JP3231271B2 - Dispensing device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dispensing apparatus, and more particularly, to a dispensing apparatus using a disposable nozzle tip.

[0002]

2. Description of the Related Art A dispensing apparatus includes a nozzle, a nozzle transfer mechanism, a dispensing pump, and the like. As the nozzle, a nozzle made of stainless steel or the like, or a nozzle attached to a disposable resin nozzle tip (hereinafter referred to as a tip) on a metal nozzle base (tip fitting) is used.

When high-precision nozzle positioning is required,
Conventionally, a non-disposable nozzle made of the above stainless steel or the like has been used, or a chip that has been formed well has been selected and used.

[0004] If there is any problem at the time of chip formation, a chip having a bent tip is manufactured, or if the chip is not properly mounted, the chip is mounted at an angle to the central axis of the nozzle base. In either case, the chip cannot be correctly positioned, and there is a problem that the nozzle tip collides with the edge of the container and jamming occurs. The conventional dispensing apparatus has a sensor for detecting such jamming.

[0005]

In recent years, various reagents such as DNA reagents have been dispensed to each well (small container) of a microplate using a dispensing apparatus. In such an application, it is necessary to use a disposable chip for each reagent in order to prevent contamination between the reagents.

[0006] In this case, if the chip has a molding failure or a mounting failure at the time of mounting the chip, the positioning accuracy of the tip of the chip cannot be ensured, causing a problem of chip contact with the container or discharge to an unexpected place. Problems such as contamination occur.

[0007] By the way, in applications where genes are handled, the chip may be sterilized at a high temperature. Since the chip is generally a resin-formed product, it has a property of being easily bent at a high temperature. In particular, since the entire length of a chip that handles a large amount of reagents is long, the bending in the sterilization treatment as described above is likely to be noticeable.

The present invention has been made in view of the above-mentioned conventional problems, and an object of the present invention is to provide a dispensing apparatus capable of detecting a problem caused by bending of a chip or improper mounting of a chip.

Another object of the present invention is to improve the positioning accuracy of the tip of a chip by effectively utilizing existing equipment.

[0010]

To achieve the above object, the present invention provides a nozzle comprising a nozzle base and a nozzle tip detachably mounted on the nozzle base, and a nozzle moving mechanism for moving the nozzle up and down. A dispensing device including a tip-facing hole, a misalignment detection member having a periphery of the tip-facing hole as a tip-facing surface, and lowering the nozzle from above the misalignment detecting member; A descent control means for performing control for stopping the descent of the nozzle when the tip of the nozzle tip reaches a position slightly higher than the level of the tip-facing surface, and discharging air from the nozzle when the nozzle is stopped Or, the air is sucked by the nozzle, and the tip of the nozzle tip faces one of the tip facing hole and the tip facing surface based on a change in the pressure in the nozzle at that time. Characterized in that it comprises a counter-destination determining means for determining dolphin, a.

According to the above arrangement, if the tip of the chip is displaced from the proper position due to a chip defect or a defective mounting, etc., the air is discharged or sucked in by bringing the tip of the chip close to the displacement detecting member. In addition, since the tip opening is covered by the tip-facing surface in a non-contact manner, the air discharge pressure or the air suction pressure increases, so that the displacement of the tip position can be determined. According to the present invention,
Since the nozzle tip does not directly contact the misalignment detecting member, contamination of the tip of the tip can be prevented. The opposing destination judging means includes a pressure sensor, a judging circuit and the like.

Further, the present invention provides a dispensing apparatus including a nozzle including a nozzle base and a nozzle tip detachably mounted on the nozzle base, and a nozzle moving mechanism for moving the nozzle up and down. And a member for detecting a position shift in which the periphery of the tip insertion hole is a tip contact surface, and lowering the nozzle from above the position shift detecting member,
A descent control means for controlling the tip of the nozzle tip to stop descent of the nozzle at a predetermined height at which the tip can enter the tip insertion hole, and discharging air from the tip of the nozzle tip when the descent of the nozzle is stopped or Contact detecting means for sucking air from the tip and detecting that the tip of the nozzle tip has contacted the tip contact surface based on the pressure in the nozzle at that time.

