WO2019187996A1

WO2019187996A1 - Dispensing device and dispensing method

Info

Publication number: WO2019187996A1
Application number: PCT/JP2019/008228
Authority: WO
Inventors: 匡章平野; 晃啓安居; 昌史深谷
Original assignee: 株式会社日立ハイテクノロジーズ
Priority date: 2018-03-29
Filing date: 2019-03-01
Publication date: 2019-10-03
Also published as: JP2019174318A

Abstract

The purpose of the present invention is to provide a dispensing device with which, even if there are individual differences in the backlash amounts of syringe drivers, it is possible to suppress errors in the dispensed amount due to said differences. A dispensing device according to the present invention stores in advance, as the backlash amount, a drive device operation amount measured from when the drive device is instructed to reverse the operation direction of a syringe driver up until the operation direction has actually been reversed, and corrects the drive device operation amount in accordance with said backlash amount.

Description

Dispensing device, dispensing method

The present invention relates to a dispensing device for dispensing a liquid.

Dispensing devices mounted on automatic analyzers that perform qualitative and quantitative analysis of biological samples such as blood and urine are required to dispense samples and reagents with high accuracy. The dispensing device of the automatic analyzer is equipped with a nozzle that sucks and discharges the sample / reagent to be dispensed from the opening at the tip, and a plunger inserted into the syringe tube connected by the nozzle and tube. Generally, a syringe pump that changes the volume and performs suction and discharge is provided. Since these components have dimensional errors caused by processing variations, there are machine differences in the dispensing apparatus. Such a machine difference causes variations in the dispensed amount between the devices and fluctuations in the dispensed amount at the time of parts replacement, and affects the measured value of the analyzer. Particularly, in recent years, in order to reduce the burden on patients and reduce analysis costs, the amount of samples and reagents has been reduced, and such variations and fluctuations cannot be ignored.

In Patent Document 1 below, in order to eliminate the machine difference due to the difference in the inner diameter of the probe, the liquid sample is dispensed from the regular probe under the same conditions as the reference dispensing amount when the liquid sample is dispensed from the reference probe. A dispensing amount correction method is proposed in which a difference from the dispensing amount is acquired and the drive condition is increased or decreased by an amount corresponding to the difference.

JP 2008-256564 A

Patent Document 1 can eliminate an error in the dispensing amount due to the instrumental error of the probe. On the other hand, the error of the dispensing amount due to the machine difference of the syringe pump is not necessarily fully considered. For example, a gap exists in a connecting part of mechanical parts such as a feed screw, a gear, and a timing belt of a syringe pump, and due to the gap, an idling operation occurs when the operation direction of the syringe pump is switched. This idling operation causes a shift (backlash) in the operation amount of the syringe pump, which causes an error in the dispensing amount. Patent Document 1 does not fully consider such machine differences.

The present invention has been made in view of the above circumstances, and even if there is an individual difference in the backlash amount of the syringe pump, a dispensing device that can suppress an error in the dispensing amount due to this difference. The purpose is to provide.

The dispensing device according to the present invention stores in advance the amount of operation of the drive device from when the drive device is instructed to reverse the operation direction of the syringe pump until it is actually reversed as the backlash amount, The operation amount of the drive device is corrected according to the backlash amount.

According to the dispensing device according to the present invention, an optimum driving amount for removing backlash can be given to each individual syringe pump. Thereby, even if it is a case where the machine difference and the secular variation have arisen in the syringe pump, the error of the dispensing amount resulting from the individual difference can be suppressed. Problems, configurations, and effects other than those described above will become apparent from the following description of embodiments.

It is a schematic block diagram of the dispensing apparatus 100 which concerns on Embodiment 1. FIG. 1 is a schematic configuration diagram of a syringe pump 105. FIG. It is a schematic diagram explaining a general dispensing sequence. 5 is a flowchart for explaining a procedure by which the dispensing apparatus 100 according to the first embodiment measures the backlash amount of the syringe pump 105. It is a schematic diagram explaining the dispensing sequence in Embodiment 1. It is a flowchart explaining the procedure in which the dispensing apparatus 100 which concerns on Embodiment 2 measures the backlash amount of the syringe pump 105. FIG. It is a schematic diagram explaining the dispensing sequence in Embodiment 2.

