JP2001169771A - Automatically pipetting unit - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatically pipetting unit capable of always performing the pipetting of a test sample and a microorganism-containing solution with high accuracy without causing operational errors, capable of achieving labor saving and an improvement in operation efficiency. SOLUTION: This automatically pipetting unit is equipped with plural mixing containers 31, plural sampling containers 61, and plural microorganism containers 36 which are dispersedly arranged in prescribed positions, support arms 21, 71, 72 which are accessible to the mixing containers 31, the sampling containers 61, and the microorganism containers 36, pipetting probes 65, 66 which are attached to the support arms, liquid amount-adjusting means 78, 79 which lead to the probes so as to adjust a pipetting amount to be injected, controlling means 2, 3 which control drives of the support arms and the liquid amount- adjusting means so that the test sample and the microorganism-containing solution are pipetted and injected into the mixing container 31 according to a prescribed amount to be pipetted and injected, and further with a memory means 3 which memorizes data about the pipetting and injecting operations so that the data can be read out and corresponding to the prescribed amount to be pipetted and injected.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a mutagenicity test (Ames test) using bacteria as one of safety tests for evaluating the carcinogenicity (mutagenicity) of a chemical substance, and an aseptic operation. The present invention relates to an automatic dispensing apparatus that is suitably used for a biological test that requires the above-mentioned method, and also for pretreatment of a specimen for performing a chemical analysis, and that dispenses at least a test sample and a microorganism-containing liquid.

[0002]

2. Description of the Related Art For example, in the Ames test, a flow chart is shown in FIG. 14 for a sample treatment group, a negative control group, and a positive control group for each of Buffer (buffer) and S9mix (metabolizing enzyme) solution for five kinds of bacteria. The test operation is performed according to the following procedure.

First, the number of test tubes used for the test is prepared for a test tube stand (S1). Next, the sample is weighed (S2), a dilution series having several levels of concentration is prepared using a solvent, and is dispensed into test tubes using a handy pipettor according to the concentration. Further, the negative control substance and the positive control substance are dispensed (S3), and it is confirmed that the dispensation has been made to all the test tubes.

[0004] Next, at regular time intervals, a reagent of a non-metabolic buffer solution is dispensed (S4), mixed gently, and the test bacteria are dispensed with a micropipette (S5). Then, cap the test tube, 37 ° C, 100 times / min.
Pre-incubation (referred to as pre-incubation method) in a constant temperature water bath for 20 minutes (S6). The same operation is performed for the metabolic activation system using the reagent of the S9 mix solution (S
7 and S8). These series of operations are performed for each strain.

After 20 minutes, the test tube is taken out of the water bath at the same fixed time interval as before the pre-incubation, the water drop on the bottom of the test tube is gently wiped with a Kim towel, the test tube cap is removed, and the temperature is maintained at about 45 ° C. The dispensed top agar is dispensed with a dispenser (S9). After that, put the test tube between both hands and mix by rubbing so that it does not foam, remove the lid of the plate, drop the last drop on a minimal glucose agar plate medium by lightly contacting the agar, and drop the lid. Then, it is spread uniformly (S10).

Thereafter, the plate is left standing on a flat surface for about 2 to 3 minutes to solidify, and then the plate is placed upside down in a Petri dish and cultured for about 2 days in a 37 ° C. incubator (S1).
1) After the culturing, the mutant colonies that have appeared are counted by an automatic colony counter or visually (S12).

[0007] A series of operations of the above test is repeatedly performed for each test tube by the same operation for the number of test tubes. There is also a plate method in which preincubation is not performed in a constant temperature water bath at 37 ° C. for 20 minutes.

The above-mentioned Ames test is based on the G
Performed in accordance with LP (Good Laboratory Practice)
There are GLP (Ministry of Health and Welfare), GLP (Ministry of Labor), GLP (Ministry of Agriculture, Forestry and Fisheries), etc., and legally secure the test results. In addition, international OECD (Or
ganization for Economic Cooperation and developmen
t; the Organization for Economic Co-operation and Development), and is a widely used test method in Europe, the United States and around the world. Therefore, in order to guarantee the reliability of the dispensing operation whether the liquid to be dispensed has been dispensed into a predetermined test tube, it is necessary for the person responsible for reliability assurance to audit.

[0009]

However, in the dispensing operation in the Ames test, as shown in the flow chart of FIG. 14, (1) the concentration from the dispensing of the sample and the control substance to the working process before the pre-incubation. The effect of the sample is examined by changing the conditions. (2) Five types of bacteria are used, and (3) There are test systems of a non-metabolically activated system and a metabolic activated system. There are test quality and labor problems as shown below.

There are many types of samples, positive control substances, negative control substances, bacteria (5 strains), buffers, and S9 mix liquids, which are complicated by restrictions on test methods, and the total number of test tubes used is large. This is a cause of dispensing mistakes such as misplacement or forgetting to place. Dispensing intervals are not constant due to the complexity of manual work. An error in the dispensed amount due to manual operation is likely to occur. The work operation by the repetition operation is a work load.

