JP7122283B2 - Liquid delivery device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a liquid delivery device in which two pumps and a flow meter are provided in series between a liquid reservoir and a supply destination.

Patent Literatures 1 and 2 disclose a sheath fluid flow path that branches into two after the sheath fluid flows in, a specimen flow path into which a liquid specimen flows, and these two sheath fluid flow paths and the specimen flow path. A flow cell is disclosed that includes a confluence channel where material components contained in a specimen converge for imaging.

JP 2018-112516 A JP 2019-7893 A

For example, for the measurement using the flow cell disclosed in the above prior art, in addition to the measurement pump whose flow rate should be accurately measured, another pump (for example, for cleaning the measurement system) is provided in series. If the flow rate of that other pump is out of, or specifically beyond, the measurable range of the flow meter that precisely measures the flow rate of the measuring pump, the flow meter will cannot measure the flow rate of the pump. In addition, if the measurable range of the flowmeter includes a range that can be measured particularly precisely, even if the flow rate of the other pump is within the measurable range of the flowmeter, the flow rate that can be measured precisely If it is out of the range of , the flow rate of the pump cannot be measured accurately. Therefore, in order to accurately measure the flow rate of that other pump, it is necessary to separately provide a flow meter dedicated to that other pump. In that case, the apparatus becomes large, and the flow path and control become complicated. In addition, when the flow rate of the other pump is measured only at the time of shipment of the device having the other pump, or when maintenance is performed about once a year, etc., the flow rate of the other pump is measured less frequently. In addition, if a separate flowmeter dedicated to the other pump is provided, the device becomes excessively large and the manufacturing cost of the device increases.

Accordingly, an embodiment of the present invention provides a flow meter for precisely measuring the flow rate of one of the pumps in a liquid transfer device in which two pumps and a flow meter are provided in series between a liquid reservoir and a supply destination. The object of the present invention is to make it possible to measure the flow rate of the other pump.

Embodiments of the present disclosure include:
liquid reservoir,
a channel that connects the reservoir and a liquid supply destination of the reservoir;
a first pump provided in the channel and supplying the liquid to the supply destination;
a second pump that is provided in the flow path on the downstream side of the first pump, has a retention tank that retains the liquid, and supplies the liquid to the supply destination;
A liquid transfer device comprising: a flow meter provided downstream of the second pump; and a control section for controlling the first pump and the second pump,
The control unit controls the first pump to supply the liquid to the flow channel, and controls the second pump to supply the liquid supplied from the first pump to the flow channel. The flow rate measured by the flow meter in a state in which the liquid retained in the retention tank is sucked into the retention tank of the second pump, or the liquid retained in the retention tank is sent to the flow path on the downstream side of the second pump is Calculating the first pump supply flow rate, which is the flow rate supplied to the flow channel by the first pump, by correcting the suction flow rate sucked into the holding tank by the second pump or the delivery flow rate sent from the holding tank. is possible.

In an embodiment of the present invention, in a liquid delivery device in which two pumps and a flow meter are provided in series between a liquid reservoir and a supply destination, a flow meter for precisely measuring the flow rate of one of the pumps is used. , the flow rate of the other pump can be measured.

1 is a schematic diagram of a liquid transfer device according to an embodiment of the present disclosure; FIG. FIG. 2 is a functional block diagram of the liquid transfer device of FIG. 1; FIG. 3 is a block diagram showing a hardware configuration of a controller in FIG. 2; FIG. It is a schematic diagram which shows one state of the flow measurement in the liquid delivery apparatus of this embodiment. 4 is a flowchart showing an outline of sample processing in the liquid transfer device of the present embodiment; 5 is a flowchart showing an overview of supply flow rate measurement processing in the liquid transfer device of the present embodiment; FIG. 5 is a schematic diagram showing another state of flow rate measurement in the liquid transfer device of the present embodiment;

Embodiments of the present disclosure are as follows. In addition, although the code|symbol given to each structure by the following description is made to correspond with the code|symbol described in drawing, it cannot be overemphasized that this invention is not limited to this. In addition, in the present disclosure, in each channel, the side closer to the liquid inflow source is referred to as "upstream", and the side closer to the liquid outflow destination is referred to as "downstream".

In addition, the “flow rate” in the present disclosure refers to the volume of liquid that flows per unit time, and is expressed in units such as “ml/min”, for example. Also, the term "liquid volume" referred to below refers to the volume of liquid, and is expressed in units such as "ml", for example.

[Liquid sending device]
The liquid delivery device 10 of the embodiment of the present disclosure includes a liquid reservoir 13 , a flow path 31 connecting the reservoir 13 and a liquid supply destination 20 , and provided downstream of the reservoir 13 to supply the liquid to the supply destination 20 . A first pump 41 for supplying, a second pump 42 for supplying a liquid to a supply destination 20, which is provided in the flow path 31 downstream of the first pump 41 and has a holding tank 42A for retaining the liquid. It has a flow meter 60 provided downstream of 42 and a control unit 100 for controlling the first pump 41 and the second pump 42 .

The control unit 100 controls the first pump 41 to supply the liquid to the channel 31 , and also controls the second pump 42 to supply the liquid supplied from the first pump 41 to the channel 31 . The flow rate measured by the flow meter 60 in a state in which the liquid retained in the retention tank 42A of the second pump 42 is sucked from the second pump 42, or the liquid retained in the retention tank 42A is sent to the flow path 31 on the downstream side of the second pump 42 is corrected by the suction flow rate sucked by the second pump 42 into the holding tank 42A or the delivery flow rate sent from the holding tank 42A, so that the first pump supply flow rate, which is the flow rate supplied to the flow path 31 by the first pump 41, is It is possible to calculate

The liquid supply destination 20 includes, for example, a flow cell 20 used for measuring floating matter and contained components in a specimen (for example, a liquid sample such as blood or urine collected from a living body). When such a flow cell 20 is used as the liquid supply destination 20, the supplied liquid is, for example, a sheath liquid that flows inside the flow cell 20 together with the specimen. Of course, other than such a flow cell 20, any device intended to control the flow rate and subject the liquid to some kind of operation including measurement can be used as the liquid supply destination 20 in the present embodiment. .