<Embodiment 1>
FIG. 1 is a schematic configuration diagram of a dispensing apparatus 100 according to Embodiment 1 of the present invention. The dispensing nozzle 101 sucks or discharges liquid. The arm 102 holds the dispensing nozzle 101 and can be driven to rotate. The shaft 103 can drive the arm 102 up and down. Dispensing nozzle 101 / pressure sensor 104 / syringe pump 105 are connected via a pipe 106. The dispensing flow path is configured such that the distal end side is opened by the dispensing nozzle 101 and the base side can be opened / closed by the electromagnetic valve 107. When dispensing the liquid, the solenoid valve 107 is closed and the syringe pump 105 applies pressure to the inside of the dispensing nozzle 101, whereby the dispensing nozzle 101 sucks and discharges the sample / reagent. After dispensing, the electromagnetic valve 107 is opened from the base side and cleaning water is supplied. The control unit 108 controls each unit of the dispensing device 100. The storage unit 109 stores data such as driving conditions.

FIG. 2 is a schematic configuration diagram of the syringe pump 105. A stepping motor 111, a syringe tube 112, and a photo interrupter 113 are fixed to the mechanism base 110. A ball screw 114 is installed on the drive shaft of the stepping motor 111. When the stepping motor 111 rotates, the plunger drive arm 115 is moved up and down. The plunger 116 is attached to the plunger drive arm 115 and is inserted into the syringe tube 112. When the plunger drive arm 115 moves up and down, the plunger 116 moves up and down accordingly, and changes the internal volume of the syringe tube 112. As a result, the sample / reagent is aspirated / discharged. The detection plate 117 is installed on the plunger drive arm 115, and the origin position can be detected by checking whether or not the optical path of the photo interrupter 113 is shielded by the detection plate 117.

FIG. 3 is a schematic diagram for explaining a general dispensing sequence. Here, a process of dispensing the sample 119 contained in the sample container 118 to the reaction container 120 is illustrated. In FIG. 3A, the dispensing nozzle 101 is filled with system water 121. In FIG. 3B, the segment air 122 is sucked, and in FIG. 3C, a discharge operation for removing backlash is performed. Assuming that the driving pulse number corresponding to the amount finally sucked into the dispensing nozzle 101 is P _air and the driving pulse number for removing backlash is P _BL , P _air + P _BL is sucked in FIG. In FIG. 3C, _PBL is discharged. In FIG. 3D, the dispensing nozzle 101 is inserted into the sample container 118, and the sample 119 is sucked in FIG. 3E. When the number of drive pulses corresponding to the dispensing amount of the sample and _{P S,} in FIG. 3 (e) sucking the _{_P} S ₊ _P _BL.

3 Move the dispensing nozzle 101 to the position of the cleaning tank 123 in (f), the sample 119 ejected P _BL for removing backlash in the running water, that extra ejected as shown in FIG. 3 (g) is Wash away. In FIG. 3 (h), the dispensing nozzle 101 is moved to the reaction container 120, and the sample 119 held in the dispensing nozzle 101 in FIG. 3 (i) is discharged to the reaction container 120 together with the system water 121. _Assuming that the number of drive pulses corresponding to the amount of system water 121 discharged together with the sample 119 is PSW, P _S + P _air + P _SW is discharged in FIG. In FIG. 3 (j), the outer periphery of the dispensing nozzle 101 is washed with running water in the washing tank 123, and the inside is washed with system water.

In FIG. 3C and FIG. 3G, the discharge operation for removing the backlash is performed, for example, in the gap existing in the fitting portion of the ball screw 114 and the plunger drive arm 115 in the syringe pump of FIG. However, this is to eliminate the phenomenon of slipping when the suction and discharge are switched and the amount of movement of the plunger drive arm 115 deviating, that is, the influence of backlash. In general, a drive pulse larger than the maximum value of the assumed backlash amount is applied. However, since the backlash amount varies depending on the individual syringe pump 105 and varies depending on the wear of the parts, the amount of the sample 119 to be discharged as an extra amount in FIG. In the conventional dispensing sequence, an error caused by backlash is removed by dispensing the sample 119 after discharging the excess amount.