[0011] Because of the above problems, there is a concern that in the above-mentioned Ames test, data may vary, which may seriously affect the reliability of the test. On the other hand, although techniques for automating operations by various humans have been advanced, automation of assembling heavy objects and processing with a high processing speed (for example, within 5 seconds) and complicated processing is prosperous. No attempt has been made to automate so that audits can be tailored to the task.
Furthermore, it can be said that it is a difficult task to efficiently perform continuous work in a closed environment to prevent contamination from the outside in a small space, or to make it capable of being audited.

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned conventional problems. At least the test sample and the microorganism-containing liquid can be dispensed with high accuracy without causing a dispensing error. It is an object of the present invention to provide an automatic dispensing device capable of improving efficiency and work efficiency.

[0013]

In order to achieve the above object, the invention according to claim 1 is an automatic dispensing apparatus for dispensing at least a test sample and a microorganism-containing liquid. A plurality of mixing containers arranged, a plurality of sample containers containing a test sample, and a plurality of microorganism containers containing a test microorganism-containing liquid, and the mixing container, the sample container and the microorganisms A support arm accessible to the container, a dispensing probe attached to the support arm, a liquid amount adjusting means communicating with the probe to adjust the dispensed amount, and a cover in the sample container. A control system for controlling the driving of the support arm and the liquid amount adjusting means such that the test sample and the microorganism-containing liquid in the microorganism container are dispensed to the mixing container according to a preset dispensing amount. Means, is characterized in that it has a storage means for readably stores to accommodate the dispensing amount set information regarding dispensing operation.

According to a second aspect of the present invention, in the automatic dispensing apparatus according to the first aspect, the liquid amount adjusting means is a pneumatic pressure control means for causing a change in air pressure in a portion where the probe is sucked or discharged. And a pressure sensor for detecting an air pressure generated by the air pressure control means, wherein the storage means is configured to store the air pressure detected by the pressure sensor in a readable manner for each dispensing operation. Is what you do.

The invention according to claim 3 is the invention according to claim 1 or 2
In the automatic dispensing apparatus according to the above, at the dispensing position of the test sample and the microorganism-containing liquid, a holder mechanism for detachably holding the mixing container, and tiltably and swingably, At the time of dispensing the sample and the microorganism-containing liquid, the mixing container is tilted, and the test sample and the microorganism-containing liquid are dispensed by bringing the tip of the probe into contact with the inner wall of the mixing container at different discharge positions. After dispensing the test sample and the microorganism-containing liquid, the mixing container is rocked and stirred.

According to a fourth aspect of the present invention, in the automatic dispensing apparatus according to the first, second or third aspect, the sample container and the microorganism container are selectively rocked and agitated to be stirred. It has a rocking means and a vessel rocking means for microorganisms.

According to a fifth aspect of the present invention, there is provided the automatic dispensing apparatus according to the first aspect, further comprising an air-cleaned closed chamber, and the mixing chamber to which the test sample and the microorganism-containing liquid are dispensed. Discharging means for discharging the container out of the closed chamber in a sealed state, wherein a dispensing position for the mixing container is provided near an outer side of a movement trajectory of the support arm.

The invention according to claim 6 is the invention according to claim 1 or 2
In the automatic dispensing apparatus according to the above, a plurality of dispensing probes are attached to the support arm, and the control means sequentially executes dispensing operations by the plurality of dispensing probes so as not to overlap. The control is characterized in that:

[0019]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIGS. 1, 2 and 3 are a front view, a plan view and a perspective view, respectively, showing the overall schematic configuration of an embodiment of the automatic dispensing apparatus according to the present invention.
This automatic dispensing device is used for Ames test samples,
Positive control substance, negative control substance, bacteria (5 strains), buffer,
S9mix Automatically dispenses each liquid of the liquid into test tubes. It consists of a main unit 1 and a control unit 2. The control unit 2 has control means for controlling the operation of each unit and storage for storing various data. A personal computer 3 constituting the means and a printer 4 for printing out dispensing results and the like are provided.

In the main body 1, a sterile chamber (closed chamber) 11 is formed on a base 10. In the sterile chamber 11, a test tube setting section 12, a bacterial solution setting section 13, a liquid injection section 14, and an S9mix Liquid set part 15, buffer set part 16, sample set part 1
7, a small chip setting unit 18, a large chip setting unit 19, a chip disposal unit 20, and a robot unit 21 are provided. In the sterile room 11, a transparent cover 22 is provided on the base 10 so that the inside can be observed from the outside, an intake device 23 having a HEPA filter is provided on the upper surface thereof, and an exhaust device 24 is provided inside the base 10. Formed. In addition, the sterile room 1
For example, a light projector 25a and a light receiver 25b
A main body switch 28, a temperature indicator 29 for displaying the temperature of the S9 mix liquid, and a display for displaying the progress of the dispensing operation, etc. A part 30 is provided.

