JPH1133394A - Automatic synthesizing apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic synthesizing apparatus unnecessary for washing a means for distributing a liquid raw material and a solvent and a means for stirring a reaction soln. and having no possibility of contamination and reduced in noise. SOLUTION: A automatic synthesizing apparatus is equipped with a raw material container housing part 2 housing a liquid raw material container 10, a nozzle tip housing part 4 housing a disposal nozzle tip 15, a rotary shaking machine 6 having a reaction container housing stand 38 housing a reaction container 48 to vibrate the same and a distribution apparatus 7 movable between the housing parts 2, 3, 4 and the reaction container housing stand 38 of the rotary shaking machine 6 and automatically detaching and attaching the nozzle tip 15 and using the mounted nozzle chip 15 to suck the liquid raw material in the raw material container 10 and the solvent in the solvent container 13 to discharge them into the reaction container 48.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an automatic synthesizing apparatus,
More specifically, the present invention relates to an automatic synthesizer suitable for, for example, synthesizing various kinds of samples for pharmacological evaluation.

[0002]

2. Description of the Related Art When performing pharmacological evaluation, it is necessary to synthesize a large number of small samples, and an automatic synthesizing apparatus has been developed to automatically perform this. A conventional automatic synthesizer uses, for example, a tube to inhale a liquid raw material in a raw material container and a solvent in a solvent container, discharge the raw material into a reaction container containing a solid raw material, and stir the reaction solution in the reaction container. And stir with
The reaction solution in the reaction vessel is concentrated to dryness.

However, in such a conventional apparatus, it is necessary to clean the tube each time the type of the liquid raw material and the solvent to be sucked into the tube is changed.
Different kinds of liquid raw materials or solvents may be mixed in the tube to cause contamination. Further, since the liquid raw material remains in the tube, it may be uneconomical. Further, it is necessary to wash the stirrer every time the type of the reaction solution changes, and even if the washing is performed, contamination may occur. Further, there is a problem that the noise of the stirrer is large.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems and eliminate the need for washing a means for dispensing a liquid material and a solvent and a means for stirring a reaction solution. An object of the present invention is to provide an automatic synthesizer which is free from contamination and has low noise.

[0005]

SUMMARY OF THE INVENTION An automatic synthesizing apparatus according to the present invention comprises a raw material container storing section for storing a plurality of raw material containers containing at least a liquid raw material, and a nozzle chip storing section for storing a plurality of disposable nozzle chips. Unit, a rotary shaker having a reaction container storage table for storing and shaking a plurality of reaction containers, and movable between the respective storage units and the reaction container storage table of the rotary shaker, the nozzle tip Dispensing means for automatically performing desorption and using the attached nozzle tip to suck in the liquid raw material in the raw material container and the solvent in the solvent container and discharge it into the reaction container. It is assumed that.

[0006] In this specification, the term liquid raw material is used to include all liquid raw materials, solid raw materials or liquid raw materials dissolved in a solvent.
Note that the raw materials also include reagents and the like.

[0007] Disposable nozzle tips are used, and for each type of liquid material, etc., the previously used nozzle tip may be discarded and a new nozzle tip may be used. There is no risk of contamination due to mixing.

Further, the reaction vessel is shaken using a rotary shaker to stir the reaction solution in the reaction vessel, and there is no need to stir the reaction solution using a stirrer. For this reason, noise is small, and there is no need to clean the stirrer as in the related art, and there is no risk of contamination due to mixing of the liquid material or the solvent.

For example, there is provided a reaction solution drying means for concentrating and drying the reaction solution in the reaction vessel.

For example, a rotary shaker has a driving device provided on a fixed portion, and a vertical driving shaft which is rotatably supported by the fixed portion and rotated by the driving device. A drive crank provided with a vertical drive pin eccentric in the direction, and an upper part of a vertical driven shaft rotatably supported on a fixed portion, with respect to the axis of the driven shaft in the same direction as that of the drive crank. A driven crank provided with a vertical driven pin having the same amount of eccentricity, and a reaction vessel storage table rotatably connected to the drive pin and the driven pin via a connecting member and being eccentrically rotated by rotation of the drive shaft. And a balance means having a plurality of eccentric balancers for suppressing vibration caused by eccentricity of the position of the center of gravity of the reaction vessel storage table with respect to the axis of the drive shaft.

In the case where the rotary shaker is configured as described above, the vibration generated in the reaction vessel housing table and the drive shaft due to centrifugal force during rotation is suppressed by the balance means having a plurality of eccentric balancers. Since the balance means has a plurality of balancers, the combined force of the centrifugal force and the combined bending moment due to the centrifugal force acting on the combined portion of the reaction vessel housing and all the balancers during rotation is reduced, and the static force due to the centrifugal force is reduced. And the imbalance of the bending moment due to the centrifugal force can be reduced, whereby the vibration can be suppressed. Therefore, noise is reduced, and damage to the bearing portion can be prevented, and safety is improved.

In the above-mentioned rotary shaker, for example, the balance of the centrifugal force acting on the portion where the reaction vessel housing table and all the balancers are combined and the resultant bending moment due to the centrifugal force are reduced so as to reduce the combined bending moment due to the centrifugal force. A balancer is located.

In this case, the static force due to the centrifugal force is reduced by reducing the combined force of the centrifugal force and the combined bending moment due to the centrifugal force acting on the portion where the reaction vessel housing and all the balancers are combined during rotation. Vibration and the bending moment imbalance due to centrifugal force can be reduced to suppress vibration.

In the above rotary shaker, for example, the balance means has at least one balancer of a first type and at least one balancer of a second type,
The position of the center of gravity of the first type balancer is opposite to the position of the center of gravity of the reaction vessel storage table with respect to the axis of the drive shaft, and the position of the center of gravity of the second type balancer reacts with the axis of the drive shaft. It is on the same side as the center of gravity of the container storage.

In this case, the position of the center of gravity of the first type of balancer is on the opposite side to the position of the center of gravity of the reaction vessel housing with respect to the axis of the drive shaft, and the position of the center of gravity of the second type of balancer is By being on the same side as the center of gravity of the reaction vessel storage table with respect to the axis of the drive shaft, the combined force of centrifugal force and the combined bending moment due to centrifugal force are reduced, and the imbalance of static force due to centrifugal force and Imbalance in bending moment due to centrifugal force can be reduced, thereby suppressing vibration.

In the above rotary shaker, for example, one balancer of the first type is provided above the drive shaft, and one balancer of the second type is provided below the drive shaft.

In this case, by merely providing two balancers on the drive shaft, the combined force of the centrifugal force and the combined bending moment due to the centrifugal force are reduced, and the imbalance of the static force and the centrifugal force due to the centrifugal force are reduced. The imbalance in bending moment can be reduced, thereby suppressing vibration.

In the above rotary shaker, for example, the weights of the reaction vessel housing, the first type balancer and the second type balancer are M0, M1 and M2, respectively, and the reaction vessel storage with respect to the axis of the drive shaft. , The horizontal eccentric distances of the center of gravity of the first type balancer and the second type of balancer are a, R1, and R2, respectively, and the vertical eccentricity from the center of gravity of the reaction vessel housing to the center of gravity of the first type balancer. When the directional distance is L1 and the vertical distance from the center of gravity of the first type balancer to the center of gravity of the second type balancer is L2, P and Q represented by the following equations are represented by
Each is in a predetermined range including 1.

P = M1 × R1 / (M0 × a + M2 × R2) Q = M0 × a × L1 / M2 × R2 × L2 If P is 1, theoretically, the weight and the number of revolutions of the reaction vessel storage table Regardless of, the resultant force of the centrifugal force becomes 0,
The imbalance in static force due to centrifugal force is eliminated. If Q is 1, theoretically, the resultant bending moment due to the centrifugal force becomes 0, regardless of the weight and the number of rotations of the reaction container housing, and the imbalance of the bending moment due to the centrifugal force is eliminated. Therefore, by setting P and Q to a predetermined range including 1, the combined force of centrifugal force and the combined bending moment due to centrifugal force are reduced, and the imbalance of static force due to centrifugal force and the bending moment due to centrifugal force are reduced. Imbalance can be reduced, thereby suppressing vibration.

In the above rotary shaker, for example, P
Is in the range of 0.8 to 1.2 and Q is in the range of 0.8 to 1.2.

In this case, since P and Q are close to 1, the resultant force of the centrifugal force and the resultant bending moment of the centrifugal force are reduced, and the imbalance of the static force due to the centrifugal force and the Imbalance in bending moment due to centrifugal force is reduced, thereby suppressing vibration.

For example, the dispensing means includes a cylindrical nozzle having a nozzle tip mounted at the lower end, a nozzle driving means for moving and elevating the nozzle in a horizontal plane, and a pressure supply for supplying a positive pressure and a negative pressure to the nozzle. Means, a conduit connecting the nozzle and the pressure supply means, and a liquid level detection means for detecting that the liquid suction / discharge port at the lower end of the nozzle tip has reached the liquid level. When the nozzle is descending toward the liquid level, a pressure difference between the pressure in the nozzle and the pipe communicating with the nozzle and the atmospheric pressure is detected, and when the pressure difference becomes larger than a predetermined value, the nozzle tip is detected. This detects that the liquid inlet / outlet of the liquid has reached the liquid level. That is, the liquid level detecting means is connected to the pipeline, and detects the pressure difference between the pressure in the nozzle and the pipeline communicating with the nozzle and the atmospheric pressure, and the differential pressure detecting means is configured to make the differential pressure larger than a predetermined value. Accordingly, a determination means is provided for detecting that the liquid inlet / outlet of the nozzle tip has reached the liquid level.