Since the sample 119 discharged excessively from the tip of the dispensing nozzle 101 is washed away, it has been considered that there is no error in the amount of the sample 119 to be dispensed. However, in reality, a small amount of the sample 119 remains on the inner wall of the dispensing nozzle 101 once touched the sample 119. The residual amount is affected by the amount of back-return discharge. The smaller the dispense amount and the greater the discharge amount, the greater this effect becomes and cannot be ignored. By measuring the backlash amount of the syringe pump 105, the present invention minimizes or completely eliminates the backlash removal, thereby achieving high-precision dispensing.

FIG. 4 is a flowchart for explaining a procedure by which the dispensing apparatus 100 according to the first embodiment measures the backlash amount of the syringe pump 105. Hereinafter, each step of FIG. 4 will be described.

(FIG. 4: Step S401)
The control unit 108 returns the syringe pump 105 to the origin. Specifically, the plunger drive arm 115 is moved to the origin position. As a result, the detection signal of the photo interrupter 113 is turned on.

(FIG. 4: Steps S402 to S403)
The control unit 108 causes the syringe pump 105 (that is, the stepping motor 111, the same applies hereinafter) to be sucked by one pulse (S402). The control unit 108 repeats step S402 until the detection signal of the photo interrupter 113 is turned off (S403).

(FIG. 4: Steps S404 to S407)
The control unit 108 initializes (= 0) the value of the variable _PBL that stores the measured value of the backlash amount (S404). The control unit 108 discharges the syringe pump 105 by one pulse (S405). The control unit 108 checks whether or not the detection signal of the photo interrupter 113 is turned on (S406). Control unit 108, if the detection signal is not ON counts up the _{P BL} (S407). The control unit 108 repeats steps S405 to S407 until the detection signal is turned ON.

(FIG. 4: Step S408)
Control unit ₁₀₈ stores in the storage unit 109 the _{P BL} as backlash of the syringe pump 105.

FIG. 5 is a schematic diagram for explaining a dispensing sequence according to the first embodiment. In FIG. 5A, the dispensing nozzle 101 is filled with system water 121. In FIG. 5B, the segmented air 122 is sucked at the drive pulse number P _air + P _BL , and in FIG. 5C, discharge for backlash removal is performed at the drive pulse number P _BL . Since _PBL is measured based on the backlash amount measuring method according to the present invention described with reference to FIG. 4, a predetermined amount of segmented air 122 is held in the dispensing nozzle 101 in FIG. No extra 122 is aspirated. Further, even when the discharge for backlash removal is performed in FIG. 5C, the amount of driving at that time is not excessive or insufficient, so that the liquid and air in the dispensing nozzle 101 do not move.

In FIG. 5D, the dispensing nozzle 101 is inserted into the sample container 118, and in FIG. 5E, the sample 119 is sucked with the drive pulse number P _S + P _BL , and in FIG. After moving the dispensing nozzle 101, _{PBL is} discharged in order to remove backlash in FIG. Also in FIG. 5E, a predetermined amount of sample is held by the dispensing nozzle 101, and the sample is not sucked excessively. Even when the backlash removal discharge is performed in FIG. 5G, the liquid or air does not move. In FIG. 5 (h), the dispensing nozzle 101 is moved to the reaction vessel 120, and the sample 119 held in the dispensing nozzle 101 in FIG. 5 (i) is driven with the number of drive pulses P _S + P _air + P _SW together with the system water 121. It discharges to the reaction container 120, and in FIG.5 (j), the dispensing nozzle 101 is wash | cleaned with the flowing water and system water of the washing tank 123. FIG.

