DE2316111A1 - METHOD AND APPARATUS FOR TESTING SAMPLES - Google Patents

Description

■ ■. March 50, 1973

Patent attorneys MUNICH 22. Stejnsdortstr. IU

Hs / M.

Vickers Limited
Vickers House, Millbank Tower, Mi11bank,

London SW 1 / England

Patent application

Method and device for testing samples

The invention relates to the testing of samples and can are particularly applied to the testing of biological samples.

When testing certain biological samples, when the testing process is of the extent or the speed the heat between the sample and the reagent depends,

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it is essential that both the Both the sample and the reagent remain free from contamination. In particular, it is essential that ^ none mutual "contamination or irrigation of the samples occurs. ■■■ - "'"

The testing of samples using reagents is known, with a quantity of a sample material withdrawn from a vial and added to an amount of reagent on a slide. The slide is shaken to add the mixture to stir up a reaction. A microscopic examination is then carried out to determine the outcome of the reaction, if any. This procedure can only be done manually laboriously to carry out. No successful attempt to automate it is known.

The invention provides a method for testing Samples in which the individual quantities or types of samples follow one another at an application station to a applied upper surface of an elongated support element in order to form separate sample areas in each case on this surface. On the upper surface will a reagent is applied, and the carrier belt is <& nt in the longitudinal direction from the application station to.einer Test station moved on, at which the results the contact between the samples and the reagent can be determined one after the other.

The invention also provides a device for Testing samples with means for limiting a path for longitudinal movement of an elongated one Carrier element, with a device in front

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is seen to the carrier element in the longitudinal direction and in a predetermined direction of movement along this Move train. Furthermore, application devices are available for the respective quantities or types of samples to be applied successively to the upper surface of the carrier element and on this surface to form separate sample areas in each case. Finally, there is a device forming a test station present, which, seen in the direction of movement, at a distance to the application devices. At this test station, the results of the contact between the samples and the reagent present on the upper surface are detected in sequence.

Further advantages and features of the invention can be found in the following description of preferred exemplary embodiments in connection with the accompanying drawing. The drawing shows in:

1 shows a schematic side view of an apparatus for testing sample materials;

2 shows, in a schematic representation, a device for dispensing a liquid reagent a running belt;

FIG. 2a shows a view through the belt in the direction indicated by A in FIG. 2; FIG.

3 shows partly in section, partly in side view Means for applying liquid sample material to the tape;

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Fig. 4 shows a Horiz.ontalschnxtt through the. contraption after Pig. Jj -.

. FIG. 5 - is a side view of the apparatus of Fig ~ with some parts "are omitted for reasons of clarity;

6 is a front view of part of a device for 'cutting a thermoplastic pipe into pieces of shorter lengthj

Fig. 7 is a partially sectioned side view of Device according to FIG. 6;

8 is a perspective, partly broken away Up-to-date view of a device for agitating agglomerations of reagent and sample material Tape;

Figure 8a is a plan view of a portion of the tape; ■ "^

9a shows a schematic representation of a longitudinal section by a first modification of the device according to Fig. 8; -

FIG. 9b shows, in perspective illustration, a broken away view of a second modified embodiment of the device according to FIG. 8;

Fig. 9c is a plan view of part of the tape;

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Pig. Io, on an enlarged scale, shows a vertical section through part of the device according to FIG. 1 and at the same time a block diagram;

11 shows a length of a first embodiment of the belt;

12 shows a length section of a second embodiment of the tape.

The device shown in the drawings is used to check serum samples obtained from animals or children for Brucella antibodies. If the concentration of Bruceila antibodies is above a certain level, it can be assumed that the cow from which the sample was obtained The presence of Bruceila antibodies is determined by bringing the sample material into contact with a reagent, for example Rose Bengal Bruceila antigen. The reagent consists of a particle suspension of diseased Brucella cells in a liquid carrier while The sample material is a solution, such as a serum or plasma. If the sample material contains Brucella antibodies, it reacts with the reagent and forms sticky solids in the otherwise clear liquid mixture. The concentration of the agglutinates depends on the concentration of Brucella antibodies in the sample material . Usually concerned If the diameter of the agglutinates is more than ^ o pm, however, finer agglutinates, so-called microagglutinates, with a diameter of only Io μνα also occur. The single ones

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Brucella cells usually have a diameter less than 5 pm. ~

Pig's device. 1 comprises a dispensing or application station 1, one; Reaction station 2 and one Test station 5 (see also Fig. Io). At the company Device is a transparent tape 4, which is from a Supply sink 5 comes in at one speed. " from Io mm / sec. through stations 1, 2 and j> on a -. drawn through a predetermined path and onto a take-up spool 6 wound. The tape is pulled through stations 1, 2 and 3 at a constant speed, due to the fact that it is engaged lies between two rollers 7. One of these roles runs freely while the other of one not shown Synchronous motor is driven at a constant speed. An alternative solution is that the band 4 has perforations on its edge and a cogwheel is driven. It is then a form-fitting belt drive, although this is not possible there is a slip of the belt relative to the rollers 7 occurs.

At the dispensing or application station 1, a dispensing device 8 is arranged, which is shown in detail in FIG. 2 emerges. It serves to dispense a reagent onto the upper surface of the belt 4 as it passes through the station 1. According to FIG. 2, the dispensing device 8 comprises a microsyringe 21 with a nozzle 22 and a plunger 2 ^. The nozzle 22 is connected to a valve 24, and the piston 2.'j is connected to the piston of a double-acting pneumatic cylinder 25

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in connection. The valve 24 is in turn connected to a pipe 26, whereby a siphon connection between the reagent contained in a reservoir 27 and the valve 24 is created. Furthermore, the valve 24 is connected via a tube 28 to a tube head 29, which is shown schematically in FIG. 1. The tube head 29 comprises a metal tube, the lower end of which is compressed so that a substantially rectangular outlet opening is formed as shown in FIG. 2a. The tube head 29 is carried by a relay 31 which serves to lower and raise the tube head relative to the moving belt 4. The valve 24 is moved back and forth between two positions by a double-acting pneumatic cylinder 33. In the first position it connects the nozzle 22 of the microsyringe 21 to the tube 26, and in the second position it connects the nozzle 22 and the tube 28. The reservoir 27 sits in a cooled container (not shown) and is provided with an agitator 34 which is driven by a motor (not shown). The agitator is used to keep the reagent within the reservoir in an agitated state. A circumferential nook, also not shown, determines the sequence and the direction in which the pneumatic cylinders 25 and 33 are actuated. It also controls the power supply to relay 3I. The speed of rotation of the cam depends on the running speed of the belt 4 at which the latter moves along the lower end of the tube head.