When the liquid suction / discharge port at the lower end of the nozzle tip reaches the liquid level, the liquid penetrates into the nozzle tip by capillary action, whereby the internal volume of the air layer in the nozzle and the conduit communicating therewith is reduced. Slightly changes, and the internal pressure changes slightly. Therefore, by detecting that the pressure difference between the pressure in the nozzle and the pipeline and the atmospheric pressure has become larger than a predetermined value, it is possible to detect that the liquid inlet / outlet of the nozzle tip has reached the liquid level. it can.

Since the nozzle tip is merely inserted into the container, the liquid level can be detected even if the small-diameter containers are densely packed.

While the nozzle is lowered, it is not necessary to supply pressure (positive pressure or negative pressure) into the nozzle. Therefore, in addition to the pressure supply means for sucking and discharging the liquid, a pressure supply means is provided. There is no need to provide, and after the nozzle tip reaches the liquid level, the nozzle tip can be immersed in a predetermined amount of liquid, and then the pressure supply means can be operated to accurately aspirate the desired amount of liquid, The control of the pressure supply means is easy.

[0026] Even if the ambient temperature changes, the pressure difference between the pressure in the nozzle and the pipeline communicating therewith and the atmospheric pressure does not change. Further, even if vibration is applied to the nozzle or the pipeline when the nozzle is descending, the internal volumes of the nozzle and the pipeline do not change, so that the pressure in the nozzle or the pipeline does not change.
Therefore, the liquid level can always be accurately detected.

Therefore, according to the above arrangement, it is possible to always accurately detect that the nozzle tip has reached the liquid level and to accurately detect the liquid level, and the configuration and control therefor are simple. .

In the above dispensing means, for example, a gas supply means for supplying a gas such as air or nitrogen into the nozzle connected to the pipe and the pipe communicating with the nozzle is provided.

In this way, before the detection of the differential pressure, gas can be supplied into the nozzle and the pipe communicating therewith, so that the residual steam pressure in the nozzle and the pipe can be eliminated. The liquid pressure can be accurately detected by accurately detecting the differential pressure.

[0030]

Embodiments of the present invention will be described below with reference to the drawings.

FIGS. 1 to 3 show the overall configuration of the automatic synthesizing apparatus. 1 is a partially cutaway plan view, FIG. 2 is a partially cutaway front view, and FIG. 3 is a partially cutout left side view. In the following description, the lower side in FIG. 1 (the right side in FIG. 3) is the front, the upper side in FIG. 1 (the left side in FIG. 3) is the rear, and the left and right when viewed from the front is the left and right. That is, the left and right in FIGS. 1 and 2 are left and right.

The main part of the automatic synthesizing device is provided in a substantially rectangular parallelepiped housing (1) having a door (1a) on the front surface. That is, the raw material container storage section (2), the solvent container storage section
(3), sample container storage (152), nozzle tip storage
(4), a nozzle tip disposal section (5), a rotary shaker (6), a dispensing device (7) constituting dispensing means, and a reaction liquid drying means provided in the dispensing device (7). A reaction liquid drying device (8) is provided.

The raw material container storage section (2) is provided at the lower rightmost position in the housing (1). The raw material container storage section (2) is provided with a plurality of raw material container storage tables (9a) (9b), and each storage table (9a)
A plurality of raw material containers (10) containing various types of liquid raw materials are stored at predetermined positions in (9b). Raw material container (1
The liquid raw materials contained in 0) include aniline, cyclohexylamine, piperazine and the like.

The solvent container storage section (3) is a raw material container storage section (2).
And is provided at the lower left portion in the housing (1). The solvent container housing section (3) is provided with a horizontal solvent container positioning turntable (12) that is driven to rotate about a vertical axis by an electric motor (11).
2) A plurality of solvent containers (13) accommodating various types of solvents are accommodated in predetermined upper positions. A lid (13a) for closing the solvent container (13) is placed on the upper end opening. Although not shown, an iron plate for adsorption is fixed to the upper surface of the lid (13a) of each solvent container (13). Examples of the solvent contained in the solvent container (13) include water, ethyl acetate, dimethylformamide, dichloromethane and the like.

The sample container storage section (152) is provided immediately in front of the raw material container storage section. Although not shown, the sample container storage section (152) stores a plurality of sample containers for storing synthesized samples. Have been.

The nozzle chip storage section (4) is provided immediately to the left of the raw material container storage section (2). The nozzle tip storage part (4) is provided with a plurality of nozzle tip storage bases (14a) (14b) (14c), and each storage base (14a) (14b) (14c) has a plurality of new disposable nozzle tips (15). Is stored. The nozzle tip (15) is classified into a plurality of types according to the type of liquid to be dispensed and the amount of dispensed liquid.

The nozzle chip disposal section (5) is provided in a part of the nozzle chip storage section (4), that is, immediately to the left of and below the front nozzle chip storage table (14a). The used nozzle tip (15) is located in the nozzle tip disposal section (5).
There is provided a nozzle tip removal section (16) for removing the nozzle tip from a dispensing device (7) described later, and a used nozzle tip storage container (151) for storing the removed nozzle tip (15).

The rotary shaker (6) is provided substantially at the center of the housing (1) between the solvent container storage section (3) and the nozzle chip storage section (4), and details thereof are shown in FIGS. It is shown in FIG. FIG.
FIG. 5 is a partially cutaway right side view of the rotary shaker (6), FIG. 5 is a cutaway plan view of the same part, FIGS. 6 and 7 are longitudinal sectional views each showing a part of FIG. FIG. 7 is an explanatory diagram showing a part of FIG. 6 in an enlarged and simplified manner to explain the balance of static force due to centrifugal force and the balance of bending moment due to centrifugal force during rotation.

As shown in FIGS. 4 and 5, on the bottom wall (1b) of the housing (1), a plurality of (in this example, six) rubber vibration isolating members (17) are rotated. A fixed base (18) constituting a fixed portion of the shaker (6) is fixed. The fixed base (18) is a rectangular horizontal support plate (19) (20) arranged in parallel with each other up and down.
And a plurality of (eight in this example) struts connecting them
(21), and the lower support plate (20) is fixed on the vibration isolating member (17). The lower support plate (20) is connected to the upper support plate (1
9) Overhangs more outward, especially toward the front.

As shown in detail in FIG. 6, the upper support plate (19)
Concentric circular holes (22) and (23) were formed in the center part of the lower support plate (20) and directly below it, and were fixed to the lower part of the hole (22) in the upper support plate (19). The vertical drive crank is inserted into the bearing housing (25) fixed to the upper part of the hole (23) of the bearing housing (24) and the lower support plate (20) via the rolling bearings (26) and (27). (28) is rotatably supported. The drive crank (28) is formed by integrally forming a vertical eccentric drive pin (28b) on the top of a vertical drive shaft (28a).
(28a) is supported by bearings (26) and (27). The lower part of the drive shaft (28a) projects downward through the hole (23) of the lower support plate (20). The drive pin (28b) is located inside the hole (22) of the upper support plate (19), and its upper part projects slightly above the upper support plate (19). As shown in detail in FIG. 8, the drive shaft (28a)
The axis (B) of the drive pin (28b) is eccentric to one side in the horizontal direction (the front side in the state shown in the drawing) with respect to the axis (A) of FIG. Rotation axis (A) and drive pin (28b)
The eccentric distance in the horizontal direction with respect to the axis (B) is denoted by a. An electric motor (29) constituting a driving device is fixed downward on the upper surface of a portion of the lower support plate (20) that protrudes to the left from the upper support plate (19), and protrudes downward from the lower support plate (20). A pulley (30) fixed to a drive shaft (not shown) of the electric motor (29) and a drive shaft (2
A timing belt (32) is hung on a pulley (31) fixed to a portion protruding below the lower support plate (20) in 8a). Then, by driving the electric motor (29), the driving crank (28) rotates about the rotation axis (A), whereby the driving pin (28b) rotates eccentrically.

Holes (33) are formed at a plurality of positions (four in this example) around the holes (23) of the lower support plate (20), and are formed above the respective holes (33) of the lower support plate (20). A vertical driven crank (37) is rotatably supported by a vertical cylindrical bearing housing (34) fixed to the portion through rolling bearings (35) and (36) provided at the upper and lower portions thereof. ing. Follower crank (37)
Has a shape similar to the drive crank (28). That is, the driven crank (37) is formed by integrally forming a vertical eccentric driven pin (37b) on a vertical driven shaft (37a), and the driven shaft (37a) has a bearing (35). Supported by (36). The axis of the driven pin (37b) is eccentric with respect to the driven shaft (37a) by the same amount (a) in the same direction as that of the driving crank (28). The driven pin (37b) protrudes above the bearing housing (34) and is located at substantially the same height as the drive pin (28b). The lower part of the driven shaft (37a) of one driven crank (37) protrudes downward through the hole (33) of the lower support plate (20), and is formed on the bottom wall (1b) of the housing (1). After the rotation and shaking, a sensor (39) for stopping the electric motor (29) at a predetermined rotation position of the driven crank (37) is used to find the origin of the stop position of the reaction vessel storage table (38) described later. Is provided.

