JPS6388458A - Tube connector for solid-phase conversion reagent producing equipment - Google Patents

Abstract

PURPOSE:To enable the production of a solid-phase conversion reagent which is safe for workers and is uniform, by arranging a connector section having a liquid reservoir section with the diameter larger than the inner diameter of a tube on the tube for connection of a liquid sucking and draining nozzle and a sucking/draining device as communicating with one another. CONSTITUTION:A tube 194 for suction and draining is connected to a tube connecting section of a liquid sucking/draining device and then, to a nozzle 106b for sucking and draining a cleaning liquid of cleaning a liquid nozzle arm section through a liquid reservoir section 156, which comprises a liquid reservoir body section 157, a liquid pooling space section 158 and joints 159, 160 and 161 arranged at both ends thereof 158. The inner diameter of the liquid pooling space section 158 is made larger than the inner diameter of the tube 194. The capacity of the liquid pooling space section 158 is set enough to absorb a cleaning liquid storable in the tube 194. This enabled the removal of bubbles within the tube 194 while preventing the infiltration of the liquid into a liquid sucking/draining device or the like.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention is a solid-phase reagent! Regarding the tube connector device in the A-manufacturing equipment, more specifically, it is a solid-phase system that automatically dispenses reagents into solid-phase reagent containers and solidifies the reagents on the inner wall of the solid-phase reagent container. The present invention relates to a tube connector device in a reagent manufacturing device.

[Prior Art] Patients with acquired immunodeficiency syndrome (AIDS) have recently been identified in many countries. Many efforts have been made to identify patients and investigate the causative agent of the disease, and epidemiological data suggest that AIDS is caused by horizontal transmission of infectious substances through body fluids such as blood.

When infected with AIDS, the immune system is severely weakened.

Deaths occur due to infectious diseases, Kaboshi meat type, which is a type of cancer, and pneumonia caused by mold. AIDS,
r! ! As is known, the mortality rate of AIDS patients is extremely high, and since the infection is transmitted through patients, there is an urgent need for early detection of AIDS patients. Recently, U.S. Patent 4,520,113
was granted (issued) to R, CGa11o, etc., but
This patent of Ga1lo et al.
uno 5orbent As5ay) or as an antigen in strip RIA based on Western blotting or indirect immunofluorescence.
This is a method for detecting antibodies in the serum of AIDS and Pre-AIDS patients by using a cell fragment named /HTLV-m. More specifically, AIDS
Using a viral antigen, immobilize this AIDS virus antigen on the bottom of a hole in a plastic plate, put each serum to be tested into the bottom of the hole, and observe the long color reaction to determine whether antibodies against the AIDS virus have been detected. It detects the presence.

According to this method, if the serum contains antibodies against the AIDS virus, it is bound onto the immobilized antigen and the presence of anti-AIDS virus antibodies can be detected by a long color reaction after several runs. As a result, AIDS, @
It is possible to confirm whether the person is a person or not, and it is possible to prevent the person from being infected with Axpsg.

In addition, as another method, EIA (Enzyme Immunoassay) using solid phase method (beads) is available.
y), HTLV-In in the specimen (serum or plasma)
There are ways to detect antibodies.

[Problems to be Solved by the Invention] In the above-mentioned prior art, one worker manually inserts an AIDS virus antigen into a hole in a plate made of plastic, and places the AIDS virus antigen at the bottom of the hole in the plate. Since reagents were produced by immobilization (coating), it was not possible to produce uniform reagents, which resulted in a significant decline in the quality of the reagents and extremely low reliability as reagents. In addition, when using the manual method, the thickness of the film coated on the bottom of the hole in the plate is not constant, so the reliability of detection is low, and the reagent cannot be manufactured in large quantities using the manual method, so production is slow. The quality was extremely low.

In addition, AIDS virus antigen (HTLv-m) is used as a reagent.
requires extreme vigilance during the preparatory steps for producing the reagents and is extremely dangerous for healthy laboratory workers.

Also, even if an inactivated virus is used, contact with the inactivated virus can cause healthy workers to produce antibodies, and if antibodies are produced,
They are AIDS, ARC (AIDS Re1ate)
d Complex) or Pre-AIDS may be misdiagnosed. Additionally, the presence of intracellular material of H9 cells or E. coli (E, Co11) in the reagent can elicit erroneous results in HTLV-III antibody screening tests from individuals with antibodies to E. coli (E, Co11) or H9 cells. There is sex. These false positive tests cause severe anxiety for healthy individuals and their families, and may also result in them being incorrectly diagnosed as having AIDS, preventing them from participating in normal social activities. There is a risk of being expelled from.

The present invention has been developed in view of the problems of the prior art described above, and has been devised to provide a reagent for detecting the presence of antibodies or AFP (embryonic antigen), which is prepared by Yuki Soba and Yuki Soba.
, rgE (immunoglobulin E), etc. can be automatically coated (filmed) into each of a large number of microwells on a plate, so that a uniform immobilized reagent that is safe for workers can be produced. An object of the present invention is to provide a tube connector device for a Nishida solid-phase reagent manufacturing device.

[Means and effects for solving the problems] The present invention provides a solid-phase reagent that is configured to automatically dispense a reagent into a solid-phase reagent container and solidify the reagent on the inner wall of the container. In tube connector devices in reagent manufacturing equipment.

A part of the connector having a liquid reservoir portion having a diameter larger than the inner diameter of the tube is attached to a tube that communicates and connects a liquid suction/drainage nozzle with a suction/drainage device for suctioning and discharging liquid such as a reagent solution or cleaning liquid from the nozzle. By arranging and configuring the tube, it is possible to remove bubbles in the tube and prevent liquid from entering the syringe (liquid suction and discharge device).

C Example 1 Examples of the present invention will be described below with reference to the drawings, but before that, the schematic structure of a solid-phase reagent assembly including a tube connector device for reagents related to final IJI will be explained. This will be explained using Figure 1.

FIG. 1 is an overall configuration diagram of a solid-phase reagent manufacturing apparatus 2 including a tube connector device according to the present invention, and arrows connecting each component in FIG. 1 indicate the order of steps.