According to the above configuration, if the tip end position is deviated from the proper position due to a chip defect or a mounting defect, the tip end is inserted into the tip insertion hole of the displacement detecting member when the tip end is inserted. Abuts the tip abutment surface
If a collision occurs and air discharge or air suction is performed in that state, the contact state can be detected by an increase in pressure. As a result, it is possible to determine whether or not the tip of the tip is displaced. According to the present invention, the tip end opening is directly sealed by the end contact surface, so that a pressure change can be reliably detected.

It is desirable that the above-described positional deviation detection be performed before dispensing and immediately after chip mounting. According to the present invention, there is an advantage that the displacement can be detected using the existing pressure sensor and drive mechanism as they are.

In a preferred aspect of the present invention, when the opposing destination determining means determines the front end opposing surface as the opposing destination,
Alternatively, it includes an error determination unit that determines an error when the contact detection unit detects a contact.

In a preferred aspect of the present invention, a correction means is provided for calculating the correction data relating to the positional deviation of the tip of the nozzle tip by executing the determination of the opposite end or the determination of the contact at a plurality of points. Preferably, the correction means includes an X direction and a Y direction orthogonal to the Z direction as a vertical direction.
Correction data is calculated for both directions.

Preferably, the misalignment detecting member has a plurality of distal end opposing holes or distal end insertion holes having different shapes.
For example, the tip facing hole or the tip insertion hole may be appropriately selected and used depending on the shape of the container to be dispensed. Each of the distal end opposing holes or the distal end insertion holes is formed to be the same as or slightly smaller than the container corresponding to the shape of the container to be dispensed.

Preferably, at least the front end contact surface of the displacement detecting member is formed of a material softer than the nozzle tip. According to this configuration, the problem of breakage of the nozzle tip can be solved. Of course, an elastic means such as a spring or rubber for absorbing a collision may be provided on the nozzle side.

In a preferred aspect of the present invention, the misalignment detecting member is substantially an upper surface plate of a tip rack holding the nozzle tip in an upright position, and the tip facing hole or the tip insertion hole is provided with the nozzle tip. Holding holes. According to the above configuration, the chip rack can also be used as a member for detecting a displacement, thereby reducing the apparatus cost and simplifying the control. That is, after the tip is mounted on the nozzle base, the nozzle is raised, and then the nozzle is lowered, whereby the displacement of the tip of the tip can be detected. Incidentally, the position shift detection is executed every time the chip is mounted, or is executed periodically. The dispensing device according to the present invention can also be used as a liquid suction device and a liquid discharge device.

[0020]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 shows a preferred embodiment of a dispensing apparatus according to the present invention, and FIG. 1 is a conceptual diagram showing a configuration of a main part thereof.

For example, a nozzle tip (hereinafter, referred to as a tip) 12 made of resin or the like is detachably attached to a tip attachment portion 10 formed of a metal pipe or the like.
A nozzle is configured by the chip mounting portion 10 and the chip 12. The dispensing pump 14 is connected to this nozzle. The dispensing pump 14 generates a suction force and a discharge force. A pressure detector 16 is provided between the dispensing pump 14 and the nozzle. The pressure detector 16 has a sensor for detecting the pressure inside the chip 12. The control unit 20 controls the entire dispensing apparatus, and particularly performs control for detecting a displacement of the tip of the tip 12. The drive mechanism 22 drives the entire movable part including the dispensing pump 14 and the nozzle. These movable parts can move freely in three dimensions.

The output signal of the pressure detecting section 16 is input to a judging section 24, and the judging section 24 makes the pressure detecting section 1
Based on the output signal of No. 6, the displacement of the tip of the chip is determined. The device of the present embodiment, as described below,
There are a non-contact mode and a contact mode as the displacement detection mode. In either mode, air is discharged from the tip of the tip under predetermined conditions or air is sucked in from the tip of the tip, and the displacement is determined based on the pressure change (fluctuation from normal pressure) at that time.

In the dispensing apparatus of the present embodiment, a misalignment detecting member 26 is provided to detect bending of the tip of the chip 12 due to defective molding or improper mounting of the chip 12. This member 26 can be used in both the non-contact mode and the contact mode. Member 26
Is fixedly arranged at any place of the dispensing device, and has a hole 26A functioning as a tip facing hole (in a non-contact mode) or a tip insertion hole (in a contact mode) at an upper portion thereof. Have. The periphery of the hole 26A is an upper surface 26B that functions as a front end facing surface (in a non-contact mode) or a front end contact surface (in a contact mode). Hole 26
A has a depth of, for example, 5 mm and a diameter of, for example, 4 m.
m. The diameter of the hole 26A is determined according to the positioning accuracy at the time of dispensing.
mm is required, a diameter of 4 mm
Hole 26A is used.

