DE19514521A1 - Laboratory equipment for simultaneous manual performance of chemical reactions - Google Patents

Abstract

The laboratory appts. to carry out several chemical reactions manually and simultaneously comprises sealable hollow vessels (1) contg. a reaction component (24) or a soln. of this, inserted in openings in a lower plate (3), while an upper plate (3a) contains a mirror-image arrangement of the second reaction component or soln. (24a) in vessels (1a). Both sets of vessels have closures (14) with orifices contg. predetermined breaking points (15). A middle plate (18) has corresp. apertures (22) contg. mandrels (19) of hard metal, glass, ceramic and/or plastics of sufficient length to puncture the orifices when upper and lower plates are moved towards the middle plate, so that liq. in the upper vessels runs into the lower vessels. Sealing and elastic plastic material (20) surrounds both sides of the middle plate and can be compressed to cause mandrels to act, while forming a reaction space seal. Plates are mounted in a frame (12) and temp. adjusting fluid is supplied to vessels (2,2a) on upper and lower plates.

Description

The invention relates to a laboratory device for simultaneous, manual execution of several chemical reactions with sensitive Micro-scale reagents after a Plug system for temperature control below the Boiling points of the components involved and under oxygen and water free conditions.

Series chemical reactions are common not for the purpose of immediate extraction performed a substance but serve then getting an analytical quantity like Yield, selectivity or speed of Response necessary for the optimization of Synthetic processes or to find new ones Synthetic pathways is necessary. In addition, in of modern synthetic chemistry more and more Reactions with very reactive reagents investigated the exclusion of oxygen and / or require moisture, and that on Because of the high reactivity of the reagents Reaction control at very low temperatures (e.g. down to -100 ° C).

In such series of investigations, the Refurbishing is usually not done by insulation of individual substances, but that The reaction mixture becomes a direct one analytical investigation e.g. B. with HPLC or NMR subjected to a statement about the Get response history.

In chemical research laboratories such micro-preparative series of tests in small sizes (0.5-5 ml) usually with laboratory equipment and methods carried out as by the preparative Working method are known. These In principle, laboratory devices only stand out by scaling down conventional laboratory equipment. The Working methods are therefore also the methods for the production of individual substances by preparative synthesis borrowed.

This way of working results in a A number of disadvantages:

Only a very limited number of Reactions are carried out simultaneously because the constant goes into the experiment itself Rebuild the equipment. These are often very unstable as it consists of several components (Cologne, cocks, tripod clamps) with Connection points such as cuts or couplings consist. In addition, the structure of the equipment often only provisional due to time constraints executed. Measuring and entering the in usually in a dissolved form Reagents are made using disposable syringes. Problems often arise here due to external factors Influences such as air humidity and oxygen during the transfer of the reagents in the Syringe needle. This means changes in the chemical composition oxygen or moisture-sensitive reagents. Furthermore, it is not in this way of working possible to use several devices at the same time operate and in all devices simultaneously the reaction by adding reagents to it start or end.

Thermostat at low temperatures is usually done by hanging the Reaction flasks in open temperature baths, the an organic solvent as Use bath fluid. The work with aggressive substances over the open one Bath fluid is for safety reasons the manual is also questionable and difficult Test execution.

It can be seen that a number of Inadequacies of the equipment and the Working process influence the process and that Can take result of the reaction. Straight  but when working with small amounts such influences have great impact on the Test result (yield, selectivity of the Reaction). It is also because of the high Time often not possible, so many To perform reactions that would be necessary to Fluctuations in the test result balance and the investigations to be statistically secure.

There are already processes and devices known to be chemical or biochemical Reactions simultaneously, with high Reproducibility and simple Perform handling manually. From In principle, it is about Devices in which the reaction vessels are arranged in a matrix, usually in the form small depressions ("wells", "microwells"), which are embedded in rectangular plates. These Reactions are typically caused by synchronous Pipette in the reagent solutions or through Place a counter plate with protrusions ("Pins") that protrude into the wells and that carry immobilized reagent, initiated. A such known execution is as Utility model under the roll number G 90 15 317.0 deposited.

These devices and those with them associated reaction processes, however not suitable for reactions with sensitive Substances under oxygen and water free Conduct conditions as there is no protection against environmental influences and none Possibility of tempering the Low temperature reaction vessels are provided. In addition, they are only suitable for very small reaction volumes.

Only the principle of the arrangement of Reaction vessels in matrix form are from here Interest.

For certain chemical-analytical reactions, e.g. B. in water analysis, are reaction kits available on the market. This procedure are based on the application of closed Tubes as reaction vessels. To already predosed reaction solution in the tubes are the required one after the other Given reagents. This happens through Pipette in solutions or through Entering solid substances, e.g. B. by Throw in a capsule or a ball that the Contains substance, or by unscrewing one Lid that contains the substance and from which it can come loose.

