JPS6029901B2 - Dispensing device - Google Patents

Description

[Detailed Description of the Invention] This invention relates to a sample tube holding frame arranged in a sample tube holding frame that is sequentially pumped in a direct separation vessel used in radioimmunoassay. When a sample, reagent, etc. is dispensed into a tube more than once, a means is provided to rotate the pipette inlet/outlet at a position opposite to the sample tube, with the rigid axis of the sample tube as the central axis, and the inner wall of the sample tube and the inlet The present invention relates to a dispensing device that can be changed to a contact position with a dispensing device.

For example, in radioimmunoassay, various hormones and protein substances are labeled using radioactive isotopes (RI), and subsequent steps include a dispensing step in which the labeled hormone is quantitatively added to a sample, such as patient serum, along with an antibody. In this process, the conjugate of labeled hormone and antibody is separated from the free labeled hormone, and the amount of hormone in the patient's serum is determined from the respective radioactivity measurements.The dispensing process requires extremely high separation accuracy. (Absolute error within 1% over 10 mm) is required.

Therefore, when sucking up a fixed amount of the serum, RI reagent, and antibody with a pipette and discharging it into a sample tube, the suction and discharge port should be brought into oblique contact with the inner wall of the sample tube, and the discharged liquid will flow into the suction and discharge port due to its surface tension. The final drop formed is attached to the wall and separated when the pipette is pulled up, increasing the accuracy of the pipette.

This means that even if serum, RI reagent, and antibody are sequentially dispensed into the same sample tube using dedicated pipettes,
It also provides an opportunity for them to mix with each other through the suction mouth.

For the serum dispensing pipette, after aspirating the serum, a buffer solution of approximately 5 times the amount of aspirated serum is added to the serum from another pump through a valve and sent into the pipette from the direction opposite to the aspirating direction. The serum is pushed out through the suction port and discharged into the sample tube, and the serum adhering to the inner wall of the pipette is completely washed out.The pipette is then transferred to the washing section to wash off the serum adhering to the outside of the pipette. .

Therefore, (1) to prevent serum from mixing with the RI reagent and antibody in the RI reagent bottle and antibody bottle through the suction spout, and (b) to prevent the RI reagent and antibody in the RI reagent bottle and antibody bottle through the suction spout. - Particular attention must be paid to preventing mixing of antibodies. It goes without saying that (1) contamination with serum must be avoided; however, in (0), if the RI reagent and antibody mix, a reaction will occur, making accurate measurement impossible. Because it will be.

Conventionally, measures to prevent (1) and (0) have been taken, as shown in FIG. The method was to change the position of the suction mouth by increasing the position (height) of the suction port one after another.

When this method is used, when the pipette is pulled up after the separation is completed, the last droplet to be discharged may be pulled up along the inner wall of the sample tube by the suction/discharge port, and the RI reagent and antibody droplets may be pulled up along the inner wall of the sample tube. Serum/RI due to carryover
Cross-contamination between reagents and antibodies could not be completely prevented. This invention provides a means for giving rotation about the rigid axis of the sample tube at a position where the pipette suction □ and the sample tube face each other, and changes the contact position between the inner wall of the sample tube and the suction port in the circumferential direction. By doing so, the above-mentioned drawbacks in the use of conventional dispensing devices are solved.

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

FIG. 2 is a perspective view showing the main parts of the sample tube twisting device of the partial pressure device.

In the figure, 0 is the pipette suction port, 1 is the serum tube containing patient serum, and 2 is the sample tube, which are fed in the direction of the arrow at specified pitches into the receiving holes provided at regular intervals in the tray 3. Retained. Reference numeral 4 denotes a clamping plate, and an elastic body, such as a rubber pad 5 made of rubber, is adhered to the side in contact with the sample tube 2, and is fixed to the tips of the arms 6, 6'.

Reference numerals 7 and 7' denote front and rear bearings that slidably support the arms 6 and 6', and are fastened to the machine base 8.

