WO2000061280A1

WO2000061280A1 - Reaction block

Info

Publication number: WO2000061280A1
Application number: PCT/EP2000/002989
Authority: WO
Inventors: Johann Schwartz; Heinz STADTMÜLLER; Walter Hudler; Wolfgang JÖRG; Martin Schmidt; Gerhard Steiner
Original assignee: Boehringer Ingelheim Pharma Kg
Priority date: 1999-04-08
Filing date: 2000-04-04
Publication date: 2000-10-19
Also published as: CA2372804A1; MXPA01010015A; JP2002540932A; DE19915809A1; DE19915809C2; AU4543000A; EP1183099A1

Abstract

The invention relates to a reaction block (1) for receiving reaction vessels (101) which consists of a base frame (11) and a support frame (21) into which receiving openings (24) for accommodating the reaction vessels (101) are integrated. The area of said supporting frame (21) that accommodates the reaction vessels (101) is subdivided into individual sections (22) that are arranged spaced apart from one another laterally and at a distance to the wall (12) of the base frame (11), thereby forming a flow channel (S). The inventive design makes it possible for a medium that can heat or cool the reaction vessels (101) to flow through the flow channel (S) without changing the position of the reaction block (1), thereby facilitating an even temperature change of all reaction vessels (101) that are filled with a reaction liquid (101) and that are stored in the reaction block (1).

Description

Reaction block

The invention relates to a reaction block for receiving reaction vessels, which are held in the latter for carrying out solid-phase syntheses and can be filled with a reaction liquid, consisting of a base frame and a support frame which can be inserted therein, and are incorporated in the receiving openings for holding the reaction vessels.

Such a reaction block is known from US Pat. No. 5,770,157 A. Both the receptacle openings for the reaction vessels and the cutouts assigned to them in order to accommodate pieces of tubing attached to the reaction vessels, which form a siphon outlet, are incorporated into the support frame. The space of the reaction block predetermined by the microtitre plate into which the reaction vessels are to be emptied after completion of a solid phase synthesis is thus fully used, rinsing the reaction vessels in order to heat or cool them is therefore not possible. Rather, the entire reaction block with the reaction vessels is to be introduced into a heating or cooling device. However, this is sometimes very time-consuming, and the sequence of the solid-phase synthesis cannot be optimally influenced in this way, since uniform heating or cooling cannot be achieved.

It is therefore an object of the invention to design a reaction block of the type mentioned at the outset in such a way that it is possible to heat or cool the reaction vessels located therein in a short time without the reaction block having to be transported into a corresponding unit. In doing so be ensured that there is a uniform change in temperature of all the reaction vessels stored in a reaction block and that shaking movements can also be carried out during these phases in order to promote the mixing of the reaction liquid. Furthermore, the reaction vessel that can be used in the reaction block should be designed in such a way that considerable space can be saved, so that larger free spaces can be created in the reaction block.

According to the invention, this is achieved in a reaction block of the aforementioned type in that the support frame in the area receiving the reaction vessels is divided into individual sections which are arranged to form one or more flow channels at a lateral distance from one another and / or the wall of the base frame.

It is useful here to arrange the sections worked on the support frame in mirror image to each other and to provide the individual sections in their cross-sectional shape alternately with thickening and constrictions, such that a meandering outer contour is formed, and in the thickening two receiving openings parallel to the Side walls next to each other and in the constrictions axially offset a receiving opening and work in the middle of the adjacent receiving openings.

According to a special embodiment, in order to form a continuous meandering flow channel in the reaction block, it is appropriate to alternately support adjacent sections with a thickening on the opposite side walls of the base frame and to design the free ends of the individual sections as constrictions and at a distance from the assigned side walls to arrange. It is also advantageous to provide the base frame with connections for supplying and discharging a liquid and / or gaseous medium, the connections each being equipped with check valves and opening into a flow duct via an intermediate duct in the vertically lower region.

The reaction vessels which can be inserted into the reaction block can each have, for example, a siphon tube connected centrally to its outlet and, at a radial distance from it, a riser tube which is designed to be closed in the upper end region, the riser tube communicating with its receiving space in the lower region of the reaction vessel and should be connected to the siphon tube in the upper area.

It is furthermore expedient to design the siphon tube in one piece with a housing forming the receiving space of the reaction vessel and, for example, to spray it onto the bottom thereof and to insert the riser pipe into the housing at an axial distance from it, with the riser pipe being held in the housing for this purpose Bottom in the edge area with an all-round extension, z. B. in the form of a paragraph, can be provided on which the riser pipe is supported with a molded collar, and the collar should have, for example, symmetrically arranged through openings. Furthermore, it is advisable to form an outlet nozzle on the outside of the bottom of the housing, for example to spray it on centrally.