The tip 12 is formed from, for example, polypropylene or the like. In the case of dispensing a large amount of 3000 ml reagent, the tip 12 has a length of about 130 mm and a maximum outer diameter of 11 mm. The outer shape of the tip is 2mm
It is. In the case of such a large nozzle tip, if a bend occurs due to thermal deformation or the like, the tip displacement of the tip is about 5 mm at the maximum. The device of the present embodiment is capable of reducing the displacement of the tip by the member 26.
And by controlling the movable parts.

FIG. 2 shows a specific configuration of the nozzle. As described above, the proximal end of the tip 12 is fitted and connected to the distal end of the tip mounting section 10. Chip mounting part 1
A passage 30 </ b> A is formed in the shaft 30 of the
A communicates with the space 12A in the chip 12. Axis 30
Is formed with a branch path, and the branch path is connected to the pressure sensor 36 functioning as the pressure detection unit. The pressure sensor 36 is a sensor that monitors the pressure in the nozzle. The dispensing pump 14 is connected to the shaft 30. The dispensing pump 14 includes a syringe 33 and a piston 37.

The entire nozzle is elastically supported by a base 35, and more specifically, the entire nozzle is urged downward with respect to the base 35 by a jamming spring 38. The spring 38 can absorb the collision force when the nozzle tip comes into contact with any member. The base 35 is three-dimensionally driven by the driving mechanism 22 in FIG.

In the apparatus of this embodiment, the pressure sensor 3
6 can be used to detect positional deviation. That is, after the chip 12 is mounted on the chip mounting section 10 in the configuration shown in FIG. 1, all the nozzles are lowered from above to below. In this case, in the above-mentioned non-contact mode, the lowering of the nozzle is stopped when the tip of the tip 12 is positioned at the lowering stop position 100 slightly higher than the upper surface level 102 of the hole 26A. In the stopped state, the operation of the dispensing pump 14 causes air to be discharged or sucked from the tip of the tip. At this time, if the tip position of the tip 12 is appropriate, the tip is
The air pressure inside the chip is normal pressure, facing the hollow portion of 6A. On the other hand, if the tip position is shifted, the tip will face the upper surface 26B, and the air pressure will rise (or fall) below the normal pressure because the tip opening is covered. Therefore, comparing the pressure value with the threshold value, whether the tip of the tip faces the hole 26A,
Alternatively, it can be determined whether or not it faces the upper surface 26B. That is, the presence / absence of a position shift can be determined.

In the contact mode, the upper level 102
The lowering control is performed so that the tip of the chip is positioned at the lowering stop position 104 slightly lower than the lowering. Then, air discharge or air suction is performed at the descent stop position in the same manner as described above. Here, if no displacement occurs, the tip of the tip faces the inside of the hole 26A, and the air pressure in the nozzle becomes the normal pressure. On the other hand, if a positional shift has occurred, the tip of the chip collides with the upper surface 26B when descending, and the collision force is absorbed by the jamming spring 38. At this time, the tip of the tip comes into contact with the upper surface 26B and the tip opening is almost closed, so that when air is discharged (or sucked), the air pressure in the nozzle rises (or falls) more than usual. Become.
Therefore, as in the case of the above-mentioned non-contact mode, the presence / absence of displacement can be determined by comparing the pressure value with the threshold value. L1 shown in FIG. 1 is 1 mm, for example, and L2 is 1 mm.

The judging section 24 shown in FIG. 1 judges the presence or absence of a position shift as described above based on a signal from the pressure sensor. When the displacement is determined, for example, an alarm signal is output from the determination unit 24 to the control unit 20. The control unit 20 executes control for replacing the chip 12 and acquiring correction data as necessary, as described later.

When the above-mentioned contact mode is selected, the member 26 is desirably configured as a member that is softer than the chip 12. According to such a configuration, FIG.
The tip of the tip can be protected even in the event of a collision that cannot be absorbed by the action of the spring 38 shown in FIG. Of course, if it is assumed that the chip 12 is replaced when it is defective, the member 26 does not necessarily need to be made of such a soft material.