In the test tube setting section 12, a large number of sterilized test tubes with caps (mixing containers) 31 are housed and held in a test tube rack 32 which can be separated for each strain, and are set detachably. In this embodiment, the test tube rack 32 contains 14 test tubes of a sample treatment group having 7 concentrations in two horizontal rows as a non-metabolic activation (buffer solution) test system for one strain in the test tube rack 32 for use in the Ames test. , Three test tubes for the negative control group and three test tubes for the positive control group, and the test tubes for the metabolic activation system (S9 mix solution) were similarly stored in the next two rows.
200 test tubes 31 with caps sterilized in the same arrangement for each kind of strain are stored and held.

The bacteria solution setting section 13 is provided with five L-shaped bacteria solution container holders 35 corresponding to five types of strains, and each of the bacteria solution container holders 35 holds a required bacteria solution. The tube (microorganism container) 36 is selectively set. Further, as shown in FIG. 1, each bacteria solution container holder 35 is provided with a rocking mechanism 37 having a motor and an eccentric cam, whereby the set L-shaped pipe 36 is made to perform a seesaw motion independently at a desired speed. Then, the contained bacterial solution is stirred. In addition, since the bacteria liquid container holder 35 is supported so that the set L-shaped tube 36 can turn up and down around the bent portion thereof, the bacteria solution in the L-shaped tube 36 is swung at the time of swinging. It can smoothly move back and forth between the horizontal tube side and the vertical tube side of the L-shaped tube 36, and can effectively keep the bacterial solution in a uniform suspension state under mild conditions.

The liquid injection unit 14 holds a test tube 31 in a detachable manner, selectively tilts and swings the test tube 31, and a test tube 31 held by the holder mechanism 41. And a transfer mechanism 42 for transferring the sample from the sterile room 11 to the test tube take-out section 26 outside the front of the apparatus.

As shown in a front view in FIG. 4 and a schematic perspective view in FIG.
b, and U-shaped members 44 that are swingably supported by b, and air hands 45a, 45 that are provided on the U-shaped member 44 and that detachably clamp the test tube 31 using air as a driving source.
b, a motor 47 connected to the U-shaped member 44 via an eccentric cam 46, and an angle sensor 48 for detecting the rotation angle of the eccentric cam 46.
In a state where the test tube 31 is held between the test tubes 31a and 45b, the eccentric cam 46 is rotated in a predetermined direction by the motor 47 based on the output of the angle sensor 48 so that the test tube 31 is rotated at a predetermined angle (for example,
°) The test tube 31 is swung by inclining or rotating the eccentric cam 46 by a fixed angle in the forward and reverse directions.

The transfer mechanism 42 includes a holder mechanism 41
Extending from the dispensing position for the test tube 31 held in the test tube take-out portion 26 to the two parallel rails 49a, 49
9b, and the entire holder mechanism 41 is connected to the rails 49a, 49.
It is moved by a drive mechanism (not shown) along b.

In the S9mix liquid setting section 15, an S9mix liquid container (beaker) 51 containing the S9mix liquid is detachably set. The S9mix liquid setting part 15 is covered with a case 52 made of, for example, aluminum, except for the setting part of the S9mix liquid storage container 51, and a Peltier element 53 is provided therein to cool the set S9mix liquid storage container 51. Thereby, the S 9 contained in the S9 mix liquid container 51 is
Prevent decrease of enzyme activity of 9mix liquid. Also,
The S9mix liquid setting section 15 is provided with a swing mechanism 56 having a motor 54 and an eccentric cam 55. The swing mechanism 56 eccentrically rotates the set S9mix liquid container 51 at a desired speed, and the stored S9mix liquid is rotated. To stir.

In the buffer setting section 16, a buffer storage container (beaker) 58 that stores a buffer is detachably set.

In the sample setting section 17, 16 sample containers 61 containing a dilution series sample solution, a negative control solution, and a positive control solution are stored and held in a sample rack 62, and are set detachably. In addition, the sample setting unit 17
Is provided with a swinging mechanism similar to the swinging mechanism 56 provided in the S9mix liquid setting section 15 to set the sample rack 6
2 is eccentrically moved at a desired speed, whereby the sample liquid contained in each sample container 61 is stirred.

A plurality of unused sterilized small chips (small probes) 65 are set for each case in the small chip set section 18, and a plurality of unused sterilized sterile chips are similarly set in the large chip set section 19. A large chip (large probe) 66 is set for each case, and a detachable chip accommodating section 67 for accommodating used chips is provided in the chip disposal section 20.