The liquid reservoir 13 is positioned at the most upstream position in the liquid transfer device 10 of the present embodiment, and is a structure that reserves the liquid to be supplied to the liquid supply destination 20 . As the reservoir 13 for the liquid, for example, the above-described sheath liquid reservoir 13 for storing the sheath liquid can be used. From the liquid reservoir 13 , the liquid to be reserved is sent to the downstream side of the channel 31 by the first pump 41 , which will be described later.

The first pump 41, the second pump 42, and the flow meter 60 are arranged in series in this order from the upstream side to the downstream side in the flow path 31, in other words, from the reservoir 13 toward the supply destination 20. It is connected to the. Of course, as long as these components are connected in this order, other structures (for example, valves for branching the flow path 31 or opening/closing or switching the flow path 31) may be interposed in the middle.

The second pump 42 is a pump whose flow rate is measured by the flow meter 60 . Even if the amount of liquid that can be delivered is limited within a certain range, the second pump 42 controls the flow rate of the liquid to be delivered to a constant level, sucks the liquid from the flow path 31 or supplies the liquid to the flow path 31. It is desirable to be configured by a pump capable of delivering (for example, a syringe pump or a tube pump). In particular, a syringe pump is desirable.

Further, the second pump 42 has a holding tank 42A capable of holding liquid therein, sucks the liquid from the channel 31, and holds the sucked liquid in the holding tank 42A. Then, the liquid retained in the retaining tank 42A is delivered to the channel 31. FIG. That is, the second pump 42 sucks the liquid flowing through the channel 31 from the channel 31 to the holding tank 42A, and reduces the flow rate of the liquid flowing through the channel downstream of the second pump 42 . In addition, by sending the liquid retained in the retention tank 42A to the channel 31, the flow rate of the liquid flowing through the channel 31 on the downstream side of the second pump 42 is increased. The retention tank 42A of the second pump 42 may be of any type as long as it can retain the liquid sucked by the second pump 42 . For example, when the second pump 42 is a syringe pump, when the liquid in the flow path 31 is sucked by the syringe pump, the liquid stays in the syringe, the flow rate of that amount is removed from the flow path 31, and the flow rate of the flow path 31 is removed. The flow rate flowing downstream from the second pump 42 decreases. Then, when the piston of the syringe is pushed out and the liquid remaining in the syringe is delivered to the channel 31, the flow rate of the liquid flowing downstream of the second pump 42 in the channel 31 increases. Therefore, the syringe of the syringe pump corresponds to the holding tank 42A of the second pump 42. FIG. Further, the second pump 42 may have a branched flow path between the first pump 41 and the flow meter 60, and a retention tank 42A and a tube pump may be provided in the branched flow path. In this case, when the liquid is sucked from the channel 31 by the tube pump and sucked into the holding tank 42A from the branched channel, the liquid is similarly removed from the channel 31 and stays in the holding tank 42A. The flow rate flowing downstream of the second pump 42 is reduced. Then, when the liquid in the holding tank 42A is sent to the channel 31 from the branch channel by the tube pump, the flow rate of the fluid flowing downstream from the second pump 42 in the channel 31 increases.

The flowmeter 60 preferably includes the rated flow rate of the second pump in its measurable range, and its method is not particularly limited. For example, electromagnetic flowmeters, Karman vortex flowmeters, impeller flowmeters, float flowmeters, thermal flowmeters, and the like can be selected as appropriate. A flow meter that can measure the direction of the liquid flowing through the channel 31 is desirable. A thermal mass flow meter or a non-contact liquid flow sensor that measures the flow rate by irradiating a fluid with infrared rays or ultrasonic waves is suitable for the liquid transfer device 10 of this embodiment. Here, the measurable range of flow rate means the range of flow rate in which the output value of the flow meter 60 changes according to the flow rate of the liquid flowing through the flow meter 60 .

The first pump 41 is a pump that sucks the liquid from the liquid reservoir 13 and delivers it to the downstream side of the flow path 31 , that is, to the supply destination 20 side. As the first pump 41, a pump capable of delivering a flow rate exceeding the measurable range of the flow meter 60 or a flow rate exceeding the precisely measurable range of the flow meter 60 is used. As the first pump 41, a pump (for example, a tube pump), a syringe pump, or the like that can continuously deliver liquid can be appropriately selected. A tube pump is preferably used as the first pump 41 .

In the liquid delivery device 10 , the reservoir 13 , the first pump 41 , the second pump 42 , the flow meter 60 and the supply destination 20 are connected in series via the flow path 31 .

The control unit 100 controls each component of the liquid delivery device 10 using the hardware configuration of a computer as will be described later. Specifically, the control unit 100 controls the driving of the first pump 41, the second pump controlling means 142 controlling the driving of the second pump 42, and the first pump controlling means 141 to control the driving of the first pump. The first pump 41 is driven to supply the liquid to the flow path 31, and the second pump control means 142 drives the second pump 42 to suck or deliver the liquid to the flow path 31, and the flow meter 60 is operated. Flow rate adjusting means 160 for adjusting the flow rate of the flowing liquid to a flow rate included in the measurable range, synthetic flow rate measuring means 161 for measuring the flow rate of the liquid flowing through the flow meter 60 adjusted by the flow rate adjusting means 160 as a synthetic flow rate, and The first pump 41 corrects the combined flow rate measured by the combined flow rate measuring means 161 with the adjusted flow rate, which is either the suction flow rate sucked into the flow path 31 by the second pump 42 or the delivery flow rate delivered. It functions as a first pump supply flow rate calculator 171 that calculates a first pump supply flow rate, which is the flow rate to be supplied to the path 31 .