Reference numerals 9 and 9' are sliding pieces that are oppositely shaped and are attached to the arms 6 and 6' in fixed positions with dowel pins at the front and rear, respectively, and are located at the lower center of the left and right arms. A cam follower driven by the cam 10' is rotatably attached to the upper surface of the protrusion located at the lower surface of the protrusion, and a coil spring latched between the spring receiving pins 12 implanted in the lower surface of the protrusion. 13, the cam follower 1
1 is pressed against the armature power arm 10 from the front and rear.

Reference numerals 14 and 14' denote rocking pieces having the arm parts 9 and 9' as rocking pillars, which are engaged with each arm part so as to be freely movable in the axial direction thereof, and have two upper and lower slides. Via the IJ key, each arm 6, 6' is twisted by a rocking movement.

Reference numeral 15 denotes a cam foot rotatably attached to the upper end surface of the swing pieces 14, 14'.

A. 16 is an arm twisting cam. Reference numeral 17 denotes a coil spring, which is engaged between the spring bearing pins 18 installed in the swing pieces 14 and 14', and serves to press the cam follower 15 against the arm twisting cam 16 from the left and right sides.

19 is a machine frame fixed to the machine base 8, and the swing pieces 14, 1
4', and also serves as a mounting base for the upper bearing (not shown) of the drive shaft 20 of the arm sliding force 0 and the arm twisting cam 16.

21 is a drive gear fixed to the output shaft of a small gear motor (not shown) attached to the bottom surface of the machine base 8, 22 is a driven gear that meshes with it, and 23 is locked to the left and right machine base sliding shafts 24 with knock pins. 25 is a sliding arm of the machine.

The machine base sliding shaft 24 is slidably engaged with the machine base 8 and is fixed to the main body 26. 27 is a coil ' engaged with the machine tank moving shaft 24 between the coupling 8 and the main body 26;
By imitation, the machine sliding arm 25 is brought into pressure contact with the contactor 23.

28 is a microswitch, and 29 is a rotation control cam.

Next, the twisting operation of the sample tube 2 by this device will be explained. For example, when the first separation is completed, the pipette is pulled up, the sample tube is fed one pitch and reaches the predetermined stop position, the gammotor (not shown) rotates at the same time as the pipette suctions, and the machine When the sliding arm 25 rotates 60 degrees, the contactor 23 follows and moves closer to the camshaft.

That is, the machine base 8 is slid forward by the biased distance of the coil spring 27 relative to the main body 26 by the distance. D in FIG. 3 shows the clamping plate 4 of the arms 6, 6' in this case.
The position of the tip of the tube facing the sample tube 2 is shown. When the gear motor (not shown) further rotates by 15 degrees, the position of the machine base 8 remains unchanged, and the cam follower 15 is rotated by the operation of the arm twisting cam 16 driven via the drive gear 21, driven gear 22, and drive shaft 20. The swinging pieces 14 are pushed apart from side to side.
, 14', the arms 6, 6' are each twisted outwardly. By this operation, the distance between the lower ends of the left and right holding plates 4 is narrowed, and the left and right holding plates 4 are
holds the sample tube 2. This state is shown at E in FIG.
When the next gear motor (not shown) rotates by 30 degrees, the armature power unit 0 driven through the drive shaft 20 is activated.
The cam follower 11 is pushed forward. That is,
The swinging piece 9 is moved forward, and the sliding piece 9' is moved backward by a corresponding cam follower (not shown).

Therefore, the arms 6 and 6' slide in opposite directions, and the clamping plates 4 and 4' at their tips hold the sample tube 2 through the pad 5 by the frictional force therebetween. It is rotated around its axis.

F in FIG. 3 shows this state. Further, by rotating the next gear motor (not shown) by 15 degrees, the operating position of the arm twisting cam 16 comes to a position where the cam follower 15 is pulled inward, so that the swinging pieces 14, 14' return to the vertical position. be done. As a result, the left and right clamping plates 4 and pads 5, which have been jammed inside, return to their vertical positions, and the sample tube 2 is unclamped. G in FIG. 3 shows this state. By rotating the next gear motor (not shown) by 60 degrees, the operating positions of the machine frame lever power arm 25 and the arm slide power arm 10 are brought to a position where the contactor 23 is pushed out and the front and rear cam followers 11 are retracted into each other. Therefore, the machine base 8 is connected to the coil spring 2.
7, the arm 6 retreats and the arm 6' moves forward, returning to their initial states. This state is shown in the day in Figure 3. As described above, one cycle of the twisting operation of the sample tube 2 is completed by a 180 degree rotation, that is, a half rotation, of the output shaft of the gear motor (not shown).

