DE2241646C3 - Device for the production of a strip with a series of radioimmunological precipitate samples of an incubation mixture in a discrete sequence - Google Patents

Description

For the preparation and evaluation of radioimmunological samples, the technical term "radio-immunoassay" naturalized.

In the radio-immunoassay currently carried out as standard, depending on whether a calibration or a measurement on an unknown sample is intended, a standard or a serum of an antigen, which can be a hormone or another biological substance, for example a thyroid-stimulating hormone ( TSH). An antigen-specific first antibody is pipetted into the antigen located in a test tube, and the approach is optimal time periods, e.g. B. for a few days to react with each other, ie "incubated". Then a radioactively labeled antigen corresponding to the antigen, a so-called “tracer”, is pipetted into the same test tube, and this mixture is again incubated for several days. Finally, a y-globulin-specific second antibody is pipetted into the same test tube and this incubation mixture is left to stand for about one or more hours. As an antigen, for. B. 0.3 ml TSH standard or serum, which is pipetted together with 0.5 ml of an anti-TSH serum of suitable concentration, after two days of incubation ^{mixed with 0.1 ml of J 125} radioactively labeled TSH, incubated for three days and finally with 0, 2 ml of an antiglobulin serum of suitable concentration are added and z. B. be incubated for three hours, in each case at room temperature in closed vessels. When 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, the radioimmunoassay antibody could be replaced by receptors in an equivalent manner. There would be no second antibody

per necessary.

The various incubation mixtures located in a number of test tubes will be subsequently sedimented by centrifugation in the simple standard method mentioned. The S liquid supernatant is then removed by suction, and that containing the radioactive precipitate ProLcube is placed in a counting stirrer, to measure the radioactivity.

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

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

Various possibilities have also become known, the method with semi-automatic (Bottermann, Ermler and Henner, 11. Medical Clinic of the University of Munich, »Semiautomatic Method for Immunoassay of Insulin and Human Growth Hormone ”in Horm. Metab. Res. 3: 55-56, 1971) or fully automated devices (Pollard and W a 1 d rο η »Automatic Radio Immunoassay "in" Automation in Analytical Chemistry ", 1966, Technicon Symposium, N.Y., pp. 49-58, and Technicon Corporation, Ardsley, New York 10 502, entitled "Interim Bulletin" "Automatic Radio Immuno-Assay, 1967"). In these known devices the precipitate from the incubation mixture is in contrast to the standard method mentioned at the beginning deposited not by centrifugation, but by filtration. While with the said semi-automatic The device still requires the expenditure of a large number of parallel suction lines and filter holders is very large and the need for manual work is still considerable, has the aforementioned fully automatic Process functional disadvantages, including a continuous advance of the filter belt and possible cross-modulations of the continuously adjoining and therefore caused by this samples may be smeared into one another.

Furthermore, a device is known (DT-OS 21 23 210 corresponding to FR-OS 20 92 146) in which the The filter strip is fed intermittently. With intermittent feed, the individual Samples are deposited discreetly one behind the other on the filter strip and so in an orderly manner be fed to a measuring station for measuring the specific sample radioactivity.

The known device looks at the removal of a sample from a reaction vessel - if necessary while moving the reaction vessel with the filter belt - the following three application options before:

a) The washing liquid is fed to the same station where the sample is placed on the filter belt is pipetted on.

b) The washing liquid is applied to several consecutive Stations applied to wash out the samples in several stages.

c) The washing liquid is only in a last station, namely in one of the sample application station downstream station applied.

A simultaneous application of samples from several reaction vessels is known generic device is not provided. Now it is known per se (CH-PS 4 57 708), in devices for Analyzing liquids, e.g. B. of blood samples, several samples at the same time on a liquid-absorbent Pipette the paper web transversely to the transport direction of the paper web. However, this continues accordingly wide sample carrier tracks ahead and also complicates the measurement of the samples. So it is not possible to measure such a strip with a measuring device in which only a single measuring head provided and only a feed in the transport direction of the web is possible.

The invention is based on the object of providing a device according to DT-OS 2123 210 or FR-OS 20 92 146 to train known device so that a plurality of discrete samples from different reaction vessels be applied simultaneously in the direction of extension of the filter strip one behind the other on this can.

This object is based on a device according to the preamble of claim 1 by the im Characteristic part of claim 1 specified features solved.

