JP2000117098A - Automatic synthesizer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily confirm and verify the chemical synthesis in each vessel in the synthesis protocol which is carried out in an automatic synthesizer. SOLUTION: The automatic synthesizer 1 in which compds. are automatically synthesized by chemical reaction of reagents is equipped with a plurality of vessels 22 used for the synthesis of compds., a selecting means 5 to select specified vessels from the plurality of vessels 22, and an analyzing means 9 to analyze the synthesis protocol which regulates a series of commands to determine the procedure for the synthesis of compds. and to extract commands relating to the selected vessels 22 from the synthesis protocol. When compds. are to be synthesized by using the vessels 22, a part of the protocol relating to a specified vessel 22 is extracted from the synthesis protocol which is the procedure for the synthesis of compds. so as to easily confirm and verify the chemical synthesis of each vessel 22.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic synthesizer for automatically synthesizing a compound, and more particularly to an automatic synthesizer suitable for preparing a synthesis protocol for determining a synthesis procedure.

[0002]

2. Description of the Related Art In research fields such as pharmaceuticals, life sciences, chemistry, and materials, a plurality of compounds are synthesized simultaneously on a trial basis.
In some cases, properties of compounds, synthesis conditions, and the like are measured. An automatic synthesizer is known as an apparatus for simultaneously synthesizing a plurality of compounds. The automatic synthesizer includes a plurality of reaction vessels, and a product synthesized in each reaction vessel is collected for each reaction vessel.

In order to automatically synthesize a product using an automatic synthesizer, a chemical synthesis procedure called a protocol is set up.
Compounds are produced by synthesizing reagents and solvents according to the synthesis protocol.

In some cases, the purpose of automatic synthesis is to synthesize many kinds of compound groups at once. Conventionally, in order to synthesize various kinds of compound groups, a reaction rack is formed by arranging a plurality of vessels containing reagents, solvents, and products in a matrix in a matrix, and the operation of each vessel and the vessel (aspiration or injection) is performed. ) Is created according to the synthesis procedure.

[0005]

In a synthesis protocol created by a conventional automatic synthesizer, a vessel to be used is specified, and an operation of sucking or injecting a reagent, a solvent, a product, or the like into or from a set vessel is specified. By doing so, the synthesis procedure is set. Therefore, according to the synthesis protocol, a series of synthesis procedures can be confirmed, but there is a problem in that it is not possible to easily confirm or verify a chemical reaction process when viewed in each vessel.

Therefore, in order to confirm the chemical reaction of each vessel, the protocol creator interprets the synthesis protocol,
It is necessary to verify after assembling the chemical reaction for each vessel. Accordingly, an object of the present invention is to solve the above-mentioned conventional problems and to facilitate the confirmation and verification of chemical synthesis of each vessel in a synthesis protocol performed by an automatic synthesizer.

[0007]

The automatic synthesizer of the present invention comprises:
When synthesizing a compound using a vessel, a part relating to a specific vessel is extracted from a synthesis protocol which is a procedure for synthesizing the compound, thereby easily confirming and verifying the chemical synthesis of each vessel.

An embodiment of the automatic synthesizer of the present invention is an automatic synthesizer for automatically synthesizing a compound by chemically reacting a reagent.
A plurality of vessels used for the synthesis of the compound, a selection means for selecting a specific vessel from the plurality of vessels, and a synthesis protocol that specifies a series of instructions that define a procedure for synthesizing the compound were analyzed and selected from among the synthesis protocols. Analysis means for extracting a command related to the vessel, whereby the chemical synthesis in the vessel can be easily confirmed and verified.

In the automatic synthesizer of the present invention, the compound is synthesized using a plurality of vessels, and the procedure for synthesizing the compound is determined by a series of instructions that define the order and conditions of chemical reactions called a synthesis protocol. The automatic synthesizer performs an operation of sucking or injecting a reagent, a solvent, or a product contained in a specified vessel according to a procedure specified by the synthesis protocol.