The robot unit 21 has a disk-shaped head unit which is rotatable about the vertical direction at the arm tip of a horizontally articulated biaxial arm unit 71 movable in a horizontal plane and a vertical plane. The head unit 72 is configured to be three-dimensionally movable within a range indicated by a virtual line in FIG. In addition,
In FIG. 2, the illustration of the biaxial arm unit 71 and the head unit 72 is omitted. As shown also in the front view of FIG. 6, the head 72 has a test tube knob mechanism 73, a sample dispensing mechanism 74, a reagent dispensing mechanism 75, and a germ dispensing mechanism 76 around the periphery thereof. Are provided at substantially equal intervals. The two-axis arm section 71 may be a horizontal articulated arm. The horizontal articulated arm has a large horizontal compliance, so that it can be accurately applied to any object placed within the above-mentioned movement range on the base 10. Suitable for quick positioning. However, the present invention is not limited to the horizontal articulated type, and may execute each process at an operation speed that can be confirmed by the operator's eyes. It can also be changed so as to be constituted by. In addition, when the biaxial arm 71 moves up and down, the base 1
0 can be selectively accessed. Furthermore, a head section 72 whose rotation is controlled is provided at the forward end of the biaxial arm section 71, and a plurality of processing mechanism sections 73, 74, 75, and 76 are provided in the head section 72, so that complicated multifunctional processing is performed. Can be executed by a single robot unit 21, and each processing mechanism unit 7 is rotated by the rotation of the head unit 72.
3, 74, 75, and 76 can be selectively positioned in an easy-to-process direction, and the processing mechanisms 73, 73 are always located outside the main body 1 without being restricted by the arrangement of objects on the base 10.
By orienting 74, 75, and 76, processing along the GLP is possible in that the operator can observe and monitor the operation. In this case, the two-axis arm 7
By arranging the holder mechanism 41, which is the dispensing position for the test tube 31, near the outside of the movement trajectory 1, the inspection is further facilitated. In this regard, in the present embodiment, the holder mechanism 41
The various set units 12, 13, 15, 16 are not limited to
Since the shaft arm 71 is dispersedly arranged in the movement trajectory, particularly on the outer side, the layout is such that all processes can be inspected in the same manner as individual processes by hand. The head 72
The rotation of the two-axis arm unit 71 and the two-dimensional movement of the two-axis arm unit 71 result in a synergistic effect of simplifying the movement trajectory of the two-axis arm unit 71 and reducing control errors and countermeasures for abnormal operation. It also produces effects.

The test tube knob mechanism 73 includes a head 72
Air hands 77a, 77 which can move up and down with respect to and hold the test tube 31 detachably using air as a driving source.
b. Each of the sample dispensing mechanism 74, the reagent dispensing mechanism 75, and the germ dispensing mechanism 76 includes a chip mounting section 78, a cylinder 79 connected to the chip mounting section 78, and a cylinder 79. And a pulse motor 80 to be driven. In the present embodiment, the small tip 65 is attached to the tip mounting portion 78 of each of the sample dispensing mechanism 74 and the bacteria dispensing mechanism 76 by moving the biaxial arm 71 in the horizontal plane and the vertical plane. The large chip 66 is removably mounted on the chip mounting portion 78 of the reagent dispensing mechanism 75.

As shown in FIG. 7, the syringe 79 of each of the sample dispensing mechanism 74, the reagent dispensing mechanism 75, and the bacteria dispensing mechanism 76 has a pressure having, for example, a semiconductor strain gauge as shown in FIG. A sensor 81 is provided.
In step 1, the pressure fluctuation generated when the liquid is sucked and discharged by the corresponding syringe 79 is detected in real time, and the output is stored in the storage means of the personal computer 3.

Next, the operation of the automatic dispensing apparatus having the above configuration will be described. First, prior to the start of the operation of the automatic dispensing device,
A large number of sterilized capped test tubes 31 are stored and held in a test tube rack 32 and set in the test tube setting section 12, and a dilution series sample solution, a negative control solution, and a positive control solution are respectively prepared in the sample container 61. Sample rack 6
2 and is set in the sample setting section 17. Further, the buffer solution and the S9mix solution were prepared in the buffer solution container 58 and the S9mix
The ix solution setting unit 15 and the buffer solution setting unit 16 are set, and the five types of bacterial solutions are respectively set in the respective bacterial solution container holders 35 of the bacterial solution setting unit 13 without changing the L-shaped tubes (glass tubes) 36 at the time of the preculture. I do.

When the above setting is completed, the main switch 28 is turned on, and the test condition of the automatic dispensing device is set from the operation panel 27 and the personal computer 3 of the control unit 2. When the condition setting is completed, the start on the operation panel 27 is started. The indicator is turned on to start the dispensing operation. Here, the test items can be set in combination with the buffer or S9mix and each strain. Further, the amount of suction air, the amount of excess air, the suction speed, and the discharge speed of each syringe 79 of the sample dispensing mechanism 74, the reagent dispensing mechanism 75, and the bacteria dispensing mechanism 76 are determined according to the liquid to be dispensed. Set according to the viscosity.