FIG. 3 exemplifies various misalignment determination holes provided in the dispensing apparatus of the present embodiment. (A) and (B) each show a circular hole, the diameter of which is D1 and D2, respectively. (C) and (D) illustrate elongated holes along the Y and X directions. It is desirable to use holes corresponding to the shape of the container to which the liquid is to be dispensed. The holes shown in (C) and (D) can be used, for example, when acquiring correction data described later in the X direction and when acquiring correction data in the Y direction.

As shown in FIGS. 4 and 5, the member 26 is
It is also possible to configure by the upper surface plate 42 of the chip rack 40. That is, a plurality of holding holes 44 are formed in the chip rack 40, and a new chip 12 is inserted and held in each holding hole 44. When any one of the chips 12 is mounted on the chip mounting portion 10 and dispensing is started, the entire nozzle is lowered from above before using the holding hole 44 in which the chip 12 is held. The positional deviation of the tip position may be detected by using the following method. The holding hole 44 functions substantially as the hole 26A shown in FIG.
2 functions as the upper surface 26B shown in FIG. FIG. 4 shows the concept of position shift determination in the non-contact mode. Here, a chip without position shift is denoted by reference numeral 12C, and a chip with position shift is denoted by reference numeral 12D. ing.

FIG. 5 shows the concept of the position shift determination in the contact mode. A chip having no position shift is indicated by reference numeral 12A, and a chip having a position shift is indicated by reference numeral 12B.

Therefore, according to the configuration shown in FIGS. 4 and 5, there is no need to provide a separate member 26 in addition to the chip rack 40, so that the apparatus can be simplified and the displacement can be detected immediately after the chip 12 is mounted. , The dispensing operation can be speeded up.

FIG. 6 is a flowchart showing the operation of the dispensing apparatus according to this embodiment.

First, in S101, the chip 12 is mounted on the chip mounting section 10. In S102, the nozzle is positioned on the member 26 shown in FIG. 1, and the nozzle is pulled down from above toward the hole 26A.
In this case, in the non-contact mode, the tip of the chip is positioned at the descent stop position 100 shown in FIG. 1, and in the contact mode, the tip of the chip is positioned at the descent stop position 104 shown in FIG.

In S103, air discharge (or air suction)
Is performed, and the presence / absence of a position shift is determined based on whether the pressure in the chip at that time has increased (or decreased) than usual. If there is no misalignment, the nozzle is transported in S104 and liquid dispensing is performed in the same manner as in the related art, and then the used chip is removed from the chip mounting unit 10 in S105.

On the other hand, if it is determined in S103 that there has been a positional shift, it is determined in S106 whether or not correction data is to be obtained. If it is set by the user that acquisition of such correction data is unnecessary, S1
At 07, the defective chip is replaced with a new chip, and the steps from S102 described above are repeatedly executed.

On the other hand, if it is set in S106 that it is necessary to acquire correction data, the same control (downward positioning, air discharge) as described above is performed in S108 at a position different from the position where the positional deviation has been detected. Or suction). In S109, it is determined whether the nozzle tip is facing or inserted into the hole 26A, or is facing or is in contact with the upper surface 26B, based on the pressure change as in S103. If the former, the steps from S108 are repeatedly executed, and if the latter, it is determined whether or not to perform detection at another position.

For example, when correction data is obtained in both the X and Y directions, the presence or absence of a pressure change in both the positive and negative directions of the X direction and the positive and negative directions of the Y direction is determined. Will be inspected.

By repeating the above steps, as a result, the presence or absence of a pressure change is determined for each two-dimensional address. Based on the data, in S111, the tip position in the X direction and the Y direction is corrected. Data is calculated.
This indicates the amount of deviation in the X and Y directions from the proper position. In S112, it is determined whether or not the correction data is within an appropriate range. If the correction data is within the appropriate range, each step after S104 is executed. On the other hand, S
If it is determined in step 112 that the correction amount exceeds the appropriate range, the currently mounted chip is defective and cannot be used as it is, and thus is replaced with a new chip in step S113.

By the way, when the calculation of the correction data is performed, the driving mechanism 2 is used in the dispensing process in S104.
The correction data is used in the control of (2). That is, nozzle positioning is performed in consideration of the correction amount.