When the dispenser is in operation, tubes 16 and 28 are filled with the reagent. "Same for

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for the nozzle 22 of the microsyringe, the tube head 29 and the internal flow paths of valve 24. Let it be Assume that the valve 24 is initially in his first position is in which it connects the nozzle 22 with the tube 25 that the plunger 23 of the microsyringe is inserted and that the relay 3I is de-energized, the lower end 30 of the tube head is in its raised position. The following sequence of movements then results:

a) The pneumatic cylinder 25 is operated to the Pulling out plunger 25, whereupon reagent is drawn into microsyringe 21;

b) The pneumatic cylinder 33 is actuated and brings the valve ^ 24. into its second position, in which it connects the tube 28 to the nozzle 22 ;.

c) The relay 3I is supplied with energy and lowers the lower end 30 of the tube head from so that this end almost touches the band 4;

d) The pneumatic cylinder 25 is actuated and pushes the plunger 23 inwards, thereby expelling reagent from the nozzle 22, which results in that exits an equal volume of reagent from the lower end 30 of the tube head, with the Band 4 comes into contact and at. the progressive movement of the tape to a track 'on it Surface is pulled out;

e) The relay J> 1 is de-energized, whereupon the tube head 29 is lifted off the belt 4, and the pneumatic cylinder 33 is actuated in order to return the valve 24 to its first position.

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So if the belt 4 is at a uniform speed is moved and if the movements described repeat with a uniform frequency, so The dispenser 8 places a succession of evenly spaced reagent traces on the tape away.

The stroke of the pneumatic cylinder 2 ^ can be changed, so that the volume of the reagent which is drawn into the microsyringe 21 when the plunger 23 is withdrawn is, and consequently also the volume of the reagent, which when inserting the piston 2 ^ from the Tubular head 29 emerges, can optionally set. In each movement cycle a) to e), a track is preferably generated that is 12 mm long, 4 mm wide and o, l mm thick, where it has a volume of 5 μΐ and wherein the traces are applied every three centimeters along the length of the tape.

The stroke of the relay j> l can be adjusted using an adjusting screw _pp in order to guarantee an optimal distance between the band 4 and the lower end of the tube head 29 in the energized state.

The shape of the outlet opening of the tube head 29 it follows that it is better to have reagent build-up of some width than to form narrow tracks, as might be the case if an outlet opening with a circular cross-section Would benefit.

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Next to the dispensing or application station 1 is a sample feed magazine (not shown) for the successive dispensing of a plurality of vials, which the. individual liquid sample materials. to a sample receiving station A according to. Pig. 4 that are in the. Neighborhood of the belt is arranged. At der.Abgabeoder application station 1 an application device 9 is provided for the samples, which a. A predetermined volume of liquid sample material is withdrawn from a vial located in the sample receptacle A and applied to the band 4. The application device 9 *, which lies behind the dispensing device 8 in the running direction of the belt 4, is shown in detail in Figures>, 4 and 3. It has a rotary head 41 which can rotate around a support tube 42 with a vertical axis. The rotary head 4l carries four separate liquid applicators I, II, III and IV, which, based on the axis of the support tube 42, in one. Angular distance of 90 ° to each other. Around the axis of the support tube 42, four work stations A, B, G and D are arranged, which, in relation to the axis of the support tube 42, are also at an angular distance of 90 from one another. The turret 41 is comparable with a shaft ^4J5: inhibited and is rotated by this stepwise by 90 ° so that the FlüssigkeltsappllkatorΊ, which initially is for example in the work station A, reached in successive steps to the Arbel.tsstationen B, C and D , while the liquid applicators II, III and IV are gradually brought to workstation A.

The support tube 42 hangs with its upper end on one horizontal beam 44, which is connected to a not

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showed cam follower connected. The latter takes effect on a cam, also not shown, and is periodically raised and lowered by this. He takes the support tube 42 and the rotary head 41 with it. The rotation of the cam is with the drive of the shaft 4 ;? synchronized, in such a way that the carrier 44 with each rotation step of the shaft 4j5 in raised Position. During the intervals between. the carrier 44 is lowered and remains in this lowered position for a predetermined dwell time. Then he will then returned to its raised position. The raised and lowered positions of the rotary head 4l result in each case on the right and left from Fig. 5-

Each of the liquid applicators I, II, III and IV comprises a vertically disposed microsyringe with a vertical glass cylinder 45 having one protruding upwardly Piston 46 has. A double-acting pneumatic cylinder 47 is also provided. The piston rod of the Pneumatikzylxnders 47 protrudes upward from the cylinder and carries a connecting arm 48, which is attached to the piston 46. The glass cylinder 43 of the microsyringe is at the lower end with a nozzle 49 provided, which are sealed in a body 5o elastically deformable material sits. The body 5o carries on its underside a sleeve 51 with a Through-opening which is connected to the nozzle 49 via a through-opening in the body 5 °. Of the double-acting pneumatic cylinder 47 has an upper connection piece 52 and a lower connection piece 53. If the upper connection piece 52 is connected to a

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Pressurized gas supply and the lower connector 53 are connected to an outlet opening, so the piston rod is pressed into the cylinder, whereby the piston 46 migrates into the microsyringe. If the connections to the connecting pieces 52 and 53 are interchanged, the piston rod is pushed out of the cylinder, whereupon der.Kolben 4o is accordingly pulled out of the microsyringe. The stroke of the piston rod can be adjusted via a variable stop ^ k. The stroke of the piston can thus be changed accordingly. . "■.

The support tube 42 is connected at its lower end to a component 55 which has two channels 56 and 57 having. The channel 56 is via a not shown Valve connected to a compressed gas supply, and the channel 57 is via an adjustable, also not shown Throttle in communication with an outlet opening. The valve is controlled by the rotating cam in such a way that that it "opens when the rotary head 4l assumes its lowered position, and otherwise closed is. The channel 56 opens into two horizontal channels 56 '., While the channel 57 with two horizontal channels Channels' 57 'communicates. The four' Channels 56 'and 57 * are in a common vertical Level. The upper connecting pieces 52 and: the lower ones Connection pieces 53 of the pneumatic cylinder 47 are on associated radial passages connected in the rotary head 41, these passages in the same vertical Like channels 56 'and 57 * are on the same level. The radial Passages in the rotary head 4l are related to the axis of the support tube 42, distributed at an angular distance of 45 °. The angular distance between the outer ones. Ends of

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Channels 56 ', based on the axis of the support tube 42, is 45 °. The outer end of each of the channels 57 * is separated by 45 ° from the outer end of one of the channels 56 '. The outer ends of the channels 57 * are, based on the axis of the support tube 42 , at an angular distance of Ij55 ° from one another. The pneumatic cylinder 47 of the liquid applicator located in work station A is connected with its lower connection piece 5J> to one of the channels 56 'and with its upper connection piece 52 to one of the channels 57', while the pneumatic cylinder 47 of the liquid applicator located in work station B is connected to its upper connection piece 52 with the other channel 56 'and with its lower connection piece 52 with the other channel 57 ¹ in connection. The connection pieces of the pneumatic cylinder of the liquid applicators located in the further work stations C and D are not connected to any of the channels 56 ^f or 57 '. When the rotary head 41 assumes its lowered position, the pneumatic cylinder 47 of the fluid applicator located in work station A is actuated in such a way that the plunger pulls out of the microsyringe. At the same time, the pneumatic cylinder on the liquid applicator in work station B is actuated in such a way that the plunger is pushed into the microsyringe. The pneumatic cylinders of the liquid applicators in workstations G and D remain unactuated. The speeds at which the plungers of the microsyringe at work stations A and B are either pulled out or pushed in can be adjusted using the diu

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bare throttle vary.

A plurality of vials of liquid sample material are gradually brought to the work station, and along line 58 in Pig. 4. Band 4 is also seen in Fig. 4, along line 59 funded by workstation B. In work station B there is a guide tube 60 - von.dem from a piece 61 of a polyamide tube protrudes upwards. At the work station C sits a gripper 6 ^. 'This includes two jaws mounted on associated coaxial shafts 64 and 65. The latter are like that connected together so that the shaft 64 rotates in one direction, while the shaft 05 rotates executes in the opposite direction. Rotation of shaft 64 in one direction thus leaves both of them Jaws come together to grab any objects in between. One rotation of the shaft 64 in the opposite direction, however, separates the two Baking, releasing the previously grasped objects.

The operation of the application device is described below, starting at the beginning a time interval, which is based on a rotation step of the Turning head 4l connects. It .appears appropriate ;, with this description in the work it s tati on D. It is assumed that the preceding Rotation step of the rotary head 4l. the liquid applicators I, II, III and IV respectively into the. Workstations A, B, C and D have reached. The figures

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j, 4 and 5 show a corresponding illustration in which the liquid applicators are in each case in these workstations. Fig. 3 I and II 5 di ^e Plüssigkeitsapplikatoren III and IV shows the liquid applicators in the work stations A and B as shown in FIG. Workstations C and D occupy. At the beginning of the intermediate interval, the carrier 44 is lowered, the opening at the lower end of the sleeve 51 of the liquid applicator IV reaching the protruding piece 61 of the polyamide tube. The upper end of this protruding piece is pressed upwards through the sleeve into the body 5o. This deforms elastically and thus grips the polyamide tube. The space between the polyamide tube and the body is sealed by a seal o2 (Fig. ~ J>). While the carrier 44 remains in its lowered position, nothing is changed on the liquid applicator IV in the work station D *. If, however, the carrier rises, the piece of polyamide tube remains clamped in the body 50 and is accordingly pulled out of the guide tube Öo. At the end of the time interval, the sleeve 51 of the liquid applicator IV is provided with the piece 61 of the polyamide tube. The rotary head 4l is then rotated 90 and brings the liquid applicator IV into the work station A. When the carrier 44 is lowered, around which on the. To initiate the subsequent time interval, the polyamide tube is brought down into the vial filled with the liquid sample material, so that the lower end of the polyamide tube is immersed in the liquid sample material. While the carrier 44 is in its lowered position, the valve controlling the compressed gas supply is opened, whereupon the pneumatic

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2 3

cylinder 4-7 of the applicator IV is actuated in such a way that the plunger protrudes from the microsyringe. As a result, a small volume, preferably 5 μΐ, of the sample material is drawn into the polyamide tube. The size of the volume of sample material that migrates into the polyamide tube is determined by the adjustable stop 54. This volume is chosen in such a way that it is not sufficient to completely fill the polyamide tube with sample material. The carrier 4.4 is then raised, causing the polyamide tube to migrate out of the vial with sample material. At the end of this second time interval, the polyamide tube thus contains a small amount of sample material. The rotary head 41 is then rotated to bring the liquid applicator IV into the work station D. When the carrier is lowered to initiate the time interval following the second turning step, the piece of polyamide tube in the sleeve 51 of the applicator IV is brought down in such a way that its lower end is only a very small distance from the upper surface of the .Bandes lies. While the carrier 44 maintains its lowered position, the valve, pressurized gas supply controlling is opened, whereupon the pneumatic cylinder 47 actuates the applicator IV to introduce around the piston in the micro-syringe. This allows the sample material to emerge from the lower end of the polyamide tube onto the tape. The distance between the lower end of the polyamide tube and the tape is critical. If this distance is chosen too large, the sample material will stick to the tube due to surface tension effects and cannot be applied to the reagent material. The distance must be chosen so small that a droplet of the sample material, which is at the lower end of the polyamide

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tube forms, comes into contact with the upper surface of the track and by surface tension effects is pulled off the lower end of the Polya.midroh.res. After inserting the plunger into the microsyringe and after expelling the sample material, the carrier becomes 44 is raised and takes the rotary head 41 upwards. The lower end of the polyamide tube is also lifted off the tape. At the end of this third time interval is that in the sleeve of the applicator IV Seated polyamide tube soiled with sample material. l. The rotary head 41 is then rotated through 90 ° and brings the applicator 4 into the work station C. If the carrier 44 is lowered at the beginning of the time interval following the third rotation step, the polyamide tube in the sleeve of the applicator IV passes down between the jaws of the gripper 6j5. While the carrier maintains its lowered position, the gripper is actuated, whereby the piece of polyamide pipe is gripped between the jaws. Does the Carrier 44 so-then at the end of the time interval, so the polyamide tube is held back by the gripper and pulled out of the sleeve in this way. At the end During this graceful time interval, the sleeve no longer carries a polyamide tube.

It should be noted that as the rotary head 41 rotates, each of the applicators sequentially applies a predetermined amount of sample material to the tape. Since the Applxkationsvorrichtung 9 lieyt spaced from the Aogabevorrichtung 3, seen in the running direction of the tape, so the latter performs the up -in • ^r: .nclcix * follow riden traces of Jtteagenzmaterials by the 3t- 'tion B. The operation of the application device

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is with the operation of Abgabevorrich-Tung synchronized 8, and the distance between the discharge device 8 and the applicator device 9 in such a way to the actual, movement speed of the belt 4 tuned to the successive amounts of sample material. are applied by the liquid applicators to the successive traces of the reagent material. Accordingly, successive accumulations consisting of sample material and reagent material are formed on the tape. Each accumulation preferably contains 5 μl of sample material and 5 μl of reagent material, with a length of 12 mm, a width of 4 mm and a height of 0.2 mm.

After the carrier 44 has been raised at the end of each time interval and before the carrier is lowered again at the beginning of the next time interval, the following sequences of movements take place: · _. (

a) At work station D, a fresh piece of 6l made of polyamide tube is pushed up through the guide tube oo pushed to from the sleeve 51 of that applicator to be recorded, which is in the next time interval in the workstation Ό;

b) If so, no further test with that sample material is to be performed from which the sample during the previous time interval-; was taken> then at work station A

'the-vials' with the sample material advanced to the next vial for a sample taken from it during the ¹ next ^; Time interval is to be taken, bring it into the correct position; ·

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c) Nothing happens at station B, apart from that the tape continues;

d) At work station C the gripper gives the one Polyamide tube free, which from the sleeve 51 during the previous time interval in the Workstation C located applicator has been pulled out, which soiled Polyamide pipe falls from the gripper into a waste container.

It should be noted that the application device 9 offers the possibility of a sequence of samples of different sample material automatically to be applied to a tape without the risk of the different samples being mutually exclusive infect. Such mutual contamination is avoided above all by the fact that the pieces Jl made of polyamide tube used only once and then thrown away.

The guide tube mentioned above in connection with the work station D of the application device forms part of a device for feeding the pieces of oil from polyamide tube. This device is not shown in FIG. 1, but can be seen from FIGS. 3 and 7. Here, a polyamide pipe J1 is fed from a reel, not shown, and it cuts this polyamide pipe into pieces 61 of shorter length. The device comprises a vertical tube 72, the inner diameter of which is slightly larger than the outer diameter of the polyamide tube ¹ Jl .

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The lower area of the tube 72 is surrounded by a heater 73 * and the upper area by a cooler 74. The heater and cooler are thermally insulated from one another via a disk 75. The heater 73 is operated electrically, while the cooler 74 has a coiled tube which is wound around the tube 72 and through which coolant flows. A pneumatic clamp J6 sits above the tube 72. The bracket 7o is mounted on a carriage which slides on a pair of vertical rods 77 and is connected to the piston of a double-acting pneumatic cylinder 78. The latter is used to guide the carriage along the rods 77 up and down. Above the 'bracket 76 there is a second pneumatic bracket 79. " which is arranged stationary relative to the rods 77. A knife guide 80 is located above it. Near the bracket 79 is a circular knife 81 ₅ which can rotate about a vertical axis and pass through a slot in the knife guide. Above the knife guide 80 lies the guide tube 00. This is vertically aligned and has an inside diameter that is slightly larger than the outside diameter of the polyamide tube. Jl is. . The knife 81 is connected to a shaft 84 which is rotated by a motor (not shown) in steps of 150 °. . In this way the knife also rotates in steps of 150 ° around the axis of the shaft 84. The actuation of the clamps Jo and 79j of the pneumatic cylinder 78 and the motor is synchronized. If the knife 8l takes its rest position immediately after having passed through a rotation step of 360 ⁰ about the axis of the shaft 84, the carriage for the clamp J6 is in its lower position, and the clamps 76 and 79 are closed, -to the polyamide tube Jl the following sequence of movements takes place:

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a) The clamp 79 is opened, releasing the polyamide tube 71, whereupon the pneumatic cylinder 78 is actuated to raise the carriage and the clamp 76 , whereby the polyamide tube is advanced through the clamp 79 and the knife guide 80;

b) The clamp 79 is closed and the clamp opened, whereupon the pneumatic cylinder 78 is actuated is to lower the carriage and bracket 76;

c) The clamp J6 is closed to grasp the polyamide tube 71 again;

d) The motor is actuated and rotates the shaft 84 through 360 ^° , whereby the knife also rotates around the axis of the shaft 84 and cuts off the piece of oil from the polyamide tube that protrudes over the slot in the knife guide 80. The knife is also rotatable about its own axis which is spaced parallel to the axis of the shaft. So when the knife cuts through the polyamide tube, the resistance of the polyamide tube to the knife movement causes the knife to rotate a few degrees around its own axis. This avoids uneven wear of the knife 81.

Then the same sequence of movements is repeated, so that this device is a succession of pipe pieces, the length of the stroke of the piston in the Pneumatic cylinder 78 corresponds to the polyamide tube

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cuts off and pushes the individual Rohrsfcücke upwards through the guide tube 60 after cutting. This is effected by _s that the polyamide tube is replenished from below. The pipe sections are pushed up so far that they protrude beyond the upper end of the guide tube 60.

The heater 73 and the cooler ¹ Jk are provided due to the fact that polyamide is a thermoplastic material. When the polyamide pipe is unwound from a reel, it is not ^% straight, but rather curved *, because it was stored on the reel: .. As soon as the polyamide pipe 7I enters the pipe 72, the heater 73 warms and thus softens. If the polyamide tube 7I then migrates from the heater 73 into the cooler 74j, it is cooled down and hardened again. It then retains the shape that was impressed on it by the tube 72 during cooling. The polyamide tube 71 is straightened in this way. .

The actuation of the device according to Figures ο and 7 is also synchronized with the operation of the application device. Every time the turret 4l is lowered, a new piece 61 protrudes of the polyamide tube out of the guide tube 60, the clamp 79 being closed.

The belt K _1, which carries the successive accumulations of reagent and sample material, is conveyed through the reaction station 2, at which a pneumatic

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matic mixing device Io is located. This is shown in FIG. 8. Possible modifications of the Mixing device Io emerge from FIGS. 9 and 9b. The mixing device Io comprises a tape guide 9o with a groove 91 that has a flat bottom and rectilinear Owns edges. Above the tape guide 9o, a distributor block 92 is arranged in such a way that it is extends completely over the top of the groove 91. A seal 93 lies on the distribution block 92, and ' A line plate is located above this. The components 92, 93 and 94 are held by screws 95 held together. A spring clip 90 is used to connect the tape guide 90 to the arrangement 92/93/94.

Manifold 92, gasket 93, and line B-plate 94 together form a chamber 97 * which is located above the groove 9I extends. The chamber 97 communicates with the space of the groove 9I through a plurality of outlet openings 98 in connection. From a supply cylinder IJ (Fig. 1) pressurized air can enter the chamber 97 through an inlet port 99 which is attached to the conduit plate 94 is provided. The compressed air leaves the chamber through the outlet ports 98, each against the bottom of the groove form directed rays. The outlet ports 98 are alternating as double outlets and individual outlets distributed over the length of the groove.

The mixing device Io serves to remove the accumulations Stir loo the sample material and reagent and run along the top surface of the tape are distributed. To keep the mixing device in operation

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the spring clip 96 is removed, whereupon the assembly 92/9 ^ / 94 is removed from the tape guide 90 lifts off, thus exposing the groove 9I. A threading section of the tape is inserted into the groove, and the arrangement 92/93/94 is then clamped back into place their location firmly. The threading section of the tape is inserted between the rollers 7, which serve to pull the tape through the groove in the direction of the arrow. The inlet connection is then connected to the supply cylinder 13 for compressed air. While the tape travels through the mixing device along the path passing through the groove in the Band guide is formed, one leads air., Into the chamber a. The air exits through the outlet openings 98, which create air jets that are directed onto the upper, sample-bearing surface of the belt. As soon as an accumulation of sample material and reagent wanders under one of the individual outlets, this accumulation tends to spread out and out of the Center of the band.:. Get the gathering following a double outlet, it is driven back again towards the center line of the belt. These relationships emerge from FIG. 8a. So if the tape is pulled through the mixing device, this leads to a stirring up of the sample material and the mixture consisting of the reagent. The extent of the stir is determined by the total number of Intended for single outlets and double outlets; during the time interval of the mixing operations from the length measure between the single outlets and the double outlets depends along the groove.

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The stirring process as it is done by the mixing device according to Pig. 8 is brought about, serves the chemical Promote reaction between the sample material and the reagent. In this reaction arise as above mentioned the agglutinates, to prevent excessive dehydration To prevent the additives and / or the reaction product, the air is humidified by adding them from the supply cylinder 1 ^ through a water bath 11 (Fig. l) leads and mixes with dry air from a second cylinder 14. The temperature of the air is also controlled, the temperature of the water bath 11 is kept at approximately 30.degree. A thermostatic is used for this controlled immersion heater 12. In certain circumstances it may be desirable to use the reaction product to dry. In this room there will be temperature and humidity of the air adjusted accordingly.

In the device according to Fig. 8, Perspex was used to manufacture components 9o, 92 and 94, while the seal 93 was made of butyl rubber. the Apparatus provided a satisfactory stirring effect when the inlet port 99 was connected Compressed air of approximately 0.35 atmospheres (5 p.s.i.).

It has been found that it can be used to produce a homogeneous mixture of reagent and sample material is more advantageous instead of the alternating single outlets and double outlets as they are related are described with Fig. 8 and 8a to use a modified embodiment, as shown schematically from Pig. 9a results.

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In this modified embodiment there are two Individual outlets in the form of needle nozzles lol at a distance

arranged to each other along the groove, without w ■

Intermediate switching of a double outlet. The needle nozzles lol have a cylindrical cross section and their central axis is inclined by 45 ° to the vertical, but in one and the same vertical plane. The inclined needle nozzles are directed forward, ie in the direction of movement of the belt. The air jets emerging from the needle nozzles cause a whirling movement in the liquid of the accumulations, which results in a very intensive mixture of the reaction components. The depth of the groove is chosen so that the free. The distance between the needle nozzles and the surface of a cluster 0.2 mm deep is less than five times the inner diameter of the needle nozzles. It has been found that with accumulations of lö μΐ, which contain blood serum and a water-based reagent, and. at a belt speed of. Io mm / s-ec. A very good mixing effect could be achieved if each needle nozzle was exposed to air at approximately 0.6 l / min. The effectiveness of the jet effect is reduced if the free distance between the needle nozzles and the accumulations is increased to more than five times the needle diameter, or if the inclination of the needle nozzles to the vertical is chosen to be less than 45 °.

Attempts that involve agglutination reactions are best done by using a mixture of blood serum and a reagent shakes for a while. This shaking effect

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can be produced by letting the tape pass under a series of double outlets as shown in FIG. 9b. In this head the double outlets are each made up of passages with cylindrical. Cross-section formed. The central axis of each passage is inclined at 30 to the vertical, together with the central axis of the other passage belonging to the same double outlet in a common vertical plane which extends perpendicular to the direction of movement of the belt. The two jets emerging from the double outlet converge to form an air curtain above the belt. This air curtain allows the liquid to migrate to the rear of the accumulation and then, when the accumulation finally passes the air curtain, flow again to the front. The double outlets are distributed along the groove at a distance that is slightly greater than the length of the clusters. In this way, the flow process of the back and forth flow is stabilized. If, for example, the accumulations are 12 mm long, the double outlets are arranged at a distance of 15 mm along the groove. The outlets are approximately 4 mm above the belt, and if Io pl accumulates, an air supply of approximately 0.6 l / min is required for each double outlet.

If you want the modified embodiment according to Use FIG. 9 for reactions that require long mixing times and require a high number of shaking operations, so this leads to an undesirably long length of the shaking stage. Under these circumstances it has Proven to be more beneficial, a number of stirring nozzles

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to be used according to FIG. 9a, the staggering of these nozzles (ie the distance between successive nozzles) being smaller than the length of the accumulations on the strip. For example, in the case of accumulations of Io jil and a length of 12 mm, this distance between the nozzles is 8 mm. This leads to the build-up of a stabilized vortex flow in the accumulations, as shown in FIG. 9c. In Fig. 9 ^C ,, the locations at which meet the air jets on the raising loo and the tape are in., Shown as circles Io2. In the event of accumulations of Io ul, each nozzle should be exposed to air at 0, ^ / min. sufficient. To increase the mixing effect, you can also reduce the belt speed.

The emerging from the reaction station 2 accumulations are approximately 15 mm long and 4 mm wide _s o, 2 mm deep. They contain agglutinates depending on the concentration of Bruceila antibodies in the respective amount of the sample material. The successive accumulations are fed into the test station j5- on the belt, in which each accumulation is automatically checked. In order to make this possible, the device at the test station comprises a lamp 15 for generating an intense light beam which is directed upwards through the belt into a projection microscope with an objective 16.

The microscope has a partly reflective and partly transparent mirror. This mirror reflects the light from the lens 16 to a pinhole 117 (Fig. Lo), on which the lens 16 an image of his

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Field of vision can arise. Furthermore, the mirror transmits light from the lens to a projection screen 118 to create an image. This can be viewed by an operator in order to to check the focus of the microscope. The aperture plate II7 has an opening II9, namely at a point that coincides with the center line of the belt. So when the tape through the field of vision of the objective wanders through, the opening 119 pulls a single scan line through the center of each cluster.

A photo amplifier 12o (photocell) is arranged in such a way that it receives the falling through the opening II9 Collects light. It supplies an electrical output signal, the strength of which changes, depending on the situation on the light permeability of the moving through the central area of the lens field of view Band. If an agglutinate is scanned, there is a reduction in the output voltage of the photo amplifier. The photo amplifier is 12o connected to a circuit 121 which provides an output signal whose voltage is inverse to Light transmission in the middle area of the lens field of view changes. The appearance of an agglutinate in the middle area of the objective »light field results i.e. a pulse in the output signal of circuit 121, the height of which depends on the density of the agglutinate, while its duration is determined by the size of the agglutinate. The optical resolution of the Microscope is set to 7 pn to micro-agglutinate to include cells, however. The circuit 121 has a corresponding one

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High frequency limit of approximately 7oo Hz, which determines is due to the optical resolution of 7 pm and the belt speed of Io mm / sec *

The output of circuit 121 is converted into a Gate circuit 122 passed, whose periodic counting signal has a duration of 0.6 seconds. owns. The periodic Counting signal is obtained from the output of the circuit using a delay circuit 125 won. The delay line supplies theirs Output ο, 2 seconds after scanning the front edge any accumulation provided the decrease in the Light transmission at the leading edge exceeds a threshold value set by the delay circuit is fixed. A monostable multivibrator is also used to generate the periodic counting signal 124, which switches to its quasi-stable state when the delay circuit I23 supplies an output. 0.6 s.ec. later it returns to its stable state. The signal from the gate circuit 122 is passed to a counter I25 which has an alarm circuit 126 excited as soon as the number of pulses generated during the quasi-stable state of the multivibrator occur, exceed a predetermined value. This value is set in the counter. Exciting the Alarm circuit is a sign that the cow, from which the sample material is in the just checked collection with Bruceila bacteria is infected. (Assuming the quantity values given above, the value set in counter 125 is at 17). The alarm circuit 126 sounds a buzzer. Furthermore, the counter value is

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The display device 128 is visible and printed out by a printer 129.

The device described is used in connection with a conveyor system (not shown). The latter leads the vials or test tubes from the dispensing and application station 1 next to the collections on the tape containing the associated sample materials to test station 3 · There are labels read on the test tubes by a scanning head, not shown. The labels bear information regarding the source of the sample materials in the respective test tubes. This information is provided by means of read from the labels of the readhead. If the number of pulses generated during the quasi stable State of the monostable multivibrator occur, exceed the predetermined value, the Details of the labels visible on the numerical display device 128 and printed by the printer 129. This takes place simultaneously with the display and printing of the counter value.

The used tape that leaves the test station 3 is wound onto the take-up reel 6 and then thrown away. Due to the fact that the tape is contaminated with potentially dangerous bacteria it is physically cleaned before it is thrown away.

For a reliable function of the device described, it is important that the accumulations on

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the tape have a uniform shape within certain tolerances. Therefore are testing options provided to generate an alarm signal and have the printer 129 print out a "false report". The following test options are available, among others. see: that a collection is not too short (^ Io mm); that a collection is not too long (^ 17 mm) j that an accumulation is not too deep (_ \, Q, 3 mm); and that a cluster is not too shallow («C0, o5 mm) .. The figures are approximate.

After passing the scanning head, each test tube automatically directed in one of two ways, depending on whether it is on the one hand found that the test tube did not infect test material from a Brucella bacteria Contains a cow or that, on the other hand, a "negative report" with respect to the accumulation that contained test material from this test tube, or that it has been found that the test material originating from this test tube is from one with Brucella bacteria infected cow originated.

The tape 4 is made of polyethylene terephthalate with hydrophobic properties, i.e. that it is made of aqueous solutions are difficult to wet. For correct operation of the microscope and the electronic equipment in the test station it is essential that- the accumulations on the tape occupy a substantially rectangular area of the tape surface and that their width and Length measurements are within very tight tolerances.

309848/1087

It is also important that the clusters retain their original shape on the tape. However, since the accumulations are aqueous in nature, the hydrophobic properties of the tape are an obstacle in achieving these requirements. Accordingly, the upper surface of the belt is with provided a coating, as in the following Examples 1 and 2 in connection with the figures 11 and 12 will be explained.

According to FIG. 11, the belt 4 consists of polyethylene terephthalate with a surface coating 40 'made of wettable material. The surface coating Ho extends over the entire length of the tape, but only covers its central portion, so that the hydrophobic material is exposed on both sides of the surface coating. The surface properties of the coating Ho are chosen so that when a substantially rectangular accumulation loo of aqueous material is applied to the central region of the tape, the coating will accept that accumulation and also prevent the accumulation from expanding in length or width, even then when the aqueous solution is stirred, for example, by air jetting. Should the accumulation shift across the belt, the exposed hydrophobic material prevents the aqueous solution from leaking over the edges of the coating.

According to FIG. 12, too, the band H has a surface coating 40 made of wettable material. This upper

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3M ■■■ .-. -.

Surface coating covers rectangular areas of the tape that are spaced from one another over the length of the tape and are each surrounded by exposed hydrophobic material »In the case of the embodiment according to Pig. 12, the surface coating has a higher wettability than in the embodiment according to FIG. 11. This surface coating can actually be called hydrophilic, ie it has a strong affinity for water. If an aqueous material is applied to the rectangular areas, it flows over the surface coating 4o to its limits and forms rectangular accumulations. The exposed hydrophobic 'material ensures ⁷ that the aqueous solution does not also occur over the edges of Oberflachenbeschiehtung. The rectangular clusters retain the shape of the coated areas of the tape, even when jets of air pass through them.

example 1

A solution of one part of polyethylene glycol (molecular weight looo) to nine parts of cellulose nitrate, dissolved in alcohol ether with 25 volumes of diethyl ether and 75 volumes of industrially denatured alcohols (preferably the solution comprises one part solute to nine parts solvent) was "on the Tape applied to form a strip of the solution in the center of the web. The solvent was then left evaporate, whereupon the polyethylene glycol and cellulose nitrate remained on the belt. the

3 0 9 8 4 8/1087

The resulting coating of polyethylene glycol and cellulose nitrate gave surface properties of such quality that when a substantially rectangular collection of aqueous. Material was applied to the layer, it accepted the build-up and still prevented it from settling the congregation shortened or narrowed. This even if the aqueous solution with air jets was stirred.

Example 2

A solution of 2 $ polyvinylpyrrolidone dissolved in ' 98 $ of industrially denatured alcohols was added to the ' Tape is applied to form several rectangular areas of solution that run the length of the tape were arranged and separated from exposed tape areas. The solvent was allowed to evaporate, whereupon the polyvinylpyrrolidone remained on the tape. The coating of polyvinylpyrrolidone proved proved to be hydrophilic, so that when an amount of aqueous material is applied to one of the coating areas this material flowed to the edges of the coating and formed a rectangular cluster. The exposed tape material, which was hydrophobic, prevented the aqueous solution from getting over the edges the coating to flow out.

The invention is not limited to examining serum samples for Brucella antibodies by one serum samples for traces of Rose Bengal Bruceila

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Applying antigen. So the Rose Bengal Brucella do not need antigens in separate areas but can extend across the tape as a continuous path, provided the individual Samples at a sufficient distance along the length of the tape to ensure that no substantial mixing of the samples is possible is. In addition, it can "in the case of certain reactions be possible on the upper surface of the belt, to apply a coating made with a reagent is impregnated.

The sample material does not have to be in the form of a clear liquid. It can also look like a Act emulsion or suspension. In addition, there is the possibility that the samples are powdery if the reagent is liquid. It is It is essential that a liquid is present to allow the required reaction to take place.

Instead of an automatic test there is also a Testing by suitably trained personnel is possible. Nor is it essential that it is a microscopic examination. Other methods can be used, such as ultraviolet fluorescence methods or isotope scanning.

It may be desirable to perform several different tests on each serum sample. In one In such a case, several dispensing devices 8 are arranged in the form of batteries, with their tube heads

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. £ 316111

seen in the direction of movement of the belt 4, at a distance lie to each other. The reservoirs 27 of the various dispensing devices can be different in each case Reagent contained so that a succession of tracks is deposited on the tape with each lane containing only a single reagent. The battery can be so operate that the individual devices work exactly in sequence, with each device is used only once during an operating cycle of the battery. To this In this way it is possible to run a series of different tests on each sample by using place the applicator 9 samples of the same material on each during one actuation cycle can hang up the resulting trace before the vial at the receiving station through a vial with different Sample content is replaced. In relation to this, the dispensing devices can also be used without a precise working cycle operated to enable various selected tests with various selected samples. In the latter pail, the sequence of operations of the determine different dispensing devices via a program, which is on a magnetic tape or a punched Tape is stored.