Note that the gammotor is started by the suction action of the pipette, and after half a rotation, the rotation is stopped by the action of the rotation control cam 29 and the microswitch 28. FIG. 4 is a schematic diagram showing the relative position of the sample tube 2 placed on the tray 3 and the clamping plate 4 of the twisting device. Assuming that the tube positions are predetermined positions for dispensing serum, RI reagents, and antibodies, respectively, when the tray 3 is sent in the direction of the arrow, the positions at which the sample tube 2 is twisted are B and W, and P and W. Two sets of twisting devices Q are required.

Therefore, if the ball holding plate 4 in Fig. 2 is a fake, for example, the Q in Fig. 4 is
If it corresponds to the position, extend the machine base 8 to the left,
Another pair of bearings and arm parts corresponding to the arm parts 6 and 6' having the bearings 7 and 7', the support plate 4, and the pad 5 are arranged at a distance of twice the pitch of the sample tube 2 arrangement pitch. , and link the left and right arms at right angles to the wisteria direction at the top or bottom to form a lotus arrangement.

Next, another embodiment will be described based on the drawings.

FIG. 5 is a schematic diagram of a sample tube twisting device related to another embodiment of the dispensing device. In the figure, 2 is a sample tube, 3 is a tray,
31 is a sector gear supported by a bearing (not shown) so that the center of rotation is the center 30 of the sample tube 2 held in a predetermined position; 32 is fixed to the sector gear 31 with its radial direction oriented; The guide tube 33 is an arm that is slidably supported on the guide tube 32. A fork-shaped clamping part is attached to the tip of the arm part 33, the right clamping piece 34 is fixed to the arm part 33, and the left clamping part 35 is fixed to the arm part 33.
A pad 36 made of an elastic material such as soft rubber and having a chamfered tip is adhered to the inner side of each pad.

Reference numeral 37 denotes a coil spring, which is engaged between the left and right holding pieces 34 and 35, and the relationship between the left holding piece 35 and the left and right pad spacing is determined by
Together with the abutment 38, it is regulated to be slightly smaller than the outer diameter of the tube 2, and serves to hold the subject tube 2 in a spontaneous manner.

Reference numeral 39 denotes a coil spring whose one end is locked to the rear end of the guide tube 32 and the other end to the rear end of the arm 33.

40 is a drive pinion supported by a bearing (not shown) fixed to a machine base (not shown) meshing with the sector gear 31; 41 and 42 are rotatably supported by brackets fixed to the sector gear 31; They are friction wheels that transmit rotation to each other.

43 is an arc-shaped friction plate, the convex arc of which has its center at the center 30 of the sample tube 2, and the right end swings with a pin 44 shielded in the machine stand (not shown). It is freely engaged, and the left end is a counterfeiting mechanism 45 attached to the machine base (not shown).
is pressed into contact with the coil spring 46.

Reference numeral 47 denotes a solenoid that is integrally (not shown) attached so as to be swingable, and its operating shaft is engaged with the inner left end of the friction plate 43 via a joint.

Further, a friction wheel 41 is in contact with the friction plate 43, and the friction wheel 42 is connected to a friction band 48 bonded to the left side of the arm portion 33.
is in contact with.

Next, the twisting operation of the sample tube 2 by this device will be explained.

When the drive pinion 40 rotates in the direction of the arrow, the sector gear 31 is driven in the direction of the arrow.

Therefore, the friction wheel 41 in contact with the friction plate 43 is driven in the direction of the arrow, and then the friction wheel 42 is rotated in the direction of the arrow. As a result, the friction wheel 42 pushes the friction band 48, that is, the arm portion 33, out from the guide tube 32 in the direction of the arrow against the tensile force of the coil spring 39. Since the movement of the arm portion 3 described above is superimposed with the movement of the sector gear 31 around the center 30 of the sample tube 2, the clamping pieces 34 and 36 elastically hold the outer diameter portion of the sample tube 30. While being held, the sample tube 2 is given a certain angle of rotation about its rigid axis as the central axis.