The device according to the invention enables the measuring station to discreetly display a strip with a row to provide successive radioimmunological precipitate samples from which always have a group applied to the strip at the same time. This allows the same measuring station are used, which are also used for the evaluation of samples-carrying strips of the known generic Device is used in which all samples are applied one after the other. Even if you're in known way several samples at the same time next to each other in the transverse direction of the strip on one applies correspondingly wide strips, the invention offers advantages over this, namely a further increase in sample processing capacity per unit of time. The invention makes it possible through Corresponding dimensioning of the step size also very high volume of reaction vessels with samples in to cope with short periods of time fully automatically, usually even with a single sample track and a correspondingly narrow filter band gets by.

In the following, reference is made to the developments of the invention described in the subclaims taken. A device already present per se in the known device of the generic type to switch off the suction force of the suction head during the advance phase of the filter belt ensures that the lifting of the filter belt to its wide step is not hindered by residual suction on the suction head will. The same purpose serves a preferably arc edge of the filter belt attacking, up and down existing lifting device, which lifts the carrier strip for its advance from the suction head and after the Feed again applies to the suction head.

It is known per se (DT-AS 10 55 849), a reagent by means of an up and down lifting device paper web intermittently to a chamber opening; to be applied tightly, from the one to be measured Traces of mixed gas is present under excessive pressure.

The evenness of lifting and putting on again can be promoted by the fact that di Lifting device has a double support for both side edges of the filter strip. The Hubeii direction can with a side guide d <

Filter belt and / or its drive can be provided with a cross register control.

To ensure that the filter belt is also reliably attached to all suction heads working at the same time applies, it is expediently provided that to apply the filter belt a rising and falling Hold-down device is provided.

As well as the possible cross register control, a longitudinal register control of the intermittent Longitudinal advance of the filter belt in relation to the suction head and the first pipette of the pipetting device for the fact that despite the "big step" the rehearsals are always in the desired sequence and length can be applied to the filter belt.

A device for applying a cover layer ij also prevented on the underside of the applied precipitate samples despite the relatively large applied sample amount an undesired contamination of the environment.

Some filter materials are not suitable for x> to form a sufficiently high tensile strength and dimensionally stable filter belt, as required for the implementation of the "Big step" between the application phases of the samples according to the invention required or is desired. The filter tape therefore preferably has a support strip which holds the filter material supports. A lifting device and a hold-down device may also be better fulfill their function on a support strip than on the filter material itself.

The filter material can also be known in the known device of the generic type Way to be supported by windows of the support strip. This is especially true when the suction surface of the Suction head is formed by a, preferably flat frit.

However, it can also sometimes lead to investment difficulties on a relatively extensive frit-like Suction area come, since the filter tape must be tight on several suction heads at the same time. In In such a case, for example, a suction nutsche can be provided on the side of the suction head in which a tight suction along a closed boundary needs to take place without the Throughput is hindered by frit pores. In one such a case, but also if generally a greater load-bearing capacity of the filter strip itself in it Central area is desired, it can then be provided that the support strip, the filter material with a wide-meshed central area supported. Here, the z. B. made of gauze material Central area of the support strip, if necessary, the function of the central support of the filter material with take over, which otherwise offers the surface of a frit.

The invention is illustrated in the following with the aid of a schematic Drawings on Ausführungsbeispiclcn explained in more detail. It shows

1 shows a flow chart to illustrate a possible preparation of the incubation mixture,

Fig. 2 in a schematic representation of the operationally part of a device for producing a strip, which follows the flow diagram of FIG. 1 with a series of discretely successive radioimmunological precipitate samples of an incubation mixture,

3 shows a device area which adjoins the device area according to FIG. 2 or can be configured for measuring a rich in the Vorrichtungsbc according to FIG. 2 strips provided with samples,

4 and 5 side view and top view of a Lifting device for lifting and placing a filter tape forming the strip on the suction head,

6 and 7 in section along the central axis of the strip, a suction head with means of the lifting device according to Figures 4 and 5 applied or lifted strip,

8 shows a plan view of the suction head according to FIGS. 6 and 7,

9a to 9g different successive operating phases of a section of the device area according to FIG. 2,

FIG. 10 shows a view of a device design alternative to FIG. 2,

FIGS. 11a, 11b and 11c are top views of alternative Embodiments of the strip with double-sided, single-sided and transport perforations, and

F i g. 12 shows a plan view on an enlarged scale Another embodiment of the strip, partly with filter spots placed on windows, partly without.

In the illustrated in Fig. 1 possibility one For the preparation of the incubation mixture, the antigen 10 is initially located as a liquid in a test tube 12. A dosed sample of this antigen is obtained according to arrow 13 by means of a suitable sampler transferred to one of the three test tubes 14, 16 and 18. This triple approach 20, 22 and 24 des Antigen is also sampled using a suitable sampling device 26 in accordance with the arrows of the Diagram of an adjusted amount of an antigen-specific first antibody 28 from a Vorral vessel 30 mixed in via pipettes 32, 34 and 36. The tripling of the mixture approach is only done for the purpose of averaging errors. in the In principle, one could start from a single vessel 14 with antibody 20. Also come of course also doubles or higher multiples of the original sample preparation of a starting antibody in question. The multiplication is both when the relevant mixed components are combined in the In series as well as in multiple passes a carousel possible.

After closing the respective single, multiple or quadruple test tube, here the triple Test tubes 14, 16 and 24, it will initially take a suitable time from hours up to usually incubated for several days. For this purpose, in the device according to FIG. 1, optionally heated or coolable, incubation vessel 38 is shown, in which the three test tubes in the to the described recorded Preparatory phase I following preparatory phase 11.

In the subsequent third preparatory phase III have the three test tubes 14, 16 and 18 moved back out of the incubation vessel 38 into a position radioactive in the by three pipettes 40, 42 and 44 via a suitable sampling device 46 labeled antigen 48 from a further storage vessel 50 / ug mixed wild.

In the fourth preparatory phase, this approach is again in an incubation vessel 51 Incubated for hours to a few days. Then in the preparation phase V are the three test tubes 14, 16 and 18 removed again from the incubation vessel 51 and further pipettes 52, 54 and 56 supplied, which in turn has a /

Sampling device 58 a gamma-globulin specific pipette in second antibody 60 from a storage vessel 62.

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

In the wording of this application, the incubation mixtures, which are in principle the same, represent in the different test tubes 14, 16 and 18 represent three different approaches to the incubation mixture, which have only been prepared in the same way for statistical reasons. Prepared in the same way further batches of incubation mixtures are then fed to the transfer zone VII in series. According to FIG. 2, the test tube 18 is currently at a transfer point 68. The arrows 69 are intended one requesting and conveying the test tubes through the various preparatory phases Indicate transport facility.

In principle it is irrelevant and depends on the type of apparatus available in which way the individual approaches of the incubation mixture go through the preparatory phases I to VII, whether this z. B. according to the diagram of FIG. 1 takes place one after the other, in parallel or in a different order. It is essential that each a new vessel with incubation mixture in the cycle of the subsequent device at the transfer point 68 for each sample to be cut off at the same time is available.

The following device is intermittent or with step-by-step operation by the control and Actuating unit 70 operated.

In the area operated by this unit 70 Device is a plurality or multiplicity of in 6 to 8 each individually illustrated suction heads 72 with a horizontal upper suction surface 75 arranged. The suction side of the respective suction head 72 is connected to a collecting container via a solenoid valve 74 76 connected, which is arranged below the suction head 72 and solenoid valve 74 and above the Mirror of the stored supply 78 is connected to a suction pump 80.

A strip material serving as a support tire 82, which is made of filter material at predetermined intervals existing areas 84 is occupied, is either from a supply roll 86 via the suction head 72 to a recording roller 88 or according to the dash-dotted line Arrow 90 continues continuously into the device area according to FIG. 3. Between the Supply roll 86 and the suction head 72, the strip material 82 first passes a reading device 92, which in cooperation with the unit 70 on the basis of index marks applied to the strip material 82 controls the incremental advance of the strip 82 so that each step a new area 84 of the Filter material is guided onto the suction surface 75 of the suction heads 72. The edge of the strip material 82 is not covered with filter material 84. Lifting jaws 94 and% as well as pressure jaws can be used on this edge 98 and 100 attack a lifting device in order to move the suction head 72 guided filter material region 84 either to apply to the suction surface or to lift off from it. An alternative embodiment of such a lifting device is shown in connection with FIGS described in detail.

In the next step, the filter material 84 arrives from the suction heads 72 to a drying device, which with two drying heads 102 and 104 on both the top and bottom of the dated Acts filter material area 84 occupied area of the strip. This drying device can of Air blowers, in particular hot air blowers, or else from other heating devices, preferably with I Jmwälzung, for example from Infrared radiant heaters. A fan is indicated in the drawing.

It can be seen that a pair of jaws 94 and 98 and a pair of jaws 96 and 100 in front of and behind the Suction heads 72 cooperate to raise and lower the strip evenly. It can such a gap should be provided between the jaws that the strip between them without large Free play under the action of a transport device, possibly just a drive for the rollers 86 or 88, can slide freely. The strip can also be in the gap between the two dryers 102 and 104 move slightly up and down, respectively, from their normal horizontal position.

In the next step, the dried filter strip 84 passes into a gap in a cover device two cover heads 106 and 108, which are on the filter strip and on the carrier strip below the Either a cover strip, such as a self-adhesive film, or simply stick on the filter strip spray on a fast, self-curing topcoat.

A transport device of the strip is symbolized only symbolically by 110, which either consists of two friction wheels 112 and 114 may exist, which are attached to the Attack both edges of the support strip, or else with gears, pins or the like in perforations can attack the edge of the strip material. The representation of this transport device 110 in FIG is only to be understood symbolically and functionally uncritical, while the sequence of suction heads 72, Drying device 102,104 and covering device 106,108 is essential.

A pipette 116 is placed on each suction head from above to a point in the center of the suction surface 75 aligned, by both the incubation mixture and the washing liquid according to the drops shown can be dripped onto the filter material 84 resting on the suction head. To do this, the pipettes are over the line 118 and the peristaltic pump 120 respectively a sampling tube 122 connected which; from a sampler 124 intermittently in there; each test tube arrived at the transfer point 68 momentarily the test tube 18 and then the reagent glass 16, etc., can be immersed.

Another pipette 121 is in the sampling tube

arranged above the reagent vessel at the point of delivery, which is connected to a pipette animal automat 128 or alternatively a hose pump ai a storage vessel 130 with washing liquid 132 angc is closed.

In the direction of advance (arrow 130) of the strip material 82 behind the respective transfer pipette 116, but in the immediate vicinity of this, are second pipettes 13 laterally a little opposite the center of the Ansauf

709 650/1!

surface 74 of the suction heads 72 arranged offset and via a further hose pump 134 and a corresponding hose line 136 each with a vessel 138 with moistening liquid 140, for example distilled Walser or alcohol.

The operation of this portion of the device shown in Fig. 2 results from the successive ones Operating phases of the F i g. 9a to 9g, each showing a section from FIG. 2 in different operating states represent a singly picked suction head.

In Fig.9a it is assumed that the Hold-down jaws 98 and 100 apply the filter area 84 of the strip material 82 to the suction surface 75 of the Hold down the suction head 72, with either the filter material protruding over the suction surface and this protrudes completely or the edge region of the strip material 82 outside the filter material has a sealing effect.

The solenoid valve 74 is turned on in this case according to the arrow 142, so that according to the Arrow 144 full suction force is applied to the suction head 72. The hold-down position of hold-down jaws 98 and 100 is also indicated by arrows.

In this state, the reagent vessel 18 with the incubation mixture 66 is first placed at the transfer point 68 arranged, and further 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 through the line 132 according to the arrow 146 Filter material area 74 applied by corresponding actuation of the one shown in FIG Peristaltic pump 134. The automatic pipetting device 128 holds the sampling tube 126 out of engagement with it the incubation mixture 66 of the test tube 18.

In the next phase according to FIG. 9b, the hold-down jaws 98 and 100 of the lifting device and with unchanged setting of the solenoid valve according to arrow 142 the The sampling tube 126 is immersed in the reagent vessel 18 and the incubation mixture 66 is passed through Corresponding operation of the peristaltic pump 120 according to the arrow 148 shown and pumped out completely and via the Transfer pipette 116 is pumped off to the center of the filter material area 84 according to arrow 150. In Fig. 9b is an intermediate phase with a small residue of incubation mixture 66 is drawn. The transfer pipe 126 is expediently designed as a hollow needle. As can be seen from the arrow 144, the liquid supernatant of the Incubation mixture, following the moistening liquid, sucked down through the suction head, while on the filter material Jas precipitate remains as a deposit. In the next phase according to F i g. 9c, the operating state of hold-down jaws 98 and 100 and of the solenoid valve are still unchanged. The peristaltic pump 120 is also still in operation according to the arrow. The difference, however, is in that after the remainder 66 of the incubation mixture has been pumped off according to the state of FIG. 9b by switching on the peristaltic pump 152 according to the arrow 154 washing liquid 132 into the Test tube 18 is refilled, which continues through the still immersed sampling tube 122 is bottled. You can either continue pumping at the same time as refilling Make washing liquid nrW in ιι; ~ μ: .. ι r ■ ·

ppg to be carried out in good time with the refill of washing liquid or, with a view to the The cleaning effect is better, first refill the test tube with washing liquid and then replace it Pump off and repeat this process once or several times as required. This results in both: Test tube 18 and the transfer line 118 around the transfer pipette 116 in the flow through see.

After this phase, according to FIG. 9d the two peristaltic pumps 148 and 154 are put out of operation again. Furthermore, according to the arrow 156 which is reversed in relation to arrow 142, the solenoid valve 74 is switched over, so that suction force is no longer applied to the suction head 72. Finally, the hooks 94 and% are raised in accordance with the reversed arrows 158 and ₅ in order to lift the support strip from the suction surface 75 as shown in the drawing.

The next phase according to FIG. 9e differs from the previous phase only in that now, in accordance with the arrow 160, the one from FIG Apparent transport device 110 is put into operation to advance the strip material by one step to move and a new, not yet covered with precipitated filter area 84 again over the suction surface 75 of the suction head 72 to lead. The exact compliance with the required step size and, if necessary, also the transverse register setting is done by the reading device 92. That on the transported The precipitate applied to the filter area is thereby activated by the hot air blower 102, 104 dried.

In Fig. 9f it is shown how otherwise unchanged operating condition the filter material between the two cover heads 106 and 108, here brought together according to the two arrows facing one another shown, are covered with cover stripes.

It should be noted that the phases of FIG. 9e and 9f do not need to follow the phase of Fig. 9d, but in another step at the same time the phase of FIG. 9a can take place. The phase of FIG. 9g finally shows that now the reagent vessel 18 has been moved further empty, while the reagent vessel 16 has moved to the transfer point 68 is. In addition, the solenoid valve is according to the new 42 switched on again and the two hold-down stackers, 98 and 100 have a new Filtermalcrialbere.ch 84 again on the suction surface 75 according to newly applied 144 again sucking suction head 72, so clali now the moistening process according to Fig. 9a can connect again immediately.

^From «η different line connections of the unit 70 m Fig. 2 it can be seen that this in the desired, successive step-by-step cycle, both the transport device 110 and _ft ^Ab . ^deck device 106, 108, the heating devices 102, 104, the suction pump 80, the solenoid valve 74, the lifting device 94, 96, 98, 100, the hose pump 120 and 134, the sampler 124 and the η Γ 'r ^aUt n ^{mat m or in the} alternative Draw-152 flow ^{g dCr l} '' ^g - ^{9a to 9d dic peristaltic pump In fig} . 6 _and η _{isl dcr cinzdne Silu head 72 still}

. Ordinary Γ, "')" ^{Cn dar} 8 ^cs ' ^{c |} It has the shape of a UDlicntnι glass frit with a ground suction surface

6, Knnfni, '" ^eneinsa ·' -« 160 within an enlarged H ₁ , S ^m " ^rUndcm cross-section, which is attached to a til 74 r · ι! ^a "B ^eschlo " cn is that of the Magnctvenbranihi L diameter of the suction surface 75

only needs about 1 to 3 cm, as with conventional fries

be, for example 2 cm. The outside diameter D of the suction head, the diameter A of the suction surface and the uniform tapering to the suction tube 164 with a smaller inside diameter d as well as the circular cross section of the suction head can be seen from FIG.

It should be noted that the glass frit shown can also be replaced by a commercially available plastic frit or a suction filter. 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.

6 and 7 is above the suction head 72 a preferred lifting device alternative to the lifting device of FIG. 2 in detail in connection with the F i g. 4 and 5 shown. In the case of FIG. 6, the lifting device is in contact with the Suction surface 75 of suction head 72 corresponding to the operating phase according to FIG. 9a, while the lifting device In the illustration in FIG. 7, corresponding to the operating phase in FIG. 9d, of the suction surface 75 is shown lifted. Accordingly, in FIG. 6 shows the strip material 82 in a straight line and in FIG. 7th due to its elevation, it is shown slightly curved upwards.

The lifting device designated as a whole by 170 is overlaid according to the double arrow 172 in FIG a plunger 174 moves vertically up and down. As can be seen from FIG. 5, the plunger 174 engages on a lateral extension 176 of the lifting device. This lateral extension consists of a lengthways of strip material 82 extending block 178 from which extends both in front of and behind the suction head 72 one upper web 180 and 182 and one lower web 184 and 186 each across or across under the Strip material 82 extend.

The two lower webs 184 and 186 carry a pair of rails 188, each of which is under one of the two Attack edges of the strip material 82 so that they do not get in the way of the narrower filter material region 84 are. A hold-down web 192 and 194 is arranged in pairs above opposite one another. The rails 188 and the hold-down webs 192, 194 each form a guide slot 196 proportionally small width, through which, however, the strip material 82 together with the filter material area 84 without large Friction can slide through. It can be seen that the two pairs of hold-down web and rail are each in The inlet direction and in the outlet direction of the strip are open in a funnel-shaped rounded shape to the inlet and Ensure that the strip runs out smoothly. The function of the two rails 188 corresponds to that of Lifting jaws 94 and% according to FIG. 2 as well as the function of the lowering webs 192 and 194 of the Nicder holding jaws 98 and 100.

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

The further processing of the according to FIG. 2 produced strips with in certain mutual offshore areas applied and, after drying, covered on both the top and the bottom Samples are carried out according to FIG. 3.

Under certain circumstances, the supply roll 88 of FIG. 2 can be dispensed with and further processing takes place corresponding to the dashed arrow 90 immediately. Instead, however, from the supply roll 88 be assumed, it is not necessary that this is used in the same place. she can also to the measuring station in FIG. 3 be convicted.

The strip material 82 with the filter material areas 84, which have now received samples and are covered on both sides, are first of the roller 88 in turn by a serving for positioning Reading device 200 corresponding to the reading device 92 of FIG. 2 and then through a measuring slot 202 of a

ίο 4P measuring head 204 out, which is used to measure the Radioactivity of each between two scintillation crystals 206, such as NaJ monocrystals for measuring Gamma radiation, guided sample is used. The two large blocks 208 indicate the required Shielding of a single sample 210 on a filter area 84. The rectangular boxes 212 should Represent photomultiplier. Of course, other measuring heads can also be used.

After the sample has been measured, it is advanced by one step until the next sample 212, and although on the following filter material area 84, is fully indented into the measuring slot 202.

With 214 a friction wheel drive is again symbolically indicated, which is also in turn by a Gear drive and the like. Can be replaced. Finally, the diameter strip is placed on reel 216 wound up.

With 218 is a second control unit for operating the transport device 214, the measuring head 204 and of the reader 200 designated. Of the last two devices, the with Lines marked with arrows processes the signals. Finally, a writer or printer 220 holds the obtained measurement results of the individual samples.

The measuring device of FIG. 3 can be operated fully automatically and the corresponding Markings and control indices on the strip material automatically convey the necessary signals.

In the case of the device described, the capacity is due to the simultaneous application of several samples compared to a device of the conventional type which, for. B. the processing of more than a thousand samples allowed per day or the processing of around 600 samples in ten hours, correspondingly multiplied. the A configuration that allows a plurality of samples to be applied at the same time is shown in greater detail in FIG made clear.

In accordance with the arrangement of FIG

jo are in Fig. 10 the solenoid valve 74 on the suction head 72, the Collection vessel 76 and a suction pump 80 are provided. The strip material is also taken from a supply roll 86 released and taken up by a take-up reel 88.

However, a strip material provided with areas of filter material is not already on the supply roll 88 Rial wound, but only a support strip 229, which is subsequently step by step over the magazine 230 is covered with individual filter leaves 232.

The magazine 230 is followed by a positioning device 234 which, like the reading head 92 Read register marks on the strip and send corresponding signals to a positioning device, if necessary the transport device or the drive of one of the rollers 86 or 88 can be active or actively aligning acts on the strip.

As in the arrangement of FIG. 2, the subsequent suction head 72 consists of a rear inlet

22 4

1 64ί

switching of four frits 236, 238, 240 and 242, which the detailed in connection with the F i g. 6 and 7 can have the structure described and with mutual distance corresponding to the distance to be generated from samples on the strip are arranged one behind the other. All of these individual saiig heads are connected to a single one, to the solenoid valve 74 leading suction line 244 connected.

Alternatively, one could also think of providing a single elongated suction head that is connected to the suction line 244 is connected.

One of four similar pipettes 246, 248, 250 and 252 is arranged above each suction head 236, 238, 240 and 242. These pipettes 246 to 252 correspond to the pipettes 116 according to FIG. 2 in that each of these pipettes is assigned a completely independent system for the intermittent supply of incubation mixture. Each of these pipettes 246, 248, 250 and 252 also replenishes washing liquid before a new batch of incubation mixture is fed in, as is the case in connection with FIG. 2 has already been explained.

An additional pipette, not shown, of the type of pipette 132 for dripping on moistening liquid can also be provided. However, you can also use the moistening liquid as well as the Pass washing liquid through the respective pipette for applying the incubation mixture, if the the resulting delay is not critical.

With a drying station 254 is referred to, which acts here nu ^r unilaterally on the application side of the precipitate on the strip and otherwise corresponds to the drying device 102, 104 in FIG. 2.

This is followed by a station 256, in which one of each supply roll 258 or 260 is self-adhesive Cover film 262 or 264 by means of the pressure rollers 266 and 268 on the top and bottom of the strip 270 is launched. It can be seen that the strip is guided horizontally as a whole through this entire device will.

The longitudinal extension of the individual stations is not shown proportionally in FIG. What is essential is that the step size of the operation carried out intermittently as in FIG. 2 moves the band in one step over all four suction heads 236,238,240 and 242 so that after the application of precipitate by one of the pipettes 246, 248, 250 and 252 on the strip 270 in the next step again fresh filter material area at the same time for all four individual suction heads come to rest.

A pair of rails 272 is used to lift the strips 270 from the four individual suction heads 236 to 242, which attack the edge of the strip where there is no filter material. The renewed investment to the individual suction heads are carried out by the transport mechanism itself, which then tightens the strip again pulls.

The zigzag storage 280 can also take the place of the receiving roller 88, from its underside if necessary, the strip 270 is removed again at 282 and at the appropriate time a measuring station according to FIG. 3 can be fed.

It is advisable to choose the width W of the zigzag memory 280 so that an integral multiple of the number of samples that are simultaneously applied to the strip in the device can be arranged in one side length. If, for example, this width W is the step width of the device according to FIG. 10, four samples can in each case be simultaneously on a straight section de; The strip.

If the strip is also designed as it is explained in detail in FIGS is that namely Filtei material areas only in The kink between the filter material areas can follow certain distances from one another be provided as a special joint stone alone in a support strip carrying the filter material.

It was already mentioned in the introduction that ah

Carrier strips for filter material areas water-

permeable material, e.g. B. gauze, so that in In this case, the carrier strip enables filtration at any point on the strip.

However, it is preferred to form the carrier tire according to FIG. 12 from water-impermeable and inextensible material 300, in that windows 302 are cut out at predetermined intervals D, for example of 100 mm. In the exemplary embodiment, the window has a width of 20 mm.

A filter material sheet is placed on each of these windows 304 placed with a diameter of 26 mm,

so that in the case of the circular cross-section of the window and the filter leaves an all-round covering edge of 3 mm arises.

It can be seen that the filter lamellae 304 each leave an edge zone 306 and 308 free on both cables, unier which can attack a support device next to the suction heads.

This edge zone is shown in dashed lines to indicate that there is also a magnetic strip along it can extend as a recording medium, optionally on both sides. At the same time or alternatively Transport holes 310 can be provided for the engagement of toothed transport wheels. For hint this alternative, only individual such perforations are shown here.

In addition, the space in the center of the carrier strip 300 with register marks 312 and 314 be provided, which are shown here in pairs offset to the longitudinal center line of the strip and from each of which the middle one is used for longitudinal register control and the one on the side for cross register control can.

The F i g. 11 a to 11 c represent similar strips at each of which in turn has filter spots 304 with a circular cross-section in the middle of a carrier strip 300 are arranged, whereby between the filter spots each here symmetrically to the edge, however, index marks 316 arranged asymmetrically with respect to the filter corners are provided.

The three embodiments shown differ in that in the case of the embodiment according to no marginal perforation at all is provided in the figure is, so that the strips can be transported about by friction wheels, while in the case of Embodiment of Fig. Lib cine relatively quickly successive edge perforations 318 on a 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 pads 304 to the carrier strip can be done by means of a rubber band or a

Indere adhesive connection, if necessary by clicking on a self-adhesive rear tire. Under certain circumstances, the JCi ¹ H ^- Ii filter can simply be pressed onto the carrier strip and then only finally fixed later by placing the cover strip. A discrete sample 305, which is covered by the cover strips, is indicated on a filter leak.

The shape of the filter spots does not have to be round either, it can also be square or rectangular with extension in the longitudinal direction of the rectangle or along the strip. Other forms can of course also be used. The circular shape is but when pipetted up because of the / entral symmetry this process and the maximum material savings achieved in this way are particularly useful. The rectangular shape, on the other hand, offers more space for round windows. One can but also choose the window shape rectangular or square or otherwise.

The areas 320 on the carrier strip /. Wipe the Filter stains can be used to apply various marks, such as holes according to the ones drawn Register marks, reflective or translucent, colored, black or white imprints. FIs is also coming any kind of suitable filter material in question, like it in paper form, a plastic filter or a membrane filter being.

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

The carrier strip itself can be, for example, a suitable plastic film. When the filter stain out Cellulose acetate consists and a pore size in the range of 0.01 to 0.5 μm, preferably 0.45 μm has, the filter spot in a practical embodiment has a thickness of 120 μm.

It should be noted that the space between the filler patches, which in the embodiment of FIGS. 12th 72 mm long, also with notes on the nature of the individual specimens for their identification and further details

Description can be provided. In this area, therefore, one can also set up appropriate regulations Provide fields, for example by arranging a; certain highlighted labeling areaci with special color-accepting ability.

The distance between the individual sample spots is z. B. mi approx. 80 mm selected. It depends on whether soft or hard y-radiation or / J-radiation is measured unc must be shielded. As a rule, he should! be at least a few cm. The value of about 80 mn

is suitable for standard dimensions! Scintillation crystals adapted.

Borosilicate glass, fiber diameter 0.75 to 1.49 μίτΐ, can also be used as filter material.

In addition 9 sheets of drawings

Claims (12)

Patent claims: 1. Device for the production of a strip with a number of discretely successive radicimmunological Precipitate samples of an incubation mixture with a filter belt, a suction device, a drive for the intermittent advance of the filter belt over the suction device, a conveying device for the intermittent supply of reagent vessels with incubation mixtures, an intermittently switched on delivery device of washing liquid, a Device for pipetting on an incubation mixture and through the relevant Reaction vessel replenished washing liquid on the same at the suction device opposite this stationary sucked-in filter material section of the filter belt, a synchronizing device from Filter belt feed and pipetting process and, if necessary, one in the conveying direction of the filter belt upstream moistening station and / or one downstream in the conveying direction of the filter belt Station for applying a cover layer to the precipitate samples, characterized by the following features: a) the pipetting device has a plurality in the conveying direction of the filter belt (229; 82, 84) successive pipettes (116; 246, 248, 250,252); b) the suction device (72) has a corresponding plurality of the individual pipettes the suction areas of a suction head opposite the pipetting device or separately Suction heads (236,238,240,242); c) Each pipette has its own device for supplying incubation mixtures and Associated washing with washing liquid; d) the step size of the intermittent drive of the filter belt is chosen so that this in in one step the applied by all pipettes of the pipelines Incubation mix preparations from the area of all pipettes of the pipetting device and removes all suction sections of the suction head. 2. Apparatus according to claim 1, characterized by means (74) for switching off the Suction force of the suction head (72) during the advance phase of the filter belt (229). 3. Apparatus according to claim 1 or 2, characterized by one at the edge (306, 308) of the The lifting device (94, 96, 98, 100; 170) engaging the filter belt (229) and going up and down, which the filter belt (22S; 82, 84) lifts off the suction head (72) for its advance and after the advance rests on the suction head again. 4. Apparatus according to claim 3, characterized in that the lifting device has a double Has support (188, 272) for both edges (306, 308) of the filter band (229; 82, 84). 5. Device according to one of claims 3 to 4, characterized in that the lifting device with a side guide of the filler hancles (229; 82. 84) and / or its drive is provided with a cross register control. 6. Device according to one of claims 1 to 5, characterized in that for applying the Filter belt (229; 82, 84) on the suction head (72) a holding-down device (192, 194) is provided. 7. Device according to one of claims 1 to 6, characterized by a longitudinal register control of the intermittent longitudinal advance of the filter belt (229; 82, 84) with respect to the suction head and the first pipette (246) of the pipetting device. 8. Device according to one of claims 1 to 7, characterized in that the suction surface of the Suction head (72) is formed by a, preferably flat, frit (160). 9. Device according to one of claims 1 to 7, characterized in that the suction head as Suction nutsche is formed. 10. Device according to one of claims I to 9, characterized by a device (260, 264, 268) for applying a cover layer (264) also on the underside of the applied precipitate samples. 11. Device according to one of claims 1 to 10, characterized in that the filter belt a support strip (82; 229; 300) which supports the filter material (84; 232; 304). 12. The device according to claim 11, characterized in that the support strip for support of the filter material has a wide-meshed central area.