At the start of the dispensing operation, first, the robot unit 21 moves the head unit 72 to the small chip setting unit 18 and the large chip setting unit 19 sequentially,
The small chip 65 is mounted on each of the chip mounting portions 78 of the sample dispensing mechanism 74 and the fungus dispensing mechanism 76 by rotating and appropriately rotating the sample dispensing mechanism 74 and the reagent dispensing mechanism 75. The large chip 66 is mounted on the chip mounting portion 78 of the first embodiment. Thereafter, the robot unit 21 moves the head unit 72 to the test tube setting unit 12 and clamps the test tube 31 with a cap stored and held in the test tube rack 32 by the air hands 77a and 77b of the test tube knob mechanism 73. And take it out and transport it to the liquid injecting unit 14 for delivery.
Remove the cap from the test tube 31.

FIGS. 8A to 8F show the operation of transferring the test tube 31 from the test tube knob mechanism 73 to the liquid injection unit 14. FIG. First, as shown in FIG. 8 (a), after the test tube 31 is transported above the liquid injection unit 14 by the robot unit 21, the head unit 72 is lowered and the liquid injection is performed as shown in FIG. 8 (b). Air hands 45a, 45b of part 14
Holds the test tube 31. Thereafter, as shown in FIG. 8C, the test tube 31 is moved by the test tube knob mechanism 73.
8D, the air hands 77a, 77b are raised until the air hands 77a, 77b are located at the cap position of the test tube 31, as shown in FIG. As shown in FIG.
77b holds the cap. Then, FIG.
As shown in (f), the head part 72 is raised, and the cap is removed from the test tube 31.

After that, the robot unit 21 moves the head unit 72 to the sample setting unit 17 while holding the cap by the test tube knob mechanism unit 73, and rotates the head unit 72 appropriately, so that the sample dispensing mechanism 74 The small chip 65 is positioned above the sample container 61 for accommodating the diluted and prepared sample liquid, and after lowering the head 72 in that state, the pulse motor 80 of the sample dispensing mechanism 74 is driven, A predetermined amount (for example, 50 μl, 100 μl, or 200 μl) of the sample liquid is aspirated into the small chip 65 via the syringe 79. When the sample suction operation is completed, the head section 72 is slowly raised in order to improve the drainage of the liquid from the small chip 65.

Next, the robot unit 21 moves the head unit 72 to the buffer solution setting unit 16 and rotates the head unit 72 appropriately to move the large chip 66 of the reagent dispensing mechanism 75 above the buffer solution container 58. Then, in this state, a predetermined amount (for example, 500 μl) of the buffer is sucked into the large chip 66 of the reagent dispensing mechanism 75 in the same manner as described above, and the head 72 is slowly raised.

Thereafter, the head section 72 is moved to the liquid injection section 14, and the sucked sample liquid and buffer solution are sequentially discharged to the test tube 31 held by the liquid injection section 14. At this time, the test tube 31 rotates the eccentric cam 46 by a motor 47 in a predetermined direction to incline the eccentric cam 46 by, for example, 45 degrees, and in this state, as shown in FIG. The tip of each tip is brought into contact with the inner wall of the test tube 31 by changing the position in the height direction of, so that the inner wall of the test tube 31 is suspended and dispensed.

Thereafter, the robot section 21 moves the head section 72
Is moved to the germ solution setting unit 13 and rotated as appropriate to position the small chip 65 of the germ dispensing mechanism 76 above the L-shaped tube 36 containing the desired germ solution. A predetermined amount (for example, 100 μl) of the bacterial solution is sucked into the small chip 65 of the bacterial dispensing mechanism 76 in the same manner as described above, and the head 72 is slowly raised.

On the other hand, after dispensing the above-mentioned sample solution and buffer solution, the liquid injection section 14 moves the head section 72 to the bacterial solution setting section 1.
3 while moving away from the liquid injection unit 14
7, the eccentric cam 46 is rotated by a predetermined angle in the forward and reverse directions to swing the test tube 31 held in the liquid injection unit 14, whereby the dispensed sample solution and buffer solution are stirred and mixed. I do.

When the suction of the desired germ solution is completed in the germ solution setting unit 13, the robot unit 21 moves the head unit 72 to the solution injection unit 14, and transfers the sucked germ solution to the solution injection unit 14.
To the test tube 31 held at At the time of dispensing the bacterial solution, as shown in FIG. 9, similarly to the dispensing of the sample solution and the buffer solution, the test tube 31 is inclined, and the height of the test tube 31 is different from that of the sample solution and the buffer solution. By contacting the tip of the tip with the inner wall of the test tube 31 at the discharge position, the inner wall of the test tube 31 is extended and dispensed. In the present embodiment, as shown in FIG. 9, the ejection position is increased in the dispensing order of the sample solution, the buffer solution, and the bacterial solution, and the inner wall to which the liquid dispensed earlier in the test tube 31 is connected. Is washed away with the liquid to be dispensed next, so that the conditions of the sample can be kept constant. The mixing may be completed by rocking the test tube 31 from which the dispensing of the bacterial solution has been completed.

Thereafter, the robot unit 21 moves to the position shown in FIG.
The cap is attached to the test tube 31 by performing the reverse operation of the cap removing operation from the test tube 31 shown in (e) and (f), and the head portion 72 is removed from the test tube 31 with the next cap. Move to the setting unit 12.

