JPH05861Y2 - - Google Patents

Description

[Detailed description of the invention] [Technical field of the invention] This invention relates to the improvement of a fixed-quantity dispensing diluter used when testing a large number of specimens at once in hospitals, various laboratories, and laboratory departments. It is.

[Prior art]

For example, in order to measure or test the potency of various pharmaceuticals such as interferon, it is necessary to efficiently add interferon and the like to a large number of specimens (samples).

The titer of interferon can be measured by: filling the first row of recesses of a microplate with a large number of recesses with interferon whose concentration has been prepared in advance; A step of dropping a predetermined amount of the medium into many (almost all) wells of the plate, a step of thoroughly stirring the mixture of the medium and interferon dropped in the above step, and diluting it one after another. A step of adding predetermined cells to diluted interferon having different titers and culturing the same to impart different virus resistance to the cells, to the cells cultured in the above step. In the process of applying the virus, cells that have died due to the action of the virus are dropped from the microplate, and the remaining cells are colored and their absorbance is used to measure the ``end point'' and the ``titer'' of interferon. It consists of processes, etc.

The above step is to supply, for example, 50 to 100μ of interferon to about 100 depressions formed on the microplate, and the step is to supply a medium of the same amount as the interferon supplied in the above step. This is a step of supplying a mixture of interferon and interferon.

Then, in the process, half of the mixture of culture medium and interferon accommodated in the recesses of the first row is taken out and supplied to the recesses of the second row, and thoroughly stirred. Half of the mixture contained in the container is taken out and supplied to the third row of recesses, and thoroughly stirred, and thereafter the concentration of interferon is similarly diluted by half.

As described above, there are methods for dropping a fixed amount of liquid into a large number of concave portions formed in a microplate, or for suctioning and stirring a fixed amount of liquid, and methods that process each liquid individually and those that simultaneously process a plurality of liquids.

A typical example of the former is a direuter that aspirates 50μ of liquid; this device aspirates and stirs a minute amount of liquid contained in individual recesses formed on a microplate. Therefore, there is a drawback that the dispensing results vary depending on the skill level and physical condition of the operator, and above all, there is an essential drawback that a large number of workers are required for this monotonous work.

For example, as a device for dispensing liquid contained in multiple concave portions of a microplate at the same time,
No. 59-29295 proposes a "multipipette" device. However, this multipipette has the disadvantage that it is an expensive device, the precision of dispensing is not as high as expected, and it takes a considerable amount of time to get used to its operation.

As mentioned above, manual dispensing work inherently has drawbacks, but Japanese Utility Model Application Publication No. 55-3754 discloses a device that eliminates these drawbacks and automates the dispensing work. is proposed.

The dispensing device according to this invention is extremely innovative in that it operates multiple pistons at once with a constant stroke to suck the liquid into the dispensing needle and drip it, and it will be useful for future dispensing operations. This is highly expected to improve efficiency.

However, the device according to this invention was developed mainly for supplying a predetermined amount of liquid at once to a large number of recesses formed in a microplate.
For example, the dilution step described above cannot be carried out.

[Purpose of invention]

An object of the present invention is to provide a fixed-quantity dispensing diluter that can uniformly dispense into a large number of plates.

[Summary of the invention] The quantitative dispensing diluter of the present invention capable of achieving the above object is a quantitative dispensing diluter equipped with an intermittent transfer device that intermittently transfers a microplate, and is equipped with an intermittent transfer device that transfers a microplate intermittently. Three heads consisting of a first head for supplying culture medium, a second head for quantitative dilution, and a third head for supplying cells are arranged in series, and the liquid dish of the third head is equipped with a stirrer. Features.

〔Example〕

Next, referring to the drawings, an embodiment of the present invention will be described in which it is applied to an interferon titer measuring device.

Figure 1 is a partially cutaway front view of the quantitative dilution device;
3 is a front view showing essential parts of the dispensing device, and FIG. 4 is a sectional view showing details of the dispensing needle portion of the dispensing diluting device.

An operation panel 2 is provided on the front surface of the main body 1 on the microplate insertion side (right side in the figure), and a set of a first head 4, a second head 5, and a third head 6 are mounted on the top surface by a frame 3. are arranged as .