When the sector gear 31 is rotated to the position shown by the two-dot chain line on the left, the friction wheel 41 is brought to a position that matches the notch groove 49 cut in the friction plate 43, so that the arm portion 33 The operation of the friction wheels 41 and 42 that feed out the 36
The arm portion 33 is pulled back into the guide pulp 32 by the tensile force of the coil, and the clamping pieces 34 and 35 are removed from the sample tube 2. Next, the friction plate 43 is moved to the concave side by the action of the solenoid 47 against the tensile force of the coil spring 46.
4 as a bridge dynamic support shaft, the friction wheel 41 and the friction plate are brought into contact by swinging slightly as shown by the two-dot chain line. During this time, the drive pinion 40 is reversed to return the sector gear 31 to its original position. Next, the operation of the solenoid 47 is stopped, and the left end of the friction plate 43 is brought into pressure contact with the stratification gear 45 by the coil spring 46 in preparation for the next start. The following is a description of yet another embodiment of the apparatus.

FIG. 6 is a side sectional view of the sample tube twisting device according to this embodiment of the dispensing device. In the figure, 0 is the pipette suction port,
2 is a sample tube, 3 is a tray, and a gate up to 50'. The gate 50 is fixed in position and holds the tray 3 slidably therein. The tray 3 is driven to be fed intermittently at the arrangement pitch of the sample tubes 2 by a separately provided tray feeding mechanism (not shown), so that the position occupied by the pipette suction opening ○ coincides with the sample tube 2. The pipette is stopped at the position where the pipette is placed, and the pipette is dispensing via the pipette ◯. Reference numeral 51 denotes a contactor, as shown in FIG. 7, the contact portion with the sample tube 2 is largely chamfered, and is made of rubber.

Reference numeral 52 denotes a shaft, the contact 51 is fixed to the left end thereof, and the right end is a hollow shaft, which is engaged with the support shaft 53 so as to be freely movable.

Therefore, the contact 51 is inserted into the gate 50 through a hole provided in the direction of the bag via the shaft 52 supported by the bearing part of the machine frame 54 attached to the gate 50 and the support shaft 63. It is held slidably. The support shaft 53 is fixed to the machine frame 54' in a cantilevered manner by its metal part and the threaded portion at the right end. 55 is a washer,
A coil 56 is attached to the support shaft 53 between it and the flange, and its elastic force causes the contact 51 to come into pressure contact with the outer wall surface of the sample tube 2 via the washer 55. There is.

Now, when the tray 3 is fed in the direction of the arrow shown in FIG. The contact 51 is pushed to the right side against the elastic force of the tray 3.
That is, the sample tube 2 is sent in the direction of the downward arrow. During the feeding operation, the sample tube 2 is rotated about the rigid axis of the sample tube 2 in the counterclockwise direction of the arrow by the friction force generated at the contact point between the outer wall surface and the rubber contact 51. be done. Therefore, by appropriately setting the spring constant of the coil spring 56 and the shape of the chamfered part of the contactor 51, the sample tube 2 can be moved, for example, by 90° while the sample tube 2 is fed by one neck pitch on the tray 3. You can make it possible to only twist it. When the sample tube 2 is fed one pitch as described above and separated from the contactor 51, the coil spring 56
Due to the resilient force, the contactor 51 returns to its original state and comes into contact with the second sample tube 2 at the position shown in the figure, in preparation for the next start-up. Figure 8 shows the three pipette suction ports ○, 02, and 03 for each serum/RI reagent and antibody sample provided at predetermined positions at the above-mentioned arrangement pitch and held in tray 3. The sample tube 2 is sequentially fed one pitch at a time over the gate 50 by the tray feeding mechanism,
FIG. 3 is a diagram illustrating in a formal manner how dispensing is performed sequentially.

