JP5157950B2 - Dispensing device - Google Patents

Description

  The present invention relates to a dispensing apparatus that performs dispensing for inhaling and discharging a liquid sample in a specimen test or the like.

  2. Related Art Dispensing devices that dispense liquid samples such as chemical solutions are known. This dispensing apparatus includes a nozzle, a pump for sucking and discharging a liquid sample in the nozzle, a nozzle transport mechanism for transporting the nozzle, and the like.

  In addition, the dispensing device is incorporated in, for example, an ISH (In Situ Hybridization) processing device for performing gene function analysis, and the liquid sample in the well is sucked by the nozzle, or the liquid sample in the nozzle is removed. It is configured to dispense into the well and dispense.

  In addition, in the field of drug discovery screening, a dispensing device is used to give a compound that is a drug candidate to a cell, the change of the cell due to the stimulus is captured with an image, and the efficacy and side effects are tested by image processing. Yes.

FIG. 9 is a conceptual diagram showing a main part configuration of a conventional dispensing apparatus described in JP-A-11-160326.
In FIG. 9, a nozzle chip (hereinafter referred to as a chip) 28 formed of resin or the like is detachably mounted on a chip mounting portion 27 formed of a metal pipe or the like. The tip mounting portion 27 and the tip 28 constitute a nozzle. A dispensing pump 14 is connected to this nozzle. The dispensing pump 14 generates suction force and discharge force.

  A jamming detector 16 is provided between the dispensing pump 14 and the nozzle. The jamming detection unit 16 is means for detecting a collision force when the chip 28 collides with any member.

  The control unit 20 controls the entire dispensing device, and in particular performs control for detecting the positional deviation of the tip of the tip 28. The drive mechanism 22 is connected to a movable part including the dispensing pump 14, and the entire movable part including the dispensing pump 14 and the nozzle is driven by the drive mechanism 22.

  These movable parts can move freely in three dimensions. The output signal from the jamming detection unit 16 is input to the determination unit 24, and the determination unit 24 determines the positional deviation of the tip of the chip based on the output signal from the jamming detection unit 16.

  FIG. 10 is a schematic configuration diagram showing another conventional example described in Japanese Patent Application Laid-Open No. 2004-101479. A motor 2 is provided on the top of the box-shaped casing 1. A screw body 5 made of a trapezoidal screw or a ball screw connected to the rotating shaft 3 of the motor 1 via a coupling 4 is rotatably provided in the casing 1.

  The screw body 5 is provided with a slider 6 screwed through a screw hole 6b so as to be movable up and down along the direction of arrow E. The slider 6 is slidable on a linear guide 7 provided on the casing 1. It is connected and configured to move up and down without rotating, and has a dispensing piston shaft 6A protruding downward.

  A longitudinally shaped cam plate 10 is provided on the inner surface of the casing 1 through a plurality of guide protrusions (not shown) so as to be movable up and down, and a longitudinal direction having a predetermined lead in the lateral direction at the lower position of the cam plate 10. A cam portion 11 having a shape of a cam groove or a cam hole is formed.

  The cam plate 10 is constantly urged downward by the other end of a spring member 13 such as a spring having one end connected to the upper end 12 of the cam plate 10 being locked to the locking portion of the casing 1. It is configured to be movable up and down along E.

  An operating position adjusting screw is provided on a mounting piece (not shown) formed by bending integrally with the upper end 12 of the cam plate 10, and the upper end of the slider 6 is in contact with the lower end of the operating position adjusting screw. The slider 6 is configured to lift the cam plate 10 upward against the spring force of the spring member 13.

JP-A-11-160326 JP 2003-344427 A JP 2004-101479 A

By the way, in the above-mentioned conventional apparatus, although there is a function of detecting tip end bending, abnormality such as molding failure, and jamming, there is no function of detecting the presence or absence of a chip when mounting a chip from a chip rack. .
For this reason, there is a problem in that a drop (dispensing) operation is performed without a chip and an inaccurate test is executed.

  Therefore, an object of the present invention is to add a function of detecting whether or not there is a chip in the chip rack when mounting the chip from the chip rack in the automated dispensing apparatus, thereby reliably mounting the chip, An object of the present invention is to realize a dispensing device capable of performing dripping without mistakes.