<Embodiment 1: Summary>
The dispensing apparatus 100 according to the first embodiment instructs the stepping motor 111 to reverse the operation direction of the syringe pump 105 and then the photo interrupter 113 indicates that the syringe pump 105 has started to move in the opposite direction. Until the detection, the number of pulses output to the stepping motor 111 is stored as a backlash amount. The dispensing apparatus 100 corrects the number of pulses output to the stepping motor 111 when the operation direction of the syringe pump 105 is reversed using the backlash amount. As a result, even if there is a difference in the backlash amount of the syringe pump 105, the sample and air are not sucked or discharged again, so that an extra sample remains on the inner wall of the dispensing nozzle 101. The sample 119 can be dispensed with high accuracy.

<Embodiment 2>
In the first embodiment, it has been described that the photo interrupter 113 is used to detect that the operation direction of the stepping motor 111 is reversed. In the second embodiment of the present invention, an example will be described in which it is detected that the operation direction of the stepping motor 111 is actually reversed by measuring the pressure in the syringe pump 105. Since the configuration of the dispensing apparatus 100 is the same as that of the first embodiment, the difference will be mainly described below.

FIG. 6 is a flowchart for explaining a procedure by which the dispensing apparatus 100 according to the second embodiment measures the backlash amount of the syringe pump 105. Hereinafter, each step of FIG. 6 will be described.

(FIG. 6: Step S601)
The control unit 108 sucks the syringe pump 105 until the plunger 116 reaches the measurement start position. At this time, the backlash in the suction direction of the syringe pump 105 needs to be reliably removed. If the suction operation amount is less than the assumed maximum backlash amount, perform the discharge operation immediately before the start of suction so that the suction operation amount exceeds the maximum backlash amount, and then exceed the maximum backlash amount. To suck.

(FIG. 6: Steps S602 to S603)
The control unit 108 opens the electromagnetic valve 107, fills the dispensing nozzle 101 with the system water 121, and closes the electromagnetic valve 107 (S602). The user operates the dispensing mechanism so that the tip of the dispensing nozzle 101 is closed (S603). For example, (a) the dispensing nozzle 101 may be lowered to the bottom surface of the dispensing apparatus 100, or (b) a member that closes the tip of the dispensing nozzle 101 is installed in advance within the movable range of the dispensing mechanism. Alternatively, the dispensing nozzle 101 may be moved to that position. As a member for closing the tip of the dispensing nozzle 101, a soft material such as rubber is suitable.

(FIG. 6: Steps S604 to S607)
The control unit 108 initializes (= 0) the value of the variable _PBL that stores the measured value of the backlash amount (S604). The control unit 108 discharges the syringe pump 105 by one pulse (S605). The control unit 108 determines whether or not the pressure detected by the pressure sensor 104 has increased (S606). Control unit 108, if not detected pressure increase increments the _{P BL} (S607). Control unit 108 repeats steps S605 to S607 until an increase in pressure is detected.

(FIG. 6: Step S608)
Control unit ₁₀₈ stores in the storage unit 109 the _{P BL} as backlash of the syringe pump 105.

FIG. 7 is a schematic diagram for explaining a dispensing sequence in the second embodiment. In the first embodiment, the conventional dispensing sequence is followed to remove backlash and switch between suction and discharge. However, if the backlash amount can be measured accurately, it is considered sufficient to operate the stepping motor 111 in consideration of the backlash amount when switching between suction and discharge. In consideration of this, FIG. 7 illustrates a modification of the dispensing sequence described in FIG.

In FIG. 7A, the dispensing nozzle 101 is filled with system water 121. In FIG. 7B, the segment air 122 is sucked by the number of drive pulses P _air + P _BL . It is the same as in the first embodiment that the segment air 122 is not sucked excessively. Figure 7 Insert the sample vessel 118 the dispensing nozzle 101 (c), the aspirating the sample 119 in the driving pulse number _{P S} in FIG. 7 (d). Since the suction operation is performed immediately before FIG. 7D, backlash removal is not necessary in FIG. 7D.

In FIG. 7 (e), the dispensing nozzle 101 is moved to the reaction container 120, and the sample 119 held in the dispensing nozzle 101 in FIG. 7 (f) is driven with the system water 121 and the number of drive pulses P _S + P _air + P _SW + P _It discharges to the reaction container 120 by _BL . Since the sample suction operation is performed immediately before FIG. 7F, the backlash removal is added to the discharge amount. In FIG. 7G, the dispensing nozzle 101 is washed with running water and system water in the washing tank 123.

<Embodiment 2: Summary>
The dispensing apparatus 100 according to the second embodiment uses the pressure sensor 104 instead of the photo interrupter 113 to measure the backlash amount. Thereby, even if the plunger 116 is not necessarily in a position that can be detected by the photo interrupter 113, the same effect as in the first embodiment can be exhibited.

In the second embodiment, it has been described that the tip of the dispensing nozzle 101 is closed. Instead, an electromagnetic valve is added between the dispensing nozzle 101 and the pressure sensor 104, and the electromagnetic valve is turned on in step S603. You may close it.

<Modification of the present invention>
The present invention is not limited to the embodiments described above, and includes various modifications. The above-described embodiment has been described in detail for easy understanding of the present invention, and is not necessarily limited to the one having all the configurations described. Further, a part of the configuration of an embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of an embodiment. In addition, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

In the above embodiment, the drive mechanism using the ball screw 114 is exemplified, but a similar drive mechanism can be realized by using a gear or a timing belt. Although the use of the stepping motor 111 has been described in the above embodiment, even when another motor (for example, a servo motor) is used, the back amount is measured by measuring the drive amount of the motor as in the above embodiment. Rush amount can be measured.

In the above embodiment, the photo interrupter 113 is used as a sensor for detecting the position of the plunger 116, but the position of the plunger 116 may be detected by other sensors. For example, (a) a contact sensor or proximity sensor using magnetism or electricity, (b) a change in distance between the plunger drive arm 115 and the plunger 116 is measured by a displacement sensor, and (c) a plunger drive arm 115 by an image sensor. Alternatively, the movement of the liquid in the plunger 116 or the pipe 106 may be measured.

In the above embodiment, in order to improve the measurement accuracy of the amount of backlash, the number of divisions of the stepping motor 111 is increased by microstep driving the stepping motor 111, and the measurement result is converted to the original number of divisions. Good.

In the above embodiment, when the backlash amount differs for each position where the operation direction of the plunger 116 starts to reverse, the backlash amount is set for each position of the plunger 116 by, for example, arranging the photo interrupter 113 at a plurality of positions. You may measure. In this case, the backlash amount is stored in the storage unit 109 for each position where the operation direction of the plunger 116 starts to reverse, and the backlash is removed using this.

In the above embodiment, when the result of measuring the backlash amount according to the flowchart of FIG. 4 or 6 exceeds a preset allowable value, the control unit 108 may issue a warning to the user. .

In the above embodiment, for example, the following may be considered as the timing for executing the flowchart of FIG. 4 or FIG. 6: (a) performed before shipping the dispensing apparatus 100; (C) Perform every predetermined period. Furthermore, (a) may be performed for each model of the dispensing apparatus 100.

100: Dispensing device 101: Dispensing nozzle 102: Arm 103: Shaft 104: Pressure sensor 105: Syringe pump 106: Piping 107: Electromagnetic valve 108: Control unit 109: Storage unit 111: Stepping motor 113: Photointerrupter 116: Plunger

Claims

A dispensing device for dispensing a liquid,
A dispensing nozzle for sucking or discharging the liquid;
A syringe pump that applies pressure to the liquid in the dispensing nozzle;
A driving device for driving the syringe pump;
A storage unit that stores the amount of operation of the drive device as a backlash amount from when the drive device receives an instruction to reverse the operation direction of the syringe pump until the operation direction of the syringe pump is reversed,
With
The driving device drives the syringe pump according to the operation amount after correcting the operation amount using the backlash amount stored in the storage unit when reversing the operation direction of the syringe pump. Dispensing device characterized by.
The dispensing apparatus further includes a measuring unit that measures the backlash amount,
The dispensing device according to claim 1, wherein the measurement unit stores the measured backlash amount in the storage unit.
The dispensing device further includes
A control unit for controlling the driving device;
A detection unit for detecting that the operation direction of the syringe pump is reversed;
With
From the time when the control unit instructs the drive device to reverse the operation direction of the syringe pump until the detection unit detects that the operation direction of the syringe pump has been reversed. The dispensing device according to claim 2, wherein an amount of operation of the driving device is measured as the backlash amount.
The driving device is configured as a stepping motor that operates according to the number of pulse signals supplied thereto,
The control unit instructs the driving device so that the dispensing nozzle discharges the liquid after the dispensing nozzle sucks the liquid,
The measurement unit indicates that the syringe pump has started to operate in a direction of discharging the liquid after the control unit instructs the driving device to discharge the liquid. The dispensing apparatus according to claim 3, wherein the number of pulses supplied to the stepping motor is measured as the backlash amount until detection by the detection unit.
The drive device sucks the liquid after the dispensing nozzle sucks segmented air, the dispensing nozzle sucks the segmented air, and discharges the liquid after the dispensing nozzle sucks the liquid. So as to drive the syringe pump,
When the dispensing nozzle sucks the segmented air, the driving device switches the syringe pump from the discharge direction to the suction direction, and then operates the driving device corresponding to the amount of the segmented air to be sucked. The suction operation is performed according to the operation amount obtained by adding the backlash amount,
When the dispensing nozzle discharges the liquid, the drive device switches the syringe pump from the suction direction to the discharge direction, and then the operation amount of the drive device corresponding to the amount of the liquid to be discharged; The dispensing apparatus according to claim 1, wherein the discharge operation is performed according to an operation amount obtained by adding the backlash amount.
The storage unit stores the backlash amount for each position of a plunger provided in the syringe pump,
The dispensing device according to claim 1, wherein the driving device drives the syringe pump according to an operation amount after correcting the operation amount using the backlash amount corresponding to the position of the plunger. .
The said detection part is comprised using the position sensor which detects that the operation direction of the said syringe pump was reversed by detecting the position of the plunger with which the said syringe pump is provided. The dispensing device described.
The said detection part is comprised using the pressure sensor which detects that the operation direction of the said syringe pump was reversed by detecting the pressure in the said syringe pump. Dispensing device.
The detection unit is configured using an image sensor that detects that the operation direction of the syringe pump is reversed by capturing an image of the syringe pump or an image of a fluid in the syringe pump. 4. The dispensing device according to claim 3, wherein
A dispensing method for dispensing the liquid using a dispensing device for dispensing the liquid,
The dispensing device is
A dispensing nozzle for sucking or discharging the liquid;
A syringe pump that applies pressure to the liquid in the dispensing nozzle;
A driving device for driving the syringe pump;
With
The dispensing method is:
The backlash amount is measured as the amount of operation of the drive device after the drive device receives a signal instructing to reverse the operation direction of the syringe pump until the operation direction of the syringe pump is reversed. Step to do,
When reversing the operation direction of the syringe pump, driving the syringe pump according to the operation amount after correcting the operation amount using the backlash amount;
A dispensing method characterized by comprising:
The dispensing method further includes:
The dispensing nozzle sucks segmental air;
Aspirating the liquid after the dispensing nozzle has aspirated the segmental air;
Discharging the liquid after the dispensing nozzle has sucked the liquid;
Have
In the step in which the dispensing nozzle sucks the segment air, the drive device switches the syringe pump from the discharge direction to the suction direction, and then the operation amount of the drive device corresponding to the amount of the segment air to be sucked The suction operation is performed according to the operation amount obtained by adding the backlash amount,
In the step of discharging the liquid by the dispensing nozzle, the drive device switches the syringe pump from the suction direction to the discharge direction, and then the operation amount of the drive device corresponding to the amount of the liquid to be discharged; The dispensing method according to claim 10, wherein the discharge operation is performed according to an operation amount obtained by adding the backlash amount.
The step of measuring the amount of backlash includes:
Filling the dispensing nozzle with a fluid;
Closing the tip of the dispensing nozzle;
The amount of operation of the drive device from when the drive device is instructed to operate the syringe pump in the discharge direction until the pressure in the syringe pump increases is measured as the backlash amount. Step,
The dispensing method according to claim 10, further comprising: