KR20040091829A - Device for chemical synthesis - Google Patents

Abstract

PURPOSE: Provided is a device for chemical synthesis which is able to automatically control injection and reaction of samples and solutions and significantly reduce reaction deviation and reaction time caused by manual work when synthesizing chemical materials requiring many reactions such as polypeptide. CONSTITUTION: The device comprises a well plate fixing part (30) fixing a well plate (31) where samples are stored, a solution supplying device (40) supplying solution required for synthesis or reaction, an reactor (60) reacting the samples with the solution, a reactor shaker (70) swinging the reactor to allow the content therein to be reacted, a dispenser (10) having a probe to collect the samples from the well plate and dispense them to the reactor or collect the solution from the solution supplying device and dispense it to the reactor, a horizontal direction moving means consisting of a first shaft member (21) and a second shaft member (22) and moving the dispenser in horizontal direction, a vertical direction moving means moving the dispenser crossing the horizontal direction moving means in horizontal direction and consisting of a third shaft member (23), an upward and downward moving means moving the dispenser crossing the vertical direction moving means upward or downward direction, a probe washer (70) washing the probe of the dispenser, a collecting and dispensing syringe pump (15) connected to the probe of the dispenser sucking in or dispensing the samples of the well plate or the solution of the solution supplying device or dispensing the washing solution with the probe washer and a control part (80) controlling the operation of the dispenser, the horizontal direction moving means, the vertical direction moving means, the upward and downward moving means, the collecting and dispensing syringe pump, the solution supplying device, the reactor shaker and the probe washer.

Description

Chemical Synthesizer {DEVICE FOR CHEMICAL SYNTHESIS}

The present invention relates to a synthesizer for automatically reacting or synthesizing chemicals, and more particularly, to a synthesizer for automatically controlling a reaction or synthesis that proceeds several tens of thousands of times sequentially, such as synthesis of a polypeptide.

Twenty-two major amino acids were discovered over 100 years, up to the discovery of threonine in W.C. Rose in 1935. In addition, various amino acids are found in nature as a component of peptides and special proteins, and the number is about 80 or more.

Polypeptides are produced by binding tens of thousands of these amino acids to each other, depending on the sequence of amino acids. These polypeptides are used as a major raw material for various medicines or as experimental materials.

Polypeptides can be obtained from nature, but polypeptides with specific amino acid sequences can be artificially synthesized.

Synthesis of such a polypeptide is to synthesize a peptide having a large molecular weight gradually by binding each amino acid according to the amino acid sequence to obtain.

However, if this is done by hand, the amount of work that can be performed by one person is limited, it takes a long time due to synthesis, requires a high level of skill of the operator, and there is a limit of reproducibility due to differences in functions between individuals, and also simple repetition. There is a big problem that causes errors and errors in the work process.

Therefore, in the present invention, in order to solve the above problems, the sample and solution are automatically added, the reaction and the like are quantitatively aliquoted and dispensed with high accuracy, and the reaction conditions are controlled to minimize errors and multi-channel work through a large amount of samples. It is an object of the present invention to provide a chemical synthesizer that improves the production and work efficiency by processing a short time.

The chemical synthesizer of the present invention includes a well plate fixing part for fixing a well plate (WELL PLATE) in which a sample is stored, a solution supply device for supplying a solution used for synthesis or reaction, a reactor for reacting the sample or solution, and A reactor shaker for synthesizing the reactor, a dispenser for collecting or dispensing a sample, a moving means for moving the dispenser, a probe washer for washing the probe, and a syringe for dispensing or discharging the sample or solution into the probe It consists of a pump and a control part.

1 is a plan view showing a chemical synthesizer according to the present invention,

2 is a front view showing a chemical synthesizer according to the present invention,

3 is a side view showing a chemical synthesizer according to the present invention;

4 is a block diagram showing a solution supply device of the present invention,

5 is a block diagram showing a probe cleaner of the present invention,

6 shows a reactor according to the present invention;

7 is a front view showing a reactor shaker equipped with a reactor according to the present invention,

8 is a side view showing a reactor shaker equipped with a reactor according to the present invention;

9 is a view showing the operating state of the reactor according to the present invention.