Dispensing by inserting a tip having a tapered hole inserted into the hole of the tip rack and having a tapered hole inserted into the hole of the tip rack in order, and sucking and discharging the liquid sample through the tip. In a dispensing device that performs
An upper lid having a first hole at the center and fixed over one end of the cylinder, and a housing having a cavity formed by a lower lid having a second hole at the center and fixed at the other end of the cylinder; ,
A dispensing pump disposed in the upper lid;
A shaft having one end connected to the dispensing pump and disposed through the first and second holes and having a first through hole formed in the center;
A ring which is fixed above the inside of the cavity and is formed so as to be stretchable and penetrated by the shaft;
A second through-hole is formed in the central portion, which has a large-diameter portion and a small-diameter portion having a flange portion formed at one end thereof, and the flange portion is disposed in the cavity and formed in the lower lid. locked to the second hole, and the absence rider to penetrate the large diameter portion is the second hole,
A first sensor element disposed near a second hole formed in the lower lid and a second sensor element disposed near a lower end of a large-diameter portion of the slider; , Signal output means for outputting a signal when the second sensor element approaches,
A control unit for driving the housing mounted on the conveying means in the XYZ directions;
The shaft is smaller than the maximum diameter of the taper portion of the tip and larger than the minimum diameter, and a flange portion formed at one end of the large-diameter portion of the slider is in contact with the lower lid from a lower end of the slider. Formed to protrude length,
The hole formed in the chip rack is larger than the diameter of the small diameter portion of the slider, smaller than the diameter of the large diameter portion, and larger than the maximum diameter of the tapered portion,
In a state where the chip is “present” in the hole portion of the chip rack, when the housing is lowered, the small diameter portion of the slider comes into contact with the flange of the chip inserted into the hole portion of the chip rack, and the first rack , The second sensor element approaches, outputs the signal, the tip of the shaft is inserted into the tapered portion, and a chip is mounted,
In a state where the chip is not in the chip rack, when the housing is lowered, the small diameter portion of the slider is inserted into the hole portion of the chip rack, and the large diameter portion of the slider is at the edge of the hole portion. Abutting to prevent the first and second sensor elements from approaching and preventing the signal from being output;
When replacing the tip attached to the tip of the shaft, the expandable ring is extended to lower the slider, and the tip is dropped from the shaft by pushing the heel at the small diameter portion . It is characterized by that.

In Claim 2, in the dispensing apparatus of Claim 1,
The signal output means comprises a Hall element and a magnetic field generating means.

  According to a third aspect of the present invention, in the dispensing apparatus according to the first aspect, the housing is mounted on a transport unit and is driven in the XYZ directions by a control unit.

According to the first aspect of the present invention, the small diameter portion of the slider is inserted into the hole portion of the chip rack when the housing is lowered in a state where the chip is “present” in the hole portion of the chip rack. The first and second sensor elements are in contact with each other and output the signal, and the tip of the shaft is inserted into the tapered portion to attach the chip,
In a state where the chip is not in the chip rack, when the housing is lowered, the small diameter portion of the slider is inserted into the hole portion of the chip rack, and the large diameter portion of the slider is at the edge of the hole portion. Since the contact is made to prevent the first and second sensor elements from approaching and the signal is not output , the dropping operation is ensured by sensing the signal and reflecting it in the subsequent dispensing operation. It is possible to realize a dispensing apparatus that performs the test without mistakes.
According to the second aspect of the present invention, since the Hall element and the magnetic field generating means are used as the signal output means , a signal can be emitted without the first and second sensor elements colliding with each other.

It is a block diagram which shows an example of embodiment of the dispensing apparatus of this invention. It is the top view and partial cross section front view of the chip | tip inserted in the chip rack. It is explanatory drawing which shows the position of the slider when a chip | tip is in a rack, and when it is not. It is sectional drawing which shows the operation | movement which attaches / detaches a chip | tip. It is a figure which shows the example of a search for determining the presence or absence of a chip | tip. It is a figure which shows the example of a search for determining the presence or absence of a chip | tip. It is a figure which shows the example of a search for determining the presence or absence of a chip | tip. It is a figure which shows the example of a search for determining the presence or absence of a chip | tip. It is a block diagram which shows an example of the conventional dispensing apparatus. It is a block diagram which shows the other example of the conventional dispensing apparatus.