As shown in the figure, the solid-phase reagent manufacturing apparatus 2 dispenses reagents into each well 5 on a microplate 4 that is supplied and transported from a supply magazine 3, and coats the inner wall surface of each well 5 with a reagent film. Reagent coating equipment Wl for
l. It's incubator (culture device) 6 for dispensing and incubating the coated reagent into each well 5, draining the excess reagent solution from each well 5 and washing the inside of each well. 7. First washing n1 device (reagent solid phase container cleaning device device) for cleaning. A gelatin coating device 8 for coating the reagent coated on the inner wall and bottom of each well with gelatin to cover pinholes, etc., and a second incubation device for culturing the reagent after gelatin coating. 9. Second cleaning device (reagent solid phase container cleaning device) 10 for cleaning the reagent incubated through the second incubation device 9, and completely drying the cleaned reagent in an atmosphere at a required temperature. It consists of a drying bag 2211 for storage.

The tube connector according to the present invention belongs to the third and sixth process sections, and is as follows: 1 of the apparatus according to the present invention.
Examples will be described in detail.

Note that since the cleaning device 7 and the cleaning device 10 have the same configuration, only the cleaning device 7 will be described, and a description of the other side will be omitted.

FIGS. 2a, b, and c are a plan view, a front view, and a side view showing an embodiment of the reagent solid phase container cleaning device 7 including the tube connector device according to the present invention. As shown in FIG. 1, the reagent solid phase container cleaning device 7 includes a microplate 4 having (equipped with) microwells (hereinafter simply referred to as wells) 5 into which a reagent solution is dispensed and coated.
3. Supply magazine that stores the. A plate transport mechanism section 12 for transporting the microplate 4 at a constant pitch, aspirates and discharges excess reagent solution in each well (solid phase container) 5, and dispenses and discharges a washing solution to each well 5. cleaning liquid nozzle arm 13 for cleaning, cleaning liquid shelf 14 for storing cleaning liquid; electrode cleaning shelf for cleaning the liquid level detection electrode (not shown in FIG. 1) in the cleaning liquid nozzle arm 13; Part 16. A cleaning liquid dispensing unit section 46 for aspirating the amount of cleaning solution to be dispensed three times and dispensing the aspirated cleaning liquid three times to each well 52.
．． and an ejection magazine 17 for storing the microplate 4 whose wells have been completely washed.

Incidentally, in the case where the microplates 4 that have been completely washed are continuously and directly conveyed to the next process, the ejection magazine 17 may be omitted.

The supply magazine 3 that stores the microplates 4 that have gone through TJJ (coating process, ink, etc.) is configured as a hollow container as shown in FIG. A groove-like stepped portion 18 is provided for locking and holding the plate 4. Ten groove-like steps 18 (not limited to ten) are formed in the vertical direction at a constant pitch, and therefore ten microplates 4 are housed in the supply magazine 3. There is. A hole 19 for determining the first place is located on the lower surface (bottom surface) of the supply magazine 3.
is provided through the hole 19, and is J-shaped so that the supply magazine 3 can be positioned by engaging this hole 19 with the positioning pin 21 of the magazine elevating device 20. The groove-like stepped portion 18 in the supply magazine 3 is formed so that the microplate 4 can be inserted only when inserted from the position direction side, and is configured so that it cannot be inserted when inserted from the other direction. The microplate 4 is fixed at 1;q so that the microplate 4 stored therein always maintains a constant orientation. Reference numeral 22 indicates a handle.

The supply magazine 3 is configured to be able to be raised and lowered freely via a magazine lifting device 20 (see FIG. 3) disposed inside the loading and unloading main body, and the configuration of this magazine lifting device 20 is shown in FIG. In Figure 2, which will be explained using d, 23 is a support base for mounting and supporting the supply magazine 3, and the support base 25 is driven up and down by a motor 24.
It is fixed to the upper end of the frame via a fixing screw 26.

The motor 24 is composed of a motor that converts rotational motion into linear motion. The motor 24 is fixed on an intermediate base 27 located at an intermediate portion of the main body of the device.
A guide rail plate 29 is fixed on the intermediate base 27 for guiding a guide roller 28 rotatably supported by the support base 23. Guide rail plate 2
9 is fixed to the intermediate base 27 via a support post 30. Reference numeral 31 indicates a fixing screw. As shown in FIG. 3C, the guide rollers 28 are arranged so as to sandwich the guide surface of the guide rail plate 29.
It is configured so that it can be guided stably by a pair of guide rollers 28. Each guide roller 28 is formed with a 7-shaped guide groove 32, and the engaging portion of the guide rail plate 29 that engages with this guide groove 32 is connected to the guide groove 32.
It is shaped like a matching V-shape. What is indicated by 33?

This is a support pin for the guide roller 28. Reference numeral 34 denotes a sensor plate for controlling the amount of movement of the support base 23, that is, the amount of lifting and lowering of the supply magazine 3 in cooperation with a sensor 35 fixed to the support base 23. It is arranged. The sensor 35 has a light emitting part and a light receiving part, and is connected to the support base 23 via a support plate 36.
It is fixedly installed. Notches 37 are formed in the sensor plate 34 at a constant pitch, and when the sensor 35 reaches a position corresponding to the notches 37 when the support base 23 is lowered, the light receiving part of the sensor 35 is connected to the light emitting part. It is set to receive light from the support base 23 and stop the lowering of the support base 23. The number of notches 37 is the same as the number of microplates 4 stored in the supply magazine 3 (10 in this embodiment).
It's just a formality. Reference numeral 38 indicates a sensor for detecting the presence of the microplate 4 housed in the supply magazine 3, and is fixed to the upper end of the support post 30 via a bracket 39. What is indicated by 40?

This sensor plate is fixed to the support base 23 and cooperates with the sensors 41 and 42 fixed to the support post 30 to regulate the upper and lower limit positions of the lifting and lowering operation of the support base 23. 43.44 shows.

The support plates for the sensors 41, 42, indicated at 45, are support posts to which the sensor plates 34 are fixed. The supply magazine 3 containing ten microplates 4 is set at an elevated position via the magazine lifting device 20 shown in FIG. 3, as shown in FIG. 2C.

The configuration of the ejection magazine 17 (see Figures 1 and 2) is
As shown in FIG. 1, the discharge magazine 17 has the same structure as the supply magazine 3, as shown in FIG. The ejection magazine 17 is set in a lowered position via the magazine lifting device 20 as shown in Fig. 2c, :fS3, e, and as shown in Fig. 3e. The microplates 4 that have been cleaned are stored in the discharge magazine 17, which is set in an empty state, in order from the top.

