KR100307976B1 - Multi-Solid Phase Synthesis Device - Google Patents

Abstract

The present invention relates to a multi-chemical synthesis apparatus for use in solid phase synthesis, combinatorial chemistry, etc., wherein the multi-well reaction plate (1), and separately separable for holding and supporting the reaction plate Holding frame, the holding frame is an upper holding frame 6 for pressing-sealing the upper part of the multi-wall plate, a lower holding frame 8 containing the lower part of the plate, an upper part of the plate by a one-touch sealing clamp while surrounding the plate The first gasket (2) to cover the upper surface of the multi-well plate, the second gasket blocking the bottom of the multi-well plate is formed of an intermediate holding frame (1) for pressing and tightly fixing the lower part of the plate in the lower holding frame (3), and the first clamp (4) and the intermediate holding frame and the lower sealing between the upper holding frame and the intermediate holding frame The seal comprising a one-touch clamp and a second clamp 5 for sealing between the holding frame relates to a solid phase multi-synthesizer according to claim.

Description

Multi-Solid Phase Synthesis Device

The present invention relates to an apparatus for use in solid phase synthesis, combinatorial chemistry, and the like. Specifically, multiple compounds can be synthesized simultaneously and simultaneously, including the preparation of a library of compounds through equilibrium synthesis. And multiple chemical synthesis devices capable of purification, analysis and analysis.

Combination chemistry has been actively used in recent years as a method for creating a library of compounds for the development of new medicines and catalysts, and in particular, solid phase synthesis technology has become a major driving force for this. Solid-state organic synthesis is particularly popular among pharmaceutical companies because it is effective in finding new drug candidates. One of the first steps in drug development is to find inhibitors or ligands of enzymes or receptors that you want to control. Until now, you have been testing a single compound at a time, which has been costly and time-consuming. Therefore, as a result of studying various methods to overcome this inefficiency, a new synthetic technique called combinatorial chemistry has recently been developed. Combination chemistry has made it possible to produce tens of thousands or hundreds of thousands of compounds at once. Of course, it is essential to develop technologies and devices capable of effectively synthesizing and analyzing numerous compounds. However, despite the many advantages of such combinatorial chemistry, there are many limitations in performing experiments in practice, especially in equilibrium synthesis, where the importance is increasing. not.

The organic synthesis devices in use today are manufactured by Robbins Scientific Corporation, whose components include the composite block, the upper clamping collar and the lower clamping collar, the upper cover, the lower cover, and a pair of them. It consists of a gasket, and each cover is equipped with a clamp such as a clip or tongs. Place the gasket, the lower clamping collar and the reaction block in the lower cover, and then the upper clamping collar. The gasket and top cover are then mounted. A clamp in the form of a clip attached to the lower and upper covers is caught by a fixing means attached to a fixed position of the clamping collar. That is, eight clamps are used separately to seal the reaction block. There is also a hole in the center of both sides of the relatively small side of the collar, where the screw is engaged.

Such systems are prone to failure and unnecessarily expensive in experiments, and therefore inconvenient to use and inefficient. The use of clamping collars also complicates the device, making its necessity a problem. There was also a disadvantage that the reaction block did not meet the standard. Thus, there has been a recognized need for device simplification and elimination of unnecessary elements and the need for device improvements.

Therefore, in order to overcome the disadvantages of the conventional apparatus, it is possible to manufacture a one-touch sealing clamp that can be used at one time to eliminate unnecessary clamping, and to efficiently improve the reaction block, and to fix and seal it. The present invention has been completed by adopting a method of using three unique upper holding frames, an intermediate holding frame and a lower holding frame separately.

After all, it is an object of the present invention to provide a simple and efficient multiple, simultaneous chemical and biological synthesis apparatus for use in solid phase synthesis, combinatorial chemistry and the like.

Another object of the present invention is to provide an apparatus that can economically and efficiently produce a library of many compounds through equilibrium synthesis.