FIG. 1 is a block diagram showing an example of a dispensing apparatus of the present invention.
In FIG. 1, reference numeral 100 denotes a housing. In this housing, the upper end of the cylindrical body 100a is closed by an upper lid 100c having a first hole 100b in the center, and the lower end is closed by a lower lid 100e having a second hole 100d in the center. Thus, a cavity 100f is formed.

  Reference numeral 101 denotes a dispensing pump which is disposed at a substantially central portion of the upper lid of the housing. Reference numeral 102 denotes a ring whose upper end is fixed above the cavity 100f and is formed to be extendable and contractable in the direction of arrow A by, for example, an air cylinder or a motor. Reference numeral 103 denotes a shaft having a first through hole 103a formed at the center, the upper end of which is fixed to the dispensing pump 101 and the lower end of which is a free end.

  Reference numeral 104 denotes a slider composed of a large diameter portion 104b and a small diameter portion 104c having a flange portion 104a formed at one end, and a second through hole 104d through which the shaft 103 passes is formed at the center. The flange portion 104a is disposed in the cavity 100f, the large-diameter portion 104b passes through the second hole 100d formed in the lower lid of the housing, and the flange portion 104a is locked in the second hole 100d. Slide to. The free end of the shaft 103 is formed so as to protrude from the lower end of the slider 104 by a predetermined length in a state where the flange portion 104a is in contact with the lower lid 100e.

  Reference numeral 105 denotes a hall element disposed at a predetermined location near the second hole 100d of the lower lid, and 106 denotes a magnetic body (permanent magnet). When the flange portion 104a of the slider comes close to the lower end of the expandable ring 102, a signal Is output. Reference numeral 107 denotes a control unit that performs control for moving the housing 100 including the dispensing pump in the X, Y, and Z directions in order to suck and discharge a sample to a chip to be described later.

  FIG. 2 is a plan view and a partially sectional front view of the chip 109 inserted into the chip rack 108. Such chip racks and chips are generally commercially available. As shown in the figure, for example, 8 × 12 chips 109 are detachably inserted in the chip rack 108 in the XY direction. This chip rack is placed on a transport device (not shown), and is controlled so that the shaft 103 is positioned immediately above the chip indicated by C in the upper left in the initial state at the start of the test.

Subsequent test operations are performed according to the following sequence.
1. The housing 100 is lowered in the Z direction, and the chip 109 is mounted.
2. The housing 100 is raised in the Z direction.
3. The housing 100 is transported onto a container (not shown) in which a compound (drug candidate) is placed with the chip 109 mounted.

4). The housing 100 is lowered in the Z direction, and the tip of the tip reaches the liquid level of the compound.
5. Aspirate a certain amount of compound.
6). After aspirating the compound, the housing 100 is raised.
7). The housing 100 moves in the X and Y directions, and moves to above the container (not shown) in which the cells to be measured are placed.

8). The housing 100 is lowered in the Z direction, and the compound sucked at a predetermined position on the cell culture liquid level (not shown) is discharged onto the sample.
9. The housing 100 is raised in the Z direction.
10. The housing 100 moves in the XY directions to the chip disposal site (not shown).
11. The dispenser rejects the chip.
12 The housing 100 moves in the X and Y directions and is positioned directly above the place where the chip is located.
13. Thereafter, steps 1 to 13 are repeated.

In such a measurement sequence, the measurement sequence is started from a case where chips are inserted in all of the chip racks. However, the test may be completed before using all the chips in the chip rack (eg, at position D in FIG. 2). In that case, the used tip rack will be used until the next time.
In such a case, the dispensing apparatus operates according to the sequence from the initial state, but there is no tip from the position C to the position D shown in FIG . Therefore, it is necessary to confirm the presence or absence of a chip.