※ Description of the main parts of the drawings

Base 10. Divider

11. Probes 15. Preparative syringe pumps

21. First shaft member 22. Second shaft member

23. Third shaft member 30. Well plate fixing part

31. Well Plate 40. Solution Feeder

41. Solution container 42. Supplement solution storage tank

43. Filling pipe 44. Water level sensor

45. Syringe pump for solution supply 50. Probe cleaner

51. Wash Liquid Container 52. Supplemental Wash Liquid Storage Tank

53. Washing fluid refill pipe 54. 3-way valve

60. Reactor 61. Sample and solution inlet

62. Solution outlet 70. Reactor shaker

71. Reactor holder 72. Reactor holder support member

73. Swing motor 74. Vacuum pump

75. Control valve 80. Control unit

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

1 is a plan view showing a chemical synthesizer according to the present invention, Figure 2 is a front view showing a chemical synthesizer according to the present invention, Figure 3 is a side view showing a chemical synthesizer according to the present invention.

The chemical synthesizer of the present invention includes a dispenser 10 equipped with a probe 11 for aliquoting or dispensing a sample or solution (solvent) necessary for synthesis or dispensing a washing solution for cleaning the probe 11.

The sample is stored in a well plate, and the chemical synthesizer of the present invention includes a well plate fixing part 30 for fixing the well plate 31 to the base 1.

The well plate 31 is a rectangular kit in which dozens of test tube-shaped wells are arranged at regular intervals, and each well is stored with samples necessary for synthesis or chemical reaction. In the synthesis of the polypeptide, various amino acids are stored in their respective wells.

The well plate is generally sold in the market by the standardization of the number of the wells (WELL) and the interval between the wells (WELL), a 96-well plate consisting of 8 rows x 12 rows is generally used. Each well WELL of the well plate 31 is infused with a sample of amino acid or the like of a different species.

The solution supply device 40 stores a solvent or a solution used for synthesis or reaction of a chemical. In the synthesis of the polypeptide, a solvent or solution such as NMP, PIPERIDINE, methanol, DCC, and the like are stored.

Figure 4 is a block diagram showing a solution supply device of the present invention.

The solution supply device 40 includes a plurality of solution containers 41 for storing respective solutions required for synthesis or reaction, and each solution container 41 stores a single type of solution. The probe 11 of the dispenser 10 fractionates the solution in the solution container 41. Each solution container 41 is provided with a level sensor 44 for measuring the level of the solution.

Each replenishing solution storage tank 42 is connected to a solution replenishment tube 43 in each solution container 41, and a syringe pump 45 for solution supply is provided on the solution replenishment tube 43. When the level sensor 44 senses the level of the solution in the solution container 41 and lowers the solution level below the appropriate level, the syringe pump 45 for supplying the solution is operated so that an appropriate amount of the solution is supplied into the solution container 41. .

A plurality of probes 11 are provided in the divider 10. The plurality of probes 11 maintain constant intervals at the same height, and each of the probes 11 has a syringe pump 15 for dispensing or dispensing a sample or a solution through the probe 11. ) Is connected.

Each probe 11 is moved up and down by each drive motor provided in the frequency divider 10. When the dispenser 10 is positioned on the well plate 31 or the solution container 41, each probe 11 is sequentially operated by the operation of the driving motor therein to collect a sample from the same well. Done.

In addition, another drive motor is provided in the dispenser to adjust the left and right spacing between the probes 11. This is because the interval between the wells (WELL) of the well plate (WELL PLATE) 31 and the reactor 60 to be described later is different, so as to adjust the interval between the probes (11).

5 is a block diagram of a probe cleaner of the present invention.

5, the preparative syringe pump 15 is connected to the probe 11 to separate or dispense a sample or a solution, and on the other hand, a supplemental wash liquid storage tank 52. It is connected to and serves to wash the probe 11 by transferring the washing liquid of the supplemental washing liquid storage tank 52 to the probe (11).

The aliquot syringe pump 15 is connected to the probe 11 of the dispenser 10 on one side through a three-way valve 54 and connected to a supplemental wash liquid storage tank on the one side.