It is also an object of the present invention to provide a device that can be easily connected to the filtering device.

It is also an object of the present invention to provide a multi-synthesis device with a sealing system in which the reactants do not leak.

Still another object of the present invention is to provide a multiple synthesis reaction apparatus which can be used stably in connection with heating, stirring and other processes.

It is also an object of the present invention to provide a holding frame that can be used for multiple purposes and a multi-composite device that is easy to seal operation.

1 shows an overall schematic view of the components of the synthesis apparatus of the present invention.

2 is a perspective view showing the assembled state of the synthesis apparatus of the present invention.

3 is a general schematic of a multi-well plate of the present invention.

4 is a side view of the upper holding frame of the present invention.

5 is a side view of the intermediate holding frame of the present invention.

6 is a side view of the lower holding frame of the present invention.

7 is a side view showing an example of the sealing gasket of the present invention.

8 shows a clamp of the present invention.

Brief description of the main parts of the drawing

1 .... multi-well reaction plate 2 .... first gasket

3 .... second gasket 4 .... first clamp

5 .... 2nd clamp 6 .... upper holding frame

7 .... middle holding frame 8 .... lower holding frame

The present invention provides a multi-well reaction plate, an individually detachable holding frame for supporting and fixing the reaction plate, the holding frame includes an upper holding frame for pressing and sealing the upper part of the multi-well plate and a lower part of the multi-well plate. The lower holding frame consists of an intermediate holding frame which presses the upper part of the plate by one-touch sealing clamps while covering the edges of the multi-well plate and tightly fixes the lower part of the plate to the lower holding frame, and covers the upper surface of the multi-well plate. One-touch comprising a first gasket, a second gasket covering the bottom of the multi-well plate, and a first clamp sealing between the upper holding frame and the intermediate holding frame and a second clamp sealing between the intermediate holding frame and the lower holding frame Multiple, characterized in that consisting of a sealing clamp Chesang relates to a synthesizer.

The present invention consists of a multi-chamber block equipped with a polyethylene filter, which is suitable for equilibrium synthesis.

In addition, the multi-well plate of the present invention is made of polyethylene, which is excellent in durability against reagents and temperature changes.

The device of the present invention provides a filtration device which can be easily used in connection with a vacuum device, which can be used to prepare a solvent very easily, and also by filtering the reactants with the same device so that a separate device is not required.

In addition, the sealing apparatus of the present invention uses a sealing device that is supplemented so that the solvent does not leak during the reaction through sufficient design review and repeated actual experiments, thereby ensuring the tightness.

In addition, when a part of the device is damaged, only the damaged part can be used without replacing the whole device, and each part is very economical because it can be easily purchased at a low price.

Hereinafter, the apparatus of the present invention will be described in more detail with reference to the drawings.

The present invention provides a multi-well plate (1), an individually detachable holding frame for fixing and supporting it, a pair of gaskets (2 and 3) covering the top and bottom of the reaction well, and for completely sealing the holding frame. Consists of one-touch sealing clamps 4 and 5.

The multi-well plate 1 of the present invention has a rectangular block shape as shown in FIGS. 1 and 3, and two corners in one of four corners are rounded in order to show directionality. The two corners in the other direction are in the form of excitation (9), with Arabic numerals indicating the position of the wells and the alphabet appearing at the edge where the inlet 11 of the top of the well is formed in the vertical direction. Each reaction well of the present invention has a tubular structure as shown, and has a standard multi-well plate type of 8 × 12 type. Other types of reaction wells, for example, 6 × 8 type reaction wells, can be used. In addition, there is an advantage that can be replaced because the size is almost similar to the various types of reaction wells on the market.