Here, since the flow rate delivered by the first pump 41 is not included in the measurable range of the flow meter 60 or the optimum measurement range of the flow meter 60, the flow rate cannot be measured accurately by the flow meter 60. can't

Therefore, the flow rate adjusting means 160 causes the first pump control means 141 to drive the first pump 41 to deliver the liquid to the flow path, and the second pump control means 142 drives the second pump 42. Liquid is delivered to or sucked from the channel 31 .

Here, when the flow rate delivered by the first pump 41 exceeds the measurable range of the flow meter 60, the second pump 42 is driven by the second pump control means 142 to adjust the flow rate of the liquid from the flow path 31. (that is, suction flow rate). By reducing the flow rate of the liquid reaching the flow meter 60 by the adjustment flow rate, the flow rate of the liquid reaching the flow meter 60 is kept within the measurable range.

On the other hand, when the flow rate delivered by the first pump 41 is less than the measurable range of the flow meter 60, the second pump 42 is driven by the second pump control means 142 to adjust the flow rate of the liquid to the flow path 31 (that is, , delivery flow rate). By increasing the flow rate of the liquid reaching the flow meter 60 by the adjustment flow rate, the flow rate of the liquid reaching the flow meter 60 is kept within the measurable range. At this time, the liquid to be sent to the flow path 31 may be the liquid sucked from the flow path 31 and stored in the second pump 42 or in a storage portion of the second pump. Alternatively, the liquid reservoir 13 may be separately connected to the second pump 42 and the liquid may be delivered to the channel 31 .

This adjusted flow rate may be appropriately changed according to the flow rate delivered by the first pump 41 .

The synthetic flow rate measuring means 161 measures the flow rate after being adjusted by the flow rate adjusting means 160 with the flowmeter 60 as a synthetic flow rate. Then, the first pump supply flow rate calculating means 171 calculates the first pump supply flow rate, which is the flow rate supplied to the flow path 31 by the first pump 41, by correcting the measured combined flow rate with the adjustment flow rate described above. calculate.

Specifically, by adding the interference value represented as the liquid suction flow rate or delivery flow rate by the second pump 42 to the flow rate value measured by the flow meter 60, the first pump supply flow rate calculation means 171 calculates the first 1 Calculate the pump supply flow rate. Here, the interference value is defined as a positive value for the liquid suction flow rate by the second pump 42 and a negative value for the liquid delivery flow rate by the second pump 42, as described above. .

That is, the second pump 42 is provided between the first pump 41 whose flow rate is to be measured and the flow meter 60 , and the flow rate after the second pump 42 is driven is measured by the flow meter 60 . Then, the value after correction by adding the interference value due to the driving of the second pump 42 to the flow rate value which is the numerical value measured by the flow meter 60 becomes the first pump supply flow rate.

In other words, when the second pump 42 is sucking the liquid from the channel 31, the sum of the flow rate value and the suction flow rate is the first pump supply flow rate. Conversely, when the second pump 42 is delivering liquid to the flow path 31, the difference between the flow rate value and the delivery capacity of the second pump 42 is the first pump supply flow rate.

Note that the control unit 100, specifically the first pump control means 141, based on the first pump supply flow rate calculated by the first pump supply flow rate calculation means 171, determines the flow rate that the first pump 41 delivers to the flow path 31. It may be adjustable. For example, if the calculated first pump supply flow rate is lower than the assumed value, or if it is lower than the flow rate of the first pump 41 set according to the purpose of the supply destination 20, the first pump 41 The flow rate to be delivered may be increased, or conversely, when the flow rate is high, the flow rate delivered by the first pump 41 may be decreased.

The adjustment of the flow rate delivered by the first pump 41 may be performed as a performance check at the time of shipment of the liquid transfer device 10 of the present embodiment, or may be performed during maintenance of the liquid transfer device 10. Alternatively, it may be performed at any time while the first pump 41 is being driven.

In addition, the control unit 100, specifically the second pump control means 142, controls the flow rate of the second pump 42 measured by the flow meter 60 when the liquid supply to the flow path 31 of the first pump 41 is stopped. The flow rate delivered by the second pump 42 may be adjustable based on the second pump delivery rate of . For example, when the flow rate of the second pump 42 is set according to the purpose of the supply destination 20, the flow rate delivered by the second pump 42 may be increased or decreased according to the actually measured second pump delivery rate. or to achieve the set flow rate.

[Flow measurement method]
The flow rate measuring method in the embodiment of the present disclosure uses the above-described liquid transfer device 10 to drive the first pump 41 to supply the liquid to the flow path 31 and to drive the second pump 42 to supply the liquid. a flow rate adjustment step S200 for adjusting the flow rate of the liquid flowing through the flow meter 60 to a flow rate included in the measurable range of the flow meter 60 by sucking or delivering it to the flow path 31; A combined flow rate measurement step S210 for measuring the flow rate downstream of the second pump 42 as a combined flow rate, and an adjusted flow rate that is a flow rate that the second pump 42 sucks or delivers the combined flow rate measured in the combined flow rate measurement step S210 to the flow path 31. and a first pump supply flow rate calculation step S220 for calculating the flow rate corrected by the first pump 41 as the first pump supply flow rate, which is the flow rate supplied to the flow path 31 by the first pump 41 .