[0010] The vessel contains reagents and solvents used for the synthesis,
This is a storage part for storing intermediate products and final products generated during the synthesis process. Each directive of the synthesis protocol is
A vessel for performing suction and injection according to the reaction process, and operations such as suction and injection for the vessel are specified.

The selection means selects a specific vessel from a plurality of vessels in order to extract a command related to the specific vessel from each command in the series of synthesis protocols. The number of vessels selected may be one or more. In one aspect of the selection means, a plurality of vessels are displayed on a display device, and a vessel is selected by designating a desired vessel from the displayed vessels. In another aspect of the selecting means, the vessel is selected by designating a code corresponding to each vessel.
In the selection by this code, when the vessels are arranged in a grid pattern composed of rows and columns, the vessel is specified by the intersecting rows and columns of a specific vessel, or each vessel is assigned a code in advance. , The sign can identify the vessel.

In another aspect of the selection means, the vessel is selected by designating an instruction including the vessel to be selected on the synthesis protocol. The display device may be a device that displays the whole vessel or a part thereof of the reaction container on a screen, and each vessel may be identifiably displayed on the screen. On the display screen, the selected vessel and the non-selected vessel are
Different display modes such as a density difference, a pattern, and a frame can be displayed so as to be identifiable. The arrangement of the vessels displayed on the display device is not limited to the same arrangement as that of the vessels provided in the synthesis reaction apparatus, and may be arbitrary as long as the correspondence with the vessel of the synthesis reaction apparatus is clear.

The analysis means analyzes the synthesis protocol,
A command related to a vessel selected from a series of commands specified in the synthesis protocol is extracted. As a result, it is possible to extract a command for each vessel from the synthesis protocol, and to confirm and verify the chemical synthesis in each vessel. Further, the analysis means may have a function of extracting a vessel related to an operation on the selected vessel. With this function, a series of chemical synthesis related to the selected vessel can be confirmed and verified.

Further, the analyzing means may have a function of correcting the corrected portion when the corrected portion is found in the combined protocol by the confirmation and the verification. The analysis results of the analysis means can be displayed on the display device, and the analysis results for each selected vessel can be individually displayed, or the analysis results of all vessels can be displayed in a list.

[0015]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIG. 1 is a schematic configuration diagram showing a configuration example of the automatic synthesizer of the present invention. In FIG. 1, an automatic synthesizer 1 includes a synthesis reaction device 2 for performing a production reaction and a control device 3. The synthesis reactor 2 includes a reaction vessel 21 formed of a rack, a reaction block, and the like, a vessel 22 housed in the reaction vessel 21, and a suction for sucking or injecting a product such as a reagent, a solvent, or a reaction solution. Injection means 23
And a drive control means 24 for performing relative movement between the reaction container 21 and the suction / injection means 23.

The suction / injection means 23 performs suction of a reagent, a solvent, a product, or the like from the vessel 22 and injection of the sucked solution into another vessel according to a reaction procedure, and causes a predetermined chemical reaction to be performed. Synthesize the product. The reaction procedure can be performed according to a preset synthesis protocol.

The control device 3 causes the synthesis reaction device 2 to perform a synthesis process according to the synthesis protocol, and creates the synthesis protocol. The control unit 3 includes a display device 4, a selection unit 5, a storage unit 6, a protocol creation unit 7, a protocol execution unit 8, an analysis unit 9, and an input unit 10.

The display device 4 includes a Bessel display screen 41, a protocol display screen 42, and a display control means 43 for controlling display of both display screens. The vessel display screen 41 is a screen that displays the vessels 22 included in the reaction vessel 21 of the synthesis reaction apparatus 2 and displays all vessels included in the reaction vessel 21 or a part of the vessels. When the vessels 22 in the reaction vessel 21 are arranged in a lattice, each vessel can be specified by rows and columns. In FIG. 1, rows are indicated by reference signs A, B, C, D,..., And columns are indicated by reference signs 1, 2, 3, 4,. The code is not limited to alphanumeric characters, and any code can be used.

The arrangement of the vessels displayed on the vessel display screen 41 does not need to match the actual arrangement of the vessels 22 contained in the reaction vessel 21.
Any arrangement can be used to identify the correspondence with the vessel 22 to be stored. In addition, by displaying only the vessels necessary for the synthesis protocol among the vessels 22 included in the reaction vessel 21 on the vessel display screen 41, unnecessary display portions can be omitted, and the vessel can be easily identified.

The protocol display screen 42 is a screen for displaying the synthesis protocol and the analysis result, and displays commands relating to the whole synthesis protocol or the vessel obtained by the analysis means. When displaying the total synthesis protocol, the vessel to be operated and the operation content for the vessel are displayed in the order of reaction. In the example of the synthesis protocol illustrated in FIG. 1, the command on the first line indicates a process of performing suction on the vessel represented by 1A by the above-described matrix display, and the command on the second and third lines indicates 2A and 2B show a process of injecting two vessels represented by 2A and 2B as operation contents. When displaying the analysis results, only the analysis results of the selected vessel can be displayed, or the analysis results of all vessels can be displayed in a list.

The display control means 43 controls the display of the vessel display screen 41 and the protocol display screen 42 based on the data sent from the selection means 5, the protocol creation means 7, the storage means 6, and the protocol execution means 8 to be described later. . The selection unit 5 is a unit that selects a vessel to be analyzed and a vessel to display an analysis result, and can perform selection in a plurality of selection modes (first to third selection modes). The first mode of selection is input means 10
Is selected based on input data from the
Is selected on the basis of the data from the protocol creating means 7, and the third selection mode is selected on the display device 4.

According to the first selection mode, the input means 10
When the vessel selection is performed based on the input data from the user, the vessel display screen 41 is operated by operating the input means 10.
Specify a specific vessel from the vessels displayed above. The input means 10 includes a keyboard, a mouse,
A pointing device such as a digitizer, tablet, trackball, or joystick can be used.

When the vessel selection is performed based on the data from the protocol creating means 7 according to the second selection mode, the protocol creation means 7 sets the protocol by a command described in the synthesis protocol. The vessel selection is performed based on the vessel. The vessel to be selected is set in the protocol creation means 7 via the input means 10, and when the protocol creation means 7 finds the data of the vessel set during the protocol creation, the display control means 43 sends it. The display control means 43 receives the vessel data described in the command set by the protocol creation means 7 and, based on this data, displays the vessel display screen 4.
Display on top.

The protocol creating means 7 performs a protocol creating process as a normal process, and displays each command of the created protocol line on the protocol display screen 42. In the protocol creation process, the vessel and the operation contents for the vessel are input by the key input of the input unit 10 or the pointing device of the input unit 10
On the vessel display screen 41, the vessel and the operation contents for the vessel are input. The created protocol is stored in the storage unit 6. In this case, a selection area for selecting an operation content can be provided on the vessel display screen 41.

According to the third mode of selection, when a selection is made on the display device 4, the selection can be made on the vessel display screen 41 or the protocol display screen 42. When a selection is made on the vessel display screen 41, a vessel to be checked and verified is designated from the vessels displayed on the vessel display screen 41. The selected vessel can be displayed on the vessel display screen 41. The state where the vessel 2A is selected is displayed on the vessel display screen 41 of FIG.

When a selection is made on the protocol display screen 42, a vessel to be checked and verified is designated in the composite protocol displayed on the protocol display screen 42. The specified vessel is displayed on the vessel display screen 41. In FIG. 1, 2A described in the first or second line on the protocol display screen 42 is designated, and the vessel 2A is selected.

In displaying the analysis results, the analysis results can be displayed for each vessel by selecting the vessel unit, and the analysis results of all the vessel can be displayed by selecting all the vessel.

The analysis means 9 analyzes the synthesis protocol stored in the storage means 6 and extracts a command related to the vessel selected by the selection means 9. The extracted command can be displayed on the protocol display screen 42 or output to an output device (not shown). The command displayed on the protocol display screen 42 can be modified and changed by the input means 10 and the protocol creation means 7.

The protocol executing means 8 sequentially reads out the protocols stored in the storage means 6 and sends them to the drive control means 24. The drive control means 24 drives the reaction container 21 and the suction / injection means 23 according to the sent protocol, and performs a predetermined operation to synthesize a product. With the operation of the protocol executing means 8, the protocol can be displayed on the protocol display screen 42, and the protocol line being executed can be shown. At the same time, the vessel displayed in the protocol line being executed and the operation content thereof can be displayed on the vessel display screen 41. The data defining the layout of the vessel display screen 41 and the protocol display screen 42 can be stored in the memory in the display control means 43 or the storage means 6.

Hereinafter, each operation of analyzing the synthesis protocol, selecting a vessel, and extracting a command related to the selected vessel will be described with reference to FIGS. FIG.
9 is a flowchart for explaining an operation of analyzing a synthesis protocol, selecting a vessel, and extracting the selected vessel. In the flowchart of FIG.
In step S10, the synthesis protocol is analyzed, and in steps S11 to S18, a vessel is selected and a command related to the selected vessel is extracted.

The analysis means 9 determines the vessel to be analyzed (step S1), sequentially reads the synthesis protocol from the storage means 6 (steps S2 to S4), and stores the vessel determined in step S1 in the read synthesis protocol line. Search (step S5). If there is a vessel being searched for in the read synthesis protocol line (step S
5) Store the contents of the protocol line in the storage means 6.
The storage means 6 can store the contents of the protocol line or the position in the synthesis protocol (step S6).

The processes of steps S3 to S6 are performed for all rows of the synthesis protocol (step S7), and a protocol of a command for each vessel is created and stored (step S8). Steps S1 to S8 are performed for all vessels. Thus, the synthesis protocol is analyzed (step S9).

Next, the device configuration such as the vessel is displayed on the vessel display screen 41 (step S10), and the vessel is selected by referring to the display. The vessel can be selected by designating the vessel displayed on the vessel display screen 41 or the vessel displayed on the protocol display screen 42 (step S).
11).

A command relating to the selected vessel is extracted from the commands for each vessel stored in the storage means 6, and
The command for each vessel is displayed on the vessel display screen 41 (step S12). The analysis means 9 analyzes the procedure of the extracted command (step S13). If there is an error in the procedure, an error command is displayed (step S
15). The erroneous command is corrected and updated by the input means 10 and the protocol creation means 7 (step S16).

The processes in steps S11 to S16 can be performed for each selected vessel, and thereby, the confirmation and verification of the chemical synthesis for each vessel can be performed (step S17). Steps S1 to S
The protocol for each vessel analyzed in the process of step 9 can be displayed as a list for all vessels without selecting the vessel (step S18).

Next, an example of the operation performed by the automatic synthesizer of the present invention will be described. Hereinafter, an example of producing a compound using the reagents 1a to 1f will be described. The following example is merely an example for explaining the operation, and does not correspond to an actual synthesis example.

Table 1 below shows the synthesis protocol.
An example is shown in which reagents 1a to 1f are synthesized by different procedures, one product is generated in vessel 4A, and the other product is generated in vessel 4B. 3 and 4 show Vessel 4
A shows the suction and injection of the reagent between the vessels when the product is generated in A, and FIGS. 5 and 6 show the suction and injection of the reagent between the vessels when the product is generated in the vessel 4B. I have.

[0038]

[Table 1] In FIG. 3, reagents 1a, 1a stored in vessels 1A, 1B are shown.
1b is sucked and injected into the vessel 2A, and the vessel 2A
, The reagent 1a and the reagent 1b are chemically reacted, and the reagents 1c and 1d contained in the vessels 1C and 1D are sucked and injected into the vessel 2B, thereby causing the reagent 1c and the reagent 1d to chemically react in the vessel 2B. The reaction product of the vessel 2A and the vessel 2B is sucked, injected into the vessel 3A, and the product is chemically reacted in the vessel 3A.
Further, in FIG. 4, the product of the vessel 3A and the reagent 1e of the vessel 1E are sucked and injected into the vessel 4A to cause a chemical reaction. The synthesis procedure is performed in the synthesis protocol shown in Table 1, 1, 3, 5, 7, 9, 11, 1
It is described by each command shown in the second and 15th lines.

In FIG. 5, the reagents 1a and 1c stored in the vessels 1A and 1C are sucked and injected into the vessel 2C, and the reagent 1a and the reagent 1c are chemically reacted in the vessel 2C. The reagents 1b and 1d contained in 1D are suctioned and injected into the vessel 2D, and the reagent 1b and the reagent 1d are chemically reacted in the vessel 2D.
The reaction product of the vessel 2C and the vessel 2D is sucked,
The product is injected into the vessel 3B, and the product is chemically reacted in the vessel 3B. Further, in FIG.
The product of B and the reagent 1f in the vessel 1F are sucked and injected into the vessel 4B to cause a chemical reaction. The synthesis procedure is as follows:
In the synthesis protocol shown in Table 1, 2, 4, 6,
It is described by each command shown on lines 8, 10, 13, 14, and 16. An example of selecting a vessel and extracting a command related to the selected vessel in the above synthesis protocol will be described with reference to FIGS.

[0040]

[Table 2] FIG. 7 and Table 2 are examples in the case of confirming and verifying the chemical synthesis relating to the vessel 3A. In the automatic synthesizer according to the present invention, when the selecting means selects the vessel 3A, the analyzing means extracts and displays a command related to the vessel 3A.
Table 2 shows the commands related to the extracted vessel 3A. In Table 2, the vessel 3A is shown as a frame. FIG. 7 shows vessels 2A and 2B that are suction sources to the vessel 3A and a vessel 4A that is an injection destination from the vessel 3A. In FIG. 7, the vessel 4
The vessel 1E that is the suction source to A is also shown.

[0041]

[Table 3] FIG. 8 and Table 3 show an example in which the confirmation and verification of the chemical synthesis relating to the vessel 3B is performed. In the automatic synthesizer of the present invention, when the selecting means selects the vessel 3B,
The analysis means extracts and displays a command related to the vessel 3B. Table 3 shows commands related to the extracted vessel 3B. In Table 3, the vessel 3B is shown as a frame. FIG. 8 shows vessels 2C and 2D that are suction sources to the vessel 3B, and a vessel 4B that is an injection destination from the vessel 3B. FIG. 8 also shows the vessel 1F that is the suction source to the vessel 4B.

The display of the chemical synthesis relating to the selected vessel can be performed by commands extracted from the synthesis protocol as shown in Tables 2 and 3, or can be selected on the vessel display screen 41 as shown in FIGS. The display can also be performed by displaying the displayed vessel and the related vessel. The arrows shown in FIGS. 7 and 8 indicate the operation directions of suction and injection, and the operation directions may be displayed on the display screen 41.

The analysis means can extract not only the vessel directly related to the selected vessel, but also all vessels related to products synthesized by the selected vessel. Tables 4 and 5 show the case where extraction is performed for all the vessels involved.

[0044]

[Table 4] When vessel 3A is selected as shown in Table 2, 11,
The commands on the twelfth and fifteenth lines are extracted. 11 extracted
The row includes the vessel 2A in addition to the vessel 3A, the extracted twelfth row includes the vessel 2B in addition to the vessel 3A, and the extracted row 15 includes the vessel 4A in addition to the vessel 3A. The analysis means includes the first line and the third line related to the vessel 2A.
The command on the line is extracted, the command on the fifth and seventh lines relating to the vessel 2B is extracted, and the command on the ninth line relating to the vessel 4A is extracted. The instructions associated with the extracted vessel 3A are arranged to form a protocol as shown in Table 5.

[0045]

[Table 5] The protocols shown in Table 5 can also be displayed on the vessel display screen 41.