The plate transport mechanism section 12 takes out the microplates 4 one by one from the supply magazine 3 and transports them at a constant pitch toward the cleaning liquid nozzle arm section 13, and also discharges the cleaned microplates 4 through the cleaning liquid nozzle arm section 13. It is for storing in the magazine 17,
The configuration of this plate transport mechanism section 12 will be explained using FIGS. 4, 5, and 6.

4 is a perspective view of the vicinity of the plate transport mechanism section 12, and FIG. 5a is a perspective view of the plate transport mechanism section 12.

In addition, Figures 5 and 5 c are enlarged views of the main parts of Figure 5 a, and Figures 6 a, b, and c are a plan view, a front sectional view, and a partially cutaway side view of Figure 5. In a certain figure, 50 indicates that the support of the microplate 1-4 is a support frame on which a stand 51 is fixedly mounted, and the support is a support frame for placing and supporting the microplate 4 on the stand 51. This is for conveying at a constant pitch. The receivers 51 are arranged in 4 pairs, 8 in total, and the distance between the centers 52 of each month is
Pitch) P is set to the same size. Reference numeral 53 indicates a fixing screw for the base 51. A plate (base plate) 54 is disposed on the lower surface of the support frame 50, and the plate 54 is fixed to the support frame 50 via fixing screws 53. An inverted-shaped slide base 55 is disposed below the plate 54, and the slide base 55 is attached to a slide 57 horizontally suspended on a fixed frame 56 of the main body of the device. It is supported so that it can slide freely. Horizontal portion 55a of slide base 55
Four pole bushes 58 are fixed to the lower surface of the plate 54, and a slide shaft 59 vertically fixed to the lower surface of the plate 54 is inserted into the pole bushes 58 so as to be vertically movable. That is, the plate 54 and the support frame 50 are connected to the slide shaft 59. It is configured to be able to move up and down (up and down) with respect to the horizontal portion 55a of the slide base 55 via the ball bush 58. Among the four wooden slide shafts 59 inserted through the four ball bushes 58, the lower end of the slide shaft 59 located on the right side in FIG. 6a is connected via a connecting plate 60. Reference numeral 61 indicates a fixing screw for the connecting plate 60. As shown in FIG. 6C, an elongated hole 61 is provided approximately in the center of the connecting plate 60, and a cam follower (roller follower) 64 that engages with the cam 63 of the cam drive section 2162 is installed in the elongated hole 61. is rotatably supported via a support shaft 64a. The cam drive device 62 is for rotationally driving a cam 63 that engages with a cam follower 64, and includes a motor 65 with a gear head and a cam connected to a drive shaft (output shaft) 66 of the motor 65 via a coupling 67. It is composed of a shaft 68, a cam 63 fixed to the cam shaft 68 via a key 69, and the like.

The motor 65 is fixed to a motor base 70 that is integrally vertically disposed on the horizontal portion 55a of the slide base 55. Further, the cam shaft 68 is connected to the horizontal portion 55 of the slide base 55.
Bearing 7 attached to camshaft support plate 71, 71 hanging vertically on a
It is rotatably supported via 2. A support frame lifting device 73 is mounted on the horizontal portion 55a of the slide base 55 to constantly press and bias the support frame 50 upward. The support frame lifting device 73 includes an lifting pin 74 that comes into contact with the lower surface of the plate 54, a pin storage i'375 that stores the upper moving bottle 74, and an attachment that always urges the upper moving bottle 74 upward. The platform support frame 50 is always moved upward by the upwardly moving pin 74 which is configured with a biasing member (for example, a coil spring) 76 and is biased upwardly via the biasing member 76. There is. The cam 63 is composed of an eccentric cam, and when the cam 63 is rotationally driven via the cam drive device 62, the cam 63 forms a cam follower 64, presses the cam follower 64 downward, and presses the cam follower 64 downward. Lifting device 73
The support frame 50 is moved upwardly through the support frame 50, so that the support frame 50 is moved downwardly.

Two detection members 77 and 78 are fixedly installed on the lower part of the slide shaft 59 at appropriate distances apart in the vertical direction, and on the other hand, two detection members 77 and 78 are fixed on the horizontal part 55a of the slide base 55. Sensors 79 and 80 are attached via support plate 81. And these detection members 77 and 78
, and sensors 79 and 80, the up and down movement of the stand support frame 50 is detected by the receiver. Reference numeral 82 indicates a spacer.

When the stand support frame 50 moves upward, the receiver is positioned above the horizontal portion 55a of the slide base 55.

The receiver is provided with a stopper plate 83 for positioning the microplate 4 by coming into contact with the upper surface of the well 5 of the microplate 4 placed a on the table 51. The stopper plate 83 is fixed to the horizontal portion 55a of the slide base 55 via a support 84. One side of the stopper plate 83 is equipped with a microwell module detection device 85 for detecting microwell modules in the microplate 4. A plurality of microwell modules 86 are installed in the microplate 4 as shown in FIG. It is for detection. The microwell module detection device 85 includes a switch base 87 and a switch plate 89 equipped with a plurality of detection switches 88, as shown in FIG. The detection switch 88 is constituted by an actuating leaf spring 90, etc., and the leaf spring 90 is configured to set the plurality of switches 88 individually to obtain ON-OFF state. So .

The plate spring 90 is configured to be able to come into contact with the flange portion 86a of the microwell module 86 in the microplate 4, and when the microplate 4 on the table 51 moves upward, the plate spring 90 is configured to come into contact with the flange portion 86a of the microwell module 86 inside the microplate 4. 4 flange portion 86
a presses the leaf spring 90, and the switch 88 is activated. Therefore, when all the switches 88 are not activated, there is no microplate 4.

When some of the switches 88 are not activated, it is determined that some of the microwell modules 86 are in short supply. Reference numeral 91 indicates a leaf spring for holding the microplate 4, and reference numeral 92 indicates a duct for wiring the switch 88.

In FIG. 6, reference numeral 93 indicates a pulse motor for controlling the movement of the slide base 55 along the slide 57, and is fixed to the fixed frame 56 of the main body of the apparatus. The support frame 50 is powered by a pulse motor 93.
The pair of receivers is controlled to move forward and backward by a pitch P between the centers 52 of each month of the platform 51. That is, the microplate 4 whose pair of supports are placed and supported on the stand 51 is controlled in movement by the pulse motor 93, and the movement of the supports is controlled by l pitch P via the stand support frame 50. There is. In addition, the microplate 4 placed on the stand 51.51 is driven by a pulse motor 93.
The movement is controlled in small pitch increments within a pitch P, and each well 5 of the microplate 4 is
The cleaning liquid can be dispensed into and discharged from the inside. The fixed cost 94 is for temporarily supporting the microplate 4 transported from the supply magazine 3 on a stand.