The flow rate adjustment step S200 is a state in which the first pump 41 is driven to supply the liquid to the flow path 31, and the second pump 42 sucks the liquid from the flow path 31 or sends the liquid to the flow path 31. A step of adjusting the flow path from the second pump 42 to the supply destination 20 side, that is, the flow rate of the liquid currently flowing in the flow meter 60 so that it is included in the measurable range of the flow meter 60 by either is. Here, in this flow rate adjustment step S200, the flow rate of the liquid sucked from the channel 31 by the second pump 42 or the flow rate of the liquid sent to the channel 31 is referred to as the adjusted flow rate. The significance of this adjusted flow rate is as described above.

This adjusted flow rate may be appropriately changed according to the flow rate delivered by the first pump 41 . For example, even if the liquid in the flow path 31 is sucked by the second pump 42 at the adjusted flow rate, if the flow rate of the liquid flowing to the flow meter 60 still exceeds the measurable range of the flow meter 60, the adjusted flow rate is It may be increased and used as a new adjustment flow rate. The second pump 42 is used to suck the liquid in the flow path 31 at this new adjusted flow rate, and the flow rate flowing through the flow meter 60 falls within the measurable range. If the flow rate through the flow meter 60 does not fall within the measurable range even with this newly adjusted flow rate, this may be repeated. Even if the liquid in the flow path 31 is pumped by the second pump 42 at the adjusted flow rate, the flow rate of the liquid flowing to the flow meter 60 is still lower than the measurable range of the flow meter 60. can be changed.

The synthetic flow rate measuring step S210 is a step of measuring the flow rate measured by the flow meter 60 through the flow rate adjusting step S200 as a synthetic flow rate.

The first pump supply flow rate calculation step S220 is a step of calculating the first pump supply flow rate by correcting the synthesized flow rate measured in the synthesized flow rate measurement step S210 with the adjusted flow rate in the flow rate adjustment step S200. For example, interference defined as a positive number for the regulated flow rate when liquid is drawn from the flow path 31 by the second pump 42 and defined as a negative number for the regulated flow rate when liquid is pumped into the flow path. This correction can be done by introducing a value called value and adding this interference value to the combined flow rate.

Then, for example, a step of adjusting the supply flow rate of the first pump 41 based on the calculated value of the first pump supply flow rate may be provided. Accordingly, the liquid can be supplied to the supply destination 20 by the first pump 41 at a desired flow rate for the supply destination 20 .

It should be noted that, apart from the series of flows of the flow rate adjustment step S200, the combined flow rate measurement step S210, and the first pump supply flow rate calculation step S220 described above, prior to performing these steps, the second pump 42 is driven to A second pump delivery flow rate measurement step S110 of measuring the second pump delivery flow rate by the meter 60 may be performed. Then, based on the driving speed of the second pump 42 and the measured second pump delivery flow rate at this time, the first flow rate for sucking or delivering the liquid to the flow path 31 at the adjusted flow rate in the flow rate adjustment step S200 is determined. 2, an adjusted flow rate driving speed calculating step S120 for calculating the driving speed (adjusted flow rate driving speed) of the pump is performed. Then, in the flow rate adjustment step S200, the second pump 42 is driven at this adjusted flow rate driving speed, and the liquid is sucked or delivered from the channel 31 at the above-described adjusted flow rate. As a result, the relationship between the drive speed of the second pump 42 and the actual flow rate through the flow meter 60 can be obtained, and an accurate adjustment flow rate can be obtained from this relationship to accurately calculate the first pump supply flow rate. . In this embodiment, the adjustment of the flow rate delivered to the flow path 31 by the second pump 42 is explained using an example in which the driving speed of the second pump 42 is adjusted. However, the adjustment of the flow rate delivered by the second pump 42 to the flow path 31 is not limited to the driving speed, and can be adjusted by any suitable method.

A step of adjusting the driving speed of the second pump 42 based on the measurement result of the second pump delivery flow rate measured by the flow meter 60 may be provided. This allows the second pump 42 to supply liquid to the destination 20 at a desired flow rate for the destination 20 .

The method of measuring the supply flow rate described above is particularly suitable when the measurable range of the flow meter 60 does not include the first pump supply flow rate. This is the case, for example, if the first pump delivery flow exceeds the optimum measuring range of the flow meter 60 or is less than the optimum measuring range of the flow meter 60 .

Hereinafter, embodiments of the present disclosure will be described with reference to the drawings.
FIG. 1 schematically shows a liquid transfer device 10 of this embodiment. In the present embodiment, a first channel 31 as a channel 31 that flows into a flow cell 20 as a supply destination 20 of a sheath liquid as a liquid, and a third channel that causes a sample (for example, urine) to flow into the flow cell 20 33 are connected. A waste liquid channel 36 is also connected as a flow channel for outflow from the flow cell 20 .

[Configuration of Liquid Transfer Device 10]
The flow cell 20 is made of a translucent material. The flow cell 20 has a sheath liquid channel 21 communicating with the outside through a sheath liquid opening 21A, a sample channel 22 communicating with the outside through a sample opening 22A, and a combined channel 23 communicating with the outside through a waste liquid opening 23A. is provided. A first channel 31 is connected to the sheath liquid opening 21A. A third channel 33 is connected to the specimen opening 22A. A waste liquid path 36 is connected to the waste liquid opening 23A.

In other words, the first channel 31 branches into two sheath liquid channels 21 in the flow cell 20 via the sheath liquid opening 21A. On the other hand, the third channel 33 reaches the sample channel 22 in the flow cell via the sample opening 22A. Then, the two sheath liquid flow paths 21 and the sample flow path 22 merge to form a combined flow path 23, which leads to the waste liquid flow path 36 via the waste liquid opening 23A.

A nozzle 12 for aspirating a sample from a sample container (not shown) is attached to the tip of the most upstream end of the third channel 33 .