Next, another configuration example of the present invention will be described with reference to FIGS. The configuration example shown in FIG. 9 is an example in which reagents are stored in a plurality of rows of vessels in a vessel array configured by arranging a plurality of vessels. FIG.
, The vessels 1A to 1F in the first row are the reagents 1a to 1
f, and the second row of vessels 2A to 2F contain reagents 2a to 2f.
2f is stored. It should be noted that it is possible to arbitrarily set which vessel row of the plurality of vessel rows contains the reagent. In addition to the configuration in which the reagents are stored in the plurality of vessel rows shown in FIG. 9, the same configuration can be applied to a plurality of vessel rows.

In addition, the present invention is not limited to a column unit or a row unit, and a block including a plurality of vessels in a vessel array may be formed, and a reagent may be stored in one block or a plurality of blocks. FIG. 10 shows a configuration example in which a reagent is stored in a vessel in block units.

The configuration shown in FIG. 11 is an example in which a plurality of vessels are arranged by arranging a plurality of vessels, one vessel being a reagent vessel and the other vessel being a reaction vessel. In FIG. 11, the vessel array for reagents is vessel 1A-1F, 2A-2F, 3
A to 3F, 4A to 4F, and 5A to 5F are provided, and a reagent is stored in each vessel. In addition, the reaction vessel array includes vessels 1a to 1f, 2a to 2f, 3a to 3f, 4a to 4f,
5a to 5f are provided, and a reaction is performed by injecting a reagent into each vessel.

[0049]

As described above, according to the automatic synthesizer of the present invention, it is possible to easily confirm and verify the chemical synthesis of each vessel in the synthesis protocol performed by the automatic synthesizer.

[Brief description of the drawings]

FIG. 1 is a schematic configuration diagram showing a configuration example of an automatic synthesizer of the present invention.

FIG. 2 is a flowchart illustrating operations of analyzing a synthesis protocol, selecting a vessel, and extracting the selected vessel.

FIG. 3 is a diagram showing suction and injection of a reagent performed between the vessels when a product is generated in the vessel 4A.

FIG. 4 is a diagram showing suction and injection of a reagent performed between each vessel when a product is generated in the vessel 4A.

FIG. 5 is a diagram illustrating suction and injection of a reagent performed between the vessels when a product is generated in the vessel 4B.

FIG. 6 is a diagram showing suction and injection of a reagent performed between each vessel when a product is generated in the vessel 4B.

FIG. 7 is a diagram showing a display example in the case of confirming and verifying chemical synthesis relating to the vessel 3A.

FIG. 8 is a diagram showing a display example when confirming and verifying chemical synthesis relating to the vessel 3B.

FIG. 9 is a diagram illustrating a configuration example in which reagents are stored in a plurality of vessel rows.

FIG. 10 is a diagram illustrating a configuration example in which a reagent is stored in a block of a vessel.

FIG. 11 is a view showing a configuration example including a reagent vessel array and a reaction vessel array.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Automatic synthesizer, 2 ... Synthesis reaction device, 3 ... Control device, 4
... Display device, 5 ... Selection means, 6 ... Storage means, 7 ... Protocol creation means, 8 ... Protocol execution means, 9 ... Analysis means, 10 ... Input means, 21 ... Reaction vessel, 22 ... Vessel, 23 ... Suction injection means , 24 ... drive control means 41 ... vessel display screen, 42 ... protocol display screen, 43 ... display control means.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Kenichi Kitamura 380-1 Matsuba, Horiyamashita, Hadano-shi, Kanagawa F-term in Hadano Plant, Shimadzu Corporation 4G075 AA39 AA61 AA65 AA70 DA04 DA05 DA08

Claims (1)

[Claims] 1. An automatic synthesizer for automatically synthesizing a compound by chemically reacting a reagent, a plurality of vessels used for synthesizing the compound, a selecting means for selecting a specific vessel from the plurality of vessels, and synthesizing the compound. An automatic synthesizing apparatus, comprising: analyzing means for analyzing a synthesis protocol defining a series of commands and extracting a command related to the vessel selected from the synthesis protocol.