The driving pin (28b) and the driven pin (37b) are connected via a rectangular horizontal connecting plate (40) constituting a connecting member.
A reaction container storage (38) is connected. A portion between the lower support plate (20) and the connecting plate (40) of the fixing base (18) is surrounded by a rectangular tubular cover (41) whose lower portion is fixed to the lower support plate (20). However, in FIG. 4, illustration of this cover is omitted. The connecting plate (40) has a hole (42) corresponding to the drive pin (28b) and a hole (43) corresponding to each driven pin (37b).
Are formed. The drive pin (28b) is rotatably supported via a rolling bearing (45) in a bearing housing (44) fixed to a lower portion of the hole (42) of the connecting plate (40). Connecting plate (4
0) Bearing housing fixed to the lower part of each hole (43)
In (46), each driven pin (37b) is rotatably supported via a rolling bearing (47). When the driving crank (28) is driven to rotate as described above, the container housing (38) rotates eccentrically about the rotation axis (A) and the driven shaft (37a).

A plurality of reaction containers (48) using test tubes or the like are stored in the reaction container storage table (38). As shown in detail in FIG. 7, the reaction vessel storage table (38) includes a horizontal substrate (49) fixed on a connecting plate (40) and a plurality of spacers (50) on the substrate (49). And a storage tank (51) fixed therethrough. The storage tank (51) has an outer case (52) and an inner case (5
3), two upper and lower holder support plates (54) and (55), a fixing frame (56), and a plurality (100 in this example) of aluminum container holders (57). The upper support plate (54) is a heat insulating material.

Each of the cases (52) and (53) has a rectangular parallelepiped box shape with an open upper surface. The inner case (53) is slightly smaller than the outer case (52), and is arranged inside the outer case (52) with a space therebetween. The bottom wall (53a) of the inner case (53) and the bottom wall (52a) of the outer case (52) are fixed to the connecting plate (40) at regular intervals up and down via a spacer (50). . An outward flange (52b) is formed horizontally at the upper edge of the outer case (52), and a hanging wall (52c) bent downward at a right angle is formed on the outer peripheral edge thereof. A flange (53b) extending horizontally above the flange (52b) of the outer case (52) is formed on the upper edge of the inner case (53), and a rectangular shape is formed between these flanges (52b) (53b). Insulation (58) is sandwiched. Each of the support plates (54) (55) has a rectangular shape, is vertically stacked, and has a peripheral edge placed on a flange (53b) of the inner case (53). The fixed frame (56) has a rectangular shape and is a hanging wall bent at right angles to the outer peripheral edge of the outer horizontal wall (56a).
(56b) is formed. The lower part of the hanging wall (56b) of the fixing frame (56) is fixed to the outer surface of the hanging wall (52c) of the outer case (52),
Horizontal wall (56a) of fixed frame (56) and flange of outer case (52)
(52b), upper and lower support plates (54) and (55), inner case (5
The outer periphery of the flange (53b) and the heat insulating material (58) of 3) is pinched and stopped. A heat insulating material (150) is provided in a space inside the hanging wall (56b) of the fixed frame (56). Also, 2
A heat insulating material (59) is also provided in the space between the two cases (52) and (53).

A plurality of rows and columns (in this example, 10 rows in the vertical (front-rear direction) and 10 rows (horizontal in the left-right direction)) are provided in a portion inside the fixed frame (56) and the inner case (53) of the upper support plate (54). Circular hole
(60) are formed at equal intervals, and the lower outer diameter of the lower support plate (55) just below each hole (60) is the hole of the upper support plate (54).
A stepped circular hole (61) is formed slightly larger than the inner diameter of (60) and the outer diameter of the upper part is slightly larger than that of the lower part. The container holder (57) has a bottomed cylindrical shape with an open top, and a flange that slightly projects outward on the upper edge.
(57a) is formed. Flange (57a) of each holder (57)
Is loosely fitted to the upper large diameter part of the hole (61) of the lower support plate (55), and the part immediately below the flange (57a) is tightly fitted to the lower small diameter part of the hole (61), (57a)
Is sandwiched between the middle step portion of the hole (61) of the lower support plate (55) and the periphery of the hole (60) of the upper support plate (54), whereby each holder (57 ) Are fixed to the support plates (54) and (55). The inside diameter of the holder (57) is the hole (60) of the upper support plate (54).
The reaction vessel (48) is slightly smaller than the inside diameter of the upper support plate (54).
The hole (60) is inserted into the inside of the holder (57), and its upper part protrudes above the storage tank (51). Reaction vessel (48)
Is a disposable glass or plastic container that is tightly fitted to the holder (57) so as not to move with respect to the holder (57).

Of the vessel holders (57) of 10 rows and columns of the reaction vessel storage table (38) and the reaction vessels (48) held therein, three rows at the right end (first to third rows from the right). 30 sets in the first set, and 30 rows in the three rows on the left (the fourth to sixth rows from the right)
This is referred to as a second set, and 30 pieces in the three columns on the left (the seventh to ninth columns from the right) are referred to as a third set.

Around the holder (57) in the inner case (53),
A heat medium circulation space (62) sealed by the lower support plate (55) and the holder (57) is formed. On the side of the storage tank (51),
Two hose connection fittings (63) and (64) communicating with the heating medium circulation space (62) are fixed, and the heating medium supply hose (65) is connected to one of the fittings (63) and the other is connected to the other fitting (64). Is connected to a heat medium discharge hose (66). These hoses (65) (66)
A temperature control device (not shown) for circulating the heat medium in the heat medium circulation space (62) of the storage tank (51) to heat or cool the reaction vessel (48) in the holder (57). It is connected.

The position of the center of gravity (G0) of the reaction container housing (38) is on the axis (B) of the drive pin (28b). Therefore, the rotation axis
The horizontal eccentric distance of the position of the center of gravity (G0) of the reaction container housing (38) with respect to (A) is a. The total weight of the reaction container housing (38) is M0.

Eccentric balancers constituting balance means are provided at two positions above and below the drive shaft (28a) of the drive crank (28).
(67) and (68) are fixed. That is, the upper support plate (19)
A first type of balancer (first balancer) (67) is fixed to a portion of the drive shaft (28a) between the bearing housing (24) and the bearing housing (25) of the lower support plate (20). A second type balancer (second balancer) (68) is fixed to the lower end of the drive shaft (28a) projecting further below (31).
The position of the center of gravity (G1) of the first balancer (67) is on the opposite side (rear side in the state shown in the drawing) to the position of the center of gravity (G0) of the reaction vessel storage table (38) with respect to the rotation axis (A). is there. The position of the center of gravity (G2) of the second balancer (68) is positioned with respect to the axis of rotation (A).
It is on the same side as the center of gravity (G0) of (38) (the front side in the state shown in the drawing). The horizontal eccentric distance of the center of gravity (G1) of the first balancer (67) with respect to the rotation axis (A) is R1, the second balancer
The horizontal eccentric distance of the position of the center of gravity (G2) of (68) is R2.
From the position of the center of gravity (G0) of the reaction vessel storage table (38), the first balancer (6
7) The vertical distance to the center of gravity (G1) position is L1, the first balancer
The vertical distance from the position of the center of gravity (G1) of (67) to the position of the center of gravity (G2) of the second balancer (68) is L2. In addition, the first balancer (6
The weight of 7) is M1, and the weight of the second balancer (68) is M2.

The balancers (67) and (68) are provided on the reaction vessel storage table (38).
And the balancer (67) and (68) (hereinafter referred to as the “main rotating portion”) reduce the combined centrifugal force acting during rotation and the combined bending moment due to the centrifugal force. The imbalance in static force due to centrifugal force and the imbalance in bending moment due to centrifugal force are reduced, and the reaction vessel storage table (38) with respect to the rotation axis (A) is reduced.
This is for suppressing vibration due to eccentricity of the position of the center of gravity (G0). The combined force of the centrifugal force acting on the main rotating part during rotation and the combined bending moment due to the centrifugal force are minimized, and the imbalance of the static force due to the centrifugal force acting on the main rotating part during rotation and the bending moment due to the centrifugal force are reduced. It is desirable to minimize the imbalance. To reduce the resultant force of the centrifugal force acting on the main rotating part during rotation and the resultant bending moment due to the centrifugal force, the following equation is used.
P and Q represented by (1) and (2) are each within a predetermined range including 1.