At the most upstream of the first channel 31 as the channel 31, there is a sheath liquid reservoir 13, which is a tank for storing the sheath liquid supplied as liquid to the first channel 31, as the liquid reservoir 13. is provided. A first pump 41 constituted by a tube pump is provided between the sheath liquid reservoir 13 and the flow cell 20 . A second pump 42 composed of a syringe pump is provided between the first pump 41 and the flow cell 20 . Further, between the second pump 42 and the flow cell 20 is provided a flow meter 60 composed of a non-contact liquid flow sensor.

In the first flow path 31, a first sheath liquid valve 54, which is a valve that can be opened and closed in one direction, is provided on the downstream side of the first pump 41, that is, between the first pump 41 and the second pump 42. It is A second flow path 32 branches off from the first flow path 31 on the upstream side of the first sheath liquid valve 54 .

The second flow path 32 merges with the third flow path 33 via a first valve 51 which is a three-way valve provided in the middle of the third flow path 33 . A third pump 43 , which is another syringe pump, is provided in the middle of the second flow path 32 . Further, in the second flow path 32 , a second sheath liquid valve 55 that is a valve that can be opened and closed in one direction is provided on the upstream side of the third pump 43 .

A second valve 52 composed of another three-way valve is provided between the first valve 51 and the flow cell 20 in the third flow path 33 . Further, in the first channel 31, a third valve 53 is provided between the second pump 42 and the flow cell 20. The third valve 53 is another three-way valve. These second valve 52 and third valve 53 are communicated by a fourth flow path 34 .

The first flow path 31, the second flow path 32, the third flow path 33, the fourth flow path 34, and the waste liquid flow path 36 are all pipes made of flexible and soft material (for example, Teflon (registered trademark)). ) tube).

A functional block diagram of the liquid transfer device 10 is shown in FIG. The control section 100 controls each section of the liquid transfer device 10 . The control unit 100 functions as a first pump control means 141 that controls driving of the first pump 41 and a second pump control means 142 that controls driving of the second pump 42 by a hardware configuration described later. In addition, a second pump delivery flow rate measuring means 152 for measuring the second pump delivery flow rate from the flow rate value measured by the flow meter 60, and an adjusted flow drive speed for calculating the above-mentioned adjustment flow drive speed from the second pump delivery flow rate It also functions as calculation means 153 . Furthermore, when calculating the first pump supply flow rate, a flow rate adjusting means 160 that adjusts the flow rate of the first pump 41 with the above-described adjusted flow rate of the second pump 42, and the flow rate after this adjustment is measured by the flow meter 60 as a combined flow rate. and a first pump supply flow rate calculator 171 that calculates the first pump supply flow rate by correcting the synthesized flow rate with an interference value based on the adjusted flow rate.

The control unit 100 has a CPU (Central Processing Unit) 101, a ROM (Read Only Memory) 102, a RAM (Random Access Memory) 103, and a storage 104, as shown in the hardware configuration of FIG. Each component is communicatively connected to each other via a bus 109 .

A CPU 101 is a central processing unit that executes various programs and controls each section. That is, the CPU 101 reads a program from the ROM 102 or the storage 104 and executes the program using the RAM 103 as a work area. The CPU 101 performs control of each configuration and various arithmetic processing according to programs recorded in the ROM 102 or the storage 104 .

The ROM 102 stores various programs and various data. The RAM 103 temporarily stores programs or data as a work area. The storage 104 is configured by a HDD (Hard Disk Drive), SSD (Solid State Drive), or flash memory, and stores various programs including an operating system and various data. In this embodiment, the ROM 102 or the storage 104 stores programs and various data related to measurement and judgment. The storage 104 can also store measurement data.

The control unit 100 controls the first pump control means 141, the second pump control means 142, the second pump control means 141, the second pump control means 142, and the second pump control means 141 in the liquid transfer device 10 as shown in FIG. It functions as two-pump delivery flow rate measuring means 152 , adjusted flow rate driving speed calculating means 153 , flow rate adjusting means 160 , combined flow rate measuring means 161 and first pump supply flow rate calculating means 171 . Details of these functions will be described later. The control unit 100 also has control means for controlling various functions of the liquid transfer device 10, but illustration and description of parts that are not directly related to the present disclosure are omitted.

[Analysis of sample]
The outline of the sample analysis in the liquid delivery device 10 of FIG. 1 is as follows.

First, while appropriately switching the flow paths of the first sheath fluid valve 54 and the second sheath fluid valve 55 and the first valve 51, the second valve 52 and the third valve 53, By driving the third pump 43 , the sheath liquid supplied from the sheath liquid storage part 13 is used to All of the channels and waste channels 36 are filled.

In this state, the driving of the first pump 41, the second pump 42 and the third pump 43 is temporarily stopped. Then, the flow paths of the first valve 51, the second valve 52 and the third valve 53 are switched, and the third flow path 33 from the nozzle 12 to the second valve 52 via the first valve 51 and the flow path from the second valve 52 The fourth flow path 34 up to the third valve 53 and the first flow path 31 from the third valve 53 to the second pump 42 are connected. In this state, by driving the second pump 42 in the aspiration direction, air is first aspirated from the nozzle 12, and immediately after that, the sample is aspirated.

When the entire amount of the sucked air is accommodated in the fourth flow path 34, the suction by the second pump 42 is stopped. Subsequently, the channels of the first valve 51, the second valve 52, and the third valve 53 are switched, and the first channel 31 from the second pump 42 through the third valve 53 to the flow cell 20 is made conductive, and the third The second flow path 32 from the pump 43 to the first valve 51 and the third flow path 33 from the first valve 51 to the flow cell 20 via the second valve 52 are electrically connected. As a result, the air remaining in the fourth flow path 34 is cut off from the first flow path 31 and the third flow path 33 .