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Claims (1)

Claims (Iy method for treating samples ,,, wherein the respective types of the samples at an application station , are successively applied to an upper surface of an elongated support element in order to form separate sample sections on this, characterized in that on the A reagent is applied to the surface and the support element is guided in the longitudinal direction from the application station to a test station at which the results of the contact between the samples and the reagent are successively determined. 2. The method according to claim I ₃ characterized geke η η ■ draws t that the support element is brought on its way from the application station to the test station in the longitudinal direction through a reaction station in which a liquid mixture of reagent and sample is stirred on the upper surface, by generating jets of gas which emerge from an outlet of a feed line and impinge on the liquid mixture, a relative movement being generated between the support element and the outlet of the feed line. . 5. Method according to claim 1 or 2, characterized in that g e that the reagent on the 309848/1087 upper surface in the form of a succession of separate spaced apart over the length of the support element Traces of reagent is applied and that each type of sample is placed on the traces to form a series of separate collections of reagent and samples. 4. The method according to any one of claims 1 to j5 below Use of liquid samples, characterized in that any type of sample liquid is used to the upper surface by connecting one end of a tube to the tip of a syringe by the other end of the tube is immersed in the sample liquid at a receiving station by using the syringe to draw sample liquid into the tube, but not into the syringe itself, by using the Place the other end of the tube directly above the top surface by actuating the syringe to dispense the sample liquid ejecting from the tube and by removing the tube from the nozzle of the syringe. 5. The method according to any one of claims 1 to 4, characterized in that the upper Surface of the support element has a predetermined wettability, so that the sample liquid and / or the Reagent after applying and covering an area of the upper surface which is determined by a certain Border is prevented by surface tension effects from flowing or flowing over the border. to withdraw from the border. - 39 - 309848/1087 6. The method according to any one of claims 1 to 4, characterized in that the upper surface comprises a succession of hydrophilic regions spaced along its length, of which each bounded by a predetermined border and surrounded by hydrophobic areas of the upper surface, so that an aqueous sample and / or reagent after application to the upper surface within a of the selected borders flows up to the border and is prevented from doing so by surface tension effects will flow past the border or withdraw from the selected border. 7. Treatment device with a device to form a path for a longitudinal movement of an elongated support element, with a drive for conveying the support element in the longitudinal direction and in a predetermined direction of movement along the track and with an application device for applying individual types of samples successively to the upper surface of the support element to separate sample areas there form, marked "ic h η e t by a reagent on the upper surface and by a test station forming device (j5), seen in fig predetermined direction of movement, at a distance from the application device (9) and on which the results the contact between the samples and the reagent can be detected in succession. 8. Apparatus according to claim 7, characterized in that a dispensing device (8) 1st provided in order to apply liquid reagent to the to apply upper surface and a sequence of separate - 4o 309848/1087 To form traces of the reagent, the traces being distributed over the length of the support element that the Application device (9) according to their arrangement serves to place the samples in each case on the tracks in order to avoid successive accumulations of reagent and samples to form that the dispensing device (8) has a valve (24) with an inlet for receiving the receptor liquid comprises, wherein the valve is connected to a syringe (21) and to a device (29) which forms an outlet for the reagent liquid, which is dispensed during operation of the device, that one Device (j53) for actuating the valve between a first and a second position is provided, wherein the valve in the first position the syringe with the Inlet connects and in the second position connects the outlet to the syringe, and that finally a device (25) is provided for actuating the syringe to dispense reagent liquid from the inlet into the syringe suck in when the valve assumes its first position, and in cfer second position of the valve reagent liquid from the syringe to thereby dispense reagent liquid from the outlet. 9. Apparatus according to claim 7 or 8, characterized characterized in that the application device (9) has four liquid applicators (I, II, III, IV), which is attached to a rotary head (4l) rotatably attached to the device about a predetermined axis. are arranged that each liquid applicator comprises a syringe which can be actuated in two directions, drawing in liquid in the first direction and in the second direction liquid through its nozzle - 41 - 309848/1087 ejects that each flow _O keitsapplikator further ei.nen holder (51) which (9 ij) of the syringe is connected to the nozzle and for receiving one end of a liquid intake tube (61) and · for holding the tube such that its interior 'is in connection with the nozzle and its other end fortragt from the holder, serves that the holder from the predetermined axis are in each case by equal distances and, based on the axis, are arranged at angular distances from one another, which are an integral multiple of 560 / n degrees, that the application device (9) has a drive for rotating the rotary head in a predetermined direction around the axis in steps of j560 / n degrees in order to bring each holder one after the other in η angular positions, that actuating devices (47) are provided to drive the syringe in one direction when the associated holder assumes the m-th of the η angular positions, where m is an integer value greater than 1 i st, but at least η minus 2, and to drive the syringe in the second direction when the associated holder is in the p-th of the η angular positions, where ρ is an integer value greater than m but less than η in that there is further provided means (60) for inserting a liquid pick-up tube into a holder in the first of η angular positions, and in that means are present for removing a liquid pick-up tube from a holder, wherein. the device is designed in such a way that, during operation, each holder successively moves into the first, m-th / p-th and q-th angular positions, in this order, with a liquid pick-up tube being placed in the holder in the first angular position, - 42 3 09 848/108 7 in the r-th angular position a sample liquid into the liquid receiving tube, but not into the Syringe is sucked in by actuating the actuator in one direction, wherein furthermore, in the pth angular position, the sample is picked up from the liquid pick-up tube onto the upper surface. is brought about by driving the actuator in the second direction, and eventually in the q-th angular position the liquid up. receiving tube is removed from the holder. 10. Apparatus according to claim 9 *, characterized in that m, η, ρ and q correspond to the numbers 2, k, j5 and 4, respectively. 11. Device according to one de.r claims 8 to 11, characterized by a device along the path between the application device and the test station for stirring the liquid mixture of reagent and sample on the upper surface with an arrangement for forming pneumatic jets, the at least one outlet * ^e & §fcher impinges for directing a jet of gas onto the upper FLAE $ ßS in operation on the fluid mixture, thereby exerting a stirring action to the liquid mixture, while the support member along the path under the or each outlet of the Strahlen__bildenden means moving along. Stop - 43 -, 309848/1087