It is also very advantageous to insert a filter insert, eg in the transition area between the receiving space of the housing and the riser pipe. B. in the form of a frit to be arranged, which can be supported on the collar of the riser pipe, and to provide the riser pipe in the upper edge region with a passage opening into the receiving space of the housing, which has a throttle, e.g. B. should be assigned in the form of a frit used in the interior of the riser. It is also appropriate to provide the housing of the reaction vessel in the upper region with an inlet opening for introducing a compressed gas and to seal the reaction vessels used in a reaction block together in an airtight manner by means of a plate.

If a reaction block according to the invention is formed, it is readily possible to transport a liquid or a gaseous medium through it in order to heat or cool the liquid in the reaction vessels for solid-phase synthesis. The design of the reaction vessels makes it possible to subdivide the support frame into sections in the area accommodating them, so that free spaces must be created between them and the walls of the base frame, in which the medium introduced into the reaction block can flow. Temperature changes can thus be carried out without changing the position of the reaction block, and this can also be subjected to shaking movements without difficulty.

The special arrangement and design of the sections further ensures that each reaction vessel is assigned a large contact area acted upon by the liquid or gas flow. This ensures uniform heating or cooling of all reaction vessels in a short time. The experiments to be carried out in the reaction block designed according to the proposal can thus be influenced effectively.

The space-saving design of the reaction vessels provided for this reaction block, for example by arranging the siphon tube inside the housing of the reaction vessel, creates the free spaces for one or more liquid or gas flows within the reaction block. An extremely versatile usability of the reaction block and also the reaction vessels over a long period of time are therefore given with simple handling. The drawing shows an exemplary embodiment of the reaction block designed according to the invention and one of the reaction vessels which can be used therein and which are explained in detail below. Here shows:

FIG. 1 shows a longitudinal section of the reaction block placed on a microplate and partially equipped with reaction vessels,

2 shows the reaction block according to FIG. 1 in a section along the line II-II of FIG. 1,

Figures 3 and 4, the base frame or the support frame of the reaction block of Figure 1, each in a perspective view, and

5 shows one of the insertable in the reaction block of Figure 1

Reaction vessels, in an axial section.

The reaction block shown in FIGS. 1 and 2 and designated 1 serves to accommodate reaction vessels 101 designed according to FIG. 5, which can be filled with a reaction liquid 102 for carrying out solid-phase syntheses, and essentially consists of a base frame 11 and a support frame 21 in which the reaction vessels 101 are inserted. The cuboid-shaped base frame 11 has four side walls 12, 12 ', 12 "and 12'" connected by a floor 13, between which the support frame 21 is arranged.

The support frame 21 is divided into individual sections 22, 22 ', 22 "and 22'" in the area receiving the reaction vessels 101, which are spaced apart at the sides. each other and to the walls 12, 12 ', 12 "and 12'" are arranged so that a flow channel S is formed between them. A liquid or gaseous medium can thus be introduced into the flow channel S via connections 14 and 15 incorporated in the base frame 11 and discharged via a drain 14 '.

The individual sections 22, 22 ', 22 "and 22"' alternately have thickened portions 25 and constrictions 26 so that a meandering outer contour 27 is formed. In the thickened portions 25 two parallel to the walls 12 "and 12 '" juxtaposed receiving openings 24 and 24' are incorporated, the constrictions 26, on the other hand, are only provided with an axially offset receiving opening 24 ", so that each of the receiving openings 24, 24 'and 24 "used reaction vessel 101 has a large contact area acted upon by the medium transported through the flow channel S and uniform and rapid heating or cooling of all reaction vessels 101 inserted into reaction block 1 is ensured.

The flow through the reaction block 1 is favored by the arrangement of the individual sections 22, 22 ', 22 "and 22'". These are namely mirror images of each other and alternately supported with a thickening 25 on the opposite side walls 12 "and 12 '" of the base frame 11. The free ends of the sections 22, 22 ', 22 "and 22'", on the other hand, are designed as constrictions 26 and are arranged at a distance from the side walls 12 "and 12 '", so that there is also a meandering flow channel S.

The reaction vessels 101 inserted in the support frame 21 are each supported on a bottom 23 of the individual sections 22, 22 ', 22 "and 22"' and can be emptied into a microtiter plate 10 which is only partially drawn in by applying the filled reaction liquid 102 or by negative pressure. In addition, the connections 14 and / or 15, as shown in Figure 1 is, each equipped with a check valve 17 and connected via a channel 16 in the lower region of the flow channel S, so that air pockets are avoided. Reliable feeding of the medium to be heated or cooled down into the reaction block 1 is thus ensured, and the reaction vessels 101 can also be emptied without difficulty.

The reaction vessel 101 shown in an axial section in FIG. 5 essentially consists of a cup-shaped housing 111, a siphon tube 116 protruding centrally from its base 113 and projecting into a receiving space 112 of the housing 111, and a riser tube placed over it and arranged at a lateral distance from it 121, which is supported on the bottom 113 of the housing 111 and communicates with the interior 112 thereof. In order to accomplish this, an annular flange 123 is formed on the riser pipe 121, and on the bottom 113 of the housing 111 a circumferential projecting extension 114 is provided in the edge region, on which the flange 123 rests. The riser pipe 121 or its flange 123 is thus supported at a distance from the floor 113. And since the flange 123 is provided with openings 124 arranged in a uniformly distributed manner, the reaction liquid 102 can flow from the interior 112 of the housing 111 into the annular space 122 formed between the siphon tube 116 and the riser tube 121. Furthermore, a filter insert 125 in the form of an annular frit is placed on the flange 123, particles in the reaction liquid 102 are thus retained and do not get into the annular space 122.

After a plurality of reaction vessels 101 have been inserted into the reaction block 1 and filled with the reaction liquid 102, these are sealed airtight together with the aid of a plate 120. If appropriate, the reaction vessels 101 are then heated or cooled in order to influence the solid phase synthesis. When this process is complete, the reaction liquid 102 is in the Transfer microplate 10. This takes place in such a way that the reaction liquid 102 located in the receiving space 112 of the housing 111 is acted upon by a compressed gas, which can be supplied via a bore 118 made in the upper region of the housing 112. The reaction liquid 102 rises in the annular space 122 because the riser tube 121 is closed in the upper end region and flows into the interior 117 of the siphon tube 116, which is connected to an outlet nozzle 115 formed centrally on the outside of the base 113 is. With the aid of the outlet nozzle 115, the reaction liquid 102 can accordingly be filled into the respective receiving space of the microtiter plate 10. Of course, it is also possible to empty the reaction vessels 101 by suction by applying a vacuum to the outlet connection 115.

Since, when the reaction vessels 101 are heated, an overpressure is built up in the part of the interior 112 of the housing 111 which is not filled with reaction liquid 102 and which can lead to the reaction liquid 102 being pressed into the siphon tube 116 and the housing 111 thus being unintentionally drained To prevent this, a through hole 126 is machined into the upper end of the riser pipe 121. With the help of the through hole 126, a pressure equalization takes place in the two rooms 112 and 122 connected to it, so that the reaction liquid 102 located in the annular space 122 is also acted on and therefore no increase takes place. And in order to exclude during the suction of the reaction liquid 102 that the liquid flow is interrupted by the air sucked in through the through hole 126, a frit 127 is also arranged in front of the through hole 126, which acts as a throttle, so that only a small amount of air can be sucked in. Despite the simple construction, the reaction vessel 101 can be used without problems over a longer period of time, in particular for carrying out solid-phase syntheses.

Claims

Patent claims:

1. Reaction block (1) for receiving reaction vessels (101) which are held therein for carrying out solid-phase syntheses and can be filled with a reaction liquid (102), consisting of a base frame (11) and a support frame (21) which can be used in them , are incorporated in the receiving openings (24) for holding the reaction vessels (101), characterized in that the support frame (21) in the area receiving the reaction vessels (101) is divided into individual sections (22) which form one or more Flow channels (S) are arranged at a lateral distance from one another and / or the wall (12) of the base frame (11).

2. Reaction block according to claim 1, characterized in that the sections (22, 22 ', 22 ", 22'") worked on the support frame (21) are each arranged in mirror image to one another.

3. Reaction block according to claim 1 or 2, characterized in that the individual sections (22, 22 'or 22', 22 "or 22", 22 '") in their cross-sectional shape alternately with thickenings (25) and constrictions (26th ) are provided, such that a meandering outer contour (27) is formed, and that in the thickened portions (25) two receiving openings (24, 24 ') parallel to the side walls (12 ", 12"') next to each other and in the Constrictions (26) axially offset a receiving opening (24 ") and are incorporated in the center of the adjacent receiving openings (24, 24 ').

4. Reaction block according to one or more of claims 1 to 3, characterized in that to form a continuous meandering ver sections (22, 22 'or 22', 22 "or 22", 22 "') of the current flow channel (S) in the reaction block (1) alternately each with a thickening (25) on the opposite side walls (12" or 12 "') of the base frame (11) are supported, and that the free ends of the individual sections (22, 22', 22", 22 '") are designed as constrictions (26) and at a distance from the associated side walls (12 '"or 12') are arranged.

5. Reaction block according to one or more of claims 1 to 4, characterized in that the base frame (11) with connections (14, 15 or 14 ') is provided for the supply and discharge of a liquid and / or gaseous medium.

6. Reaction block according to claim 5, characterized in that the connections (14, 15) are equipped with check valves (17).

7. Reaction block according to one or more of claims 1 to 6, characterized in that the connections (15) incorporated in the base frame (11) via an intermediate channel (16) each open into a flow channel (S) in the vertically lower region.