P = M1 × R1 / (M0 × a + M2 × R2) (1) Q = M0 × a × L1 / M2 × R2 × L2 (2) Desirably, P is 1 ± 0.2 and Q are in the range of 1 ± 0.2, and more preferably, P is 1 ± 0.1 and Q is 1 ± 0.2.
0.1, most preferably, P is 1 ± 0.05, Q is 1 ±
0.05. In particular, high-speed rotation, for example, 1000
When the rotation speed is not less than rpm, it is preferable that both P and Q are about 1 ± 0.05. For example, if M0 is 10.577
When kg and a are 2 mm, M1 is 1.133 kg,
0.687 kg of M2, 48.5 mm of R1, 4 of R2
By setting 7.3 mm, L1 to 90 mm and L2 to 60 mm, P becomes 1.02, Q becomes 0.99, and 1000
Vibration was suppressed even when rotated at rpm.

Assuming that the rotational angular velocity of the driving crank (28) is ω, the centrifugal force F acting on the reaction vessel storage table (38) during rotation.
0, the centrifugal force F1 acting on the first balancer (67) and the centrifugal force F2 acting on the second balancer (68) are expressed by the following equations, respectively.
(3) to (5).

[0053] ^{F0 = M0 × a × ω 2} ............ (3) F1 = M1 × R1 × ω 2 ............ (4) F2 = M2 × R2 × ω 2 ............ (5) rotation axis Due to the eccentric direction of the reaction container housing (38) and the balancers (67) and (68) with respect to the center (A), F0 and F2 are in the same direction, and F1 is in the opposite direction. Therefore, when the following equation (6) holds, the resultant force of the centrifugal force acting on the main rotating part during rotation becomes 0, and when the following equation (7) holds, the centrifugal force acting on the main rotating part during rotation becomes , The resultant bending moment becomes zero.

F1 = F0 + F2 (6) F0 × L1 = F2 × L2 (7) The above formulas (6) and (7) are replaced by F0 of the above formulas (3) to (5). , F1,
By rearranging by substituting F2, the following equations (8) and (9) are obtained.

M1 × R1 = M0 × a + M2 × R2 (8) M0 × a × L1 = M2 × R2 × L2 (9) In the above equations (8) and (9), The rotational angular velocity ω is not included. When equation (8) holds, P in equation (1) becomes 1; when equation (9) holds, equation (2) holds.
Becomes 1. Therefore, P and Q are each 1
By arranging the balancers (67) and (68) so that
Theoretically, regardless of the number of revolutions, the combined force due to the centrifugal force acting on the main rotating part during rotation and the combined bending moment due to the centrifugal force are set to 0 to eliminate static force imbalance and bending moment imbalance. Can be. Also,
By arranging the balancers (67) and (68) so that the above-mentioned P and Q fall within a predetermined range including 1, the resultant force due to the centrifugal force acting on the main rotating part during rotation and the resultant bending moment due to the centrifugal force are reduced. It can be reduced to reduce static force imbalance and bending moment imbalance.

In the above embodiment, the two balancers (67) and (68) are merely provided on the drive shaft (28a), and the combined force of the centrifugal force acting on the main rotating portion during rotation and the combined bending moment due to the centrifugal force are calculated, for example. Decrease it to almost 0,
Imbalance of static force due to centrifugal force and imbalance of bending moment due to centrifugal force can be reduced, thereby suppressing vibration.

In the above embodiment, the first type of balancer
(67) and one balancer (68) of the second type are provided, respectively, but two or more balancers of each type may be provided.

The reaction vessel storage table (38) with respect to the rotation axis (A)
By providing at least one first type balancer (67) eccentric to the opposite side to the other side and at least one second type balancer (68) eccentric to the same side as the reaction vessel storage table (38), The combined force of the centrifugal force acting on the main rotating part during rotation and the combined bending moment due to the centrifugal force are reduced to, for example, substantially zero, so that the static force imbalance due to the centrifugal force and the bending moment imbalance due to the centrifugal force are reduced. Can be reduced, thereby suppressing vibration.

FIG. 9 shows the entire configuration of the dispensing device (7), and FIG. 10 shows the configuration of the main part thereof. Dispensing device
Details of each part of (7) are shown in FIGS.

The pipetting device (7) has a vertical cylindrical nozzle (69),
The apparatus includes a nozzle driving device (70), a pressure supply device (71), a pipeline (72) connecting the nozzle (69) and the pressure supply device (71), and a liquid level detection device (73).

The nozzle (69) is composed of a tubular nozzle base (74) extending vertically and a tubular disposable nozzle tip (15) detachably attached to its lower end.
Detachment mechanism of the nozzle tip (15) with respect to the nozzle base (74),
A well-known configuration can be adopted for the removing means of the nozzle tip (15) in the nozzle tip disposal section (5) and the mounting means of the nozzle tip (15) in the nozzle tip storing section (4), and therefore, detailed description is omitted. I do. Nozzle tip (15)
The lower portion is tapered, and the lower end is a liquid inlet / outlet (hereinafter abbreviated as “supply / discharge port”) (15a). The inner diameter of the nozzle tip (15) is preferably 0.3 to 1.5 mm,
In this example, it is 0.8 mm. In addition, nozzle tip (15)
Preferably, at least the inner peripheral surface of the lower end portion and the inner and outer peripheral surfaces is coated with a non-adhesive resin such as a fluororesin such as an ethylene tetrafluoride resin or a silicon resin (silicone resin).

The nozzle driving device (70) constitutes nozzle driving means for moving the nozzle (69) in the three-dimensional directions of the left-right direction, the front-back direction, and the up-down direction, and is configured as follows.

A guide rail (75) extending horizontally in the left-right direction is disposed at the lower rear end of the housing (1), and a ball screw (77) driven by an electric motor (76) is disposed slightly above the guide rail (75). Are located. A left-right moving body (first moving body) (78) is supported on the guide rail (75), and is moved in the left-right direction by rotation of a ball screw (77). The first moving body (78) is an inverted L
It comprises a vertical column (79) having a character shape, and a girder (80) fixed to the upper end of the column (79) and extending horizontally forward. A guide block (81) fixed to the lower end surface of the column (79) is slidably supported by the guide rail (75), and a ball nut (not shown) fixed to the block (81) is a ball screw (not shown). 77).

In the left part of the digit (80) of the first moving body (78),
A guide rail (82) extending horizontally in the front-rear direction is fixed,
On the right side, a front-rear direction moving body (second moving body) (83) is supported slidably back and forth. Guide rail (82) for girder (80)
A ball screw (85) driven by an electric motor (84) is arranged in parallel in the upper part of, and a ball nut (86) fixed to the second moving body (83) is fitted to the ball screw (85). The second moving body (83) is driven by the rotation of the ball screw (85).
Move forward and backward along (80).

A guide block (87) is fixed to the right front portion of the second moving body (83), and a vertically long elevating member (first elevating member) (88) is vertically movable on this block (87). Supported. A vertically extending guide rail (89) is fixed to the left side of the front side of the first elevating member (88).
(89) is vertically slidably supported by the guide block (87). A vertically extending rack (90) is fixed to the rear left side of the first elevating member (88), and teeth (90a) are formed on the left side surface of the rack (90). Digit (80) of first mobile unit (78)
Spline shaft (91) extending horizontally in the front-rear direction
And an electric motor (92) for driving the motor. A boss (93a) of a pinion (93) is rotatably supported by the second moving body (83), and a spline shaft is attached to a sleeve (not shown) of a ball spline attached to the center of the boss (93a). (91) is passed through, the pinion (93) and the spline shaft (91)
Do not rotate with each other, but can move relative to each other in the axial direction (front-back direction). The pinion (93) is a first lifting member
It engages with the teeth (90a) of the rack (90) of (88). When the second moving body (83) moves in the front-rear direction along the spar (80), the pinion (93) also moves in the front-rear direction along the spline axis (91), and the second moving body (83) moves. ) In any position in the front-rear direction, the spline shaft (9
By rotating the pinion (1), the pinion (93) is driven to rotate, and the first lifting member together with the rack (90) engaged therewith is rotated.
(88) goes up and down. A guide block (94) is fixed to a lower right portion of the first elevating member (88), and a nozzle base (7) is provided inside a linear motion ball bearing (not shown) provided on an inner periphery of the guide block (94).
4) is passed up and down freely. Flange (74a) at nozzle base (74) projecting above guide block (94)
A horizontal plate-shaped spring receiver (95) is fixed to the right side surface of the first elevating member (88) above the first lifting member (88).
Around the nozzle base (74) between (95) and the flange (74a),
A compression coil spring (96) for urging the nozzle base (74) downward is attached. The spring (96) is connected to the nozzle base (7
This is for absorbing the impact when the nozzle tip (15) is attached to 4), and the nozzle (69) is usually provided with the first lifting member.
In contrast to (88), the spring (96) holds the flange (74a) of the nozzle base (74) at a fixed lower end position where the flange (74a) is pressed against the upper surface of the guide block (94), and the second moving member (83) With the first elevating member (88).

The pressure supply device (71) constitutes a pressure supply means for supplying a positive pressure and a negative pressure into the nozzle (69), the details of which are shown in FIG.