FIGS. 3A and 3B are cross-sectional views showing the operation of a dispensing device for confirming the presence or absence of a tip (in the drawing, the upper lid portion and the dispensing pump shown in FIG. 1 are omitted). FIG. 3A shows a case where the chip rack 108 has a chip 109.
In FIG. 3A, when the housing 100 is lowered, the lower portion of the slider 104 hits the upper portion of the chip 109, and the slider is not lowered even when the housing is lowered.

  As a result, as shown in the figure, the permanent magnet 106 attached to the large-diameter portion 104b of the slider 104 approaches the Hall element 105 attached to the housing (here, the approach means a state in which an electromotive force is generated in the Hall element). Defined). As a result, the output of the Hall element is turned on, and it is confirmed that there is a chip. Thereafter, the housing 100 is further lowered by a certain amount, the chip mounting portion 103a is inserted into the chip, and the chip is securely mounted.

FIG. 3B is a cross-sectional view showing a case where there is no chip. When the housing 100 is lowered by the same amount as in FIG. 3A, the slider 104 falls by its own weight along the shaft 103, the tip enters the hole 108a of the tip rack 108, and the lower end of the large diameter portion of the slider. 104d (stopper portion) comes into contact and stops. As a result, the permanent magnet 106 and the Hall element 105 are separated from each other, and it is confirmed that the signal output means is turned off and there is no chip.

  FIG. 4 is a cross-sectional view showing the operation of attaching and detaching the chip. When the dropping operation is completed and the tip is replaced, the extendable ring is extended and the slider 104 is pushed to drop the tip from the shaft. In addition, the expansion | extension operation | movement of an expansion-contraction ring is performed using a motor or an air cylinder, for example.

  In automatic screening, a chip rack in which some chips remain may be used in the next screening. The dispensing apparatus sequentially checks the presence / absence of a chip from the initial position C shown in FIG. 2, but there is a problem that it takes time to reach the place where it was last used. Therefore, a chip search mode is provided in the sequence, and the presence / absence check of a chip is performed prior to measurement.

FIG. 5 shows a search example for efficiently determining the presence / absence of a chip.
In this example, in a chip rack having 96 chip holders with 1 to 12 on the horizontal axis and A to H on the vertical axis, up to 75th chips are used, and 76th to 96th chips remain.

Hereinafter, a method for searching for presence / absence of a chip will be described.
The most primitive method repeats 76 times until it finds a chip.
In the present invention, the first step looks for the beginning and end (1,96) of the tip rack.
In the example of FIG. 5, 1 is “none” and 96 is “present”. At this time, if 1 is “Yes”, all are “Yes”. If 96 is “none”, it is determined that the rack is empty.

  The second step looks for an intermediate column between “Yes” and “No”. That is, 49 and 56 are searched as shown in FIG. Until “Yes” appears, search further between “Yes” and “No”. FIG. 6B shows a case where “Yes” appears in the 80th for the first time. Thus, this step is repeated until “Yes” appears in any of the above.

There are the following two cases where “Yes” appears for the first time.
Case 1: A line = “None”, H line = “Yes”
Case 2: Line A = “Yes”, Line H = “Yes”
In case 2, it can be determined that there are “chips” at all addresses after row A.

Case 1 corresponds to FIG. 6B, and then the search is performed in the column direction. Even in this case, the middle point is searched first. This is shown in FIG. Here, it is found that there is a chip at No. 76, and the next step is to search for an intermediate point 75 (or 74) with the A line where “None” appears.
In this case, since 75 is “none”, it is determined that the last “existing” number 76 is the start with the chip, and screening is started from number 76 as shown in FIG.

As other search methods, there are search patterns shown in FIGS.
After searching 1 and 96, as shown in FIG. 7 (a), the next search location is the midpoint between the last "Yes" number 96 and the last "No" address. In this case, the middle of “Yes” 96 and “No” 1 is 48.

Next, this process is repeated until “Yes” appears.
That is, as shown in FIG. 7B, 72, which is between 48 and 96, is searched.
Next, as shown in FIG. 7C, a search is made for 84 which is intermediate between 72 and 96.

  Since 84 is “Yes”, instead of 96, 84 becomes the last “Yes”, and as shown in FIG. 7D, the next search location is 84 and the last “No” 72 Intermediate, ie 78.