When dispensing or dispensing a sample or solution, the supplemental washing solution storage tank 52 is blocked and operated. When the washing solution is transferred to the probe 11 of the dispenser 10, the syringe is first cut off from the probe 11 to dispense the syringe. After the washing solution is introduced into the pump 15, the washing solution is disconnected from the supplemental washing solution storage tank 52, and the washing solution in the aliquot syringe pump 15 is transferred to the probe 11.

The aliquot syringe pump 15 is preferably provided with a cylinder of the aliquot syringe pump 15 up and down in order to reduce the control error caused by the air inside.

As shown in FIG. 5, the cleaning of the probe 11 is carried out into the cleaning solution container 51, and at this time, the cleaning solution is dispensed to the outside of the probe 11 by the operation of an aliquot syringe pump 15. While flowing outside the washing liquid container 51 having a narrow inner diameter, the outside of the probe 11 is automatically cleaned.

In this embodiment, a syringe pump of a ball screw type is used as the syringe pump 15 for aliquots.

The divider 10 moves in space by means of moving means including three axes.

The moving means includes a horizontal moving means for moving the divider 10 in the horizontal direction of the base 1, and a longitudinal moving means for moving the divider 10 across the first axis moving means in a horizontal direction. In addition, the frequency divider 10 is composed of a shank movement means for moving in the vertical direction across the second axis movement means.

The lateral movement means includes a first shaft member 21 horizontally installed around the well plate 31 and the liquid supply device 40, and a first shaft member (1) on one side of the first shaft member 21. The second shaft member 22 is movable along the longitudinal direction of the cylinder 21.

One side of the first shaft member 21 is provided with a drive motor to move the second shaft member 22 in its longitudinal direction.

The longitudinal movement means may include the second shaft member 22 and a third shaft member 23 which is slidably movable along the longitudinal direction of the second shaft member 22 on one side of the second shaft member 22. Consists of

One side of the second shaft member 22 is provided with a drive motor to move the third shaft member 23 in its longitudinal direction.

The driving means for moving the drive shaft for moving the divider 10 along the longitudinal direction of the third shaft member 23 and the third shaft member 23 on one side of the third shaft member 23. Consists of

6 is a view showing a reactor according to the present invention.

The reactor 60 is composed of a pipe bent at both ends, as shown in Figure 6, one end is a sample or solution inlet 61, the sample or solution is injected, the other end is a residual sample after the reaction Or a sample / solution outlet 62 through which the solution is discharged.

A filter 63 is provided on the sample and solution outlet 62 inside the tube, and the polypeptide having a high molecular weight is left inside the reactor 60 when the polypeptide is synthesized, and the NMP and piperidine used for the reaction (PIPERIDINE). ), A solvent or a solution such as methanol, DCC is discharged to the outside of the reactor (60).

7 is a front view showing a reactor shaker equipped with a reactor according to the present invention, Figure 8 is a side view showing a reactor shaker equipped with a reactor according to the present invention, Figure 9 is a view showing an operating state of the reactor according to the present invention to be.

The reactor shaker 70 swings the reactor holder 71 for fixing the reactor 60, the reactor holder support member 72 for supporting the reactor holder 71, and the reactor holder support member 72 for swinging the reactor holder support member 72. The swing motor 73 is comprised.

The reactor holder 71 is detachable from the reactor holder support member 72 and serves to fix several reactors 60 in parallel. In the present embodiment, eight reactors 60 are reactor holders 71. It is mounted on.

A swing motor 73 is connected to the reactor holder support member 72 to swing the reactor holder 71 at an angle to promote synthesis or reaction of a sample in the reactor 60.

After the reaction, the reaction solution in the reactor 60 is discharged to the outside of the reactor 60. The solution outlet 62 of each reactor 60 is connected to the vacuum pump 74 to operate the vacuum pump 74. It is discharged to the reactor 60 by the outside.

The control valve 75 is installed on the line where the solution discharge port 62 and the vacuum pump 74 are connected to control the discharge of the solution.

The control unit 80 uses the respective serial communication to operate and move the dispenser 10, to operate the syringe pump 15 for dispensing, the operation of the solution supply device 40, and the operation of the reactor shaker 70. And control the operation of the probe washer 50.

Synthesis of the polypeptide using the chemical synthesizer according to the present invention is as follows.

The controller 80 controls the driving motors provided in the first shaft member 21, the second shaft member 22, and the third shaft member 23, respectively, so that the divider 10 is placed on the well plate 31. After moving to a predetermined position of the dispenser 10, by controlling the drive motor provided in the dispenser 10 to move the probe 11 into the well (WELL), and then to control the preparative syringe pump 15 for dispensing the well (WELL A sample stored in) is aliquoted into the probe (11).

Then, the controller 80 moves the dispenser 10 to the sample-solution inlet 61 of the reactor 60, and then dispenses the sample to the reactor 60.

After dispensing, the controller 80 moves the dispenser to the probe washing container 51 to wash the probe, and then moves the solution container 41 to collect the solution or solvent required for the reaction, and then to the reactor 60. Bust in

The controller 80 controls the swing motor 73 of the reactor shaker 70 to swing the reactor 60 to promote the reaction. When the reaction is complete, the vacuum pump 74 is controlled to discharge the solution in the reactor 60 after the reaction. The polypeptide generated after the reaction is left inside by the filter in the reactor (60).

The controller 80 synthesizes a polypeptide having a large molecular weight by repeating the above process thousands of times. The series of procedures is programmed.

The compound synthesizer of the present invention automatically controls the input and reaction of the sample and the solution, and quantitatively divides and dispenses the sample with high accuracy, and proceeds the reaction efficiently, especially when the reaction is performed tens of thousands of times, such as the synthesis of the polypeptide. In this case, there is an effect of drastically reducing the reaction error and reaction time that occurs when a person directly proceeds by hand.

Claims (4)

A well plate fixing part 30 for fixing a well plate (WELL PLATE) 31 in which a sample is stored; A solution supply device 40 for supplying a solution used for synthesis or reaction; A reactor (60) for reacting the sample and the solution; A reactor shaker 70 for synthesizing the reactor by swinging the reactor; A dispenser 10 equipped with a probe 11 to dispense a sample from the well plate 31 and to dispense the sample into the reactor 60 or to dispense a solution from the solution supply device 40 and to dispense the sample into the reactor 60; Transverse movement means for moving the divider 10 in a horizontal direction; Longitudinal movement means for moving the divider 10 in a horizontal direction across the transverse movement means; Shanghai moving means for moving the divider 10 in the vertical direction across the longitudinal movement means; A probe cleaner (70) for washing the probe (11) of the dispenser; Connected to the probe 11 of the dispenser 10, the sample of the well plate 31 or the solution of the solution supply device 40 may be sucked or dispensed into the probe 11 or the washing solution may be dispensed with the probe cleaner 50. Dispensing syringe pump (15) for dispensing; Operation of the dispenser 10, transverse movement means, longitudinal movement means, shanghai movement means, preparative syringe pump 15, solution supply device 40, reactor shaker 70 and probe washer 50 And a controller (80) to control the chemical synthesizer. According to claim 1, The solution supply device 40, A solution container 41 containing a solution to be probed by the probe 11; A water level sensor 44 for measuring the water level of the solution container 41; A replenishment solution storage tank 42 for replenishing a solution through the solution replenishment tube 43 with the solution container 41; And a syringe pump (45) for supplying a solution for pumping the solution of the replenishment solution storage tank (42) to the solution container (41) on the solution supplement pipe (43). The method of claim 1, wherein the probe cleaner 50, A washing solution container 51 in which the probe is washed; And a supplementary wash liquid storage tank (52) for replenishing the solution through the washing liquid supplement pipe (53) with the preparative syringe pump (15). According to claim 1, wherein the reactor shaker 70, A reactor holder (71) for fixing the reactor (60); A reactor holder support member (72) for supporting the reactor holder (71); A swing motor (73) for swinging the reactor (60); A vacuum pump 74 connected to the reactor 60 to discharge the solution in the reactor to the outside of the reactor; And a control valve (75) for controlling the discharged solution.