A liquid dish 7 is provided below the first head 4, a washing dish 8 is provided below the second head 5, and a liquid dish 9 is provided below the third head 6. In this embodiment, the liquid dish 9 is used to suspend the cells, so a stirrer 10 is provided to prevent the cells from settling. It is configured to rotate at a position slightly elevated from the bottom of the That is, in the stirrer 10, for example, a pin serving as a rotating shaft is attached to the lower center of a magnetic stirrer (rotor), and the pin is inserted into a recess that serves as a bearing provided at the bottom of the liquid dish, so that the stirrer is directly attached to the liquid dish. It is constructed so that it rotates stably at a position raised several millimeters without contact.

Reference numeral 1a denotes an auxiliary stand extending in the longitudinal direction of the main body 1, and is a part that supports the processed microplate transferred from the right side to the left side of the main body 1.

Two rows of belt conveyors 13 are provided below each head section 4, 5, 6 to support both ends of the microplate 12 in the lateral direction.
It is configured to be supported by a guide roller 14 and a drive roller 15 and driven intermittently by a motor 16.

As a means for intermittently transporting the microplates 12, it is preferable to use the belt conveyor 13 as described above.
The pressing means may be a rack and pinion system, a cam system, a lever system, or the like.

In the case of the interferon titer measuring device, the first head 4 consists of a culture medium supply process, the second head 5 consists of a dispensing dilution process, and the third head 6 consists of a cell supply process.

The structure of each head portion 4, 5, and 6 is
The second head 5 (quantitative dilution device), which is an application of the "microdispensing device" described in Japanese Patent No. 3754, will be explained with reference to FIGS. 3 and 4.

Four threaded rods 21 are provided in the position fixing part 21a at the four corners of the support frame 20 formed in a U-shape when viewed from the front,
The lower part of the threaded rod 21 is screwed into a pressing plate 22, so that the pressing plate 22 presses the piston support plate 23.

24 is a pump mechanism, which constitutes a kind of cylinder device.

This pump mechanism 24 is supported by a support portion 20a of a support frame 20, and has a structure above a plate 26 that supports a dispensing needle portion 25, and includes a plate 28 and pillars 30 planted at the four corners of this plate 28. A frame-shaped "piston support structure" that supports both ends of the cylinder 27 by a support plate 31 supported at the upper end of this column 30, a plate 28, columns 32 planted at the four corners of this, and this column. A piston support plate 23 is movably supported on the upper part of the column 32, a piston 29 is fixed to the plate 23 and slides inside the cylinder 27, and a piston 29 is provided around the column 32 and supports the piston support plate 23. It consists of a "piston support structure" made up of a spring 33 that presses upward.

Each of the threaded rods 21 is provided with a sprocket wheel 35, and is configured to be driven via a motor 36, a sprocket wheel 36a, and a chain 37.

A support member 41 is provided at the center of the upper part of the support frame 20, passing through a guide portion 40 provided in the frame 3, and is supported by a vertical mechanism driven by a cam, cylinder mechanism, or motor, and is supported by a vertical mechanism driven by a cam, cylinder mechanism, or motor. move up and down in the direction.

The support frame 20 is moved up and down when the dispensing needle part 25 needs to be lowered significantly. This is the time to dip the tip of the liquid and suck it up or expel it.

The motor 36 is a driving part that operates the pump mechanism 24, and is activated when dispensing. Specifically, by driving this motor 36, the threaded rods 21 are rotated all at once, and the press plate 22 screwed onto the lower end thereof is moved in the direction of arrow B, and the press plate 22 is mounted on the piston support plate 23. The piston 29 is pushed into the cylinder, and the dispensing needle 25a is immersed in the liquid contained in the recess 12a of the microplate 12. Then, by rotating the motor 36 in the reverse direction, the liquid contained in the recess 12a is sucked in accordance with the rotation of the threaded rod 21, that is, the amount of rise of the piston 29.

The amount of liquid sucked into the dispensing needle 25a by the piston 29 as the threaded rod 21 rotates is, for example, a minute amount of about 50 to 100 microns.

FIG. 4 is a sectional view showing details of the dispensing needle portion 25.

The dispensing needle 25a is a hollow needle made of stainless steel, for example, and has been surface-treated to improve corrosion resistance. This dispensing needle 25a is fixed to the lower end of a needle support 25b made of plastic, and the lower surface of a packing member 42 made of hard rubber or plastic is in contact with the upper end of this needle support 25b. The lower part of the cylinder 27 made of a tube is fitted and fixed.

By configuring the dispensing needle portion 25 as shown in FIG. 4, the pump mechanism 24 including the plate 28 can be removed integrally from the plate 26.

In addition, since the dispensing needle portion 25 is supported by the plate 26 and supported by the support frame 20, when the pump mechanism 24 supported by the plate 28 is removed, this plate 26 can be easily removed from the support frame. It is possible to perform operations such as removing the dispensing needle 25a from the body 20 and cleaning or replacing the dispensing needle 25a.

Since FIG. 3 shows the second head 5, that is, the quantitative dispensing diluter, the microplate 1
The dispensing needles 25a are shown arranged in one row corresponding to one row of recesses in FIG.

The first head, that is, the medium supply head 4 and the third
In the case of the head 6, that is, the cell supply head, a plurality of rows of dispensing needles 25a are arranged in a number corresponding to the number of recesses 12a on the microplate 12, but these are arranged by a large number of pump mechanisms 24 shown in FIG. You can think of it as something that exists.

When performing the quantitative dispensing dilution operation, please refer to 2 in Figure 1.
The microplate 12 is moved to a position below the head 5 by the belt conveyor 13, and half of the mixture of interferon and culture medium housed in the first row of recesses 12a is pumped by the pump mechanism 24. 26 (raises the piston 29) to aspirate with the dispensing needle 25a, and then the belt conveyor 13 is intermittently moved to the left in FIG. The dispensing needle 25a is positioned above the needle 12a. Then, the pump mechanism 24 is activated (the piston 29 is lowered) to discharge half of the mixture sucked into the dispensing needle 25a into the second row of recesses 12a. Next, the pump mechanism 24 is reciprocated to sufficiently mix and dilute the mixture in the second row of recesses 12a. Dispensing and then diluting are repeated in the same manner.

Now, the first feature of the present invention is a means for intermittently driving the second head 5 and the microplate 12;
That is, it is a quantitative dispensing and diluting device that is combined with a belt conveyor 13, and the second feature is that it has a first head 4 (medium supply head), a second head 5 (quantitative dilution head), and a third head 6 ( The three heads (cell supply head) are arranged in series, and the microplate 12 is placed below these three heads.
This is an application of a fixed-quantity dispensing and diluting device, which is equipped with an intermittent feeding device 13 and configured to interlock these members, that is, an efficient addition device for interferon.

Furthermore, as shown in FIGS. 1 and 2, it is also possible to place a container 43 on the frame 3 and supply the cleaning liquid in the container 43 into the cylinder 29 through a pipe (not shown) for cleaning. However, it is also possible to wash the liquid dishes 7, 8, 9.

[Effect of idea]

As described above, the present invention has three heads arranged in series, consisting of a first head for supplying culture medium, a second head for quantitative dilution, and a third head for supplying cells, and a liquid dish in the third head. Since it was equipped with a stirrer, it became possible to dispense uniformly onto a large number of plates.

[Brief explanation of drawings]

The figure shows an embodiment of the present invention.
The figure is a front view of the Interferon titer measuring device.
FIG. 2 is a side view of the same, FIG. 3 is a partially cut-away front view of the quantitative dispensing diluter, and FIG. 4 is a sectional view showing the main parts of the dispensing device. 1... Main body, 4... First head (medium supply head), 5... Second head (quantitative dispensing dilution head),
6... (cell supply head), 12... microplate, 13... belt conveyor, 20... support frame, 21... threaded rod, 22... press plate,
23... Piston support plate, 24... Pump mechanism, 25... Dispensing needle portion, 25a... Dispensing needle, 2
6... Plate, 27... Cylinder, 28... Plate, 29... Piston, 35, 36a... Sprocket wheel, 36... Motor, 37...
Chien.

Claims (1)

[Scope of utility model registration request] A quantitative dispensing diluter equipped with an intermittent transfer device for intermittently transferring microplates, wherein above the intermittent transfer device there are a first head for supplying a medium, a second head for quantitative dilution, and a second head for supplying cells. A quantitative dispensing and diluting device characterized in that three heads consisting of a third head are arranged in series, and a liquid dish of the third head is equipped with a stirrer.