It also has a rectangular border around the entire reaction well so that it can hang over the bottom of the well so that the bottom of the well does not reach other devices, and the outlet 12 at the bottom of the well protrudes to facilitate drainage of the solution. To facilitate the coupling with other devices. The inlet 11 of the well is rounded, so there is an advantage that can be used to cover the various lids to fit here. In the embodiment of the present invention, the inlet 11 portion does not protrude but the outlet 12 portion of the bottom portion protrudes in the form of a tapered nozzle (see FIG. 2). In addition, within the present invention, a collection well may be used in which a discharge outlet 12 is not formed at the bottom of the reaction well. In the present invention, a tubular round shape is used. Use of wells in the form is also possible. The bottom of the reaction well is equipped with a filter, which can be used for various kinds of materials such as glass and plastic, but in the present invention, polyethylene is preferably used, and the filter can retain the resin in the reaction well. It is possible to drain the solution through the filter and connect the vacuum filtration device to this well. The exit 12 of the bottom of the well is abruptly pointed to facilitate drainage of the solution and the use of other devices.

As the material of the multi-well plate of the present invention, various thermoplastic materials or inert materials may be used, but in the present invention, polypropylene is preferably used. As the multi-well plate 1, a standard well-plate 96-well plate or 48-well plate may be used, and the plate is made of polypropylene, which is excellent in reagent and temperature resistance. Since the reaction well of the present invention is a reaction well of standard specification, it can be used in connection with a conventional vacuum filtration device.

Referring to the sealing gaskets 2 and 3 shown in FIGS. 1 and 7, firstly the first gasket 2 is located between the reaction well 1 and the upper holding frame 6 to cover the top of the reaction well, The second gasket 3 is located between the reaction well 1 and the lower holding frame 8 to block the bottom of the reaction well. The first gasket 2 serves as a cover of the reaction well, and the structure has a projection 23 or an elliptical protrusion that fits to each inlet of the reaction well, so as not to apply a physical force. It does not come off easily from the inlet 11 of the reaction well 1. The first gasket 2 serves to prevent leakage of volatiles or reactants when the device of the present invention is stirred or heated. Although the surface of the first gasket 2 may be smooth, it is preferable to form the protrusion 23 that fits the inlet 11 of the reaction well 1 as in the present invention. In addition, the first gasket 2 is inscribed with Arabic numerals and alphabets in the same manner as the reaction well 1, so that the first gasket 2 is easily matched with the reaction well 1, and its size is almost the same as that of the upper surface of the reaction well.

The second gasket 3 is located on the bottom face 13 of the lower holding frame 8 and is used to block the protruding reactant outlet 12 at the bottom of the reaction well. By sticking the reaction well to the gasket 3, it is possible to prevent the solution from being discharged from the well outlet. The second gasket 3 may also be flattened or formed with projections 12 to match the number of reaction wells 1. Also, the second gasket may not be selectively used. Both gaskets are angled to show directionality, like the reaction wells.

Various materials such as natural rubber, VITON, and silicone may be used as the gasket. In a preferred embodiment of the present invention, stretchable and lightweight silicone is used.

Referring to FIGS. 1 and 6, the lower holding frame 8 will be described. The lower holding frame 8 is a portion where the lower portion of the reaction well 1 is located, and the bottom portion is a protruding outlet of the reaction well. The part 12 is located where the second gasket 3 is located on the bottom face 13 of the lower holding frame and the plate 1 on it. The rectangular four edges of the multi-well plate 1 are provided with a constant width of the jaw shape 14 protruding from the frame, so that the four rectangular edges of the plate are spread over the reaction wells 1. The outlet portion of does not touch the bottom face 13 of the lower frame. The lower holding frame 8 is positioned only at the bottom of the plate, the size of the lower holding frame 8 is formed to fit the reaction well (1). The upper part of the lower holding frame 8 is formed with a shallow groove 15 so that the intermediate holding frame can be fitted thereto. In addition, a hole is formed in the center of each of the two long side edges of the widest surface of the uppermost surface 16 of the lower holding frame 8, which can be screwed with the other holding frame. The diameter of the wide open face 16 of the top face 16 of the lower holding frame 8 has the same diameter as the intermediate holding frame which is fitted here and abuts, and like the reaction well 1, half of the corners Are not rounded and are angular, indicating the directionality.

