192,194) runs. 409813/0506 38. Vorrichtuna according to claim 37, characterized in that the double rail (188,19ο) and the two Hold-down areas (192, 194) each form a guide slot (196) that gradually widens in the inlet and outlet. 39. Vorrichtuna according to one of claims 35 to 38, characterized in that the lifting device with a Lateral guidance of the strip and / or the feed device is provided with a Querreaistersteueruna. 40. Device according to one of Claims 32 to 39, characterized by a LMnasregistersteueruna des intermittent longitudinal advancement of the strip (27o) in relation to the suction head (72) and the first pipette (116; 246,248,25o, 252,27ο). 41. Device according to one of claims 32 to 4o, characterized Γ72) characterized in that the suction copy / is designed as a preferably flat frit (16o). 42. Vorrichtunq according to one of claims 32 to 41 with a Station downstream of the suction head for applying a top layer, in particular a self-adhesive cover strip, on the upper side of the strip provided with the precipitate, thereby characterized in that the station also has a device (Io8; 26o, 264,268) for applying a cover layer 40981 3/0506 (264) on the underside of the strip material (229). 43. Apparatus according to claim 42, characterized in that σ e k en η that the station with St> ritzkÖOfen for applying a top coat is provided. 44. Device according to one of the claims 32 to 43, α e indicates assigned by a marking station for applying the individual radioimmunological samples Identification marks on the strip (27o). 45. Vorrichtuna according to one of claims 32 to 44, characterized by one with the first pipette (116) connected, in the intermittent cycle of the feed device (llo) of the strip into the reagent vessels one after the other (14,16,18 ..) of the different approaches of the incubation equation immersing sample intake (66) and an intermittent washing liquid in the relevant reactor (18) with the sample suction head still submerged washing liquid supply line (126). 46. Device according to claim 45, characterized through one of the series of different reaaenza vessels TransOort facility gradually moving to a scraping location (69) and in that the sample suction head (66) and the washing liquid feed line (126) each at the transfer point (68) are operable. 40981.3 / 0506 47. Vorrichtuna according to one of claims 32 to 46 rode one Abaabe- and a receiving station of the strip, thereby characterized in that the receiving station acts as an intermediate buffer with Swischenspeicheruna of strip lengths Detour routes, to be planned as zigzag planing buffers (28o) is trained, from the side facing away from the inlet the strip (282) is removable. 48. Device according to claim 47, characterized by α e k e η ri that a measurement conf (2o4) to :; determine the Radioactivity of the respective radioimmunolocfish samples the intermediate buffer (28o) is arranged downstream. 49. Vorrichtuna according to one of claims 32 to ^, characterized by a multiple design in which a plurality, preferably a plurality, of the first pipettes (246,248,25ο, 252) in the feed direction of the strip (27o) one after the other in each case on an associated sowing area Intake head or, alternatively, separate intake pipe (236, 238,24ο, 242) is aligned, as well as by a step size of the intermittent advance of the strip (27ö) in each case around the LMnae of the working range of all these first pipettes. 50. Vorrichtuna according to claim 49, characterized in α e k e η η that the different first pipettes (236, 238,24ο, 242) separate reagent vessel rows from one another are assigned. 409813/0506 " ⁵⁵ " 2241546 51. Device according to an egg request 32 to 5o, σ e characterized by a in advance direction
Station (23o) arranged in front of the Acupressure Confectioner for Beleoen the Traa strip (229) with finite lengths (232) of filter material. Λ 0 9 8 1 3/0506 Blank page