When dispensing to a microplate on which a large number of wells or the like are formed, the above-described positional deviation detection may be performed before actual dispensing using one of the wells in the microplate. In this case, the well functions as the above-described hole 26A.

In the above embodiment, a configuration may be adopted in which the user can select the non-contact mode and the contact mode. Further, the mode may be automatically selected according to whether the chip is replaced or the correction data is acquired when the positional deviation is found. When acquiring correction data, it is desirable to select a non-contact mode in order to protect the tip of the chip and prevent contamination.

[0046]

As described above, according to the present invention,
Problems caused by chip bending and chip mounting failure can be detected beforehand. In addition, the existing equipment can be effectively used to improve the positioning accuracy of the tip end of the chip.

[Brief description of the drawings]

FIG. 1 is a conceptual diagram showing a configuration of a main part of a dispensing apparatus according to the present invention.

FIG. 2 is a diagram showing a specific configuration example of a nozzle.

FIG. 3 is a view showing various forms of holes.

FIG. 4 is a conceptual diagram showing misregistration detection using a chip rack in a non-contact mode.

FIG. 5 is a conceptual diagram showing misregistration detection using a tip rack in a contact mode.

FIG. 6 is a flowchart showing the operation of the dispensing device.

[Explanation of symbols]

10 tip mounting section, 12 nozzle tip, 14 dispensing pump, 16 pressure detection section, 20 control section, 22 drive mechanism, 24 determination section, 26 misalignment detection member, 26
A hole (tip facing hole, tip insertion hole), 26B top surface (tip facing surface, tip contact surface), 36 pressure sensor.

Claims (9)

(57) [Claims] 1. A dispensing apparatus comprising: a nozzle comprising a nozzle base and a nozzle tip removably mounted on the nozzle base; and a nozzle moving mechanism for elevating and lowering the nozzle. A misalignment detection member having a periphery of the opposed hole as the tip-facing surface, and lowering the nozzle from above the misalignment detection member, so that the tip of the nozzle tip is slightly smaller than the level of the tip-facing surface. A descent control means for performing control to stop descent of the nozzle at the time when the nozzle reaches a high position; and changing the pressure in the nozzle at that time by discharging air from the nozzle or sucking air by the nozzle when the nozzle is stopped. Opposing destination determining means for judging whether the tip of the nozzle tip faces the tip facing hole or the tip facing surface based on Dispensing device to be marked. 2. The dispensing apparatus according to claim 1, further comprising: an error determination unit that determines an error when the opposite destination determination unit determines the front end facing surface as an opposite destination. 3. The dispensing device according to claim 1, further comprising a correction unit that calculates correction data relating to a positional shift of the tip of the nozzle tip by executing the determination of the opposite end at a plurality of points. apparatus. 4. The apparatus according to claim 1, wherein the misregistration detecting member is substantially a top plate of a chip wrap holding the nozzle tip in an upright position, and the tip facing hole holds the nozzle tip. A dispensing device characterized by a holding hole. 5. A dispensing apparatus comprising: a nozzle comprising a nozzle base and a nozzle tip removably mounted on the nozzle base; and a nozzle moving mechanism for elevating and lowering the nozzle. A misalignment detection member having a tip contact surface around the insertion hole; and a predetermined height at which the nozzle is lowered from above the misalignment detection member so that the tip of the nozzle tip can enter the tip insertion hole. Then, a descent control means for performing control to stop descent of the nozzle, and when the descent of the nozzle is stopped, air is discharged from the tip of the nozzle tip or air is sucked from the tip, and the pressure in the nozzle at that time is reduced. And a contact detecting means for detecting that the tip of the nozzle tip has contacted the tip contact surface on the basis of the nozzle tip. 6. The dispensing device according to claim 5, further comprising an error determination unit that determines an error when a detection signal is output from the contact detection unit. 7. The correction unit according to claim 6, wherein correction data relating to displacement of the tip of the nozzle tip is calculated by detecting contact between the tip of the nozzle tip and the contact surface of the tip at a plurality of points. A dispensing device comprising: 8. The dispensing device according to claim 3, wherein the correction means calculates correction data in both the X direction and the Y direction orthogonal to the vertical direction as the Z direction. . 9. The apparatus according to claim 5, wherein the displacement detecting member is a top plate of a chip wrap substantially holding the nozzle tip upright, and the tip insertion hole holds the nozzle tip. A dispensing device characterized by a holding hole.