That is, the support frame 50 is controlled to move by one pitch P in the left direction in FIG. 6a via the pulse motor 93 while being lowered via the cam 63. In this case, it is inserted into the supply magazine 3 (see Fig. 1), and in this state, the cam 63 is rotated in the direction of release, and the receiver moves the table support frame 50 upward. In this case, only one microplate 4 in the supply magazine 3 is supported by the pair of supports a21 on the left end side on the stand 51. In this state, the microplate 4 is set so that the fixed cost can be moved above the upper surface of the stand 94, and with this fixed cost moved above the stand 94, the support frame 50 is It is controlled to move rightward by l pitch P via a pulse motor 93. Then, with the support frame 50 moved to the right by l pitches, the support frame 50 is moved downward to a position lower than the fixed support frame 94 via the cam 63, and at this time,
The microplate 4, which was placed on the stand 51, is temporarily placed on the stand 94. In this state, the support frame 50 is again connected to the pulse motor 9.
3 into the supply magazine 3, and carry out the microplates 4 in the supply magazine 3 out of the supply magazine 3 by the same operation as described above, and in this way, the microplates 4 in the supply magazine 3 are successively removed. It is designed to be able to be carried out and transported.

The receiver holder 51 has a tapered joint 51a that matches the joint of the microplate 4, as shown in Figure 6C.
, 51b are formed, and are set so that the position of the microplate 4 can be determined.

The cleaning liquid nozzle arm part 13 is for dispensing and discharging the cleaning liquid into each well 5 of the microplate 4 and detecting the liquid level of the cleaning liquid dispensed into each well 5, as shown in FIG. , as shown in FIG. 8, an arm main body 100 and an arm shaft 10 that supports the arm main body 100.
1, and an arm drive section 102 for raising and lowering the arm main body section 100 and rotating it.

The arm main body 100 includes an arm base 103 fixed to an arm shaft 101 and a cleaning liquid dispensing arm 104 extending from the arm base 103, as shown in FIG. 7a.
and a liquid level detection arm 105. The cleaning liquid dispensing arm 104 and the liquid level detection arm 105 are arranged orthogonally to each other, and each arm 104, 105 is configured to be able to rotate by 90 degrees via the arm drive unit 102. The cleaning liquid dispensing arm 104 is connected to the cleaning liquid shelf 14 (the first
a nozzle part 106 for aspirating the amount of washing liquid to be dispensed three times from the sample (see figure) and dispensing the washing liquid three times into each well 5, a nozzle support base 107 for supporting the nozzle part 106, and a nozzle. It consists of a presser foot 108. The nozzle support base 107 is divided into two parts as shown in FIG.
The nozzle 106a is fixed.

Further, on the inner surface of each nozzle support base 107, there is a second nozzle 106 that is set shorter than the first nozzle 106a.
b is fixed. The second nozzle 106b is shown in FIG.
As shown in , the first nozzle 106a is inclined toward the first nozzle 106a, and is configured so that the first nozzle 106a can be cleaned via the cleaning liquid dispensed from the tip of the second nozzle 106b. As shown in FIG. 7f, a pair of long and short nozzles 106a and 106b are arranged as desired in each well 5, and there are 24 pairs of long and short nozzles 106a and 106b. (12 pairs x 2 rows on one side). Each nozzle 106a, 106b has a nozzle holder 108. It is fixed and held via a fixing screw 109. The liquid level detection arm 105 has an electrode 11 for liquid level detection.
0 and an electrode base 111 for supporting the electrode 110. As shown in the seventh diagram, the electrode 110 is housed in a recess 112 formed in an electrode base 111 and is held via an electrode holding plate 113. The electrode 110 is.

As shown in the seventh drawing, the electrode needle 114 and the collar part 11
5, and an outer cylinder 116 having an electrode needle 11.
4 and the outer cylinder 116 are connected to each other via a V-shaped retaining part 117. The setting is such that it can absorb the amount of movement of the needle tip at the time of the change.

24 nozzles 106 (12 nozzles x 2 rows) are provided, and 24 sets of electrodes 110 (12 sets, 2 tosses) are provided.
column) is deployed.

As shown in FIGS. 8a and 8b, the arm drive unit 102 is
Drive unit 11 for rotating and vertically moving the arm shaft 101
It is composed of 8. The mechanism of the drive unit 118 that rotates and moves the arm shaft lot up and down includes two cams 120 and 121 that are rotationally driven and a cam follower 122 that engages with each cam 120° 121, as shown in FIGS. ,12
3, and each cam 120, 121, cam follower 12
2. Up and down operating arm 124 operated via 123
．． It is composed of a swing operating arm 125 and the like. Each cam 120, 121 is fixed to a camshaft 126, and the camshaft 126 is rotationally driven by a motor (not shown). The configuration is such that by rotating each cam 120, 121, the arm shaft 101 can be vertically operated or 1,000 times (90')L operated via the vertically operating arm 124 and the swinging arm 125. .

Reference numeral 128 indicates a cover.

The cleaning liquid shelf 14 is for storing a cleaning liquid, and is configured as shown in FIGS. 9a and 9b. 148° Overflow saucer 149. It is composed of a cleaning liquid supply unit section 150, and the like. The cleaning liquid supply unit section 150 includes a cleaning liquid supply tank 151.
°Tubing pump 152. and a supply hose 153, etc., and are configured so that the cleaning liquid 147 can be automatically supplied into the cleaning liquid container 148. Reference numeral 153 indicates a sensor for lower limit detection. 154,155
1 is a detection member for detecting the upper and lower limits of the cleaning liquid 147, and is set so that when the remaining amount of the cleaning liquid 147 exceeds the lower limit, a lamp lights up and a buzzer sounds.

The cleaning liquid 147 in the cleaning liquid container 148 is sucked through the nozzle part 106 of the cleaning liquid nozzle arm part 13, and is dispensed in three portions into each well 5 of the microplate 4, which is controlled to stop at a predetermined position. However, the operation of suctioning and dispensing the cleaning liquid 147 is performed via the cleaning liquid dispensing unit section 46.

The cleaning liquid dispensing unit 46 is shown in FIGS. 10a and 10b.

As shown in c, d, and e, a syringe 170 for suctioning and dispensing the cleaning liquid 147. Movable shaft 1 of syringe 170
a pulse motor 172 for driving 71 up and down;
and syringe 170. It is composed of a support frame 173 for supporting the pulse motor 172 and the like. As shown in FIG. 10f, the syringe 170 includes a cylinder part 174, a movable shaft 171 slidably inserted into the cylinder part 174, and a piston 175 solidly attached to the inner end of the movable shaft 171. It is composed of a cylinder head 176, a tube connecting portion 177, and the like. The syringe 170 has a short nozzle 106b (seventh nozzle) for sucking and discharging the cleaning liquid.
24 wires are provided, corresponding to the 24 wires provided in (see figure).

The 24-wood syringe 170 is shown in FIG.
As shown in d, the supporting frames 173, 173 are divided into two parts, each having 12 parts.

In addition, the 12 syringes 170 arranged on each support frame 173 are further arranged in two rows of 6 pieces each, as shown in Figure 1O. are arranged alternately in a so-called zigzag pattern. At the lower end of the movable shaft 171 of each syringe 170,
A boss portion 179 having a flange 178 is fixedly provided,
The boss portion 179 is shown in Fig. 1Og.

As shown in h, a plurality of step portions 180a, 180b, 18
A stepped portion 180b of the movable shaft support member 180 having 0c,
It is locked in the locking recesses 181 and 182 of 180c.

Reference numeral 183 indicates a screw for fixing the movable shaft 171, which is screwed onto the movable shaft support member 18. Rad to cylinder 1
A screw 185 having an engagement recess 184 is fixed to the upper part of the upper base 76.
The lower end portion of a fixing screw 187 screwed into 86 is engaged. The upper base 186 is fixed to the support frame 173 via a connecting member 188.

A member 189 having a crank part 189a is provided at the lower part of the cylinder part 174 of the syringe 170, and the cylinder part 174 is connected to a crank-shaped syringe holding member via this flange part 189a, as shown in FIG. It is held by member 190. 1 shown in Figure 10i
91 and 192 are engagement recesses that engage with the flange portion 189a. The movable shaft support member 180 has a fixing screw 190a.
It is fixed to the movable block 192 via.

The movable block 192 is configured to be controlled to move up and down via a pulse motor 172 and a guide 193. That is, the movable shaft 171 of the syringe 170 is moved up and down via the pulse motor 172, and thereby the cylinder part 174 is moved via the piston 175.
It is designed to be able to suck in and expel the air inside. A tube 194 for suction and discharge is connected to the tube connecting portion 177, and the tube 194 of each syringe 170 is connected to the cleaning liquid nozzle via the liquid reservoir 156, as shown in FIGS. It is connected to each short nozzle (cleaning liquid suction and discharge nozzle) 106b of the arm portion 13. As shown in FIGS. 10m and 10n, the liquid reservoir portion 156 includes a liquid reservoir main body portion 157, a liquid reservoir space portion 158.
and hand grips 15 provided at both ends of the liquid reservoir space 158.
It is composed of 9°160.161. The same number of liquid reservoir spaces 158 are provided as the number of cleaning liquid suction/discharge nozzles 106b, and each syringe 170 and each cleaning liquid suction/discharge nozzle 106b are connected to each other via the liquid reservoir space 158. ing. The inner diameter of the liquid reservoir space 158 is
It is formed to have a larger diameter than the inner diameter of the tube 194, and the container of the liquid reservoir space 158 is set to have a volume that can sufficiently absorb the amount of cleaning liquid that can accumulate in the tube 194.

In addition, the joint 161 side in the liquid reservoir space 158, that is,
There is a tapered part 162 on the cleaning oil absorption and discharge nozzle 106b side.
It is designed so that the bubbles can be easily removed. The liquid reservoir 156 is fixedly held on a multi-channel joint 260 erected on the arm base 103, as shown in FIG. Reference numeral 195 indicates a tube holding member.

A hole 196 for tube insertion is provided through the tube.

Reference numeral 197 indicates a support member. Reference numeral 198 indicates a cover, and reference numeral 199 indicates a base.

Multi-channel joint section 2 erected on arm base 103
60 is a long nozzle (residual liquid discharge nozzle) 106a of the nozzle part 106 and a residual liquid discharge device 21261 (Fig. 10 0+P
) and for connecting.

As shown at 0+P in FIG.
Patchkin opened between 263 (for example, 1mm thick)
It is composed of 264 etc. Stainless steel vibes 265 are inserted through the front acrylic plate 262, and the number of stainless steel vibes 265 is the same as the number of nozzles 106a. Each stainless steel pipe 265 is connected to the nozzle 106a via a tube connector 266 and a tube 267. The packing 264 has a large empty space 2 that communicates with each stainless steel pipe 265 as shown in FIG.
67 is the formation. Also, on the rear acrylic plate 263,
One joint 26 communicating with the empty chamber 267 of the packing 264
8 is attached, and the multi-channel joint section 260 is connected to the residual liquid discharge device 261 via this joint 268. The residual liquid discharge device fi261 includes a vacuum tank 269, a vacuum solenoid valve 270, a vacuum pump 271, a drain hose 272, and a tubing pump (
It is constructed of a double head (273), a drain tank 274, etc., and is set so that the remaining liquid in each well 5 can be drained into the drain tank 274 as a drain liquid 275. 27
6 is a sensor for detecting the upper limit amount of the waste liquid 275.

The electrode cleaning shelf 16 is for cleaning the electrode 110 of the cleaning liquid nozzle arm 13, and when the liquid level detection arm 105 of the cleaning liquid nozzle arm 13 is rotated to a position above the electrode cleaning shelf 16. That is, each time the liquid level detection work of the washing liquid dispensed into each well 5 is completed, the electrode 11
This is for washing the 0 with running water. The configuration will be explained below using FIG. 4 and FIG. 11.

In the figure, reference numeral 210 denotes a cleaning liquid flow member disposed within the tray 211, which includes a large number of cleaning liquid flow holes 212 for causing the cleaning liquid to flow upward, and a cleaning liquid supply hole 213 that communicates with each of the cleaning liquid flow holes 212. The cleaning liquid supply hole 213 is connected to a cleaning liquid supply device 215 via a supply hose 214. Cleaning liquid flowing member 21
0 is configured such that its four sides are fixed via fixing screws 216 and can be positioned and adjusted to a predetermined position via the fixing screws 216. The cleaning liquid water hole 212 is connected to the electrode 110.
As shown in FIG. 4, there are 24 cleaning liquid flow holes 212 arranged in two rows each having 12 holes. Each cleaning liquid flow hole 212 is formed at a position corresponding to each electrode 110. As shown in the M4 diagram, each cleaning liquid flow hole 212 has a high inner side with the center of the hole as the boundary.
It has a two-tiered structure with the outer side lowered, and the hole 21 on the upper side
The cleaning liquid flowing upward from 2a is discharged into the saucer 211 from the hole 212b on the lower side after cleaning is completed. In other words, the drained liquid after washing is used as the electrode 110 after washing.
It is designed to prevent it from adhering to the surface, and to maintain a clean state. Cleaning liquid supply device 215
A supply tank 218 that stores the cleaning liquid 217, and a magnetic gear pump 219 that sucks the cleaning liquid 217 from the supply tank 218 and automatically supplies the cleaning liquid 217.
, and 31 flow rate portions 222 consisting of a flow rate control valve 220 and a check valve 221. Reference numeral 223 denotes a drain tank for storing drained liquid after cleaning, and the drained liquid flows into the tank from a drain pipe 224 provided at the bottom of the saucer 211. Reference numeral 225 indicates a sensor for detecting the upper limit, and reference numeral 226 indicates a sensor for detecting the lower limit.

The cleaning liquid 217 is set to flow out simultaneously from 24 six holes 212 for cleaning, and the flow rate can be adjusted by a flow rate control valve 220. sensor 22
5, 226 is composed of a capacitive sensor, and a lamp and a buzzer emit an alarm when the sensor 226 for lower limit detection is OFF or when the sensor 225 for upper limit detection is ON. It is set.

In FIG. 4, reference numeral 250 indicates the microwell module detection device 85. The display section is in contact with each electrode 110 of the liquid level detection arm 105, and has indicator lights (lamps) 25 in the same number as the number of wells (96) in the microplate 4.
1 is arranged, and the detection results of liquid level detection in each of the bulk well modules 86 and each well 5 are displayed on each indicator light 251.

Next, the action of cleaning the inside of each well 5 of the microplate 4 based on the above configuration will be explained.

First, the supply magazine 3 containing 10 microplates 4 each having wells 5 coated with a reagent solution is placed at a predetermined position a on the starting end side (the left side in FIG. 1) of the plate transport mechanism section 12. and set it. Further, an empty ejection magazine 17 is set at a predetermined position on the terminal end side of the plate transport mechanism section 12. The supply magazine 3 is set at the highest position via the magazine lift 2220, while the discharge magazine 17 is set at the lowest position. Note that by connecting the first washing device 7 and the gelatin coating device 8 so that the washed microplate 4 can be directly supplied to the gelatin coating device 8, the ejection magazine 17 can be made unnecessary. It is possible. Each magazine 3, 17 is positioned in a predetermined set state via a positioning bin 21.

Next, the supply magazine 3 is
The microphone plates 4 are transported one by one, and this transport procedure will be explained with reference to FIGS. 12 and 13. First, the receiver, which has been moved upward via the support frame lifting device 73, moves the platform support frame 50 downward via the cam drive device 62, that is, drives the motor 65 to rotate the cam 63. As a result, the receiver moves the platform support i50 downward via the cam follower 64.

Next, the pulse motor 93 is driven to remove the stand support frame 5.
0 in the direction of the supply magazine 3 by 1 pift P.

This state is shown in FIG. As shown in Figure a, the acid enters the lower part of the microplate 4 in the supply magazine 3.

Next, the cam 63 is rotated via the motor 65, and the cam 63 is rotated via the motor 65.
3 and the cam follower 64 are released. Then, the support frame 50 is moved to the upper movable bin 74 of the upper movable part 73 of the support frame.
During this upward movement, the microplate 4 stored in the lowest position of the supply magazine 3
The receiver is supported by a stand 51 and moves upward. This state is the 12th
As shown in the figure, in this state, as shown in the figure,
The fixed cost of the stand support frame 50 moves higher than the top surface of the stand 94.

Next, the receiver moves the table support frame 50 by one pitch P toward the discharge magazine 17 via the pulse motor 93. At this time, one microplate 4 stored in the lowest stage in the supply magazine 3 is discharged to the outside of the supply magazine 3. This state is shown in FIG. 12C.

Next, the cam 63 is rotated via the motor 65, and the receiver, which has been moved upward, causes the stand support frame 50 to move downward.

During this downward movement, the support frame 50 is moved downward to a position lower than the base 94, and therefore the microplate 4, which was supported on the base 51, is moved downward to the base 94.
located above. This state is shown in Figure d of fS12.

Next, the supply magazine 3 is lowered by a fixed pitch via the magazine lifting device 20. During this lowering, the sensor plate 34 and the sensor 35 work together to lower the supply magazine 3 by a certain pitch and control the stop.
The lowering control is performed so that the ninth microplate 4 from the top of the stored microplates 4 is placed in the same position as the original storage position of the microplate that has already been carried out. The lowering operation of the supply magazine 3 drives the motor (speed control motor with electromagnetic brake) 24,
This state, which is achieved by lowering the support base 23 via the lift 25, is shown in FIG. 12e.

Next, the receiver moves the stand support frame 50 in the direction of the supply magazine 17 via the pulse motor 93, and the pair of receivers located closest to the supply magazine 3 move the stand 51 to the supply magazine 17.
The microplate 4 in the lowest stage, that is, the ninth microplate 4 from the top. This state is shown in FIG. 12f. FIG. 12f is the same state as FIG. 12a, and the steps of FIGS. They are carried out one after another. This operation is repeated until all ten microplates 4 are carried out of the supply magazine 3, and each microplate 4 is washed in the working section 227 as shown in FIG. Ejection magazine 17
The ejection magazine 17, which is carried in (stored) one by one, is controlled to rise at the same pitch as the supply magazine 3, and the 10 sheets that have been cleaned are placed in the empty ejection magazine F.
Microplates 4 are stored one after another.

As shown in FIG. 14a, when two microplates 4 are transferred to the stationary receiver 94, the first microplate 4 to be transferred reaches the working part 227 position. Here, when the receiver moves the table support frame 5o upward in order to carry out the third microplate 4, as shown in FIG.
The upper surface of the flange portion 86a (see FIG. 5 f) of the microwell module 86 of the microplate 4 is in contact with the lower surface of the stopper plate 83, and each microwell module 86 of the microplate 4 at the working part 227 position is
The receiver is sandwiched between the base 51 and the s-h-/par plate 83, and is positioned and fixed. Then, the residual liquid (residual liquid dispensed during the coating operation) in each well 5 of the microplate 4 fixed at the working part 227 position is discharged through the nozzle 106a.Next, the cleaning liquid is discharged through the nozzle 106b. Aspirate enough amount to dispense 3 times. This amount of suction is enough to remove bubbles even in the cleaning liquid that tends to foam due to the action of the liquid reservoir 15G, and prevent the liquid from entering the syringe 170. Dispense within. The nozzle 106b is the nozzle 10
Since it is inclined in the direction 6a, the nozzle 106a can be cleaned when dispensing the cleaning liquid from the nozzle 106b. Also, since the cleaning liquid is sprayed into the nozzle 106a,
The cleaning solution coated on the inner wall of the well 5 is passed through the nozzle 10.
6a, the cleaning liquid is discharged again through nozzle f06a, and the cleaning liquid is discharged again through nozzle 106b through nozzle 30.
Dispense 0ttl into each well 5. In this way, the amount of time required for dispensing and discharging the cleaning solution is quite large.
1-4ζ "吏19i-2.

Clean without damaging the ring part. Note that the suction amount and the three-time dispensing amount of the cleaning liquid are performed via the pulse motor 172, and can be set to the desired suction amount and two-dispensing amount by controlling the stroke of the movable shaft 171 of the syringe 170.

In this case, each of the three dispensing amounts can be set and adjusted individually, and variations in each dispensing amount can be corrected. Note that the fixed receiver is attached to the stand 94 for the microwell module detection device 85, and the fixed receiver is attached to the idle station 2 located between the stand 94 and the supply magazine 3.
The receiver 28 detects whether or not there is a microwell module 86 on the table 51, and
If there is no microwell module 86, the machine is stopped and the missing microwell module 86 is replenished.

In the work of dispensing and discharging the washing liquid to each well 5 of the microplate 4 fixed to the working part 227, first, the arm main body part 100 of the washing liquid nozzle l part I3 is rotated and the driving part for vertical operation is moved. 118 , and then the cleaning liquid dispensing arm 104 is moved up through the cleaning liquid shelf 14 .
The arm body 100 is rotated so that it is positioned directly above the washing liquid dispensing arm 10.
The pair of nozzle parts 106 of 4 are connected to the cleaning liquid 1 in the cleaning liquid shelf part 14.
Insert it into 47.

Next, the movable shaft 171 of the syringe 170, which is connected to each nozzle 106b for sucking and discharging the cleaning liquid, is moved by a pulse motor 17.
2, and through the suction action of the syringe 170, the cleaning liquid 147 is sucked into each nozzle 106b in three doses.Next, the arm main body 100 is moved upward, and then, The arm main body 100 is rotated 90 degrees counterclockwise via the rotation and vertical operation drive unit 118. At this time, the washing liquid dispensing arm 104 is set above the microplate 4 in the working section 227,
The liquid level detection arm 105 is located in the upper direction n of the electrode cleaning shelf 16.
The arm body section 100 is then moved downward. At this time, the pair of nozzle parts 106 of the arm body part 100 are inserted into each well 5, and then the movable shaft 171 of the syringe 170 is moved upward via the pulse motor 172. The cleaning liquid sucked into the nozzle 106b by compressing the air in the syringe 170 is dispensed into each well 5 in three doses of 300 JLu and discharged for cleaning. This work is performed as shown in Figure 15a and b.
- First, carry out the process to two rows (A row and E row) of the eight wells 5 in F.Next, move the arm main body 100 upwards, and transfer the microplate 4 through the table support frame 50. 229 in the direction of arrow 229. Then, the arm main body 100 is moved down again, and each well 5 in the B row and F row is
Drain the cleaning solution in three doses of 300 gu each. This operation is repeated three times, and 300 ALl of the washing solution is discharged three times into each well 5 of rows 0, G, D, and F. This completes the cleaning in each well 5.

After dispensing the cleaning liquid, the arm main body 100 is moved upward and rotated 90 degrees clockwise. Then, the arm main body 100 is moved downward, and each of the 24 nozzles 106
Add reagent solution 147 to b in the required amount (3
Aspirate only the amount (dose amount). At this time, the electrode 110 of the liquid level detection arm 105 is inserted into each well 5 where dispensing has been completed, and the two electrodes 8ill are inserted into each well 5.

The liquid level of the dispensed cleaning liquid is detected by the change in impedance (see FIG. 7C), and the liquid amount is detected.

When the cleaning liquid is suctioned by the nozzle 106b and the liquid level detection by the electrode 110 is completed, the arm main body 100 is moved upward and the arm main body 100 is rotated 90' again. At this time, the next microplate 4 which has not been cleaned is conveyed to a position above the arm main body 100 and set (positioned and fixed) in a series of operations shown in FIGS. 12a-f. Next, the arm main body 100 moves downward, and the 2
The cleaning liquid sucked into each of the four nozzles 106b is dispensed into each well 5 of the microplate 4. Since this dispensing operation is the same as that described above, the explanation thereof will be omitted. When dispensing and discharging the cleaning liquid n1 using the nozzle 106b, the lower part of each electrode 110 is placed in the L direction of the cleaning liquid driftwood hole 212 of the electrode cleaning shelf 16, and the cleaning liquid 217 is supplied via the cleaning liquid supply device 215. for each TL8i
110 to wash each electrode 110 with running water. During this cleaning, since the cleaning liquid flow holes 212 are formed in two stages, the dirty cleaning liquid after cleaning is drained into the drain tank 223 without adhering to each electrode 110.

When the dispensing of the cleaning liquid to each well 5 by each nozzle 106b and the cleaning operation of each electrode 110 are completed, the arm body loo moves upward and rotates 90 degrees counterclockwise again. Then, the arm main body lOO moves downward, and each nozzle 1
06b aspirates the necessary amount of washing liquid, and each electrode 110 detects the liquid level in each well 5 after dispensing.