In this state, the third pump 43 is driven in the delivery direction to deliver the sheath fluid to the second channel 32, whereby the sample sucked into the third channel 33 is discharged from the sample opening 22A into the flow cell 20. It flows into the channel 22 . At the same time, the second pump 42 is driven in the delivery direction to deliver the sheath liquid to the first channel 31, and this sheath liquid flows into the sheath liquid channel 21 of the flow cell 20 through the sheath liquid opening 21A.

In the flow cell 20 , the specimen that has flowed into the specimen channel 22 and the sheath liquid that has flowed into the sheath liquid channel 21 merge in a confluence channel 23 . A camera (not shown) installed in the vicinity of the combined channel 23 and serving as a measuring means captures an image of the sample flowing through the combined channel 23 together with the sheath fluid.

The sheath liquid mixed with the specimen in the combined channel 23 is discharged from the waste liquid channel 36 to the outside (not shown) as a waste liquid.

After that, the first pump control means 141 drives the first pump 41 to All of the channel and the waste channel 36 are washed with the sheath liquid 80 to prepare for analysis of the next sample.

[Measurement of second pump delivery flow rate]
1, the block diagram of FIG. 3, the schematic diagram of the flow rate measurement state of FIG. 4, and the flowchart of FIG. 2 The measurement of the pumped flow rate will be described.

First, the control unit 100 switches the third valve 53 so that the second pump 42 and the fourth flow path 34 are electrically connected, and further the second valve 52 is switched so that the first valve and the flow cell 20 are electrically connected. Switch the flow path. As a result, the flow path on the downstream side of the flowmeter 60 is closed. Further, the first sheath fluid valve 54 is opened and the second sheath fluid valve 55 is closed.

In this state, the piston of the syringe pump, which is the second pump 42, is pulled up. As a result, the sheath fluid is sucked from the sheath fluid reservoir 13 through the first channel 31 into the syringe of the syringe pump, which is the second pump 42 .

After that, the control unit 100 switches the third valve so that the syringe pump, which is the second pump, and the sheath liquid opening 21A are electrically connected. As a result, the syringe pump, which is the second pump 42, communicates with the waste liquid channel 26 connected to the outside via the flow meter 60, and the channel on the downstream side of the second pump 42 is opened. Also, the first sheath fluid valve 54 is closed. As a result, the upstream side of the second pump 42 is closed.

Then, the control unit 100 causes the second pump control means 142 (see FIG. 2) to push down the piston of the syringe pump, which is the second pump 42, at a constant driving speed in the second pump driving step S100 (see FIG. 5A). The sheath fluid sucked into the syringe is discharged, and the sheath fluid discharged from the syringe is delivered to the flow meter 60 at the second pump delivery flow rate.

The flow meter 60 has a measurable range suitable for measuring the flow rate of the sheath liquid flowing into the flow cell 20 when measuring the specimen.

The control unit 100 controls the flow meter 60 in the second pump delivery flow rate measuring step S110 (see FIG. 5A) by the second pump delivery flow rate measuring means 152 (see FIG. 2) to measure the flow rate of the sheath liquid at the constant driving speed described above. Measure the flow rate. Then, it is determined whether the measured value of the flow rate is within the range of the flow rate suitable for the analysis of the specimen (hereinafter referred to as "optimal flow rate"). If it is not within the range of this optimum flow rate, the controller 100 determines the drive speed required to deliver the optimum flow rate (hereinafter, "optimum flow rate drive speed") from the constant drive speed and the measured value of the flow rate. ) is calculated. Then, when analyzing the specimen, the second pump control means 142 drives the second pump 42 at the optimum flow rate driving speed to send the sheath liquid to the flow cell 20 which is the supply destination 20 at the optimum flow rate. do.

The flow rate delivered by the second pump 42 increases as the piston driving speed increases, and conversely decreases as the piston driving speed decreases. Therefore, the optimum flow rate driving speed for obtaining the optimum flow rate can be calculated from the relationship between the piston driving speed and the measured flow rate. For example, assuming that the drive speed and the flow rate are proportional, the optimum flow rate drive speed of the piston for obtaining the optimum flow rate may be calculated. It should be noted that the second pump 42 is not limited to a syringe pump having a piston, and other types of pumps such as a tube pump can be appropriately selected as long as the flow rate of suction or delivery is related to the amount of driving of the pump. Further, in this embodiment, the driving speed of the syringe pump, which is the second pump 42, is adjusted in order to obtain the optimum flow rate of the syringe pump. However, the method of adjusting the flow rate delivered by the syringe pump to the destination 20 is not limited to adjusting the drive speed of the syringe pump. Any suitable means for adjusting the flow rate delivered by the syringe pump to the destination 20 can be selected.

At the same time, the control unit 100 stores the driving speed of the piston of the syringe pump, which is the second pump 42 , and the measured value of the flow rate measured using the flow meter 60 . Then, in the adjustment flow rate driving speed calculation step S120 (see FIG. 5A), the adjustment flow rate driving speed calculating means 153 (see FIG. 2) calculates the interference amount ( Calculate the adjusted flow rate driving speed, which is the driving speed of the piston for obtaining the adjusted flow rate of F _I ). For example, assuming that the drive speed and the flow rate are proportional, the piston drive speed for obtaining the adjusted flow rate may be calculated. This is because the adjusted flow rate drive speed can be obtained more accurately, and the first pump supply flow rate, which will be described later, can be calculated more accurately.

[1st pump supply flow rate measurement]
Next, calculation of the first pump supply flow rate when the first pump 42 is used to deliver the sheath liquid into the flow cell will be described.

First, the control unit 100 controls the first sheath fluid valve 54 to open, and the third valve 53 to open the first flow path 31 from the second pump 42 to the flow cell 20. Control to switch (see FIG. 1).

In this state, in the flow rate adjustment step S200 (see FIG. 5B), the flow rate adjustment means 160 (see FIG. 2) controls the first pump control means 141 to drive the first pump 41, thereby As shown in , the sheath fluid is delivered downstream from the sheath fluid reservoir 13 . The driving speed of the first pump 41 at this time is, for example, as described above, the first channel 31, the second channel 32, the third channel 33, the fourth channel 34, each channel in the flow cell 20 and This is the drive speed (hereinafter referred to as "required flow rate drive speed") assumed to be necessary when cleaning the waste liquid passage 36. FIG.

Next, in the same flow rate adjustment step S200, the flow rate adjustment means 160 (see FIG. 2) controls the second pump control means 142 (see FIG. 3) to control the piston of the syringe pump in advance as shown in FIG. The fully pushed second pump 42 is operated at the adjusted flow rate driving speed calculated in the adjusted flow rate driving speed calculation step S120 (see FIG. 5A), and the sheath liquid is supplied from the first flow path 31 as the adjusted flow rate. is sucked into the second pump 42 with a predetermined suction flow rate (F _IN ). That is, by driving the first pump 41 and the second pump 42 together in the flow rate adjustment step S200, a combined flow rate of the flow rate delivered by the first pump 41 and the adjusted flow rate sucked by the second pump is generated. , and the resultant flow rate flows to the flow meter 60 . The combined flow rate at this time is a flow rate within a range measurable by the flow meter 60 . As described above, if the combined flow rate at this time exceeds the upper limit of the measurable range of the flow meter 60, a new adjusted flow rate that is greater than the adjusted flow rate is set. Then, the suction flow rate (F _IN ) as the new adjustment flow rate is used to draw the liquid into the second pump 42 . This keeps the combined flow rate within the measurable range of the flow meter 60 . Even if the combined flow rate is below the measurable range of the flow meter 60, the adjusted flow rate is set as appropriate.

Next, in the synthetic flow rate measuring step S210 (see FIG. 5B), the synthetic flow rate measuring means 161 (see FIG. 2) uses the flow meter 60 to measure the aforementioned synthetic flow rate (F ₀ ).

Then, in the first pump supply flow rate calculation step S220 (see FIG. 5B), the first pump supply flow rate calculation means 171 (see FIG. 2) converts the suction flow rate (F _IN ) as the adjustment flow rate to the interference value (F _I ), the first pump supply flow rate (F) is calculated by the following equation 1.

F=F ₀ +F _I (Formula 1)

In addition, when the first pump supply flow rate (F) calculated in the first pump supply flow rate calculation step S220 is lower than the suction flow rate (F _IN ) as the adjustment flow rate, at the position of the flow meter 60 The sheath liquid in the first channel 31 flows backward from the downstream side to the upstream side. In this case, the flow rate value (F ₀ ) of the first channel 31 measured by the flowmeter 60 is expressed as a negative number.

As described above, when the flow rate delivered by the first pump 41 exceeds the upper limit of the measurable range of the flow meter 60, the flow rate reduced by the adjustment flow rate by the second pump 42 is the combined flow rate of the first flow path 31. is measured by the flow meter 60 as The flow rate value is corrected by adding the interference value (F _I =F _IN ), which is the adjusted flow rate, to the measured synthetic flow rate (F ₀ ), and the flow rate that the first pump 41 is truly delivering is determined as the first pump supply flow rate (F).

1, the block diagram of FIG. 3, and the block diagram of FIG. Description will be made with reference to the schematic diagram of the flow rate measurement state and the flowchart of FIG. 5 as appropriate.

First, the control unit 100 controls the first sheath fluid valve 54 to open, and the third valve 53 to open the first flow path 31 from the second pump 42 to the flow cell 20. Control to switch (see FIG. 1).

5B, the first pump control means 141 (see FIG. 3) drives the first pump 41 to pump the sheath fluid downstream from the sheath fluid reservoir 13 as shown in FIG. direction.

5B, the second pump control means 142 (see FIG. 3) pulls the piston of the syringe pump in advance to aspirate the sheath liquid, as shown in FIG. The second pump 42 is operated in the delivery direction to deliver the sheath fluid from the first channel 31 to the first channel 31 at the delivery flow rate (F _OUT ), which is the adjusted flow rate described above.

Next, at the stage indicated by S210 in FIG. 5B, the flow meter 60 measures the combined flow rate (F ₀ ) of the first channel 31 .

Then, at the stage indicated by S220 in FIG. 5B, the first pump supply flow rate calculation means 171 (see FIG. 2) calculates a value obtained by adding a negative sign to the delivery flow rate (F _OUT ) as the adjustment flow rate (−F _OUT ). is the interference value (F _I ), the first pump supply flow rate (F) is calculated by Equation 1 above.

As described above, when the flow rate delivered by the first pump 41 is below the lower limit of the measurable range of the flow meter 60, the flow rate supplemented by the adjusted flow rate by the second pump 42 is the combined flow rate of the first flow path 31. is measured by the flow meter 60 as The flow rate value is corrected by adding the interference value (F _I =−F _OUT ), which is the adjusted flow rate, to the measured synthetic flow rate (F ₀ ), and the first pump 41 is truly delivering. A first pumped flow rate (F), which is the flow rate, is determined.

The flow rate supplied by the first pump is obtained as the sum of the flow rate value measured by the flow meter 60 and the interference value based on the drive amount of the second pump 42 as described above. The flow rate of the first pump 41 thus obtained is, for example, the first flow path 31, the second flow path 32, the third flow path 33, the fourth flow path 34, and each flow path in the flow cell 20. And when the flow rate is different from the appropriate flow rate when filling or washing the sheath liquid in the waste liquid channel 36, the driving amount of the first pump 41 is changed as needed by the first pump control means 141 of the control unit 100. good too. As a result, the sheath liquid is supplied at an appropriate flow rate using the first pump to the first flow path 31, the second flow path 32, the third flow path 33, the fourth flow path 34, each flow path in the flow cell 20, and the waste liquid. Channels 36 can be delivered, and these channels can be filled with sheath fluid and flushed as appropriate.