A frame (97) is fixed to the top wall (1c) on the right side of the rear end in the housing (1). The upper and lower two syringe pumps (horizontally extending in the horizontal direction) are fixed to the frame (97). 98) (99),
A ball screw (101) extending horizontally in the left-right direction, which is rotationally driven by the electric motor (100), and a moving member (103) moving in the left-right direction along the horizontal guide rod (102) by rotation of the ball screw (101). Is provided. Each pump (98) (99)
A syringe (98a) (99a) fixed to the frame (97), and a piston rod (9) inserted into the syringe (98a) (99a) from the right side.
8b) and (99b), the left end of each syringe (98a) (99a) is an air supply / discharge port (98c) (99c). Each piston rod (98b)
The right end of (99b) is connected to the moving member (103) by the connecting member (104), and as the moving member (103) moves within a predetermined range, each piston rod (98b) (99b) (98
a) A predetermined stroke is moved with respect to (99a). The two pumps (98) and (99) are appropriately switched and used depending on the amount of the dispensed amount. For example, the inner diameter of the first syringe pump (98) is 2.30 mm, and the inner diameter of the second syringe pump (99) is 7.28 mm. The stroke of the piston rods (98b) and (99b) of the two pumps (98) and (99) is 60 mm (at full stroke).

FIG. 10 shows the structure of the pipe (72) and the liquid level detecting device (73). FIG. 10 shows the syringe pumps (98) and (99) such that the actual left side is the upper side of the figure. Pipe line (72) has three solenoid valves (V1) (V2) (V3)
It has. The liquid level detection device (73) has a nozzle tip (15)
The liquid level is detected by detecting that the suction port (15a) at the lower end of the liquid has reached the liquid level, and two solenoid valves (V4)
(V5) and a slight differential pressure sensor (105). These valves (V1) to (V5) and the differential pressure sensor (105) are provided on the top wall (1c) on the left side of the pressure supply device (71) in the housing (1).
(106).

The above five valves (V1) to (V5) are all diaphragm type direct acting three-port two-position valves. In the drawings, for the sake of convenience, a diaphragm-type direct acting three-port valve is referred to as J
It is represented by using the channel symbol of the pneumatic 3-port solenoid valve of ISB8374. Exit port in drawings
(A), inlet port (P) and exhaust port (R) are COM (common) port of diaphragm type direct acting 3 port valve, NC
It corresponds to a (normally closed) port and a NO (normally open) port, respectively. For each of the valves (V1) to (V5), the non-energized state is referred to as an off state, and the energized state is referred to as an on state. In each of the valves (V1) to (V5), in the off state, the outlet port (A) (COM port) and the exhaust port (R) (NO port)
Communicates with each other to shut off the connection between the outlet port (A) and the inlet port (P) (NC port). In the ON state, the outlet port (A) communicates with the inlet port (P) and the outlet port (A) communicates with the outlet port (P). The connection between the port (A) and the exhaust port (R) is shut off.

The fine differential pressure sensor (105) constitutes a differential pressure detecting means for detecting the differential pressure between the pressure in the nozzle (69) and the pipe (72) communicating therewith and the atmospheric pressure. The sensor (105)
The differential pressure between the + side pressure port (hereinafter abbreviated as “+ port”) (105a) and the − side pressure port (hereinafter abbreviated as “−port”) (105b) is detected, and the detected value (digital value) ) Display
(107) and output to the control device (108).
As the micro differential pressure sensor (105), full scale 30mmH ₂
It is desirable that the resolution is not less than O and not more than ₂ mmH ₂ O. As the micro differential pressure sensor (105), for example, a semiconductor diffusion type micro differential pressure sensor SCXL004DN manufactured by Krone Co., Ltd. can be used. The full scale of this sensor is 100m
mH ₂ O, resolution 1 mmH ₂ O, reproducibility ± ₂ mmH ₂
O, the overload withstand voltage is 250 mmH ₂ O.

The controller (108) controls the motors (76), (84), (92), (100) and the valves (V1) to (V) based on the output of the sensor (105) and the like.
5) is controlled. The processing in the control device (108) is performed using, for example, a microcomputer or the like, but the control device (108) functionally includes a liquid level detection determination unit (109) and a drive control unit (110). I have. Judgment unit
(109) is a part of the liquid level detection device (73),
The output means (differential pressure) of (5) is larger than a predetermined determination value, and constitutes a determination means for detecting that the suction port (15a) of the nozzle tip (15) has reached the liquid level. Drive control unit (11
0) is based on the determination result in the determination unit (109),
The motors (76), (84), (92), (100) and the valves (V1) to (V5) are controlled.

The outlet port (A) of the first valve (V1) is connected to the suction port (98c) of the first syringe pump (98), and the outlet port (A) of the second valve (V2) is connected to the second syringe pump (99). ), Respectively, and the inlet port (P) of these valves (V1) (V2) is connected to the exhaust port (R) of the third valve (V3). The exhaust ports (R) of the first and second valves (V1) (V2) are open to the atmosphere. The outlet port (A) of the third valve (V3) is connected to the nozzle base (7
4) It is connected to the upper end. Then, while the third valve (V3) is off, the first valve (V1) (or the second valve (V2)) is switched on, and the piston rod (98b) of the syringe pump (98) (99) is turned on.
By lowering (99b), the air in the nozzle (69) is released from the syringe (98a) (or the second syringe pump 98) of the first syringe pump (98).
It is sucked into the syringe (99a) of the syringe pump (99) and a negative pressure is supplied to the nozzle (69). Conversely, the piston rods (98b) and (99b) of the syringe pumps (98) and (99) are By raising, the air in the syringe (98a) of the first syringe pump (98) (or the syringe (99a) of the second syringe pump (99)) is discharged into the nozzle (69), and the air in the nozzle (69) is discharged. Is supplied with a positive pressure.

The inlet port (P) of the third valve (V3) is connected to the fourth valve (V4)
Of the fourth valve (V4) connected to the outlet port (A) of the
(P) is connected to a nitrogen supply device (112) via a manual on-off valve (111). The manual on-off valve (111) is normally open. The nitrogen supply device (112) constitutes inert gas supply means for supplying an inert gas into the nozzle (69) and the pipe (72) communicating with the nozzle (69). Exhaust port of 4th valve (V4)
(R) is connected to the outlet port (A) of the fifth valve (V5), and the fifth valve (V
5) Exhaust port (R) is + port (105) of differential pressure sensor (105).
Connected to a). The inlet port (P) of the fifth valve (V5) and the minus port (105b) of the sensor (105) are open to the atmosphere.

The dispensing device (7) is provided with a container lid attaching / detaching device (113). This device (113) is for removing the lid (13a) when sucking the solvent from the solvent container (13) into the nozzle (69), and is configured as follows.

A guide block (114) is fixed to the rear portion on the right side of the second movable body (83), and a vertically long elevating member (second elevating member) (115) is vertically movable on this block (114). It is supported by. A guide rail (116) extending in the vertical direction is fixed to the left side on the rear side of the second elevating member (115), and the guide rail (116) is supported by the guide block (114) so as to be vertically slidable. A vertically extending rack (117) is fixed to the front left side of the second elevating member (115).
Teeth (117a) are formed on the left surface of (117). A drive shaft (118) having a square cross section extending horizontally in the front-rear direction and an electric motor (11)
9) is provided. The second mobile unit (83) has a pinion (1
The boss (120a) of the (20) is rotatably supported, and the drive shaft (118) is passed through the center of the boss (120a), and the pinion (12a) is
0) and the drive shaft (118) do not rotate with each other, but can relatively move in the axial direction (front-back direction). Pinion (12
0) meshes with the teeth (117a) of the rack (117) of the second elevating member (115). Then, when the second moving body (83) moves forward and backward along the girder (80), the pinion (120)
Also moves back and forth along the drive shaft (118),
(83) in any position in the front-rear direction, the motor (11
By rotating the drive shaft (118) in 9), the pinion
The (120) is driven to rotate, and the second elevating member (115) moves up and down together with the rack (117) engaged therewith.

A guide block (121) is fixed to the lower right portion of the second elevating member (115), and a linear motion ball bearing (shown in the drawing) provided on the inner periphery of a hole vertically passing through the right portion of the guide block (121). An electromagnet support rod (122) is provided inside the guide block (121), and a push rod (123) is provided inside a linear motion ball bearing (not shown) provided on the inner periphery of a hole vertically passing through the left side portion of the guide block (121). Are passed through each so as to be able to move up and down. Guide block (121)
A base end of a first stopper (124) extending horizontally to the left is fixed to a portion of the support rod (122) protruding upward.
The left end of the stopper (124) is cut out in a U-shape,
The push rod (123) has a bifurcated shape, and the push bar (123) is fitted in the notch (124a) so as to be vertically movable. A proximal end of a second stopper (125) extending horizontally to the right is fixed to a portion of the push rod (123) protruding above the first stopper (124). The right end of the second stopper (125) is cut out in a U-shape to form a bifurcated shape, and a portion of the support rod (122) above the first stopper (124) is vertically It is set to be movable. A vertical columnar electromagnet (126) is fixed to the lower end of the support rod (122) so as to be eccentric to the right. A compression coil spring (127) for urging the support rod (122) and the electromagnet (126) downward around the support rod (122) between the upper surface of the electromagnet (126) and the lower surface of the guide block (121). ) Is provided, and the electromagnet (126) is usually moved to the first stopper (12) by a spring (127).
4) is held at the lower end position where it is pressed against the upper surface of the guide block (121). Pressing member (12
8) is provided, and a flange (123a) is formed at a portion of the push rod (123) between the guide bar (121) and the guide block (121).
A compression coil spring (129) for biasing the push rod (123) downward is provided around the push rod (123) between the flange (123a) and the lower surface of the guide block (121), Push rod
(123) is normally held at the lower end position where the second stopper (125) is pressed against the upper surface of the first stopper (124) by the spring (129). Then, the support rod (122), the electromagnet (126) and the push rod (123) move up and down together with the second elevating member (115). When the second stopper (125) is in close contact with the upper surface of the first stopper (124), the lower surface of the pressing member (128) is located slightly below the lower surface of the electromagnet (126). I have.

The dispensing device (7) also has a liquid receiving device (130).
Is provided. This device (130) is for preventing the dripping of the liquid from the nozzle (69) when the dripping occurs and preventing it from dropping to other portions. The device (130) is configured as follows.

A guide rail (131) extending horizontally in the left-right direction is disposed below the second moving body (83) on the left side of the nozzle (69), and a left-right moving body (third moving body) is provided below the guide rail (131). (132)
Are movably supported left and right. A rack (133) extending horizontally in the left-right direction is fixed to the rear side of the third moving body (132), and teeth (133a) are formed on the upper surface of the rack (133). Below the spar (80) of the first moving member (78), a drive shaft (134) extending horizontally in the front-rear direction and having a square cross section and an electric motor (135) for driving the same are provided. 2nd mobile
The boss (136a) of the pinion (136) is rotatably supported below the (83), and the drive shaft (13) is centered on the boss (136a).
4), the pinion (136) and the drive shaft (134) do not rotate with each other, but can relatively move in the axial direction (front-back direction). The pinion (136) meshes with the teeth (133a) of the rack (133) of the third moving body (132). When the second moving body (83) moves in the front-rear direction along the spar (80), the pinion (136) also moves in the front-rear direction along the drive shaft (134), and the second moving body (83) moves. ) Is at any position in the front-rear direction, the drive shaft (134) is rotationally driven by the electric motor (135), so that the pinion (136) is rotationally driven, and the third moving body together with the rack (133) meshing therewith. (132) moves left and right.

An upper end of a plate-like arm (137) extending downward is fixed to the right end face of the third movable body (132). The lower end of the arm (137) is bent to the right at a right angle, and the liquid receiving container (138) is attached to this portion. The liquid receiving container (138) moves between the rightmost operating position located immediately below the nozzle (69) at the upper end position and the leftmost standby position with the movement of the third movable body (132). Let me do.

The reaction liquid drying apparatus (8) is configured as follows.

A pair of front and rear vertical linear bearings (139) are provided at the lower part of the center of the beam (80) of the first moving body (78) in the front-rear direction. Have been. The front and rear ends of the horizontal connecting rod (141) are fixed to the upper ends of the two lifting rods (140), and the left end of the horizontal support frame (142) is fixed to the lower ends thereof. Connects the two lifting rods (140) to each other. A vertical rack (143) is fixed between the middle part in the front-rear direction of the connecting rod (141) and the middle part in the front-rear direction of the left part of the support frame (142), and is fixed to the right surface of the rack (143). Teeth (143a) are formed. digit
At the lower part of (80), a pinion (145) that is rotated about a horizontal axis in the front-rear direction by an electric motor (144) is provided, and this pinion (145) meshes with the teeth (143a) of the rack (143). . Then, the pinion (145) is rotationally driven by the electric motor (144), so that the lifting rod (140) and the support frame (142) move up and down together with the rack (143) engaged therewith.

At the lower part of the support frame (142), three distribution pipes (146) extending horizontally in the front-rear direction are arranged, and at the lower part of each pipe (146), ten nozzles (147) are fixed in the front-rear direction. It is fixed downward at intervals. These 30 nozzles (147)
Position is a set of 30 container holders on a rotary shaker (6)
This corresponds to the position of the reaction container (48) held in (57).
That is, the position of the nozzle (147) in the front-rear direction is the same as that of the reaction vessel (48) held in the vessel holder (57) of the reaction vessel storage table (38) at the origin position of the rotary shaker (6). The distance between the nozzles (147) in the left-right direction is equal to the position in the left-right direction of the reaction vessel (48). Each distribution pipe (146) is connected to a nitrogen supply device (112) via an electromagnetic on-off valve (148) and a manual on-off valve (149), respectively. These manual on-off valves (14
9) is normally open.

FIGS. 21 to 24 show a dispensing device during dispensing operation.
The valves (V1) to (V1) of the pipe (72) and the liquid level detection device (73) of (7)
It is a figure which shows the switching state of 5). Next, referring mainly to these drawings, the liquid (solvent) contained in the solvent container (13) of the solvent container storage section (3) is supplied to the reaction vessel (48) of the rotary shaker (6).
The operation of the dispensing device (7) when dispensing into a dispenser is described. 21 to 24 also show the syringe pump.
(98) and (99) are shown such that the actual left side is the upper side of the figure.

First, the turntable (12) of the solvent container storage section (3) is rotated to supply the solvent container (1) to be dispensed.
3) is stopped at a position where it comes to a predetermined suction work position, and the electric motors (76) and (84) are driven to drive the first and second moving bodies (78).
(83) is moved, and the electromagnet (12
6) is stopped at a position just above the solvent container (13) at the suction working position.

Next, the lid (13a) of the container (13) is removed by the container lid attaching / detaching device (113) as follows. That is, first, the electric motor (119) is driven, and the second lifting member (115) of the container lid attaching / detaching device (113) is lowered. When the elevating member (115) descends, first, the pressing member (128) at the lower end of the push rod (123) comes into pressure contact with a portion near the outer periphery of the lid (13a) of the reaction vessel (13), and stops, and When the member (115) further descends, the electromagnet (126) comes into pressure contact with the center of the lid (13a) and stops, and then the elevating member (115) stops. Elevating member (115)
Stops, the electromagnet (126) stops at a position where the first stopper (124) is slightly above the upper surface of the guide block (121) against the elastic force of the spring (127), (one two Three)
The second stopper (125) stops at a position slightly above the upper surface of the first stopper (124) against the elastic force of the spring (129). When the lifting member (115) stops, the electromagnet (12
6) is energized, and the elevating member (115) is raised to the original upper end position. When the electromagnet (126) is energized and excited, the portion of the iron plate of the lid (13a) is attracted to the electromagnet (126). When the elevating member (115) rises, only the guide block (121) rises first, and when the upper surface of the guide block (121) hits the first stopper (124), the electromagnet (126) also rises. When the electromagnet (126) rises, the lid (13a) adsorbed on the electromagnet (126) also rises and is removed upward from the container (13). At this time, the magnetic attractive force of the electromagnet (126) is larger than the elastic force of the spring (129) of the push rod (123), and therefore,
The electromagnet (126) sucks the lid (13a) and rises while pushing the push rod (123) upward. In addition, the second lifting member (115)
Before starting the downward movement, the electromagnet (126) may be energized.

When the second lifting member (115) rises to the upper end position and stops, the second moving body (83) is moved rearward,
The nozzle (69) is stopped at the suction work position just above the container (13). Then, the liquid in the solvent container (13) is sucked into the nozzle tip (15) as follows. Nozzle (69)
When has moved to the suction work position, the nozzle (69) has risen to the upper end position of the stroke, the piston rods (98b) (99b) of the pumps (98) (99) have risen to the left end position of the stroke, As shown in FIG. 21, only the third valve (V3) is turned on. Then, since the third valve (V3) is turned on, the inside of the nozzle (69) and the +
Port (105a) is in communication. When the nozzle (69) moves to the suction position and stops, the electric motor (92) is driven and the nozzle (69) is driven.
(69) starts descending toward the liquid level in the container (13). The lowering speed of the nozzle (69) is preferably 3 to 15 mm / sec, for example, 10 mm / sec. While the nozzle (69) is descending, the determination unit (109) outputs the output of the sensor (105),
(69) and the pressure difference between the pressure in the pipe (72) communicating therewith and the atmospheric pressure are constantly monitored, and when the pressure difference exceeds the determination value, the liquid level detection signal is sent to the drive control unit (110 ). The drive control unit (110) continues to drive the electric motor (92) to continue lowering the nozzle (69) until the liquid level detection signal is output from the determination unit (109), and the liquid level detection signal is output. Then, the motor (92) is stopped to stop the nozzle (69). This determination value is appropriately set according to the type of the liquid, the type of the nozzle tip (15), and the like, and is set to, for example, 2.5 mmH ₂ O. Until the lower end of the nozzle tip (15) reaches the liquid level, the inside of the nozzle (69) communicates with the atmosphere through the suction and discharge port (15a), so that the output of the sensor (105) is almost 0, No liquid level detection signal is output from (109), and the nozzle (69) continues to descend.

When the lower end of the nozzle tip (15) reaches the liquid level, the liquid penetrates into the nozzle tip (15) through the suction / discharge port (15a) by capillary action. The internal volume of the air layer in (72) changes slightly, and the internal pressure changes slightly. For this reason, the output of the sensor (105) becomes larger than the determination value, the determination unit (109) outputs a liquid level detection signal,
The motor (92) is stopped, and the lowering of the nozzle (69) stops. When the liquid level is detected in this way and the nozzle (69) stops, the nozzle tip (15) is reduced by the amount of liquid to be sucked.
Is infiltrated into the liquid to start inhaling the liquid. The liquid is, for example, ethyl acetate, DMA (dimethylaniline), DM
In the case of an organic solvent system such as F (N, N-dimethylformamide), the nozzle tip (15)
The liquid penetrates into the nozzle tip (15) by capillary action at the moment when the lower end of the liquid comes into contact with the liquid surface. Therefore, the nozzle (69) can be stopped in a state where the penetration depth of the nozzle tip (15) from the liquid level (hereinafter, simply referred to as “penetration depth”) is almost 0, and after the stop, the nozzle tip (15) is stopped. Can be immersed in a predetermined amount of liquid, and the suction of liquid can be started as it is. When the liquid is an aqueous solution, the liquid penetrates into the nozzle tip (15) when the head at the penetration depth position of the nozzle tip (15) overcomes the surface tension at the lower end of the nozzle tip (15). For this reason, the nozzle tip (15) stops in a state where it has penetrated a predetermined amount from the liquid level. The penetration depth when the nozzle tip (15) stops varies depending on the liquid and the type of the nozzle tip (15), but is at most about several mm. In addition, since the penetration depth is determined by the type of the liquid and the nozzle tip (15) and can be obtained in advance, after the nozzle (69) stops, the penetration depth is equal to or slightly smaller than the penetration depth. Only raise the nozzle (69) and then use the nozzle tip (1
5) may be immersed in a predetermined amount of liquid to start sucking the liquid. As described above, by coating a non-adhesive resin on at least the inner peripheral surface of the tip of the nozzle tip (15), when the type of liquid or nozzle tip (15) is the same, when there is no coating In comparison, the nozzle tip (1
It has been confirmed by experiments that the penetration depth when 5) stops is halved. Further, if the outer peripheral surface of the lower end portion of the nozzle tip (15) is also coated, the liquid is less likely to adhere to the outer peripheral surface, and there is little possibility that the adhered liquid drips and the dispensed amount is changed.

As shown in FIG. 22, the liquid is sucked in the first
And one of the second valves (V1) and (V2) (in this case, the first valve
While the third valve (V3) is turned off while the third valve (V1) is turned on, the electric motor (100) is driven and the pump (9) is turned on.
8) This is performed by moving the piston rod (98b) (99b) of (99) to the right end position of the stroke. When the first valve (V1) is turned on and the third valve (V3) is turned off, the nozzle (69) communicates with the syringe (98a) of the first pump (98), and the piston rod (98b) Nozzle (69) by moving to the right
A negative pressure is supplied to the inside, and the liquid is sucked. At this time,
As for the second pump (99), the inside of the syringe (99a) becomes a negative pressure by moving the piston rod (99b) to the right.
Since the syringe (99a) is in communication with the atmosphere by the second valve (V2) in the off state, only air in the atmosphere is sucked into the syringe (99a) through the valve (V2).

When the piston rods (98b) and (99b) of the pumps (98) and (99) move to the right end position and the suction of the liquid ends, the electric motor
(92) is driven, the nozzle (69) rises to the upper end position,
The second moving body (83) is moved to the front side, and stopped at a position where the electromagnet (126) of the container lid attaching / detaching device (113) comes directly above the solvent container (13) without the lid at the suction work position. Can be Then, the solvent container (13) is covered with the lid (13a) by the container rim detaching device (113) as follows. That is, first,
The second lifting member (115) is lowered to a position slightly below the position where the lid (13a) held by the electromagnet (126) is pressed against the container (13). As a result, the electromagnet (126) moves upward with respect to the guide block (121), and the first stopper (124) separates slightly above the upper surface of the guide block (121). Next, the energization of the electromagnet (126) is stopped, and the elevating member (115) is raised to the upper end position. When the energization of the electromagnet (126) is stopped and demagnetized, the magnetic attraction disappears. When the lifting member (115) rises, the guide block (12
Only 1) goes up, and the guide block (121) is
At (124), the electromagnet (126) also rises. At this time, since the pressing member (128) of the pressing rod (123) is pressed against the lid (13a) by the elastic force of the spring (129),
(126) is securely separated from the lid (13a), and the lid (13a) is removed from the solvent container (1).
3) Leave above and rise. Then, the first stopper (124)
When the lever hits the second stopper (125), the push rod (123) also moves away from the lid (13a) and rises. When the second elevating member (115) rises to the upper end position, the electric motor (135) is driven, and the liquid receiving container (138) of the liquid receiving device (130) stopped at the standby position on the left end moves the nozzle (69). When the liquid drops from the supply / drain port (15a) of the nozzle (69), it is received.

Next, the first and second moving bodies (78) and (83) are moved, and the nozzle (69) is moved to a predetermined position on the reaction vessel storage table (38) at the origin position of the shaker (6). It is stopped at the position where it comes to the discharge work position just above the reaction vessel (48). Nozzle (6
When (9) stops at the discharge work position, the liquid receiving container (138) of the liquid receiving device (130) moves from the operating position immediately below the nozzle (69) to the leftmost standby position, and then, if necessary, the motor ( 9
2) is driven, and the nozzle (69) descends to a predetermined height. Then, in order to discharge the liquid, the electric motor (100) is driven, and the piston rods (98b) (99b) of the pumps (98) (99) move to the left end position. As a result, a positive pressure is supplied into the nozzle (69), and the liquid sucked into the nozzle tip (15) is discharged into the reaction vessel (48). At this time, also in the second pump (99), the piston rod (99b) moves to the left, so that the pressure in the syringe (99a) becomes positive. However, the second pump (99a) turns off the air in the syringe (99a). It is only discharged into the atmosphere through two valves (V2).

When the piston rods (98b) and (99b) of the pumps (98) and (99) move to the left end position and the discharge of the liquid is completed, if necessary, the electric motor (92) is driven and the nozzle (69) is driven. ) Rises to the upper end position, and then the first and second moving bodies (78) and (83) are moved and the electromagnet (126) of the container lid attaching / detaching device (113) is moved in the same manner as described above. Is stopped at a position just above the solvent container (13) in the suction working position. And
23, 24 and 21 are performed until the electromagnet (126) stops right above the solvent container (13).

First, as shown in FIG. 23, the first valve (V1) is turned off, and the third and fifth valves (V3) (V
5) is switched on. When the first valve (V1) is turned off, the syringe (98a) of the first pump (98) turns the nozzle (69)
When the third valve (V3) is turned on, the nozzle (69) is connected to the outlet port (A) of the fourth valve (V4), and the fifth valve (V5) is turned on. This allows the exhaust port (R) of the fourth valve (V4) to communicate with the atmosphere.

Next, as shown in FIG. 24, the fourth valve (V4) is turned on, and a nitrogen purge is performed. 4th valve (V
Nitrogen gas at a predetermined pressure is always supplied from the nitrogen supply device (112) to the inlet port (P) of (4), but when the valve (V4) is off, the inlet port (P) and the outlet port ( Since the air flow is cut off from the air flow, the nitrogen gas does not flow anywhere. However, when the fourth valve (V4) is turned on, the inlet port (P) and the outlet port (A) communicate with each other, so that nitrogen gas flows through the fourth valve (V4),
It flows through the third valve (V3) and the nozzle (69), and
Emitted from 5a). This nitrogen purge is for eliminating the residual vapor pressure of the organic solvent in the nozzle (69) and the pipe line (72), and accurately detecting the above-mentioned differential pressure,
For example, it is performed for a few seconds. At the moment when the fourth valve (V4) is turned on, the inlet port (P)
(R), a small amount of nitrogen gas flows to the outlet port (A) of the fifth valve (V5). However, since the fifth valve (V5) is on, this nitrogen gas is supplied to the fifth valve (V5). V5) is discharged into the atmosphere from the inlet port (P) and does not flow to the sensor (105). Therefore, the overload pressure does not act on the sensor (105).

When the nitrogen purge has been performed for a predetermined time, the fourth valve (V4) is turned off, the nitrogen supply device (112) is disconnected (the same state as in FIG. 23), and the fifth valve (V4) is further turned off. V5) is switched off, and returns to the state of FIG. Then, in such a state, the pressure difference between the pressure in the nozzle (69) and the pipe (72) and the atmospheric pressure is smaller than a predetermined minute pressure value, that is, the nozzle (69) and the pipe (72) It is confirmed that there is no residual pressure inside, and the above operation is repeated. The minute pressure value can be set as appropriate, for example, 0.3
mmH ₂ O.

In the above, when the type of the solvent to be dispensed changes, the solvent is discharged into the reaction vessel (48), and then the used nozzle tip (15) is removed from the removal section (1) of the tip disposal section (5).
6), dispose of it in the storage container (151), and a predetermined nozzle tip storage base (14a) (14b) in the nozzle tip storage section (4).
From the predetermined position of (14c), a new nozzle tip (15) to be used next is mounted.