In this case, this device has dispensing pipette inlet/outlet ○,,02,
03 at the relative positions shown in the figure.

After the serum is dispensed at A', the sample tube 2 is arranged as described above and is twisted about its rigid axis by 90° while being fed one pitch, and the RI reagent is dispensed at B', and then While the pitch is being sent, the 900-degree twist is performed again, and the antibody is dispensed at ◯. When the sample tubes 2 are installed in parallel on the tray 3, A
It goes without saying that the respective dispensing operations ', B', and C' are performed in parallel for each sample tube 2.

As is clear from the above description, the present invention is applicable to pipettes for suction and discharge directly in a separation chamber, which requires extremely high precision, and is used, for example, in the measurement of biological substances such as hormone levels in a patient's serum using radioimmunoassay. In addition to maintaining a high level of dispensing accuracy, it is possible to completely prevent cross-contamination due to carryover between serum and RI reagents or antibodies, and between RI reagents and antibodies, which had previously been considered difficult.

[Brief explanation of drawings]

Fig. 1 is a diagram showing the discharge state of serum/RI reagents and antibodies during dispensing using the conventional method, Fig. 2 is a perspective view showing the main parts of the sample tube twisting device of the dispensing device, and Fig. 3 is a diagram showing the sample tube FIG. 4 is a schematic diagram showing the relative position of the sample tube on the tray and the clamping plate of the twisting device, and FIG. 5 is a diagram of another embodiment. It is a schematic diagram of a sample tube twisting device. FIG. 6 is a side sectional view of yet another embodiment of the device according to the present invention, and FIGS. 7 and 8 are explanatory views of the operation of the device of FIG. 6. Each number used in the drawings indicates the part of the appendix. ○...pipette inlet and outlet,
1... Serum tube, 2... Sample tube, 3... Tray, 4...
- Chivalry board, 5...pad, 6, 6'...arm part, 7,
7'... Bearing, 8... Machine base, 9, 9'... Swamp moving piece, 10... Arm sliding arm, 14, 14'... Rocking piece,
16... Arm twisting cam, 19... Machine frame, 21... Drive gear, 22... Driven gear, 23... Contact, 24...
・Isodai sliding shaft, 25...Isodai sliding force arm, 26...Main body, 27...Coil spring 28...Micro switch, 29・
...Rotation control cam, 30...Sample tube center, 31...
Sector gear, 32... Guide tube, 33... Arm portion, 34,
35... Holding piece, 40... Drive pinion, 41, 4
2... Friction wheel, 43... Friction plate, 47... Solenoid, 48... Friction band, 50... Gate, 51...
・Contactor, 52...shaft, 53...support shaft, 54,5
4'...Machine frame, 56...Coil spring. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8

Claims (1)

[Scope of Claims] 1. A sample tube which is arranged to be sequentially fed intermittently so as to face the sample or reagent pipette suction and discharge port, and a sample pipette at a position opposite to the pipette suction and discharge port. A dispensing device equipped with means for applying rotation around the hard axis of the tube as a central axis. 2 A pair of parallel arms that have clamping plates at their tips and are slidably supported by bearings arranged such that the gap between the clamping plates is slightly larger than the outside diameter of the sample tube; an arm part twisting device that twists the parts in opposite directions and clamps the sample tube at the end face of the clamping part; and an arm that slides the arms in opposite directions to twist the sample tube via the clamping plate. A machine that slides a part sliding device and a machine base to which the bearing, the arm part twisting device, and the arm part sliding device are attached, and moves the holding plate to a position opposite to a sample tube held in a fixed position. 2. The dispensing device according to claim 1, further comprising a sample tube twisting means comprising a table sliding device. 3. A sector gear whose rotation center is the center of a sample tube held in a fixed position, an arm that is slidably supported on a guide tube fixed to the sector gear with its radial direction oriented, and an arm that and a clamping part configured to elastically clamp the sample tube at the tip, and the arm part is drawn out from the guide cylinder by the rotational movement of the sector gear, and the clamping part holds the sample tube. 2. The dispensing device according to claim 1, comprising a sample tube twisting means configured to twist the sample tube while pinching the sample tube.