[others]
As for the first pump 41, although a tube pump is used in the above-described embodiment, in practice, any pump may be used as long as it is capable of continuously pumping liquid. For example, a syringe pump may be used.

As for the second pump 42, a syringe pump is used in the above embodiment, but any pump can be used as long as it is capable of both feeding and aspirating liquid and has high accuracy and reproducibility. good too.

As for the drive amount of the second pump 42, if the assumed flow rate is known in advance, the drive amount should be set so that the amount of liquid flowing through the flow meter 60 is within the measurable range of the flow meter 60. Just do it. It should be noted that the drive amount of the second pump 42 may be changed at any time by the second pump control means 142 of the control unit 100 based on the measurement result of the flow meter 60 .

Note that the unit of the flow rate may be the distance over which the liquid flows per unit time instead of the volume of the liquid flowing per unit time as described above.

As an example, the first pump supply flow rate was actually calculated according to the flow rate measurement state illustrated in FIG.

A tube pump was used as the first pump 41 , and a syringe pump was used as the second pump 42 . As the flow meter 60, a thermal mass flow meter was used which is capable of measuring regardless of the direction of the liquid flowing through the flow meter and has a measurement range of 0 to 5.5 ml/min.

Then, the second pump 42 was driven at a constant speed and the flow rate was measured. Then, from the relationship between the driving amount and the flow rate, the control unit 100 was caused to calculate the adjustment flow rate driving speed necessary for the second pump 42 to aspirate the sheath liquid from the first flow path 31 at 40 ml/min. That is, the suction flow rate (F _IN ) as the adjustment flow rate of the second pump 42, that is, the interference value (F _I =F _IN ) was set to 40 ml/min.

Then, when the first pump 41 was driven to send the sheath liquid to the flow meter 60 and the second pump 42 was driven at the adjusted flow rate driving speed, the combined flow rate measured by the flow meter 60 ( F ₀ ) was reversed at −1.073 ml/min, that is, at a flow rate of 1.073 ml/min from the downstream side to the upstream side. This flow rate was within the range of 0 to 5.5 ml/min, which is the measurement range of the thermal mass flow meter, and the combined flow rate of the first pump 41 and the second pump 42 could be measured. It should be noted that if this combined flow rate exceeds the measurement range of the flow meter 60, the adjustment flow rate can be appropriately adjusted as described above.

From the above, the first pump supply flow rate (F) is
F = F ₀ + F _I = -1.073 + 40 = 38.927 (ml/min)
was calculated.

In this embodiment, a thermal mass flowmeter is used as the flowmeter 60, but a positive displacement flowmeter, a Coriolis flowmeter, or a non-contact type that measures the flow rate by irradiating the fluid with infrared rays or ultrasonic waves can be used. It can be any type of flow meter, such as a liquid flow sensor.

INDUSTRIAL APPLICABILITY The present invention can be used in a liquid delivery device in which two pumps and a flow meter are provided in series between a liquid reservoir and a supply destination.

10 liquid delivery device 12 nozzle 13 sheath liquid reservoir (reservoir)
20 flow cell (supply destination)
31 first channel (channel)
41 First pump 42 Second pump 42A Retention tank 43 Third pump 60 Flow meter 100 Control unit
141 First pump control means 142 Second pump control means 152 Second pump delivery flow rate measurement means 153 Adjusted flow rate driving speed calculation means 160 Flow rate adjustment means 161 Combined flow rate measurement means 171 First pump supply flow rate calculation means S100 Second pump drive process S110 Second pump delivery flow rate measurement step S120 Adjusted flow rate driving speed calculation step S200 Flow rate adjustment step S210 Combined flow rate measurement step S220 First pump supply flow rate calculation step

Claims (5)

liquid reservoir,
a channel that connects the reservoir and a liquid supply destination of the reservoir;
a first pump provided in the channel and supplying the liquid to the supply destination;
a second pump that is provided in the flow path on the downstream side of the first pump, has a retention tank that retains the liquid, and supplies the liquid to the supply destination;
A liquid transfer device comprising: a flow meter provided downstream of the second pump; and a control section for controlling the first pump and the second pump,
The control unit controls the first pump to supply the liquid to the flow channel, and controls the second pump to supply the liquid supplied from the first pump to the flow channel. The flow rate measured by the flow meter in a state in which the liquid retained in the retention tank is sucked into the retention tank of the second pump, or the liquid retained in the retention tank is sent to the flow path on the downstream side of the second pump is Calculating the first pump supply flow rate, which is the flow rate supplied to the flow channel by the first pump, by correcting the suction flow rate sucked into the holding tank by the second pump or the delivery flow rate sent from the holding tank. liquid delivery device. The liquid delivery device according to claim 1, wherein said second pump is a syringe pump. According to claim 1 or 2, the control unit performs the correction by adding a positive value to the suction flow rate and a negative value to the delivery flow rate to the flow rate measured by the flow meter. The described liquid delivery device. 4. The control unit according to any one of claims 1 to 3, wherein the control unit can adjust the flow rate delivered by the first pump based on the first pump supply flow rate calculated by the control unit. Liquid delivery device. Based on the second pump delivery flow rate, which is the flow rate delivered by the second pump measured by the flow meter in a state where the supply of the liquid to the flow path of the first pump is stopped, the control unit 5. The liquid delivery device according to any one of claims 1 to 4, wherein the flow rates delivered by the two pumps are adjustable.

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