The unsuitability of these laboratory devices for the Carrying out chemical reactions with sensitive reagents is based on the fact that Always use the lid to dose into the tubes must be unscrewed, with outer Influencing the reaction material.

In addition, the individual tubes treated sequentially. So it is not possible multiple reactions at the same time start and cancel.

In order to carry out a Ensuring reactions in tubes lies it makes sense to summarize them in a matrix and then simultaneously fill with the reagents. For the matrix-like arrangement of Reaction tubes are basically used a variety of embodiments of the known test tube stands and racks. However, these are not sufficient for the above Requirements as they are only for storing Test tubes or tubes are suitable.

Only the principle of performing Reactions in tubes are of interest here.

Crucial for the success of a reaction, where sensitive substances are used is avoiding interference like e.g. B. the decomposition of the reactants at Fill the tubes.

The introduction of substances into tubes  to the exclusion of environmental influences happens in the conventional way of working Syringes with cannulas (hollow needles) pierceable rubber closures (septa) through it. Known versions of apparatus for transferring liquids into tubes, which is based on the principle of transmission Hollow needles are based, for. Tie Patents EP 0 509 281 A2 and DE 38 17 101 A1 laid down.

This solution is for those interested here Area of application in the chemical laboratory not suitable. The reason is that too sensitive work when working with the greatest care Can decompose substances in the cannula. Are the decomposition products solids, so can clog the narrow cannula. Likewise, the ones to be transferred can also Liquids contain solids so that such reagents do not go through easily Cannulas are transferable.

Furthermore, the effort to make one Puncture septum, so large that manual only one tube at a time, but not several can be filled at the same time. Machine Versions for simultaneous piercing several septa with cannulas and for filling multiple tubes are unsuitable because they prone to failure, expensive and unwieldy Would require laboratory equipment.

It is therefore an object of the invention, the above Disadvantages of the prior art described to avoid and a completely new way of working for the manual execution of reactions with sensitive reagents at depth To introduce temperatures.

For the chemical synthesis laboratories, a easy to use laboratory device for Be made available that enables several small volume reactions in the liquid phase with sensitive reagents to perform simultaneously. This is supposed to be under oxygen and water free conditions and with tempering below the boiling point of the Reaction components and the solvent to be possible.

Much of the preparation of the reactions supposed to be from the actual implementation of the Synthesis can be separated in time and space can, making these preparations rationalized and sources of interference eliminated will.

After completing the synthesis, the possibility should exist, a quick connection to automatic analysis systems too guarantee.

A laboratory device developed for this purpose is characterized by
that a reaction component or a solution thereof is placed in closable hollow vessels, the hollow vessels being arranged in openings in a lower plate,
and that a second, upper plate carries an arrangement of hollow vessels which contains the second reaction component or a solution thereof, which is mirror-inverted in accordance with the lower plate, and this upper plate is arranged to be vertically movable over the lower plate, the openings of the hollow vessels being arranged face both plates,
and that the hollow vessels of the upper and lower plates each carry closures with openings, a predetermined breaking disk being located between the hollow vessel and the closure, which preferably consists of glass, ceramic or plastic, which breaks or bursts open under the mechanical pressure from outside the hollow vessel,
and that a third, middle plate with an arrangement of openings corresponding to the lower plate and the upper plate is arranged to be vertically movable between the upper and the lower plate,
and that mandrels made of a hard material, preferably of metal, glass, ceramic or plastic or combinations thereof, are fastened in the openings of this central plate in both directions perpendicular to the plane of the plate, the cross section of the openings and the openings of the closures being indicated by the thorns are only partially filled,
and that the mandrels in the openings of the middle plate have the length necessary to open the predetermined breaking disks in the closures of the hollow vessels which are arranged in the lower and upper plates when the upper and lower plates move towards the middle plate whereby the liquid contained in the upper hollow vessel can drain through the opening of the middle plate into the corresponding, simultaneously opened hollow vessel of the lower plate, so that after the opening of the predetermined breaking disks, a uniform reaction chamber, which is closed to the outside, is formed by each pair of vessels.
and that on both sides of the middle plate around the openings a sealing and vertically elastically compressible plastic material is attached, which in the compressed state releases the mandrels to such an extent that they can open the predetermined breaking disks, the plastic material compressed by the hollow vessels placed on them simultaneously being the newly created ones Seals the reaction chamber from the outside,
and that the vertically elastically compressible plastic material in the uncompressed state has such a strength that it already has a sealing effect on the area of the closures before the predetermined breaking disks are completely broken open, the mandrels only being released by the mechanical pressure that is required for the elastic plastic material press together, released and thus an unintentional opening of the predetermined breaking discs is prevented,
and that the upper plate can be replaced by a different, identical and also with corresponding, filled with a reagent or a solution of the reagent with closures, which in turn contain predetermined breaking discs, when the new, upper plate is placed on the middle plate again the predetermined breaking disks of the hollow vessels of the upper plate are opened by the mandrels under mechanical pressure, whereby the new reagent is metered into each individual lower hollow vessel and thus the next stage of the reaction is initiated, so that in this way multi-stage reactions by successively attaching the upper one Plate can be carried out with the hollow vessels,
and that the joined lower, upper and middle plates are arranged together in a frame in such a way that a space is created between the plates and the frame which can be flushed with inert gas via supply lines which are located in the frame, so that always and in particular when the upper plate is removed and the new upper plate is reinserted, the inert gas atmosphere in the hollow vessels and in the vicinity of the hollow vessel openings is maintained by intensive flushing of the space opened upwards,
and that temperature control vessels with corresponding supply and discharge lines for the heat transfer liquid are attached to the upper or lower plate or to both plates on the side facing away from the openings of the hollow vessels in such a way that temperature control liquid flows around the lower part of the hollow vessels, wherein the hollow vessels are inserted sealingly in the openings of the plates, so that the bath fluid cannot penetrate into the space between the plates and the frame.