While the head unit 72 is moving to the test tube setting unit, the test tube 31 into which the three types of liquid have been dispensed in the liquid supply unit 14 is moved by the transfer mechanism 42 to the test tube unloading unit 26. Transfer to Here, the test tube take-out unit 2
When the test tube 31 transferred to 6 is not taken out for a certain period of time, the test tube 31 is again held in the liquid injection unit 14. The light projector 25
When the human body entry sensor having the a and the light receiver 25b detects the entry of the human body, the transfer mechanism 42 stops the transfer of the test tube 31 and waits, and the robot unit 21 moves to the next position above the liquid injection unit 14. Stop and wait while holding the test tube 31 of FIG. This standby state is notified to the operator by a stop lamp or alarm means (not shown), and the operator withdraws the test tube 31 and restarts the operation on the operation panel 27 so that all the operations return to normal. Has become.

When the above series of operations is performed on the test tubes 31 of the 14 sample processing groups set in the test tube setting unit 12 for one strain, the robot unit 21 attaches the head unit 72 to the chip. The used small chip 6 of the sample dispensing mechanism 74 is moved to the discarding section 20.
5 is discarded in the chip housing section 67.

Next, the robot section 21 moves the head section 72 to the small chip setting section 18 and mounts a new small chip 65 on the chip mounting section 78 of the sample dispensing mechanism section 74. By the operation, the sample set part 1 was set to the three test tubes 31 of the negative control (solvent) treatment group set in the test tube set part 12 for the above strain.
Dispense the negative control solution set to 7.

Thereafter, similarly, the sample dispensing mechanism 7
The small chip 65 of 4 was exchanged, and 3 strains of the positive control treatment group set in the test tube setting section 12 for the above strain were set.
The positive control solution set in the sample setting section 17 is dispensed into the test tube 31.

When the dispensing operation of the non-metabolite activation test system for one strain is completed by the above operation, the sample dispensing mechanism 74, the reagent dispensing mechanism 75, and the bacterial dispensing mechanism 76 Are discarded in the chip discarding unit 20, and thereafter, S9 for the above strain
Perform the dispensing operation of the mix test system.

By the above operation, the working steps from the dispensing of the sample and the control substance to before the pre-incubation are automatically performed for each strain by the automatic dispensing apparatus.

FIG. 10 is a timing chart showing the relationship between the operation process of the robot unit 21 and the operation of the main part in the above automatic dispensing apparatus. As is clear from FIG. 10, in the present embodiment, the head 72
Moves to the test tube setting unit 12 and moves while lifting and holding the test tube 31 by the test tube knob mechanism 73, while the bacteria solution setting unit 13, the S9 mix solution setting unit 15, and the sample setting unit 17 are moved. Performs a stirring operation.
When aspirating / discharging sample solution, buffer solution or S9mi
During the suction / discharge of the x-solution and the discharge of the germ-solution, the test tube 31 held in the liquid injection unit 14 is inclined. Further, during the bacteria suction operation, the test tube 31 is
Is performed, whereby the dispensed sample solution and buffer solution or S9mix solution are mixed.

As described above, in the liquid supply section 14, the test tube 31 is inclined at the time of dispensing the sample solution, the buffer solution or the S9 mix solution, and the bacterial solution, thereby effectively preventing the dispensing solution from scattering and foaming. By stirring the test tube 31 during the bacteria suction operation, the sample solution, the buffer solution or the S9mix solution can be mixed uniformly, so that the next time the bacteria solution is dispensed, the sample Direct inhibition of bacteria by toxicity can be advantageously prevented.
Also, when dispensing the sample solution, buffer solution or S9mix solution, and the bacterial solution, the tip of each chip is brought into contact with the inner wall of the test tube 31 so that the liquid to be dispensed does not remain in each chip. In addition to the fact that the liquid can be poured into the test tube 31 and the discharge position of each liquid is increased in the order of dispensing, contamination to each chip can be effectively prevented. In addition, since the dispensing operations of the respective liquids are sequentially controlled so as not to overlap, it is also possible to perform an audit in the same manner as a manual operation. In this case, the operation speed of each dispensing operation may be set to a speed similar to a manual operation, for example, 10 seconds to 20 seconds, and preferably about 15 seconds, to make it easier to visually confirm. .

FIG. 11 shows the relationship between the voltage output from the pressure sensor 81 of the sample dispensing mechanism 74 and the amount of sample liquid dispensed by the syringe 79. FIG.
As is clear from FIG. 1, since the output voltage of the pressure sensor 81 and the sample dispensing amount are on a straight line, the output voltage value (V) indicates the sample dispensing amount (μl). It is stored in the storage means of the personal computer 3 in advance. Similarly, the reference voltage of the pressure sensor 81 provided in each of the syringes 79 of the reagent dispensing mechanism 75 and the bacteria dispensing mechanism 76 is stored in the storage means of the personal computer 3 in advance.

As described above, in the present embodiment, the output during suction and discharge from each pressure sensor 81 of the sample dispensing mechanism 74, the reagent dispensing mechanism 75, and the bacteria dispensing mechanism 76 is provided. The voltage is taken into the personal computer 3 and stored in the storage means. Based on the output voltage at the time of actual suction and discharge and the reference voltage at the time of suction and discharge of a predetermined amount, the amount of suction and discharge of each liquid is calculated. Injection is managed, the management data is output from the printer 4 as needed, and a dispensing determination result indicating whether or not each liquid is dispensed is output based on the management data.

FIG. 12 shows an example of a dispensing determination result output from the printer 4. This dispensing judgment result
In the non-metabolism activation test system of the bacterial species TA1537, the output voltage from the corresponding pressure sensor 81 at the time of suction / discharge of each liquid is ± with respect to the reference voltage at the time of suction / discharge of the set amount of the liquid. When it was within 10%, it was marked with a circle, and when it was out of ± 10%, it was marked with a cross, and the dispensing column of the cross was colored. By outputting such a dispensing determination result, a dispensing mistake can be easily confirmed, and the quality of the set dispensing amount can be easily confirmed. Here, it is possible to confirm by displaying the pressure data by the syringe operation at the time of dispensing as it is or after converting it into the dispensed amount.

FIGS. 13 (a) and 13 (b) show the test results (）) when the same sample was dispensed by the automatic dispensing apparatus of the above embodiment and the dispensing by the conventional manual method. FIG. 13 (a) shows a comparison between the test result (△) and the TA1 in the case of S9 mix.
FIG. 13 shows the test results of the negative control and the positive control of FIG.
(B) shows the test results of the negative control and the positive control in the case of the bacterial species TA100 + S9mix.

As is clear from FIGS. 13 (a) and 13 (b), by using the automatic dispensing apparatus of the above embodiment, both the negative control and the positive control values are dispensed with the same results as the conventional manual method. Data with a small error could be obtained.

As described above, according to the automatic dispensing apparatus according to the present embodiment, various liquids can be automatically dispensed in the Ames test. Dispensing can always be performed with high precision without causing dispensing errors, and labor saving and improvement in work efficiency can be achieved. In addition, automatic dispensing can be performed constantly in a facility where there are severe restrictions such as an aseptic environment and an anoxic environment.

It should be noted that the present invention is not limited to the above-described embodiment, but can be variously modified or changed. For example, in the above-described embodiment, the dispensing mechanism is provided independently for each of the sample liquid, the reagent, and the germ liquid. However, it is configured such that these liquids are dispensed while exchanging the tips with a common dispensing mechanism. Can also. Further, the present invention is not limited to the automatic dispensing apparatus used for the above-mentioned Ames test, but also includes a biological test requiring aseptic operation, a pretreatment of a sample for chemical analysis, and at least a test sample and a microorganism-containing sample. The present invention can be effectively applied to an automatic dispensing device for dispensing a liquid. Further, the temperature display 29 may display the temperature in the sterile room, or may display the humidity, the atmospheric pressure, and the air component in the sterile room in addition to the temperature in the sterile room. The temperature of the liquid may be displayed.
Further, the storage means of the personal computer 3 may store various temperatures during the above-described series of dispensing processes, and may read out and confirm the temperatures as appropriate. Further, a timer may be built in the personal computer 3 to store a dispensing time for each test tube 31 so that the dispensing time can be read out and checked appropriately. In addition, test tube 31
Identifiable and readable ID for all
(For example, a barcode), the ID may be read by an appropriate reading means (for example, a barcode reader), stored together with the dispensing information, and read and confirmed as appropriate. In the above-described embodiment,
The transparent cover 22 makes it easy to inspect continuous work in a closed room such as a sterile environment.
If the device is placed in a clean facility such as a clean room, the means 22,23,24 for air cleaning need not be provided.

[0059]

According to the present invention, at least a test sample and a microorganism-containing liquid are placed in an air-cleaned closed room,
Since it can be automatically dispensed into a plurality of mixing containers, for example, when used for an Ames test, dispensing errors do not occur as compared to when dispensing using the application method, and the dispensing is always performed with high accuracy. It is possible to reduce labor and improve work efficiency.

[Brief description of the drawings]

FIG. 1 is a front view showing an overall schematic configuration of an embodiment of an automatic dispensing apparatus according to the present invention.

FIG. 2 is also a plan view.

FIG. 3 is also a perspective view.

FIG. 4 is a front view showing a configuration of an example of a holder mechanism of the liquid injection unit shown in FIG.

FIG. 5 is also a schematic perspective view.

FIG. 6 is an enlarged front view showing a head unit of the robot unit shown in FIG. 1;

FIG. 7 is a diagram showing a configuration of each dispensing mechanism provided in a head unit.

FIG. 8 is a view for explaining an operation of transferring a test tube from a test tube knob mechanism of a head unit to a liquid injection unit.

FIG. 9 is a diagram showing a discharge position of each liquid to a test tube.

FIG. 10 is a timing chart showing the relationship between the operation process of the robot unit and the operation of the main part.

FIG. 11 is a diagram illustrating a relationship between an output of a pressure sensor of a dispensing mechanism for a sample and a dispensed amount.

FIG. 12 is a diagram showing an output example of a dispensing determination result.

FIG. 13 is a diagram showing a comparison between a test result when dispensing is performed by the automatic dispensing apparatus of FIG. 1 and a test result when dispensing is performed by a conventional manual method.

FIG. 14 is a flowchart showing the operation procedure of the Ames test.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Main body part 2 Control part 3 Personal computer 4 Printer 10 Base 11 Sterile chamber 12 Test tube setting part 13 Bacterial liquid setting part 14 Liquid injection part 15 S9mix liquid setting part 16 Buffer liquid setting part 17 Sample setting part 18 Small chip setting part 19 Large chip set section 20 Chip disposal section 21 Robot section 22 Transparent cover 23 Intake device 24 Exhaust device 25a Projector 25b Receiver 26 Test tube take-out unit 27 Operation panel 28 Main switch 29 Temperature display 30 Display unit 31 Test tube 32 Test tube rack 35 Bacterial liquid container holder 36 L-shaped tube 37 swing mechanism 41 holder mechanism 42 transfer mechanism 43a, 43b shaft 44 U-shaped member 45a, 45b air hand 46 eccentric cam 47 motor 48 angle sensor 49a, 49b rail 51 S9mix liquid container 52 Case 53 Peltier element 54 motor 55 eccentric cam 56 swing mechanism 58 buffer storage container 61 sample container 62 sample rack 65 small chip 66 large chip 67 chip storage part 71 biaxial arm part 72 head part 73 test tube knob mechanism part 74 sample dispensing mechanism Part 75 Reagent dispensing mechanism part 76 Bacterial dispensing mechanism part 77a, 77b Air hand 78 Chip mounting part 79 Cylinder 80 Pulse motor 81 Pressure sensor

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Chiaki Sato 2-43-2 Hatagaya, Shibuya-ku, Tokyo Inside Olympus Optical Industrial Co., Ltd. (72) Noriko Kato 2-43-2 Hatagaya, Shibuya-ku, Tokyo Olympus Optical Co., Ltd. F term (reference) 2G058 CD23 EA14 EB21 ED21 ED35 FA03 GB10 GC02 GD07 GE02 GE03 4B029 AA09 BB01 CC01 HA05 HA09

Claims (6)

[Claims] 1. An automatic dispensing device for dispensing at least a test sample and a microorganism-containing liquid, comprising: a plurality of mixing containers dispersedly arranged at predetermined positions; and a plurality of samples containing the test sample. Container, and a plurality of microorganism containers accommodating a microorganism-containing liquid for testing, a support arm accessible to the mixing container, the sample container, and the microorganism container, and a preparative unit attached to the support arm. A probe, a liquid amount adjusting means communicating with the probe to adjust a dispensed amount, and a preset dispensing of a test sample in the sample container and a microorganism-containing liquid in the microorganism container. Control means for controlling the driving of the support arm and the liquid amount adjusting means so as to dispense the mixture into the mixing container according to the amount, and information corresponding to the dispensing operation can correspond to the set dispensing amount. An automatic dispensing device characterized by having a storage means for storing the information in a readable manner. 2. The apparatus according to claim 1, wherein the liquid amount adjusting means includes an air pressure control means for causing a change in air pressure in a portion where the probe is sucked or discharged, and a pressure sensor for detecting an air pressure generated by the air pressure control means. 2. The automatic dispensing device according to claim 1, wherein the storage unit is configured to store the air pressure detected by the pressure sensor in a readable manner for each dispensing operation. 3. A dispensing position for dispensing the test sample and the microorganism-containing liquid, comprising a holder mechanism for holding the mixing container in a detachable, tiltable and swingable manner, wherein the test sample and the microorganism-containing liquid are contained. At the time of dispensing the liquid, the mixing container is tilted, and the test sample and the microorganism-containing liquid are dispensed by bringing the tip of the probe into contact with the inner wall of the mixing container at different discharge positions. 3. The automatic dispensing device according to claim 1, wherein the mixing container is rocked and stirred after dispensing the test sample and the microorganism-containing liquid. 4. A sample container rocking means and a microorganism container rocking means for selectively rocking and stirring the sample container and the microorganism container, respectively. Or the automatic dispensing device according to 3. 5. The automatic dispensing apparatus according to claim 1, further comprising: a closed chamber that is air-cleaned, and the mixing container into which the test sample and the microorganism-containing liquid are dispensed. An automatic dispensing device, comprising: a discharge means for discharging the mixture to the outside of the closed chamber, wherein a dispensing position for the mixing container is provided near an outer side of a movement trajectory of the support arm. 6. A configuration in which a plurality of dispensing probes are attached to the support arm, and the control means controls so that dispensing operations by the plurality of dispensing probes are sequentially performed so as not to overlap. The automatic dispensing device according to claim 1 or 2, wherein