EP0086813B1 - Device for washing and rinsing titration plates or similar - Google Patents

Abstract

The device for washing or rinsing titration plates (1) comprises a washing plate (5) provided with nozzles (11) in equal number to that of cavities (2) of the titration plate (1). During the washing operation, the titration plate (1) is sealingly held against the washing plate (5) so as to prevent the soiling of adjacent cavities. Discharge channels (13) are provided in the washing plate (5).

Description

The invention relates to a washing or rinsing device for titer plates or the like. With a plurality of cavities for receiving a medium to be examined or determined, for example antigens, with feed devices with nozzles for introducing a rinsing liquid into each of the cavities and with Suction and / or blow-out devices in order to empty liquid from the cavities and with guide devices that move the titer plate to the washing station and hold it there precisely. Such a device belongs to the prior art.

In medical laboratory technology, for example, the Elisa method (enzyme linked immunosorbent assay) or the various methods of this system are used to measure antigens and / or antibodies. For example, for the measurement of antigens, antibodies are absorbed on the titer plate in a first process step, the titer plate is then washed, then in a further process step the addition of a residual solution containing the antigen is carried out, followed by washing again, followed by enzyme-labeled specific antibodies the titer plate is given, then the titer plate is washed again, after which the enzyme substrate is added.

The actual measurement is carried out in a photometer.

From the example described above it can be seen that washing the titer plates is an essential part of the process, which on the one hand is relatively time-consuming and on the other hand also has the disadvantage that very often with highly toxic, i.e. the greatest amount of disease-causing, living matter has to be dealt with, which makes the manual handling of the titer plate undesirable.

• Die derzeit im Gebrauch befindlichen Titerplatten weisen 96 Kavitäten auf, von denen jede praktisch einer Küvette entspricht. Während des Verfahrens bzw. während der Feststellung bzw. Bestimmung der Antigene oder der Antikörper befinden sich Proben in jeder Kavität (beispielsweise Proben von verschiedenen Patienten). Es muss nun absolut verhindert werden, dass während der Handhabung der Platte, und dies ist insbesondere beim Waschen schwierig zu verhindern, Teile der Proben von einer Kavität in die andere gelangen.

However, the main problem that arises when washing the titer plates is the following:

• The titer plates currently in use have 96 cavities, each of which practically corresponds to a cuvette. During the procedure or during the determination or determination of the antigens or the antibodies, there are samples in each cavity (for example samples from different patients). It must now be absolutely prevented that parts of the samples move from one cavity to the other during the handling of the plate, and this is particularly difficult to prevent during washing.

FR-A-2358206 shows a method and a machine for washing micro test plates, in which a suction head and a washing distributor are provided, under which each row of wells of the titer plates is placed one after the other. A slide is also provided, which transports the titer plate.

FR-A-2277630 describes a device for aspirating a serum liquid on a microtiter plate and for subsequently washing the microtiter plate. Combined suction and discharge nozzles are provided, which have an inner nozzle passage that serves to suck in the serum liquid and an outer nozzle opening that opens into an annular gap at the titer plate through which the washing liquid flows. No precautions have been taken to seal the cavities of the titer plate with respect to one another during the washing process.

An apparatus and method for automatically analyzing blood or other fluid samples is described in US-A-3533744.

The object of the invention is therefore to provide a washing or rinsing device of the type mentioned at the outset with which the titer plates are washed in a functionally reliable manner and in which sample parts are prevented from getting from one cavity to the other or any contamination of the samples is avoided at all becomes.

This is achieved according to the invention by a wash plate provided with nozzles, to which the titer plate to be rinsed can be brought sealingly by means of a guide device and to which the titer plate is held with pressure during the washing or rinsing process, each cavity of the titer plate having a nozzle and a nozzle surrounding annular gap, which connects the cavity with a drainage channel, are assigned and each individual cavity is sealed off from the other cavities.

It should be mentioned again here that the method described at the outset is only intended to describe an example of the area of application of the machine. Similar procedures or similar determinations are also used in agriculture and in biology and biochemistry. Furthermore, the term “titer plate” should not be interpreted restrictively. The essential thing is that a plurality of cavities located next to one another are to be washed simultaneously. This could well be a series, or individual cuvettes could also be attached to a support frame and thus fed to the washing or washing machine.

In the basic version, tap water is used as washing or rinsing liquid for the automatic washing machine according to the invention. Compressed air is used as the drying medium.

However, it can be provided in the machine according to the invention that other rinsing liquids, for example distilled water or a buffer solution, are used. Another gaseous medium, for example oxygen, can also be used instead of compressed air.

It is preferably provided that the gaseous medium is passed through the nozzles in a pulsating manner, which significantly improves the cleaning or drying effect.