The invention enables a completely new one Working procedures in the fields of  chemical synthesis research and -development in which a variety of Small volume reactions under oxygen and comparable to anhydrous conditions have to be carried out e.g. B. at Method screening chemical syntheses or for the reaction optimization of such new found synthetic routes.

This new working method has the following advantages:
A larger number of reactions can be carried out simultaneously and under identical conditions.

These are used to carry out the synthesis filled tubes according to the planned Reaction steps in the form of a matrix in the lower one Plate (reaction matrix) and in the necessary Number of top plates (reagent matrices) arranged. These are the plates Tempering vessels coupled. These units are stable, easy to handle and easy to temper.

Compared to scaled-up preparative Laboratory equipment is the handling of the Laboratory device according to the invention essential simplified. The reaction sequence is through attaching the various top plates continued on the lower plate. Through intense Purge with an inert gas that is heavier than air , the inert gas atmosphere inside succeeds of the frame and thus also in the tubes the lower plate while changing the maintain the top plate.

Furthermore, the filling of the reaction vessels with the highly sensitive reagents important and difficult part of the Preparation of the reaction, temporally and spatially be separated from the actual reaction. Because according to the invention are the hollow vessels with closure (the tubes) at the same time for the storage and transport of the Good reaction.

Corresponding reagent sets can thus be used in larger number under the same conditions prepared and stored for a long time will. These prepared reagent sets can then at the time of the actual Execution of the syntheses are "retrieved". On the other hand, by pre-filling the reactive reagents in finished and usable, closed tubes dealing with highly sensitive and aggressive substances considerably simplified and much safer made.

After the synthesis is complete, a quick Connection to automatic analysis techniques respectively.

By using hollow vessels that the Screw and crimp glasses, as in the instrumental analytics are used is a problem-free connection to Analyzers that operate automatically (e.g. HPLC or GC / MS) using a Autosamplers possible. So in a short time a large amount of analytical information about receive the syntheses carried out and from this conclusions for the following Synthesis plans are drawn.

With the help of the described invention can thus the preparation and implementation as also postprocessing syntheses sensitive substances optimized and be rationalized. In addition to the time and With the help of described invention particularly the height of the error and thus the standard deviation significantly reduced within the experiments will. This will make certain Investigations (e.g. statistical validation of synthetic processes) only possible.

A flexible adaptation of the middle plate to the  Number of to be performed at the same time Reactions succeed in that the middle one Plate is continuously formed as a film, which makes them flexible and can be cut manually is designed.

A similar flexibility also arises from that the middle plate by individual rings for each pair of vessels is replaced, each of which Contain spines and the vertically elastic wear compressible plastic material.

To reduce environmental impact, it is sensible that the space between the lower plate, the upper plate and the Frame is formed, is sealed so that alternately flushed with inert gas and with Vacuum can be sucked off, so that thereby moisture and oxygen in it Space can be reduced to a minimum.

The puncture of the predetermined breaking discs is relieved by the on the predetermined breaking discs Fractures due to notches, etching or other methods are already trained. The predetermined breaking disc can also be part of the Cap by placing the Fractures are preformed.

The tightness of breaking discs is not self-sealing material is guaranteed by the closures one or more Sealing rings between the hollow vessel, Breakaway disc and / or closure included.

For filling with particularly sensitive It is advantageous that substances in the Closures covering the predetermined breaking discs included, a second opening is incorporated, which is sealed by a septum and by the hollow vessels with the closure closed can be filled with a syringe.