In the above description, the first syringe pump (98)
The second syringe pump (99) is also used depending on the type of liquid to be dispensed. Second
When the syringe pump (99) is used, the first valve (V1) is kept off, and the first valve (V1) in the above description is turned on and off.
The on / off operation of the second valve (V2) may be performed instead of the off operation.

Dispensing of a liquid (liquid raw material) from the raw material container (10) to the reaction container (48) is performed in substantially the same manner as described above, but since the raw material container (10) is not provided with a lid, No lid removal device (113) is used.

As described above, the dispensing device (7) detects that the nozzle tip (15) has reached the liquid level and detects the nozzle (6).
9) is stopped, and after a predetermined amount of the nozzle tip (15) is immersed in the liquid, the liquid is sucked in, so that the nozzle tip (15) does not intrude below the liquid level more than necessary. For this reason, adhesion of the liquid to the outer peripheral surface of the lower end portion of the nozzle tip (15) can be minimized, and liquid dripping and fluctuation of the dispensed amount can be prevented, and accurate dispensing can be performed. It is possible to reduce the number of times of replenishing the container with liquid. Also, since no air is sucked, the dispensed amount is accurate.

Further, since the liquid level can be detected only by inserting the nozzle tip (15) into the container, it can be used even when small-diameter containers are densely packed.

Also, while the nozzle (69) is being lowered,
There is no need to supply pressure (positive pressure or negative pressure) into the nozzle (69), so there is no need to provide pressure supply means in addition to the pressure supply device (71) for suctioning and discharging liquid. After the nozzle tip (15) reaches the liquid level, a predetermined amount of the nozzle tip (15) is immersed in the liquid, and then the pressure supply device
By operating (71), a desired amount of liquid can be accurately sucked, and control of the pressure supply device (71) is easy.

Further, even if the ambient temperature changes, the nozzle (6
9) and the pressure difference between the pressure in the pipe (72) communicating therewith and the atmospheric pressure does not change. Further, even if vibration is applied to the nozzle (69) and the pipe (72) when the nozzle (69) is lowered, the inner volumes of the nozzle (69) and the pipe (72) do not change. (69) and the pressure in line (72) also remain unchanged. Therefore, the liquid level can always be accurately detected.

In the above automatic synthesizing apparatus, the automatic synthesizing operation is controlled by a control device having a computer (not shown), and is performed, for example, as follows.

First, among the reaction vessels (48) of the reaction vessel storage table (38) of the shaker (6), the same type of solid raw material is put into the first set of 30 reaction vessels (48). Next, a first set of 30 reaction vessels is removed from the predetermined solvent vessel (13) by the pipetting device (7).
A solvent is added to (48) to dissolve or suspend the solid raw material. Next, different liquid raw materials are respectively added and mixed from the predetermined raw material container (10) into the first set of 30 reaction containers (48) by the dispensing device (7), and the reaction is started. Then, the shaker (6) is operated for a certain period of time, and the reaction solution in the reaction vessel (48) is stirred to cause a reaction. At this time, if necessary, the heat medium circulation space of the reaction vessel storage table (38) of the shaker (6)
The reaction solution is heated or cooled by circulating a suitable heat medium such as hot water or cold water in (62). When the reaction is completed, ethyl acetate and water are sequentially added from the solvent container (13) to the reaction solution in the first set of 30 reaction containers (48) by the pipetting device (7) (start of post-treatment). ). Next, shaker
(6) was operated to stir the liquid in the reaction vessel (48), the shaker (6) was stopped, and after standing still, the first liquid was dispensed by the dispenser (7).
The upper ethyl acetate layer in the set of 30 reaction vessels (48) is sequentially transferred to the corresponding one of the second set of 30 reaction vessels (48) on the left (first extraction with ethyl acetate). . next,
Fresh ethyl acetate was added from the solvent vessel (13) to the first set of 30 reaction vessels (48) by the pipetting device (7), and the shaker (6) was added.
After stirring, the mixture was allowed to stand still, and the upper ethyl acetate layer was similarly placed in the second set of 30 reaction vessels (4
Transfer to 8) (second extraction with ethyl acetate). Next, similarly, a third extraction operation with ethyl acetate is performed. Next, fresh water was added from the solvent container (13) to the ethyl acetate in the second set of 30 reaction containers (48) by the pipetting device (7), and the mixture was stirred by the shaker (6). (Wash the extract). Then, the second set of 30
The upper ethyl acetate layer in each reaction vessel (48) is sequentially transferred to the corresponding one of the third set of 30 reaction vessels (48) on the left. Next, the first moving body (78) is moved to stop the nozzle (147) of the reaction liquid drying device (8) at a position just above the third set of 30 reaction vessels, and After driving (144) and lowering the nozzle (147), the solenoid valve (14
8) is opened, and nitrogen gas is blown into the reaction vessel (48) from the nozzle (147) to concentrate and dry the reaction solution. When the blowing of the nitrogen gas is completed, the nozzle (147) is raised to the upper end position. Thus, the treatment may be terminated. If necessary, DMSO (dimethylsulfoxide) is added from the solvent container (13) to the reaction solution concentrated and dried by the dispenser (7), and the evaluation is performed. Adjust the solution for the reaction vessel (48)
Sample dispenser (7)
The sample is sequentially dispensed into the corresponding sample containers of (152), and the process is terminated.

In the above operation, the dispensing device (7)
If necessary, discard the old nozzle tip (15) into the container (16) of the disposal section (5) and install a new nozzle tip (15) from the nozzle tip storage section (4) if necessary. To use.

[Brief description of the drawings]

FIG. 1 is a partially cutaway plan view of an automatic synthesizer according to an embodiment of the present invention.

FIG. 2 is a partially cutaway front view of FIG. 1;

FIG. 3 is a left side view, partly cut away, of FIG. 1;

FIG. 4 is a partially cutaway right side view of a portion of a rotary shaker.

FIG. 5 is a partially cutaway plan view of FIG. 4;

FIG. 6 is an enlarged longitudinal sectional view showing a part of FIG. 4;

FIG. 7 is a partially cutaway right side view showing another portion of FIG. 4 in an enlarged manner.

FIG. 8 is an explanatory diagram showing a part of FIG. 6 in an enlarged and simplified manner to explain the balance of static force due to centrifugal force and the balance of bending moment due to centrifugal force during rotation. .

FIG. 9 is an explanatory diagram showing an entire configuration of a dispensing device.

FIG. 10 is an explanatory diagram showing a configuration of a main part of the dispensing device.

FIG. 11 is a partially cutaway plan view showing a main part of the dispensing device.

FIG. 12 is a right side view of a partially cut-away portion of FIG. 11;

FIG. 13 is an enlarged sectional view taken along line S13-S13 of FIG. 11;

FIG. 14 is an enlarged sectional view taken along line S14-S14 of FIG. 11;

FIG. 15 is a sectional view showing a part of FIG. 14 in an enlarged manner.

FIG. 16 is a partially cutaway plan view of the front part of FIG. 13;

FIG. 17 is a sectional view taken along line S17-S17 in FIG. 13;

FIG. 18 is a sectional view taken along line S18-S18 in FIG. 13;

FIG. 19 is a sectional view taken along line S19-S19 in FIG. 13;

FIG. 20 is an enlarged cross-sectional view taken along line S20-S20 of FIG. 2;

FIG. 21 is an explanatory diagram showing a state of a solenoid valve in a certain process of a dispensing operation of the dispensing device.

FIG. 22 is an explanatory diagram showing a state of the solenoid valve in a process different from the above in the dispensing operation of the dispensing device.

FIG. 23 is an explanatory diagram showing a state of the solenoid valve in a dispensing operation of the dispensing device in a process different from the above.

FIG. 24 is an explanatory diagram showing a state of the solenoid valve in a dispensing operation of the dispensing device in a process different from the above.

[Explanation of symbols]

 (2) Material container storage unit (3) Solvent container storage unit (4) Nozzle chip storage unit (6) Rotary shaker (7) Dispensing device (means) (8) Reaction liquid drying device (means) (10) Raw material container (13) Solvent container (15) Nozzle tip (38) Reaction vessel storage table (48) Reaction vessel

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Osamu Nakamura No. 8, Kamashitana, Nagaokakyo-shi, Kyoto Inside Dainippon Seiki Co., Ltd. (72) Shintaro Nishimura 4-3-34-517, Tsuruno, Settsu-shi, Osaka (72) ) Inventor Akito Tanaka 2-241-401 Yoneya, Takarazuka City, Hyogo Prefecture

Claims (2)

[Claims] 1. A raw material container storage unit for storing a plurality of raw material containers containing at least a liquid raw material, a nozzle chip storage unit for storing a plurality of disposable nozzle tips, a reaction container storage table for storing and shaking a plurality of reaction containers. A rotary shaker having: and, which can be moved between the storage sections and the reaction vessel storage table of the rotary shaker, automatically performs the detachment of the nozzle tip, and uses the attached nozzle tip to perform the An automatic synthesizing apparatus comprising: a dispensing means for sucking a liquid raw material in a raw material container and a solvent in the solvent container and discharging the liquid material into the reaction container. 2. A reaction solution drying means for concentrating and drying a reaction solution in the reaction vessel.
Automatic synthesis equipment.