1 and 5, an intermediate holding frame 7 is shown, which holds the rim surrounding the reaction plate 1 and the reaction wells tightly against a second gasket located at the bottom in the lower holding frame. It has a role to play, and the center is open. Positioning the reaction plate 1 in the lower holding frame 8 and inserting the intermediate holding frame 7 therein completes the open synthesis apparatus. The lower part of the intermediate holding frame is formed with a protrusion 17 of a slight height that can fit into the lower holding frame 8. The top and bottom surfaces 18 and 19 of the intermediate holding frame 7 are the same in diameter as the upper and lower holding frames 6 and 8 in contact with each other. In addition, in order to show the direction of the frame, one corner is angled and the opposite corner is rounded. The upper and lower edges of the upper and lower surfaces 18 and 19 of the middle holding frame 7 are arranged in the center, respectively. Holes are formed in accordance with the abutting position of the lower holding frame, so that they can be individually fixed. In addition, the upper part of the intermediate holding frame has a protruding step to cover the edge of the upper surface of the reaction well so that the reaction plate 1 does not fall out, so that the reaction well does not come off the frame even when turned over. Since the intermediate holding frame 7 covers the edge of the upper surface of the reaction well 1, the reaction well 1 is stably positioned in an appropriate space in the lower holding frame 8 and the intermediate holding frame 7. The upper part of the intermediate holding frame forms a step that is slightly higher than the reaction well so that the upper holding frame can fit in, and the upper surface 18 is exactly in contact with the upper holding frame. The intermediate holding frame 7 serves to press and hold the reaction well 1 located in the lower holding frame 8. By mounting the reaction wells in the lower holding frame, mounting the intermediate holding frame thereon and sealing using a second clamp, the outlet portion of the reaction well is pressed against the second gasket and blocked. After attaching only the lower holding frame 8 and the intermediate holding frame 7 to the reaction well 1, a reagent and a sample may be placed in the reaction well to proceed with the reaction.

1 and 4, the upper holding frame 6 is shown, wherein the upper holding frame 6 is formed with a plurality of holes 20, which in a preferred embodiment of the invention fits a 96-well plate. 96 holes of the same size as the 96 reaction well holes are formed, and through which the sample and the solution can be placed. The upper holding frame 6 protrudes from the bottom 21 so as to fit into the intermediate holding frame 7. It is in the form of a lid. The widths of the abutting surfaces 32 and 18 of the upper holding frame 6 and the intermediate holding frame 7 are the same, and holes are formed at the centers of both long edges of the abutting surfaces that are the same as the other holding frames. It can be screwed through the holding frame and the hole. Like the other frame, the upper holding frame 6 also has two corners on one side, so that the direction of disassembly and assembly can be known. The upper holding frame serves to completely adhere to the top surface of the reaction well by the first clamp.

As a material of each frame of the present invention, various materials such as stainless steel, a thermoplastic resin, and a combination thereof may be used. In the present invention, a light aluminum alloy is used.