An advantageous monitoring of various Reaction parameters succeed in that the Closures bear additional sensors such as Temperature sensors or fiber optics that are in the Reaction liquid protrude.

It is advantageous that the middle plate carrier additional functions such as nozzles and Supply lines for an immediate Inert gas purging at the openings in the lower one Is hollow vessels.

For sensitive reagents and their Solutions that are prefabricated in the laboratory device to be used, it is advantageous if these are filled into ampoules and stored. So it is convenient that in the top plate instead of the closable hollow vessels Ampoules are used, the shape of which Replica hollow vessels with closure that after destruction of the ampoule bottom as Breaking disc through the mandrels of the middle one Plate a smooth transfer of the reagent into the lower hollow vessels.

An alternative formation of the middle plate bears in the openings instead of the thorns Hollow cylinder made of a hard material like glass, Ceramic, plastic or metal or one Combination of these. Their Outside diameter corresponds approximately to that Inner diameter of the openings of the Closures of the hollow vessels. This hollow cylinder pierce instead of thorns Predetermined breaking disks of the closures.

In another embodiment, the middle plate mandrels or hollow cylinders only in Towards the top plate. In the lower plate are then already opened hollow vessels used. This gives you the opportunity to lower hollow vessels directly via screw thread to couple firmly to the middle plate. These  then takes over with functions of the lower one Plate like the attachment of the hollow vessels and the seal against the Bath fluid. Advantage of this Embodiment is the simpler structure of the Laboratory device from two plates and the Tempering vessels.

Some embodiments of the invention will be explained with reference to the accompanying drawings ( Fig. 1-8).

It shows:

Fig. 1, the lower plate (reaction matrix) with the hollow tubes (tube) thermostatized and frame in side sectional and plan,

Fig. 2 is a screw cap formed for hollow vessels in side section and in perspective, and two developments of the closure in perspective

Fig. 3 shows an embodiment of the middle plate in side section and in an exploded view

Fig. 4 shows two tubes with closures and a mandrel with compressible plastic material as a ring in a perspective view

Fig. 5 is a general view of a possible embodiment of the device to be protected laboratory shortly before the bringing together of the container in the side sectional

Fig. 6 shows an embodiment of the middle plate in cross-section in plan view through the middle plate with nozzles for inert gas purging at the openings of the hollow vessels and with supply lines for inert gas

Fig. 7 shows an embodiment of the middle plate for connecting two reaction tubes to form a reaction space and the resulting reaction space after connecting two tubes through the cylindrical mandrel in a perspective view

Fig. 8 shows a cross section through an embodiment of the middle plate with attached top plate and screwed lower hollow vessels.

Screw or crimp tubes 1 , which are known from analytical sample preparation, are used as hollow vessels with closures.

A set of tubes 1 , which are filled with the first reaction component 24 , is combined in a fixed arrangement on a lower plate 3 (reaction matrix). The tubes 1 are used with the seals 4 in the openings of the lower plate 3 in a liquid-tight manner.

The temperature control vessel 2 is fastened to the lower plate 3 on the side of the closed ends of the tubes 1 with the fastening clips 10 . The wall of the temperature control vessel 2 is double-walled, so that thermal insulation of the temperature control vessel 2 is achieved by applying a vacuum or by an insulating filling in the space 8 . The bath fluid is supplied and discharged via the corresponding connecting pieces 7 to and 7ab.

Because the connection between the lower plate 3 and the temperature control vessel 2 is designed to be detachable, the temperature control can be carried out with the connection 7 closed by filling the temperature control chamber 5 once with the temperature control medium (for example by throwing dry ice into the temperature control chamber 5 ).

The frame 12 is fastened on the side of the lower plate 3 on which the openings of the tubes 1 are located. It contains the connecting piece 9 for the supply of the inert gas. The frame 12 , together with the lower plate 3, forms the space 6, which is now still open at the top.

With this construction, the temperature of the tubes 1 can be achieved on the one hand, while on the other hand the openings of the tubes 1 in the upper space 6 are flushed with an inert gas. On the frame 12 guide rails 13 are attached, which ensure the guidance of the vertically movably arranged parts, which are explained below, ( Fig. 1).

The chemical reactions with sensitive reagents are carried out in tubes 1 . The next reaction component is also metered in with such tubes 1 a.

These tubes 1 and 1 a are closed with closures 14 , similar to the commercially available crimp or screw closures ( FIG. 2). However, instead of providing the opening of the closure 14 with a septum, a predetermined breaking disk 15 (made of glass, plastic or another suitable material) is provided here. A piercing of this rupture disk 15 allows later, the transfer of the contents 24 a of the above-arranged tube 1 a according to the arranged thereunder tube 1 (Fig. 5).

At the same time, the predetermined breaking disks 15 have to be pierced and the openings formed must be sealed off from the outside. According to the invention, these two important tasks are fulfilled by a middle plate 18 , which carries two vertically elastically compressible plastic films 20 , preferably made of an inert, non-absorbent foam, on both sides ( FIG. 3). In this plate 18 openings 22 are incorporated, which correspond approximately in diameter to the openings of the closures 14 . The arrangement of the openings 22 corresponds to the tube arrangement of the lower plate 3 . In the openings 22 mandrels 19 are arranged in both directions perpendicular to the plane of the middle plate 18 . These mandrels 19 are firmly anchored in the middle plate 18 and adjusted in length to the thickness of the plastic films 20 . They are designed so that they fill only a small part of the openings 22 , so that the reagent liquid 24 a can flow past the spikes 19 unhindered. The plastic films 20 fulfill two tasks: first, they seal the openings of the closures 14 towards the outside when the tubes 1 and 1 a are placed on them with moderate force. When a larger vertical force acts on the attached tubes 1 or 1 a, the foils 20 are pressed together and the mandrels 19 are released, which then open the predetermined breaking discs 15 .

The middle plate 18 is dimensioned such that it is freely movable vertically but fixed horizontally within the frame 12 .

In the closed with the shutters 14 tubes 1 and 1 a separately prepared reaction solutions 24 and the reagent 24 are mounted a (having the desired concentration, amount and temperature). For metering of the reagent 24 a to the reaction solutions 24, the respective tubes 1 a and 1 are arranged in pairs to each other standing with the caps 14 and the rupture discs 15 by means of the intermediate plate 18, shown in Fig. 4, in a particular mold 33 open, . While the upper tube 1 a and the lower tube 1 are being moved towards one another, the plastic films 20 are pressed together, thereby releasing the mandrels 19 . The mandrels 19 open the predetermined breaking discs 15 , the contents 24 and 24 a of the tubes 1 and 1 a being combined.

The tubes 1 a with the reagent solutions 24 a are arranged in the upper plate 3 a (reagent matrix) ( FIG. 5). The pattern of the arrangement corresponds in mirror image to that of the lower plate 3 (reaction matrix). The dimensions of the upper plate 3 a are chosen so that this plate 3 a is vertically movable within the frame 12 , but horizontally, however, there is little scope. The tubes 1 a are inserted through the seals 4 a in a liquid-tight manner in the upper plate 3 a. A temperature control container 2 a can also be attached to this upper plate 3 a. The container 2 a is constructed in such a way (insulating wall design 8 a, supply and discharge lines 7 to and 7 from for bath fluid) that the reagent solutions 24 a in the tube 1 a can also be temperature-controlled at low temperatures.

To carry out the reactions, the middle plate 18 and the upper plate 3 a with temperature control vessel 2 a are inserted one inside the frame 12 onto the lower plate 3 with temperature control vessel 2 , the space 6 already being flushed intensively with inert gas. This composite apparatus is inserted into the fixing frame 26 , and the inert gas flow can be reduced.

To start the reaction stage, the upper plate 3 a with the aid of the spindle 27 and the pressure plate 28 so pressed on the lower plate so that the predetermined breaking disks are pierced simultaneously 15 of the mandrels 19th In this position, the plates 3 , 3 a and 18 are fixed as long as the reaction stage takes place ( Fig. 5).

During the reaction time, the device can be clamped in a shaking or vibrating machine, or a commercially available multiple stirring system for magnetic stirrers is used. After this first reaction stage has ended, the inert gas stream is amplified again and the apparatus is removed from the fixing device 26 . The upper plate 3 a is removed, and a new upper plate 3 a (second reagent matrix) is inserted into the frame 12 and the opening of the predetermined breaking discs 15 is repeated, whereby the second stage of the reaction is initiated. Thus, the reagents 24 a necessary for the synthesis are metered in in stages ( FIG. 5).

A development of the middle plate 18 provides that it is not rigidly constructed, but that it is designed as a film. As a result, the entire middle plate 18 is flexible and can be cut manually with scissors. The background of this development is the fact that the middle plate 18 is exposed to aggressive chemicals when the reactions are carried out. This leads to wear, which in particular means that the sealing function is no longer guaranteed. Thus, the middle plate 18 needs to be replaced more often.

However, since the laboratory device is produced in several sizes (e.g. with space for 9, 12 or 24 reaction tubes), the corresponding middle plate 18 would have to be produced for each size. This effort can be minimized by designing the middle plate 18 as a film and producing only one version of this middle plate. The user can cut out the middle plate 18 with the required size from this film.

For the same reason, a special design of the middle plate 18 as a ring 33 , which is positioned individually between each pair of tubes 1 and 1 a, is provided. Thus, the number of devices for piercing the predetermined breaking disks 15 and for sealing the resulting reaction space can be adapted to the number of tubes 1 and 1 a used ( FIG. 4).

Further training 4 is provided for the use of particularly sensitive reagents. Characterized in that the space 6 formed by the lower and upper plate 3 , 3 a and frame 12 is particularly sealed, it is possible to apply vacuum through a suction nozzle in the frame 12 and thus remove the air before blowing in the inert gas. By alternately suctioning and purging with inert gas, atmospheric oxygen and moisture can be reduced to a minimum in this area.

Subclaims 5-8 deal with various developments of the closure 14 .

The later fracture lines are already incorporated in the material from which the predetermined breaking discs 15 are made. This can be done by cross-wise, circular or star-shaped scribing of the material or by pressing in weak lines. As a result, the effort required to pierce the predetermined breaking disk 15 is reduced. This predetermined breaking disk can also be integrated directly into the closure cap 14 instead of the opening and the break points can be formed there.

If the material of the predetermined breaking discs 15 is not self-sealing, the tightness of the closure 14 is ensured by inserting the sealing rings 16 .

One problem is filling tubes 1 and 1 a in the course of preparing the reaction. Less sensitive substances can be added directly to the open tubes 1 , 1 a if they are in the lower part of the laboratory device (lower plate 3 with the frame 12 attached) and the space 6 due to the inflow of inert gas, which is preferably heavier than air is protected from environmental influences. For particularly sensitive substances, however, it is advisable to fill tubes 1 and 1 a that have already been closed. In the embodiment shown in FIG. 2, the closure 14 a contains, in addition to the opening for the predetermined breaking disk 15, a second opening 17 in which there is a septum. Through this, the reagent 24 or 24 a can be given with a syringe.

For certain purposes, it may be important to monitor various parameters of this reaction during the reaction via sensors, e.g. B. the temperature. The embodiment of the closure 14 b is suitable for this. In this closure, a sensor 11 (for example a temperature sensor) is attached in such a way that it is immersed in the reaction solution 24 after the closure 14 b has been screwed onto the tube 1 . Connection lines are routed to the outside, which pass on the electrical information to a recording device ( FIG. 2).

If nozzles 35 and supply lines 36 for inert gas are attached to the middle plate 18 , it is possible to purge each individual connection point between two tubes 1 and 1 a with inert gas. This reinforces the protection of the sensitive reagents when changing the upper plate 3 a ( Fig. 6).

Instead of the tubes 1 a, specially made ampoules with the reagent solutions 24 a can be inserted into the upper plate 3 a. These have a surface modeled on the closures 14 with the predetermined breaking plate 15 . Similar to the use of the tubes, the middle plate 18 here takes over the opening of the predetermined breaking disk 15 and the sealing of the opening that is created to the outside.

Fig. 7 shows a detail of a particular embodiment of the central plate 18. The mandrels 19 are replaced here by the hollow cylinder 34 . As shown in FIG. 7, the hollow cylinders 34 can penetrate a predetermined breaking disk 15 made of a flexible and inert plastic, in which the potential breaking lines are already prefabricated. The now opened predetermined breaking disk 15 a folds out in a star shape in the direction of the tube wall. As a result, it is located between the inner tube wall and between the outer cylinder wall, so that it contributes to sealing the reaction space from the environment. After connecting two tubes through the hollow cylinder 34 , a common reaction space is created.

The hollow cylinders 34 are also combined in a matrix-like manner on the middle plate 18 , so that here too, several reactions are initiated simultaneously by piercing the fracture surfaces 15 . Tests have shown that this development of the middle plate 18 is also advantageously suitable for opening brittle fracture surfaces 15 (for example made of glass). The hollow cylinder 34 itself acts on the inner wall of the neck of the tube 1 , 1 a as a seal if it has the corresponding outer diameter.

Another embodiment of the invention can be realized in that the middle plate 18 carries mandrels 19 a or hollow cylinder 34 only in the direction of the upper plate 3 a, and in the lower plate 3 already opened hollow vessels 1 of a suitable fit are used, which seal allow the middle plate 18 .

Another embodiment of the middle plate 18 b also has the mandrels 19 a only in the direction of the upper plate and screw threads on the lower side with seals into which the lower hollow vessels 1 are screwed tightly. This eliminates the need and the thermostatized 2 and the frame 12 are attached directly to B, the middle plate 18 to the lower plate. 3 This enables a seal against the heat transfer liquid of the lower temperature control vessel 2 and a simpler construction of the laboratory device ( FIG. 8).

Claims (13)

1. Laboratory device for simultaneous, manual execution of several chemical reactions with sensitive reagents under temperature control at temperatures below the boiling point of the components involved and under oxygen and water-free conditions using a plug-in system,
characterized in that a reaction component or a solution thereof ( 24 ) is placed in closable hollow vessels ( 1 ), the hollow vessels ( 1 ) being inserted into openings in a lower plate ( 3 ),
and that a second, upper plate ( 3 a) carries such an arrangement of hollow vessels ( 1 a), which contains the second reaction component or a solution thereof ( 24 a), mirror image of the lower plate ( 3 ), and this upper plate ( 3 a) is arranged to be vertically movable above the lower plate ( 3 ), the openings of the hollow vessels ( 1 ) and ( 1 a) facing each other,
and that the hollow vessels ( 1 , 1 a) of the upper and lower plates ( 3 , 3 a) each carry closures ( 14 ) with openings, with a predetermined breaking disk ( 15. ) between the hollow vessel ( 1 , 1 a) and the closure ( 14 ) ), which is preferably made of glass, ceramic or plastic, which breaks or bursts open under mechanical pressure from outside the hollow vessel ( 1 , 1 a),
and that between the upper and lower plates ( 3 , 3 a) a third, middle plate ( 18 ) with an arrangement of openings ( 22 ) corresponding to the lower plate ( 3 ) and the upper plate ( 3 a) is arranged to be vertically movable ,
and that in the openings ( 22 ) of this central plate ( 18 ) mandrels ( 19 ) made of a hard material, preferably of metal, glass, ceramic or plastic or combinations thereof, are fastened in both directions perpendicular to the plane of the plate ( 18 ) , wherein the cross section of the openings ( 22 ) and the openings of the closures ( 14 ) is only partially filled by the mandrels ( 19 ),
and that the mandrels ( 19 ) in the openings ( 22 ) of the central plate ( 18 ) have the necessary length to the predetermined breaking discs ( 15 ) in the closures ( 14 ) of the hollow vessels ( 1 , 1 a), which in the lower and upper plate ( 3 , 3 a) are arranged to open when the upper and lower plates ( 3 , 3 a) are moved towards the middle plate ( 18 ), whereby the liquid contained in the upper hollow vessel ( 1 a) ( 24 a) can run through the opening ( 22 ) of the middle plate ( 18 ) into the corresponding, simultaneously open hollow vessel ( 1 ) of the lower plate ( 3 ), so that after opening the predetermined breaking discs ( 15 ) through each pair of vessels ( 1 , 1 a) a uniform, externally closed reaction space is formed,
and that on both sides of the middle plate ( 18 ) around the openings ( 22 ) around you and vertically elastically compressible plastic material ( 20 ) is attached, which releases the mandrels ( 19 ) to the extent that they compress the predetermined breaking disks ( 15 ) can open, the plastic material ( 20 ) compressed by the hollow vessels ( 1 , 1 a) at the same time sealing the newly formed reaction space from the outside,
and that the plastic material ( 20 ) in the uncompressed state has such a thickness that it already has a sealing effect on the area of the closures ( 14 ) before the predetermined breaking discs ( 15 ) are completely broken open, the mandrels ( 19 ) only by the mechanical Pressure that is necessary to compress the elastic plastic material ( 20 ) is released and thus an unintentional opening of the predetermined breaking discs ( 15 ) is prevented,
and that the upper plate ( 3 a) sen by another, structurally identical and also with corresponding, with a reagent or solution of the reagent ( 24 a) filled hollow vessels ( 1 a) with closures ( 14 ) which contain undamaged predetermined breaking discs ( 15 ) , occupied plate ( 3 a) can be replaced and when plugging this new, upper plate ( 3 a) onto the middle plate ( 18 ) around the predetermined breaking discs ( 15 ) of the hollow vessels ( 1 a) of the upper plate ( 3 a) be opened under mechanical pressure through the mandrels ( 19 ), whereby the new reagent ( 24 a) is metered into each individual lower hollow vessel ( 1 ) and thus the next stage of the reaction is initiated, so that in this way multi-stage reactions by successive attachment the upper plate ( 3 a) with the hollow vessels ( 1 a) can be carried out,
and that the stacked lower, middle and upper plate ( 3 , 18 , 3 a) are arranged together in a frame ( 12 ) that between the plates ( 3 , 18 , 3 a) and the frame ( 12 ) a space ( 6 ) arises, which can be flushed with inert gas via feed lines ( 9 ), which are located in the frame ( 12 ), so that always and in particular when removing the upper plate ( 3 a) and reinserting the new upper plate ( 3 a) the inert gas atmosphere in the hollow vessels ( 1 ) and in the vicinity of the hollow vessel openings is maintained by intensive flushing of the space ( 6 ) which is opened upwards,
and that tempering vessels ( 2 , 2 a) with corresponding supply and discharge lines for the bath fluid ( 7 to, 7 from) on the upper ( 3 a) or lower plate ( 3 ) or on both plates ( 3 , 3 a) each on the side facing away from the openings of the hollow vessels ( 1 , 1 a) in such a way that the lower part of the hollow vessels ( 1 , 1 a) is flowed around by the bath liquid, the hollow vessels ( 1 , 1 a) in the Openings of the plates ( 3 , 3 a) are inserted sealingly, so that the bath fluid cannot penetrate into the space ( 6 ) between the plates ( 3 , 3 a, 18 ) and the frame ( 12 ). 2. Laboratory device according to claim 1, characterized in that the middle plate ( 18 ) itself is designed as a film, whereby it is designed to be flexible and manually cut. 3. Laboratory device according to claim 1, characterized in that the central plate ( 18 ) is replaced by individual rings ( 33 ) for each pair of hollow vessels ( 1.1 a), each containing the mandrels ( 19 ) and the vertically elastically compressible plastic material ( 20 ) wear. 4. Laboratory device according to one of the preceding claims, characterized in that the space ( 6 ), which is formed between the lower plate ( 3 ) and the upper plate ( 3 a) with inserted hollow vessels ( 1 , 1 a), is sealed that alternately flushed with inert gas and vacuumed off, so that moisture and oxygen in the room ( 6 ) are reduced to a minimum. 5. Laboratory device according to one of the preceding claims, characterized in that the breaking points are already formed on the predetermined breaking disks ( 15 ) in the closures ( 14 ) of the hollow vessels ( 1 , 1 a), or in that the predetermined breaking disks in the closures ( 14 ) 15 ) are directly integrated by specifying the break points. 6. Laboratory device according to one of the preceding claims, characterized in that one or more sealing rings ( 16 ) between the predetermined breaking disc ( 15 ), hollow vessel ( 1 , 1 a) and / or closure ( 14 ) are placed. 7. Laboratory device according to one of the preceding claims, characterized in that in the closures ( 14 a), which contain the predetermined breaking discs ( 15 ), a second opening ( 17 ) is incorporated, which is sealed by a septum and through which the hollow vessels ( 1 , 1 a) can be filled with syringes when the closure is closed ( 14 a). 8. Laboratory device according to one of the preceding claims, characterized in that the closures ( 14 b) of the hollow vessels ( 1 , 1 a) support additional sensors ( 11 ) (temperature sensors, electrodes, fiber optics, etc.), which in the reaction liquid ( 24 , 24 a) protrude. 9. Laboratory device according to claims 1, 2 and 4-8, characterized in that the middle plate ( 18 ) carries additional functions such as nozzles ( 35 ) and feed lines ( 36 ) for additional inert gas flushing. 10. Laboratory device according to one of the preceding claims, characterized in that in place of the hollow vessels ( 1 , 1 a) with closure ( 14 ) and predetermined breaking disk ( 15 ) special ampoules filled with reagent solution ( 24 , 24 a) in the lower and / or upper plate ( 3 , 3 a) are used, the shape of which is simulated so that the hollow vessels ( 1 , 1 a) and the closure ( 14 ) with predetermined breaking disc ( 15 ) that after opening the ampoules through the mandrels ( 19 ) middle plate ( 18 ) the reagent solutions ( 24 a) easily pass into the lower hollow vessels ( 1 ) and the sealing is also effected by the vertically elastically compressible plastic material ( 20 ). 11. Laboratory device according to one of the preceding claims, characterized in that in the openings ( 22 ) of the central plate ( 18 ) instead of the mandrels ( 19 ) hollow cylinder ( 34 ) made of a hard material such as glass, ceramic, plastic or metal or a combination from these, are attached, the outer diameter of which corresponds approximately to the inner diameter of the openings of the closures ( 14 ) or the ampoules according to claim 10, and that these hollow cylinders ( 34 ) instead of the mandrels ( 19 ) the predetermined breaking discs ( 15 ) of the closures ( 14th ) pierce the hollow vessels ( 1 , 1 a) or the ampoules according to claim 10. 12. Laboratory device according to one of the preceding claims, characterized in that the central plate ( 18 ) spikes ( 19 a) or hollow cylinder ( 34 ) only in the direction of the upper plate ( 3 a), and that in the lower plate ( 3rd ) already open hollow vessels ( 1 ) of appropriate fit are used, so that a seal with the middle plate ( 18 ) can take place. 13. Laboratory device according to claim 12, characterized in that the middle plate ( 18 a) has screw threads for the lower hollow vessels ( 1 ), which also have screw threads at the opening, and these hollow vessels ( 1 ) without closure to the middle plate ( 18 a) be coupled so that the lower plate ( 3 ) is omitted and the lower temperature vessel ( 2 ) is attached to the middle plate ( 18 a) and thus a simpler construction of the laboratory device and a seal against the bath fluid of the lower temperature vessel ( 2 ) is achieved.