An embodiment of the invention provides that the washing plate is located in a sealed washing chamber. A sensor can be arranged in the washing chamber, which seals the seal between the washing plate and the checking the titer plates and, if a leak is detected, triggers a pre-programmed self-cleaning process for the wash plate so that the subsequent titer plates are not contaminated.

Such self-cleaning can, however, also be carried out profile-specifically after running through a predetermined number of titer plates to be cleaned. This can be done through the wash plate on the opposite side of the nozzle. However, a device for lifting the washing plate from the titer plate (or vice versa) can also be provided, wherein after the liquid has passed through the nozzles in the washing plate, there is a further liquid passage through the nozzles when the washing plate is lifted off. The fact that the washing plate and the titer plate are at a small distance from one another means that the surfaces of the washing plate and the titer plate are cleaned with the appropriate pressure of the washing medium.

The washing or rinsing machine according to the invention advantageously has guide devices which keep the titer plates free of soil, i.e. the titer plate is guided along its sides or along its lower side edges so that there is no contamination on the underside of the plate. This is important for the subsequent measurement of the samples.

Another exemplary embodiment of the invention provides a tilting device for the titer plate, preferably in the washing area. The titer plate can be tilted together with the washing plate. The advantage of this version is that the rinsing liquid can run down and under certain circumstances no drying process using compressed air is necessary.

The invention is described in detail below with reference to the figures in the accompanying drawings, but the invention is not intended to be restricted to the exemplary embodiments shown, since various design variants are conceivable and possible without thereby departing from the inventive concept.

1 schematically shows a diagram of a titer plate to be cleaned, FIG. 2 also schematically shows the washing or rinsing machine according to the invention, FIG. 3 shows a plan view of the washing plate according to the invention, FIG. 3a shows a section along the line II of FIG. 3 with a titer plate attached, FIGS. 4 to 6 show sections through the wash plate with different nozzle shapes, FIG. 7 shows schematically a section through a wash plate, FIG. 8 shows a cross section through a further exemplary embodiment of a wash plate the line II of Fig. 3, and the Fig. shows a same section in a further embodiment of a washing plate with articulated titer plate.

1 shows a titer plate 1 with cavities 2. In the case of the titer plates 1 which are in use today, there are generally eight rows, each with twelve cavities 2, which gives a total of ninety-six.

In the exemplary embodiment, the washing or rinsing machine according to the invention has a stacking device 3, a washing point 6 and a stacking device 4.

The titer plates 1 to be washed or rinsed are placed, for example, in a stack of ten in the stacking device 3, individually by a conveyor device which has toothed belts 7, brought in the direction of arrow V to the washing point below the washing plate 5 and come after this Rinsing in the stacking device 4.

Below the washing plate 5, the titer plates 1 come to rest on a support plate 8, which has a centering device 9, for example centering bolts, for the exact positioning of the titer plate 1.

If the titer plate 1 is in its desired position, the support plate 8 is raised by means of the lifting device 10, which is, for example, a pneumatic cylinder, and the titer plate 1 is pressed onto the washing plate 5.

As can be seen in particular from FIGS. 3 and 3a, the washing plate 5 has a plurality of nozzles 11, the number and position of which corresponds exactly to the number and position of the cavities 2 in the titer plate 1. In the exemplary embodiment, the washing plate 5 has ninety-six nozzles 11. When the titer plate 1 is pressed onto the washing plate 5, a nozzle 11 is assigned to each cavity 2, as can be seen from FIG. 3a.

Around the nozzles 11 there are annular gaps 12 which allow the flushing medium to flow through or the drying or compressed air to pass into the drainage channels 13. The drain channels 13 open into the outlet A of the washing plate 5.

If the titer plate 1 is now raised and pressed onto the washing plate 5, rinsing medium, for example water, is pressed into the washing plate 5 through one or more inlets E in a first operation and passes through the nozzles 11 under pressure of up to 4 bar into the cavities 2 of the titer plate 1. Vortex formation occurs and the flushing medium in each case passes through the annular gap 12 into the drain channel 13.

In order to improve this emptying or to achieve a certain suction effect, the nozzle heads 11 'of the nozzles 11 are designed such that they have a decreasing cross section from front to back.

Various exemplary embodiments of the nozzle heads 11 'are shown in FIGS.

After flushing has been completed, the liquid medium supply is switched off and compressed air is pressed into the cavities 2 through the same inlets E and through the same nozzles 11.

The humidity and the temperature of the compressed air can be adjusted or regulated. The rest of the flushing liquid is pressed through the annular gaps 12 into the drainage channels 13 by the compressed air and fed to the outlet A.

Now the titer plate can be lowered again by means of the support plate 8 and by means of the Toothed belt 7 of the stacking device 4 are supplied.

However, it is also possible that the titer plate 1 is only slightly lowered from the washing plate 5, so that only a small gap is formed between the top surface 1 'of the titer plate 1 and the sealing plate 14 of the washing plate 5. If rinsing medium is pressed again through the nozzles 11, the sealing plate 14 of the titer plate 1 is also cleaned and the top surface of the washing plate 5 is cleaned. Such a rinsing is expediently carried out before the drying cycle, i.e. before supplying compressed air as described above.

The titer plate 1 can now be pressed onto the washing plate 5 again by means of the support plate 8, whereupon the compressed air is now supplied and the titer plate 1 is dried. In the exemplary embodiment, a sealing plate 14 made of plastic material is provided on the washing plate 5.

In the embodiment of the washing plate 5 according to FIG. 9, the washing plate 5 is divided into a fixed upper part 5a, which carries the nozzles 11, and a movable lower part 5b. The upper part 5a also contains the antechamber 16 or the feed lines 15. The movable lower part 5b has bores which are concentric with the nozzles 11 and which form the annular gap 12 with the nozzles 11. When the lower part is applied to the upper part, the nozzles 11, as shown in the figure of the drawing, protrude through the bores of the lower part 5b. In the lower part 5b there are also the drain channels 13, the sealing plate 14 between the titer plate 1 and the washing plate 5, and between the two parts 5a and 5b there is a further sealing plate 14 '.

The nozzles 11 are elongated compared to the previously described exemplary embodiments, and at the start of the washing process or immediately before, the lower part 5b is lowered to the lower end of the nozzles 11. When pressing up, the titer plate 1 initially seals with the lower part 5b of the washing plate 5. Then the lower part 5b is brought together with the titer plate 1 to the upper part 5a. The nozzles 11 penetrate into the cavities 2 of the titer plate 1 and partially displace the liquid to be emptied in the direction of the drainage channels 13 until the lower part 5b lies closely against the upper part 5a. The system is now closed and the rinsing process can begin.

• Die konzentrischen Bohrungen für jeden Ringspalt 12 sind volumenmässig so ausgelegt, dass die durch das Eintauchen der Düse 11 verdrängte Flüssigkeit in den konzentrischen Bohrungen (Ringspalt 12) aufgenommen wird und dadurch Kontamination vermieden wird. Durch die vorzugsweise zylindrisch ausgelegte Düse 11 und deren Eintauchen in die Kavität 2 wird das zu spülende bzw. zu trocknende Volumen der Kavität 2 verringert. Die Düsen 11 tauchen vorzugsweise zu zwei Dritteln in die Kavitäten 2 ein. Die dadurch entstehende höhere Strömungsgeschwindigkeit erhöht die Reinigungs- bzw. Trocknungseffizienz.

The advantages of this embodiment are as follows:

• The volume of the concentric bores for each annular gap 12 is such that the liquid displaced by the immersion of the nozzle 11 is absorbed in the concentric bores (annular gap 12) and contamination is thereby avoided. Due to the preferably cylindrical nozzle 11 and its immersion in the cavity 2, the volume of the cavity 2 to be rinsed or dried is reduced. Two thirds of the nozzles 11 preferably dip into the cavities 2. The resulting higher flow rate increases the cleaning and drying efficiency.

In order to achieve a uniform pressure at the nozzles, in particular in the case of the flushing medium, the washing plate 5 can either be provided with H-shaped feed channels 15, as shown in FIG. 7, the inlet E being arranged in the middle of the connecting web, or 8, the washing plate 5 can have one or more antechambers 16 with an inclined wall 16 ', so that the chamber cross section, seen from the inlet E for the flushing medium, decreases from row of nozzles to row of nozzles.

In the washing and rinsing machine according to the invention, the air, water and power connections are advantageously located on the rear of the device, and built-in pressure reducing valves and pressure gauges for pressure control for the rinsing medium and compressed air are also provided. The toothed belt 7 is advantageously driven by a DC motor. The washing plate 5 is advantageously exchangeable by means of a quick-release fastener. The device is controlled by a microprocessor. The times for washing, dwell and drying processes can be freely selected, as can the sequence and the repetition cycles.

Control systems are provided for checking for empty stackers, checking for available space in the stackers, checking for correct pressure conditions in the device and checking for leaks in the system. The messages are given by acoustic signals and / or a corresponding LED display.

One titer plate after another is washed automatically. After the start command, the entered rinsing and drying program is repeated until either there is no more titer plate 1 in the stacking device 3 or the program is ended by a stop button.

Claims (19)

1. Washing and rinsing device for titration plates (1) or the like having a multitude of cavities (2) to receive a medium to be examined or to be determined, for example antigens, comprising feeding means with nozzles (11) feeding a rinsing liquid into each cavity (2), suction and/or blow-out means to discharge liquid from the cavities (2), and comprising guide means for moving the titration plate (1) to the washing location (6) and retaining it in a precise position thereat, characterized by a washing plate (5) provided with nozzles (11) to which the titration plate (1) to be rinsed is, by means of guide means, movable into sealing contact and at which the titration plate (1) is held through pressure during the washing and rinsing operation, a nozzle (11) and an annular gap (12) surrounding the nozzle (11) and connecting the cavity (2). with a discharge channel (13) being associated with each cavity (2) of the titration plate (1), and each individual cavity (2) being sealed with respect to the other cavities (2).

2. Washing and rinsing device according to claim 1, characterized in that the rinsing liquid is passed through the nozzles (11) at an overpressure of up to about 4 bars.

3. Washing and rinsing device according to claim 1, characterized in that the nozzles (11) are not only connectable to feeding means for the rinsing liquid but also to a pressure line for a gaseous medium, for example compressed air, and that control means are provided for controlling the supply of rinsing liquid and compressed air through the nozzles (11).

4. Washing and rinsing device according to claim 1, characterized in that the gaseous medium is passed through the nozzles with pulsating movements.

5. Washing and rinsing device according to at least one of claims 1 to 3, characterized in that the discharge channels (13) are formed in the washing plate (5), for example milled or moulded therein.

6. Washing and rinsing device according to claim 1, characterized by one or several precham- bers (16) in the washing plate (5) to which the nozzles (11) are connected and which have feed openings E for the rinsing liquid and at least one inclined wall (16') so that the crosssection of the chamber decreases from one row of nozzles to the next row of nozzles and the pressure of the rinsing liquid is equal at each nozzle (11).

7. Washing and rinsing device according to claim 1, characterized in that the guide means hold the titration plate (1) with clearance at the base.

8. Washing and rinsing device according to claim 1, characterized by a preferably exchangeable sealing plate (14) at the side of the washing plate (5) provided with nozzles.

9. Washing and rinsing device according to at least one of claims 1 to 7, characterized by unstacking means (3) positioned before the washing location (6) in the feed direction of the titration plate (1) and by stacking means (4) positioned after the washing location (6), the guide means comprising conveying means for the transport of one titration plate (1), each, from the unstacking means (3) to the washing plate (5) and from the washing plate (5) to the stacking means (4).

10. Washing and rinsing device according to claims 1 and/or 7 or 9, characterized in that the guide means are formed by conveying means for the horizontal feed, for example toothed belts (7), and lifting means (10) with a support plate (8) by means of which the titration plate (1) is brought into sealing contact with the washing plate (5).

11. Washing and rinsing device according to claim 9, characterized in that in the stacking means (4) a cover plate for the uppermost titration plate (1) of a stack is provided.

12. Washing and rinsing device according to at least one of claims 1 to 11, characterized by means for lifting the titration plate (1) from the washing plate (5) after effected passage of liquid through the nozzles (11) and by control means for effecting further passage of liquid through the nozzles (11), with the titration plate (1) being lifted.

13. Washing and rinsing device according to claim 7, characterized in that the support plate (8) movable by means of lifting means (10) has centering means (9) for the titration plate (1).

14. Washing and rinsing device according to claim 1, characterized by cleaning nozzles lying opposite the side of the washing plate (5) provided with nozzles.

15. Washing and rinsing device according to claim 1, characterized in that the washing plate (5) together with the titration plate (1) pressed thereto is, preferably at the washing location (6), tiltable by 180° by means of the guide means.

16. Washing and rinsing device according to claim 1, characterized in that the washing plate (5) is made in two parts, comprising an upper part (5a) receiving the nozzles (11) and the precham- bers (16) and feed channels (15), and a lowerable lower part (5b) in which the discharge channels (13) are formed and which has bores which are concentric to the nozzles (11) and through which the nozzles (11) extend.

17. Washing and rinsing device according to one of claims 1 to 16, characterized in that the nozzles (11) project over the sealing surface (14) of the washing plate (5).

18. Washing and rinsing device according to claims 16 and 17, characterized in that before the start of the rinsing operation the titration plate (1) is pressed against the washing plate (5) by means of the guide means, when the lower part (5b) of the washing plate (5) is towered to the end of the nozzles (11), and that the lower part (5b) of the washing plate (5) is then together with the titration plate (1) moved to the upper part (5a) of the washing plate (5).

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