  Since 78 is “Yes”, instead of 84, 78 becomes the last “Yes”, and as shown in FIG. 8A, the next search place is between 78 and the last “No” 72. That is, 75. This process is repeated until the next "yes" appears.

That is, as shown in FIG. 8B, 77, which is between 78 and 75, is searched.
77 is “Yes”, so instead of 78, 77 becomes the last “Yes”, and as shown in FIG. 8C, the next search location is 77 and the last “No” is 75. Intermediate, ie 76.

Finally, it can be seen that 76 is “Yes” and 75 is “No”, and it can be seen from 76 that the chips are filled.
Thus, if only 9 locations are searched, the chip filling status can be determined.
In the case of 96 chips, nine search points are necessary and sufficient conditions for determining the rack filling status.

  According to the above, when searching for the presence / absence of a chip, it is always possible to efficiently determine whether there is a chip in the chip rack by using the intermediate point of presence / absence as the next search point, thereby increasing the screening throughput.

The above description merely shows a specific preferred embodiment for the purpose of explanation and illustration of the present invention. For example, other sensors may be used for the Hall element and the permanent magnet, and the number and shape of the chips 109 are not limited to the illustrated example.
Therefore, the present invention is not limited to the above-described embodiments, and includes many changes and modifications without departing from the essence thereof.

DESCRIPTION OF SYMBOLS 100 Housing 101 Dispensing pump 102 Telescopic ring 103 Shaft 104 Slider 105 Hall element 106 Magnetic body (permanent magnet)
107 control unit 108 chip holder 109 chip

Claims (2)

Dispensing by inserting a tip having a tapered hole inserted into the hole of the tip rack and having a tapered hole inserted into the hole of the tip rack in order, and sucking and discharging the liquid sample through the tip. In a dispensing device that performs
An upper lid having a first hole at the center and fixed over one end of the cylinder, and a housing having a cavity formed by a lower lid having a second hole at the center and fixed at the other end of the cylinder; ,
A dispensing pump disposed in the upper lid;
A shaft having one end connected to the dispensing pump and disposed through the first and second holes and having a first through hole formed in the center;
A ring which is fixed above the inside of the cavity and is formed so as to be stretchable and penetrated by the shaft;
A second through-hole is formed in the central portion, which has a large-diameter portion and a small-diameter portion having a flange portion formed at one end thereof, and the flange portion is disposed in the cavity and formed in the lower lid. locked to the second hole, and the absence rider to penetrate the large diameter portion is the second hole,
A first sensor element disposed near a second hole formed in the lower lid and a second sensor element disposed near a lower end of a large-diameter portion of the slider; , Signal output means for outputting a signal when the second sensor element approaches,
A control unit for driving the housing mounted on the conveying means in the XYZ directions;
The shaft is smaller than the maximum diameter of the taper portion of the tip and larger than the minimum diameter, and a flange portion formed at one end of the large-diameter portion of the slider is in contact with the lower lid from a lower end of the slider. Formed to protrude length,
The hole formed in the chip rack is larger than the diameter of the small diameter portion of the slider, smaller than the diameter of the large diameter portion, and larger than the maximum diameter of the tapered portion,
In a state where the chip is “present” in the hole portion of the chip rack, when the housing is lowered, the small diameter portion of the slider comes into contact with the flange of the chip inserted into the hole portion of the chip rack, and the first rack , The second sensor element approaches, outputs the signal, the tip of the shaft is inserted into the tapered portion, and a chip is mounted,
In a state where the chip is not in the chip rack, when the housing is lowered, the small diameter portion of the slider is inserted into the hole portion of the chip rack, and the large diameter portion of the slider is at the edge of the hole portion. Abutting to prevent the first and second sensor elements from approaching and preventing the signal from being output;
When replacing the tip attached to the tip of the shaft, the expandable ring is extended to lower the slider, and the tip is dropped from the shaft by pushing the heel at the small diameter portion . A dispensing device characterized by that. 2. The dispensing apparatus according to claim 1, wherein the signal output means includes a hall element and a magnetic field generation means.

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