1 and 7, a pair of one-touch sealing clamps 4 and 5 is provided, wherein the clamps 4 and 5 of the present invention have four edges of a rectangular holding frame. It is a one-touch sealing device that can be tightened at a time. The clamp of the present invention is free to move by connecting holes 26 to each end 25 of each of the four individual long rod-shaped blocks 24 each of which is formed in the form of a trapezoidal groove which is an appendage of the clamp. Each of the four long rod-shaped blocks connected to each end was formed with a more protruding portion 27, and then formed a jaw 28 to the end of the two jaws are fastened to cross each other. Clamps 4 and 5 are grooved so that the edge where the holding frame abuts can be inserted therein so that the clamps 4 and 5 surround the abutting edge of the holding frame so that they can be spaced between the two frames that are wedge-off during tightening. It was able to make a close contact. The parts connected by the shaft between the rod-shaped blocks 24, which are the clamp attachments, are the parts facing the edges of each frame, and the parts are rounded and curved to facilitate the engagement with the edges. The clamp is attached and detached at once because it is fixed at one place by surrounding the entire holding frame edge. The device of the invention completes the execution device with two identical clamps, the first clamp 4 having an edge where the upper holding frame 6 and the intermediate holding frame 7 abut, and the second clamp having an intermediate holding frame ( 7) and the lower holding frame 8 is pressed to tighten the edge. Therefore, if necessary, the clamps 4 and 5 can be used separately, and can be attached and detached independently and are easy to operate. By using the clamps 4 and 5 of the present invention, the frame can be easily and simply sealed in one-touch sealing manner to be used safely when performing a reaction, and can solve an experimental inconvenience or error. In addition, there is an advantage in that the shape of the frame of the present invention can be adhered and fixed between the frame by using individual forceps instead of the present clamp. This is much simpler and more efficient than using a clamp made in the form of a number of conventional clips.

1 and 2, the operation sequence of the present invention will be described. First, the second gasket 3 is installed on the bottom surface 13 in the lower holding frame 8, and the reaction well 1 is inserted therein. Let's do it. Samples and materials are added to the reaction well 1, the upper surface is covered with the first gasket 2, and the intermediate holding frame 7 is fitted. Then, cover the upper surface of the reaction well (1) with the upper holding frame (6) and then press and hold the abutment edge between each holding frame by using two one-touch sealing clamps (4 and 5) and then various reaction processes Perform. It is also possible to selectively use only a part of the device as needed.

As described above, the multi-solid-phase synthesis apparatus of the present invention can be applied to all fields of equilibrium synthesis from simple solid-phase reaction to combinatorial chemistry to produce a library of various compounds such as small molecules, peptides and oligonucleotides.

The device of the present invention is also useful for synthesizing many compounds at once and can be used in chemical and biological reactions.

The apparatus of the present invention can be readily used for other reaction processes and is easy to purify, analyze and extract.

The present invention can be effectively used in the development of new drugs in the medical and chemical fields.

In addition, the apparatus of the present invention can be easily heated and stirred by a perfect sealing system to reduce experimental contamination and errors.

Claims (3)

Multi-well reaction plate 1; An individually detachable holding frame for fixing and supporting the multi-well plate 1, the upper holding frame 6 covering and pressing-sealing the upper surface of the multi-well plate, the lower holding holding the lower part of the multi-well plate. An intermediate holding frame 7 which compresses the upper part of the plate by the one-touch sealing clamp while covering the frame 8, the periphery of the plate, and the upper edge, and adheres the plate to the lower holding frame; A first gasket (2) positioned between the upper holding frame (6) and the multi-well plate (1) to cover the top surface of the multi-well plate; A second gasket 3 positioned between the multi-well plate 1 and the lower holding frame 8 to cover the bottom of the multi-well plate; And, Four bar-shaped blocks 4 having a trapezoidal groove formed in the longitudinal direction are connected at each end, and jaws 28 are formed at both ends of the connected bar-shaped blocks 24 to be held at the time of fastening. A one-touch sealing clamps 4 and 5 that close and lock each other between the two frames by enclosing the edges at which the frame abuts to each other, the first clamps 4 sealing between the upper holding frame and the intermediate holding frame; Second clamp 5 for sealing between the intermediate holding frame and the lower holding frame Multiple solid-phase synthesis device comprising a. 2. The upper holding frame (6) is formed with a plurality of holes for inserting reagents and solutions into the multi-well plate, and the hole-forming portion protrudes to fit the intermediate holding frame. Device characterized in that. 2. Apparatus according to claim 1, characterized in that the gaskets (2 and 3) have protrusions formed on their surfaces.