The above operations are repeated to wash the inside of each well 5 of the microplate 4 that is successively transported from the supply magazine 3. This operation is performed when the microwell module detection device 85 detects that the microwell module 86 is out of stock during the zero operation that is performed continuously until the ten microplates 4 in the supply magazine 3 are empty. Stop and insert microwell module 8 into the missing part.
Fill 6. This makes it possible to prevent the microwell module 86 from being transported to the working unit 227 position in a missing part, supplying the cleaning liquid to the missing part of the microwell module 86, and preventing the cleaning liquid from scattering on the machine.

The microplate 4 that has been washed inside each well 5 is
The receiver shown in FIGS. 2a to 2f is loaded into the discharge magazine 17 by the conveying action of the stand support frame 50. When the support frame 50 is moved down via the cam 63, the microplate 4 carried into the ejection magazine 17 is placed in the ejection magazine 17 in an empty state as shown in FIG. It is stored in the top storage section (support section). Then, when the support frame 50 is moved in the direction of the supply magazine 3 and moved out of the ejection magazine 17, the ejection magazine 17 is moved up a fixed pitch via the magazine lifting device 20, and the next microplate 4 is carried in. Wait for it to come. The upward constant pitch feeding control function of the ejection magazine 17 is the same as that on the supply magazine 3 side, so the explanation thereof will be omitted.

When ten microplates 4 that have been cleaned are stored in the discharge magazine 17, the discharge magazine 17 is taken out, and the discharge magazine 17 is transferred to the magazine supply section of the gelatin coating apparatus 8 for the next process as shown in FIG. It supplies the .

As shown in FIG. 1, a gelatin coating device 8. Second incubating device a9° Second washing device 10. After passing through the drying device 11 and drying device 11, the production of the solid phase reagent is completed.

When the remaining amount of the cleaning liquid becomes lower than the lower end of the detection member 155 for detecting the lower limit, the buzzer will issue an alarm, so in this case, the cleaning liquid may be replenished.

In particular, according to the tube connector device (reservoir) 156 according to this embodiment, the action of the liquid reservoir space 158 prevents the cleaning liquid from entering the syringe 170 when the cleaning liquid is sucked, so that rusting of the syringe 170 can be prevented. At the same time, maintenance of the syringe 170 can be facilitated. Further, even when using a liquid that easily foams, the foam can be removed in the liquid reservoir space 158, so that bubbles can be reliably prevented from entering the syringe 170. Therefore, syringe 17
This has the advantage that it is possible to reliably prevent liquid from scattering from around the tube and the tube, and also to prevent rusting of the device and extend the life of the device.

Also, a large number of nozzles 106a, 106b and a large number of electrodes 11
0 are integrally constructed, it is possible to work on a large number of wells 5 at the same time, prevent loss time, and work with high efficiency.

Since the cleaning section of the electrode 110 is configured in two stages to prevent the dirty water after washing n1 from mixing with other parts, it can be kept clean and the quality of the product can be improved.

Further, since the electrode 110 is washed with driftwood every time the liquid level in each well 5 is detected, a clean state is maintained, and the quality of the product can be improved.

Furthermore, since the electrode 110 has a cushion structure, the electrode 8i
The tip of llO may interfere with external parts.

[Effects of the Invention] As described above, according to the present invention, a cleaning solution is automatically dispensed and discharged to each well of a microplate that is continuously supplied and transported to prevent fluid leakage and liquid leakage. It can prevent intrusion into the syringe, and can improve the efficiency of cleaning work, improve the productivity of solid-phase reagents, improve production efficiency, improve product quality, improve reliability, and extend the life of the equipment. .

[Brief explanation of the drawing]

FIG. 1 is a layout diagram of a solid-phase reagent manufacturing apparatus including one embodiment of the apparatus according to the present invention. Figures 2a, b, and c are a plan view, front view, and side view of an embodiment of a cleaning device including the device according to the present invention, and Figures 3a, b, c, d, and e are views of a microplate. An explanatory diagram of the magazine to be stored. Figure 4 is a perspective view showing the main parts of one embodiment. Figures 5 a and b.
, c, d, e, and f are explanatory diagrams of the main parts of this example; FIG. 6 is an explanatory diagram of the microplate transport section and electrode section; FIG. FIG. 9 is an explanatory diagram of the arm drive section; FIG. 10 is an explanatory diagram of the cleaning liquid storage section; FIGS. 10 a, b, c, d, e, f, g, h, i. J, k + l + In * n + O + P
+ q is an explanatory diagram of the dispensing neck part, Fig. 11 is an explanatory diagram of the washing part, Fig. 12 a, b, c, d, e, f, Figs. 13 and 14
Figures a and b are diagrams for explaining the operation of the main parts of this embodiment, and Figures 15a and b are diagrams for explaining the operation of dispensing to a microplate. 3... Supply magazine 4... Microplate 5... Microwell (reagent solid phase container) 12... Plate transport mechanism section 13... Washing liquid nozzle arm section 14... Washing liquid shelf section 16... - Electrode cleaning shelf section 17... Carrying out magazine 106... Nozzles 106a, 106b... Nozzle 110... Electrode 150... Cleaning liquid supply unit section 156... Liquid reservoir section 170... Syringe 227... ... Working part 228 ... Idle station patent author Olympus Optical Industry Co., Ltd. Figure 3 (a) Figure 3 (d) Figure 3 (e) Figure 5 Figure 6 (c) Figure 7 Figure 8 Figure 8 Pu99 Figure 10 (d) 1g Figure 10 (f) 7s OQ 1'40 Figure 10 Figure 10 Figure 10 (1<) Figure 10 (J) Figure 11 Figure 12 Figure 12 Figure 14

Claims (1)

[Scope of Claim] A tube connector device in a solid-phase reagent manufacturing apparatus configured to automatically dispense a reagent into a solid-phase reagent container and solidify the reagent on the inner wall of the container, comprising: A connector portion having a liquid reservoir with a diameter larger than the inner diameter of the tube is provided on a tube that communicates and connects a suction and discharge nozzle with a suction and discharge device for sucking and discharging liquids such as reagent solutions and cleaning liquids from the nozzle. 1. A tube connector device for a solid-phase reagent manufacturing device, characterized in that the tube connector device is configured by: