阅读说明：本技术 送液方法和分析装置 (Liquid feeding method and analyzer ) 是由 太田进一 增田茂树 中岛真也 于 2020-04-03 设计创作，主要内容包括：本发明提供送液方法和分析装置。利用鞘液将检体挤压至流通池的一个壁面而使检体流动,使得在拍摄位置处检体能够可靠地接触该壁面并流动。送液方法是向流通池输送检体的送液方法,所述流通池具有楔形部和设于楔形部的下游的测量流路,该楔形部具有楔形面,所述楔形面是以随着朝向下游而接近相对的内壁的方式倾斜的内壁,检体和鞘液均在该楔形部中流动,所述送液方法具有如下步骤：检体导入步骤,沿着与所述楔形面相对的内壁将检体输送至楔形部,直到检体到达测量流路为止；以及检体挤压步骤,在所述检体到达测量流路后,沿着楔形面将鞘液输送至楔形部。(The invention provides a liquid feeding method and an analyzer. The specimen is pressed against one wall surface of the flow cell by the sheath liquid to flow the specimen, so that the specimen can reliably contact the wall surface and flow at the imaging position. The liquid feeding method is a liquid feeding method for feeding a sample to a flow cell having a wedge portion having a wedge surface which is an inner wall inclined so as to approach an opposite inner wall as it goes downstream, and a measurement channel provided downstream of the wedge portion, and in which both the sample and a sheath liquid flow, the liquid feeding method including the steps of: a sample introduction step of conveying the sample to the wedge along an inner wall facing the wedge surface until the sample reaches the measurement channel; and a sample pressing step of delivering the sheath liquid to the wedge portion along the wedge surface after the sample reaches the measurement channel.)

1. A liquid feeding method for feeding a sample to a flow cell having a wedge portion and a measurement channel provided downstream of the wedge portion, the wedge portion having a1 st inner wall, the 1 st inner wall being an inner wall inclined so as to approach an opposite inner wall as it goes downstream, the sample and a sheath liquid both flowing in the wedge portion, the liquid feeding method comprising:

a sample introduction step of conveying the sample to the wedge-shaped portion along an inner wall facing the 1 st inner wall until the sample reaches the measurement channel; and

and a sample pressing step of conveying the sheath liquid to the wedge along the 1 st inner wall after the sample reaches the measurement channel.

2. A liquid feeding method for feeding a sample to a flow cell having a wedge-shaped portion including a1 st inner wall and a2 nd inner wall opposed to the 1 st inner wall, and a measurement channel provided downstream of the wedge-shaped portion, wherein both a liquid sample and a sheath liquid flow in the wedge-shaped portion, wherein the 1 st inner wall is inclined with respect to the 2 nd inner wall as follows: the distance between the 1 st inner wall and the 2 nd inner wall on the downstream side of the wedge part is shorter than the distance between the 1 st inner wall and the 2 nd inner wall on the upstream side of the wedge part,

wherein the liquid feeding method comprises the following steps:

a sample introduction step of conveying the sample to the wedge along the 2 nd inner wall until the sample reaches the measurement channel; and

and a sample pressing step of conveying the sheath liquid to the wedge along the 1 st inner wall after the sample reaches the measurement channel.

3. The liquid feeding method according to claim 1 or 2,

in the sample introduction step, the feeding of the sheath liquid to the wedge-shaped portion is stopped.

4. The liquid feeding method according to any one of claims 1 to 3, wherein,

the sample introduction step is performed after the measurement channel is filled with the sheath liquid.

5. The liquid feeding method according to any one of claims 1 to 4,

after the sample pressing step, there is a measurement step of measuring the sample flowing in the measurement flow path.

6. The liquid feeding method according to any one of claims 1 to 5, wherein,

the specimen is a liquid.

7. The liquid feeding method according to claim 6,

the liquid is a bodily fluid.

8. The liquid feeding method according to claim 7,

the body fluid is urine.

9. An analysis device, having:

a flow cell having a wedge-shaped portion and a measurement channel provided downstream of the wedge-shaped portion, the wedge-shaped portion having a1 st inner wall, the 1 st inner wall being an inner wall inclined so as to approach an opposite inner wall as it goes downstream, the sample and the sheath fluid both flowing in the wedge-shaped portion;

a sheath liquid feeding unit for feeding the sheath liquid along the 1 st inner wall;

a sample liquid feeding unit that feeds the sample along an inner wall facing the 1 st inner wall;

a measurement unit that measures the sample flowing in the measurement flow path; and

and a control unit that controls the sample liquid feeding unit to feed the sample along an inner wall facing the 1 st inner wall until the sample reaches the measurement channel, and controls the sheath liquid feeding unit to feed the sheath liquid along the 1 st inner wall after the sample reaches the measurement channel.

10. An analysis device, having:

a flow cell having a wedge-shaped portion and a measurement channel provided downstream of the wedge-shaped portion, the wedge-shaped portion including a1 st inner wall and a2 nd inner wall opposite to the 1 st inner wall, both of the liquid specimen and the sheath liquid flowing in the wedge-shaped portion, the 1 st inner wall being inclined with respect to the 2 nd inner wall as follows: the distance between the 1 st inner wall and the 2 nd inner wall on the downstream side of the wedge part is shorter than the distance between the 1 st inner wall and the 2 nd inner wall on the upstream side of the wedge part;

a sheath liquid feeding unit for feeding the sheath liquid along the 1 st inner wall;

a sample liquid feeding unit that feeds the liquid sample along the 2 nd inner wall;

a measurement unit that measures the liquid sample flowing in the measurement flow path; and

and a control unit that controls the sample liquid feeding unit to feed the sample along the 2 nd inner wall until the sample reaches the measurement channel, and controls the sheath liquid feeding unit to feed the sheath liquid along the 1 st inner wall after the sample reaches the measurement channel.

11. The analysis device according to claim 9 or 10,

the control unit controls the specimen liquid feeding unit to feed the specimen to the wedge-shaped portion until the measurement unit detects the specimen, and controls the sheath liquid feeding unit to feed the sheath liquid to the wedge-shaped portion after the measurement unit detects the specimen.

Technical Field

The present invention relates to a liquid feeding method for feeding a sample to a flow cell (flow cell) and a sample analyzer using the method.

Background

Patent documents 1 and 2 disclose flow cells having: a sheath fluid flow path into which a sheath fluid flows; a sample flow path into which a sample of liquid flows; and a joining path where the sheath fluid channel and the sample channel join each other to take an image of a visible component contained in the sample.

Patent document 1: japanese laid-open patent publication No. 2018-112516

Patent document 2: japanese patent laid-open publication No. 2019-7893

In the technique described in patent document 2, the sheath fluid flowing from the sheath fluid channel is used in the junction channel to push the specimen flowing from the specimen channel to the lower surface of the flow cell in a flat manner, in order to image the visible components of the specimen with the imaging device facing the lower surface of the flow cell. However, the specimen may not be pressed against the bottom surface, and a sheath liquid may be interposed between the specimen and the imaging device, which may make it difficult to clearly image the visible component.

Disclosure of Invention

Therefore, an object of an embodiment of the present invention is to enable a specimen to reliably contact and flow on one wall surface of a flow cell at an imaging position in the flow cell in which the specimen is pushed to the wall surface by a sheath liquid and flows.

A liquid feeding method of the present disclosure is a liquid feeding method of feeding a sample to a flow cell having a wedge portion and a measurement channel provided downstream of the wedge portion, the wedge portion having a wedge surface that is an inner wall inclined so as to approach an opposite inner wall as going downstream, the sample and a sheath liquid both flowing in the wedge portion, the liquid feeding method including the steps of:

a sample introduction step of conveying the sample to the wedge along an inner wall facing the wedge surface until the sample reaches the measurement channel; and

and a sample pressing step of delivering the sheath liquid to the wedge along the wedge surface after the sample reaches the measurement channel.

The disclosed analysis device is provided with:

a flow cell having a wedge portion having a wedge surface that is an inner wall inclined so as to approach an opposite inner wall as going downstream, and a measurement channel provided downstream of the wedge portion, the flow cell having a specimen and a sheath fluid both flowing in the wedge portion;

a sheath liquid feeding unit that feeds the sheath liquid along the wedge surface;

a sample liquid feeding unit that feeds the sample along an inner wall facing the wedge surface;

a measurement unit that measures a sample flowing in a measurement flow path; and

and a control unit that controls the sample liquid feeding unit to feed the sample along the inner wall facing the wedge surface until the sample reaches the measurement channel, and controls the sheath liquid feeding unit to feed the sheath liquid along the wedge surface after the sample reaches the measurement channel.

In an embodiment of the present invention, in a flow cell in which a sample flows by pressing the sample against one wall surface of the flow cell with a sheath liquid, the sample can reliably contact the wall surface and flow at an imaging position.

Drawings

Fig. 1 is a schematic view of an analysis device according to an embodiment of the present disclosure.

Fig. 2 is a perspective view schematically showing the positional relationship between the flow cell and the measurement unit in the analysis device of the present embodiment.

Fig. 3 is a perspective view showing the flow cell of the present embodiment.

Fig. 4 is a plan view showing the flow cell of the present embodiment.

Fig. 5 is an exploded perspective view showing the flow cell of the present embodiment.

Fig. 6 is an enlarged perspective view showing the vicinity of a junction between the specimen and the sheath fluid in the flow cell according to the present embodiment.

Fig. 7 is a sectional view showing the flow cell of the present embodiment.

Fig. 8 is a functional block diagram of the analysis device according to the present embodiment.

Fig. 9 shows a block diagram of the hardware configuration of the control unit.

Fig. 10 is a flowchart showing the operation of the analysis device according to the present embodiment.

Fig. 11 is a flowchart showing the operation of the analysis device according to the present embodiment.

Fig. 12 is a sectional view of the vicinity of the confluence portion of the flow cell.

Fig. 13 is a sectional view of the vicinity of the confluence portion of the flow cell.

Fig. 14 is a schematic diagram showing the operation of the analysis device according to the present embodiment.

Fig. 15 is a sectional view of the vicinity of the confluence portion of the flow cell.

Description of the reference symbols

10: an analysis device; 11: a measuring unit; 12: a suction section; 13: a sheath liquid supply section; 14: a housing; 14A: a recess; 15: a light source; 20: a flow-through cell; 20A: an upper plate-like member; 20B: a lower plate-like member; 20C: a lower surface (of the upper plate-like member); 20D: an upper surface (of the lower plate-like member); 21: a sheath fluid flow path; 21A: opening the sheath fluid; 21B: a bending section; 21C: a bending section; 21D: a sheath fluid inflow orifice; 21X: a top surface (of the sheath fluid flow path); 21Y: a bottom surface (of the sheath fluid channel); 22: a sample flow path; 22A: a sample opening; 22B: a sample inflow port; 22X: a top surface (of the sample channel); 22Y: a bottom surface (of the sample channel); 23: a converging path; 23A: opening a waste liquid; 23B: a merging section; 23C: a wedge portion; 23D: a flat portion (measurement flow path); 23E: a wedge-shaped surface; 23X: a top surface (of the merged path); 23Y: a bottom surface (of the merged path); 24: an end face.

Detailed Description

Embodiments of the present disclosure are described below. In the following description, the reference numerals assigned to the respective components correspond to those shown in the drawings, but the present invention is not limited thereto. In the present disclosure, a side close to an inflow source of the liquid is referred to as "upstream", and a side close to an outflow destination of the liquid is referred to as "downstream" in each flow path.

< method of feeding liquid to specimen 70 >

[ means 1 ]

The 1 st aspect of the present disclosure is a liquid feeding method for feeding a sample 70 to a flow cell 20, the flow cell 20 including: a merging path 23 through which the specimen 70 and the sheath liquid 80 flow; a sample channel 22 for introducing the sample 70 into the junction channel 23; and at least 1 sheath fluid channel 21 for introducing the sheath fluid 80 into the junction channel 23, the junction channel 23 having: a junction 23B where the sample channel 22 and the sheath fluid channel 21 join together; a flat portion 23D disposed downstream of the junction portion 23B and formed along one of the opposing wall surfaces of the junction portion 23B, the distance between the opposing wall surfaces being shorter than that of the junction portion 23B; and a wedge 23C that connects the junction 23B and the flat 23D, and gradually reduces the distance between the facing wall surfaces toward the downstream, and the sheath fluid channel 21 introduces the sheath fluid 80 into the junction 23B along the wall surface provided with the wedge 23E in the wedge 23C (the 1 st inner wall 23F), and the specimen channel 22 introduces the specimen 70 into the junction 23B along the wall surface facing the wall surface provided with the wedge 23E (the 2 nd inner wall 23F).

In other words, the flow cell 20 used in the liquid feeding method of the specimen 70 of the present embodiment includes the sheath liquid channel 21, the specimen channel 22, and the junction channel 23. The merging path 23 of the flow cell 20 has a merging portion 23B, a wedge portion 23C, and a flat portion 23D from the upstream side. The wedge portion 23C has a wedge face 23E, and the wedge face 23E is inclined in a direction approaching the opposite wall surface as going from upstream to downstream. Then, in the junction portion 23B of the junction path 23 of the flow cell 20, the sheath liquid 80 is introduced into the junction portion 23B from the wall surface side where the wedge surface 23E is provided. Then, the sheath liquid 80 flows from the upstream to the downstream along the wedge-shaped surface 23E, and thereby a force to press the specimen 70, which will be described later, against the wall surface facing the wedge-shaped surface 23E is generated. Thus, the specimen 70 introduced into the junction 23B is pressed by the sheath liquid 80 against the wall surface facing the wall surface provided with the wedge-shaped surface 23E, that is, the side to which the specimen 70 is pressed by the sheath liquid 80 flowing along the wedge-shaped surface 23E.

Here, the liquid feeding method of the specimen 70 according to the present embodiment includes the steps of: a sample introduction step of conveying the sample 70 to the wedge 23C along an inner wall facing the wedge 23E until the sample 70 reaches the flat 23D serving as a measurement channel, so that the liquid feeding pressure of the sample 70 in the merged channel 23 is higher than the liquid feeding pressure of the sheath liquid 80 in the merged channel 23; and a sample pressing step of, after the sample 70 reaches the flat portion 23D as the measurement flow path, conveying the sheath liquid 80 to the wedge portion 23C along the wedge surface 23E.

That is, until the specimen 70 reaches the flat portion 23D as the measurement channel, as the specimen introducing step, the specimen 70 is conveyed to the specimen channel 22 and the sheath liquid 80 is conveyed to the sheath liquid channel 21 so that the liquid conveying pressure of the specimen 70 in the merged channel 23 is higher than the liquid conveying pressure of the sheath liquid 80 in the merged channel 23. If the liquid feeding pressure of the specimen 70 in the merging path 23 (the merging portion 23B, the flat portion 23D, and the wedge portion 23C), that is, in the merging path 23 in which both the specimen 70 and the sheath liquid 80 flow, is lower than the liquid feeding pressure of the sheath liquid 80 until the specimen 70 reaches the flat portion 23D, the specimen 70 tends to flow in the central portion of the laminar flow of the sheath liquid 80 having the lower liquid feeding pressure ratio among the laminar flows of the sheath liquid 80. The specimen 70 flows separately from the wall surface facing the wall surface provided with the wedge surface 23E, that is, the wall surface on the side to which the specimen 70 is pushed by the sheath liquid 80 flowing along the wedge surface 23E. Therefore, by setting the liquid feeding pressure of the specimen 70 in the junction path 23 higher than the liquid feeding pressure of the sheath liquid 80 until the specimen 70 reaches the flat portion 23D, the specimen 70 can reach the flat portion 23D along the wall surface facing the wall surface provided with the wedge surface 23E without being affected by the feeding of the sheath liquid 80.

After the specimen 70 reaches the flat portion 23D, as a specimen pressing step, the specimen 70 is conveyed to the specimen flow path 22 and the sheath liquid 80 is conveyed to the sheath liquid flow path 21 so that the liquid conveying pressure of the specimen 70 in the merged path 23 is lower than the liquid conveying pressure of the sheath liquid 80 in the merged path 23. That is, the liquid feeding pressure of the specimen 70 in the merging path 23 (the merging portion 23B, the flat portion 23D, and the wedge portion 23C) through which both the specimen 70 and the sheath liquid 80 flow is lower than the liquid feeding pressure of the sheath liquid 80 flowing through the merging path 23. Therefore, the specimen 70 is pressed against the wall surface 23Y facing the wall surface 23X provided with the wedge surface 23E by the sheath liquid 80 having a high liquid feeding pressure, and is conveyed to the flat portion 23D along the wall surface. At this time, since the liquid feeding pressure of the specimen 70 in the merging path 23 is lower than the liquid feeding pressure of the sheath liquid 80 in the merging path 23, the specimen 70 flows separately from the wall surface 23Y facing the wall surface 23X provided with the wedge surface 23E, but the specimen 70 flows along one of the facing wall surfaces because it is pressed by the sheath liquid 80 having a high liquid feeding pressure in the merging path 23. The specimen 70 extends in a flat shape so that the thickness thereof is reduced along a wall surface facing the wall surface provided with the wedge surface 23E. This makes it possible to easily measure and observe the specimen 70 in the flat portion 23D. After the sample introduction step, the process may be shifted to the sample pressing step at any time.

In the above-described sample introduction step, the sample 70 and the sheath liquid 80 may be allowed to flow through the flat portion 23D in a state where the liquid feeding pressure of the sample 70 in the merged channel 23 is higher than the liquid feeding pressure of the sheath liquid 80 in the merged channel 23. For example, in the flat portion 23D, when the liquid feeding pressure of the specimen 70 flowing through the merging path 23 is lower than the liquid feeding pressure of the sheath liquid 80 even though the specimen 70 has already reached the flat portion 23D, the liquid feeding pressure of the specimen 70 may be increased to flow the specimen 70 through the flat portion 23D, and the liquid feeding pressure of the specimen 70 may be decreased from the liquid feeding pressure of the sheath liquid 80 after the specimen 70 conveyed by increasing the liquid feeding pressure has reached the flat portion 23D.

Here, the liquid feeding pressure of the specimen 70 and the liquid feeding pressure of the sheath liquid 80 in the merged channel 23 can be controlled by any means. For example, the junction path 23 may be provided with a pressure sensor or the like to measure the liquid feeding pressure in the junction path 23, and the output of a device (for example, a pump) for flowing the sheath liquid 80 or the sample 70 into the sheath liquid channel 21 or the sample channel 22 may be adjusted based on the measurement result. Further, the actual liquid sending pressure in the sheath liquid channel 21 and the sample channel 22 may be measured by a pressure sensor or the like, and the liquid sending pressure in the junction channel 23 may be calculated and controlled based on the ratio of the cross-sectional area of the channel of the sheath liquid channel 21 and the sample channel 22 to the cross-sectional area of the junction channel 23. The liquid feeding pressure is controlled as follows: the control unit provided in the apparatus measures the liquid feeding pressure of the junction path 23, the sheath liquid channel 21, the sample channel 22, and the like, and controls the output of the inflow apparatus such as the pump based on the result.

As described above, in the specimen pressing step, the specimen 70 extends in a flat shape so that the thickness thereof is reduced along the wall surface facing the wall surface provided with the wedge surface 23E. Therefore, after the specimen pressing step, a measurement step of measuring the specimen 70 flowing in the flat portion 23D can be performed. The measurement unit 11 used for measurement of the specimen 70 is not limited, and a unit corresponding to a measurement item can be used. For example, an optical unit such as a spectrophotometer or image capturing using a camera may be used, and an electrical unit such as a sensor may be used. The measurement of the specimen also includes observation and imaging of an image captured by a camera or the like.

The measurement unit 11 is preferably provided at a position suitable for measuring the specimen 70 extending in a flat shape. Specifically, the specimen 70 extends in a flat shape as it flows from the wedge surface 23E to the flat portion 23D. Therefore, the measurement unit 11 may be provided at a position opposite to the flat portion 23D or the wedge portion 23C, and may also be provided at a position opposite to a position of the wedge portion 23C to the flat portion 23D. The specimen 70 extends in the most flat shape from the wedge 23C to the flat 23D. Therefore, it is preferable to be provided at a position opposite to the position of the wedge portion 23C to the flat portion 23D, in other words, at a position opposite to the upstream portion of the flat portion 23D. Further, since the specimen 70 flows along the wall surface 23Y facing the wall surface 23X provided with the wedge surface 23E, the measurement unit 11 is preferably provided at a position facing the specimen 70 via the wall surface. This is because the sheath liquid 80 is not interposed between the measurement unit 11 and the specimen 70, and the specimen 70 can be measured by the measurement unit 11 without being affected by the sheath liquid 80. The channel connected to the downstream of the wedge 23C and through which the sample to be measured by the measurement unit 11 flows corresponds to a measurement channel. For example, when the measurement unit 11 is provided at a position facing an upstream portion of the flat portion 23D, the flat portion 23D serves as a measurement flow path. And for example, in the case where the measurement unit 11 is provided at a position opposing an intermediate portion of the upstream portion and the downstream portion of the wedge portion 23C, the intermediate portion is a measurement flow path.

Before the measuring step, a step of measuring the liquid feeding pressure of the sample in the flow path and determining whether or not the liquid feeding pressure is within a specific range may be performed. When the liquid feeding pressure at the time of introducing the specimen 70 into the junction path 23 in the specimen introducing step is different from the liquid feeding pressure at the time of introducing the specimen 70 into the junction path 23 in the specimen pressing step, the liquid feeding pressure immediately after the shift to the specimen pressing step is unstable. For example, in the sample introduction step, in order to quickly introduce the sample 70 into the sample flow path 22 and the flow path of the flow cell 20, the sample may be conveyed at a liquid conveying pressure higher than the liquid conveying pressure at the time of introducing the sample 70 in the sample pressing step. That is, the liquid feeding pressure of the specimen 70 in the merging path 23 in the specimen introducing step may be larger than the liquid feeding pressure of the specimen 70 in the merging path 23 in the specimen pressing step. In this case, immediately after the transition from the sample introduction step to the sample pressing step, the liquid feeding pressure of the sample 70 in the merged path 23 may be unstable and higher than the liquid feeding pressure when the sample 70 is introduced in the sample pressing step. When the measurement of the specimen 70 is performed in this state, the measurement accuracy deteriorates. Therefore, when the liquid feeding pressure of the specimen 70 in the merged path 23 is measured for a certain period and falls within a specific liquid feeding pressure range, the process proceeds to the measurement step. On the other hand, when the pressure is not within the specific pressure range, the sheath liquid 80 and the specimen 70 are continuously conveyed for a certain period of time, the liquid conveying pressure of the specimen 70 in the merged channel 23 is measured again for a certain period of time, and then it is determined whether or not to proceed to the measurement step. Thus, even if the liquid feeding pressure of the specimen 70 in the merging path 23 in the specimen introducing step is larger than the liquid feeding pressure of the specimen 70 in the merging path 23 in the specimen pressing step, it is possible to avoid deterioration of the measurement accuracy. In the sample introduction step, the sample 70 can be quickly introduced into the sample channel 22 and the channel of the flow cell 20.

Further, whether or not the specimen 70 has reached the flat portion 23D may be determined based on whether or not the measurement unit 11 provided in the flat portion 23D has detected a specific attribute (e.g., color of liquid, specific component) of the specimen 70. Alternatively, a sensor capable of detecting the specimen 70 may be provided in the flat portion 23D, and the determination may be made based on the reaction of the sensor.

[ means 2 ]

In the 2 nd aspect of the liquid feeding method for the specimen 70 of the present disclosure, the flow cell 20 having the flow path having the same configuration as that of the 1 st aspect is also used.

Here, the method for feeding the sample 70 according to the present embodiment includes the sample introduction step and the sample pressing step according to the above-described 1 after filling the junction path 23 with the sheath liquid 80, and stops feeding the sheath liquid 80 to the sheath liquid channel 21 in the sample introduction step. That is, in a state where the sheath liquid 80 is supplied to the sheath liquid channel 21 and the junction path 23 (the junction portion 23B, the flat portion 23D, and the wedge portion 23C) is filled with the sheath liquid 80, the supply of the sheath liquid 80 to the sheath liquid channel 21 is stopped. In the state where the supply of the sheath liquid 80 to the sheath liquid channel 21 is stopped, the specimen 70 is supplied to the specimen channel 22 as a specimen introducing step until the specimen 70 reaches the flat portion 23D. After the specimen 70 reaches the flat portion 23D, that is, in the specimen pressing step, the specimen 70 is conveyed to the specimen flow path 22 and the sheath liquid 80 is conveyed to the sheath liquid flow path 21 so that the liquid conveying pressure of the specimen 70 in the merged path 23 is lower than the liquid conveying pressure of the sheath liquid 80 in the merged path 23.

That is, in the sample introduction step, the liquid feeding pressure of the sheath liquid 80 in the merged channel 23 is substantially zero or extremely low.

In this state, the sample 70 is caused to flow into the sample channel 22 until the sample 70 reaches the flat portion 23D. At this time, since the liquid feeding pressure of the sheath liquid 80 in the junction path 23 is substantially not or extremely low as described above, the liquid feeding pressure of the specimen 70 in the junction path 23 is inevitably higher than the liquid feeding pressure of the sheath liquid 80 in the junction path 23.

After the specimen 70 reaches the flat portion 23D, the specimen 70 and the sheath liquid 80 are conveyed in the same manner as in the specimen pressing step of the above-described first embodiment, so that the specimen 70 can be easily observed.

The other steps are the same as in the 1 st embodiment.

< Analyzer 10 of specimen 70 >

The analyzer 10 for a specimen 70 according to the present disclosure adopts, in the 2 nd aspect, the flow cell 20 having: a merging path 23 through which the specimen 70 and the sheath liquid 80 flow; a sample channel 22 for introducing the sample 70 into the junction channel 23; and at least 1 sheath fluid channel 21 for introducing the sheath fluid 80 into the junction channel 23, the junction channel 23 having: a junction 23B where the sample channel 22 and the sheath fluid channel 21 join together; a flat portion 23D disposed downstream of the junction portion 23B and formed along one of the opposing wall surfaces of the junction portion 23B, the distance between the opposing wall surfaces being shorter than that of the junction portion 23B; and a wedge portion 23C that connects the junction portion 23B and the flat portion 23D, and that gradually reduces the distance between the opposing wall surfaces toward the downstream, and that introduces the sheath liquid 80 from the other wall surface side of the opposing wall surfaces of the junction portion 23B into the junction portion 23B through the sheath liquid channel 21.

That is, the meaning and structure of the flow cell 20 in the present embodiment are the same as those in the liquid feeding method of the specimen 70 described above.

The analyzer 10 for the sample 70 of this embodiment includes: a measurement unit 11 provided at a position facing the flat portion 23D, a1 st channel 31 connected to the upstream of the sheath fluid channel 21, a1 st pump 41 for supplying the sheath fluid 80 to the flow cell 20 through the 1 st channel 31, a2 nd channel 32 connected to the upstream of the sample channel 22, a2 nd pump 42 for supplying the sample 70 to the flow cell 20 through the 2 nd channel 32, and a control unit 100 for controlling the 1 st pump 41 and the 2 nd pump 42.

In the analyzer 10 of the specimen 70 of this embodiment, the controller 100 controls the 1 st pump 41 and the 2 nd pump 42 so that the liquid sending pressure of the specimen 70 in the merged channel 23 becomes higher than the liquid sending pressure of the sheath liquid 80 in the merged channel 23 before the specimen 70 reaches the flat portion 23D.

For example, before the specimen 70 reaches the flat portion 23D, the control unit 100 controls the 1 st pump 41 and the 2 nd pump 42 so that the liquid sending pressure of the specimen 70 in the merging path 23 becomes higher than the liquid sending pressure of the sheath liquid 80 in the merging path 23, and sends the specimen 70 to the specimen flow path 22 and the sheath liquid 80 to the sheath liquid flow path 21. That is, the pressure at which the 2 nd pump 42 sends the sample 70 to the merging path 23 is higher than the pressure at which the 1 st pump 41 sends the sheath liquid 80 to the merging path 23. The technical meaning of introducing the sample 70 and the sheath solution 80 into the flow cell 20 by performing such control is the same as that described in the above-described embodiment 1, and therefore, the description thereof is omitted.

After the specimen 70 reaches the flat portion 23D, that is, in a state where the specimen 70 has reached the flat portion 23D, the control unit 100 controls the 1 st pump 41 and the 2 nd pump 42 so that the liquid feeding pressure of the specimen 70 in the merged path 23 becomes lower than the liquid feeding pressure of the sheath liquid 80 in the merged path 23, and then conveys the specimen 70 to the specimen flow path 22 and conveys the sheath liquid 80 to the sheath liquid flow path 21. That is, the pressure at which the 2 nd pump 42 sends the sample 70 to the merging path 23 is lower than the pressure at which the 1 st pump 41 sends the sheath liquid 80 to the merging path 23. The technical meaning of introducing the sample 70 and the sheath solution 80 into the flow cell 20 by performing such control is the same as that described in the above-described embodiment 1, and therefore, the description thereof is omitted.

Here, the liquid feeding pressure of the specimen 70 and the liquid feeding pressure of the sheath liquid 80 in the merged channel 23 can be controlled by any means. The control means is the same as that described in the above embodiment 1, and therefore, the description thereof is omitted.

Note that the technical meaning of making the liquid feeding pressure of the specimen 70 in the merging path 23 in the specimen introducing step larger than the liquid feeding pressure of the specimen 70 in the merging path 23 in the specimen pressing step is the same as that described in the above-described embodiment 1, and therefore, the description thereof is omitted.

The means for determining whether or not the specimen 70 has reached the flat portion 23D is the same as the means described in the above-described embodiment 1, and therefore, the description thereof is omitted.

In this embodiment, the "opposing wall surfaces" are the top surface 23X and the bottom surface 23Y of the junction path 23, and the specimen 70 is pushed from above by the sheath liquid 80 "to the bottom surface 23Y, which is the wall surface opposing the wall surface provided with the wedge surface 23E, but the liquid feeding method for the specimen 70 and the analyzer 10 for the specimen 70 according to the present disclosure are not limited to this embodiment. For example, "a wall surface facing a wall surface provided with the wedge surface 23E" may be an upper surface of the junction path 23, and the specimen 70 may be pressed from the lower side to the upper surface by the sheath liquid 80. Alternatively, the "opposing wall surfaces" may be left and right opposing wall surfaces, and one of the left and right surfaces, for example, the left surface may be "a wall surface opposing the wall surface provided with the wedge surface 23E", and the specimen may be pushed from the right side to the left surface by the sheath liquid 80.

< embodiment >

Hereinafter, embodiments of the present disclosure will be described with reference to the drawings.

Fig. 1 schematically shows an embodiment of an analysis apparatus 10 for a specimen 70. In the present embodiment, the 1 st channel 31 and the 2 nd channel 32 are connected as channels flowing into the flow cell 20. A waste liquid path 36 is also connected as a flow path from the flow cell 20.

[ Structure of the analysis device 10 ]

The sheath liquid 80 is supplied from the 1 st pump 41 to the 1 st channel 31 (see fig. 13). Further, a suction portion 12 formed as a nozzle is attached to the tip of the most upstream end of the 2 nd flow path 32. As described later, the suction unit 12 sucks the specimen 70 from the specimen storage unit 60 storing the specimen 70 by the 1 st pump 41. A1 st valve 51 as a three-way valve is provided in the middle of the 2 nd flow path 32. The 3 rd channel 33 is connected to the 2 nd channel 32 via the 1 st valve 51. The sheath liquid 80 is supplied from the 2 nd pump 42 to the 3 rd channel 33. In the present embodiment, the plunger pump is used for both the 1 st pump 41 and the 2 nd pump 42, and the sheath liquid 80 can be sucked from the 1 st channel 31 and the 3 rd channel 33, respectively. As the 2 nd pump 42, a pump having no suction function and only a liquid feeding function, such as a tube pump, may be used.

The sheath liquid supply unit 13 is a tank that stores the sheath liquid 80 to be supplied to the flow cell 20 by the 1 st pump 41 and the 2 nd pump 42. The sheath liquid supply path 35, which is a tube connected to the 1 st pump 41 and the 2 nd pump 42, extends from the sheath liquid supply portion 13. In the sheath liquid supply path 35, a1 st sheath liquid valve 54 is provided between the sheath liquid supply portion 13 and the 1 st pump 41, and a2 nd sheath liquid valve 55 is provided between the sheath liquid supply portion 13 and the 2 nd pump 42. Both of the sheath 1 st valve 54 and the sheath 2 nd valve 55 are valves that can be opened and closed only in one direction.

In the present embodiment, the 1 st channel 31, the 2 nd channel 32, and the 3 rd channel 33 are defined as downstream sides on the side facing the flow cell 20, and as upstream sides on the opposite side.

In the 2 nd flow path 32, a2 nd valve 52 as a three-way valve is further provided between the 1 st valve 51 and the flow cell 20. Meanwhile, a 3 rd valve 53 as a three-way valve is provided in the middle of the 1 st flow path 31. The 2 nd valve 52 and the 3 rd valve 53 are connected by the 4 th flow path 34.

The 1 st channel 31, the 2 nd channel 32, the 3 rd channel 33, the 4 th channel 34, the sheath liquid supply channel 35, and the waste liquid channel 36 are each constituted by a tube made of a flexible and flexible material (for example, a teflon (registered trademark) tube).

Here, the 3 rd channel 33 side, the downstream side of the 2 nd channel 32, and the upstream side of the 2 nd channel 32 among the three channels merged with the 1 st valve 51 are referred to as branch 1A, branch 1B, and branch 1C, respectively. Of the three channels merged with the 2 nd valve 52, the upstream side of the 2 nd channel 32 is referred to as branch 2A, the downstream side of the 2 nd channel 32 is referred to as branch 2B, and the 4 th channel 34 is referred to as branch 2C. Of the three channels merged with the 3 rd valve 53, the upstream side of the 1 st channel 31 is referred to as a branch 3A, the downstream side of the 1 st channel 31 is referred to as a branch 3B, and the 4 th channel 34 is referred to as a branch 3C.

< flow cell 20 >

As shown in fig. 2, the flow cell 20 is mounted in an appropriate recess 14A of the housing 14 in the analysis device 10. The light source 15 and the measuring unit 11 are provided at positions facing each other across the merging path 23 of the flow cell 20, specifically, positions from the wedge portion 23C to the flat portion 23D (see fig. 7), and the wedge portion 23C has a wedge surface 23E as an inclined surface. The light source 15 irradiates the specimen 70 flowing through the merged path 23 with light. The measurement unit 11 measures the specimen 70 flowing in the junction path 23 together with the sheath liquid 80. That is, the measurement unit 11 measures the specimen 70 flowing through the flow path of the portion facing the measurement unit 11 through the bottom surface 23Y of the merged path 23. The specimen 70 pressed by the sheath liquid 80 flowing along the wedge-shaped surface 23E flows through the flow path of the portion. Therefore, in this embodiment, the flow path of this portion corresponds to the measurement flow path provided downstream of the wedge portion 23C. The measurement here includes quantitatively or qualitatively detecting a specific component of the specimen 70 by an optical measuring unit (e.g., a spectrophotometer) as the measuring unit 11, and observing or photographing the specific component of the specimen 70 as an image by another camera or the like as the measuring unit 11. The measurement unit 11 is disposed close to the bottom surface 23Y, and the bottom surface 23Y is a wall surface facing the wall surface provided with the wedge surface 23E, that is, the top surface 23X.

The flow cell 20 of the present embodiment is shown in a perspective view in fig. 3, and the flow cell 20 is shown in a plan view in fig. 4. In addition, the flow cell 20 is shown in an exploded perspective view in fig. 5. Fig. 6 is an enlarged perspective view of the vicinity of a junction 23B of the flow cell 20, which will be described later. In the drawings, an arrow H indicates a height direction of the flow cell 20, and an arrow W indicates a width direction of the flow cell 20. In the drawing, an arrow L indicates a longitudinal direction of the flow cell 20 perpendicular to the height direction and the width direction, respectively (the arrow L indicates a downstream side in a flow direction of a flow path in which the sheath liquid 80 and the specimen 70 are merged). In fig. 5 and 6, the height direction (H direction), that is, the vertical direction is shown in a state reverse to that of fig. 1 and 2 in order to facilitate understanding of the structure of the flow cell 20.

The flow cell 20 of the present embodiment can be used for, for example, urine formation partial testing in which a urine specimen, which is an example of the specimen 70, is caused to flow into the sheath liquid 80, and the measurement means 11 captures a visible component of the urine specimen and analyzes the visible component based on the shape of the visible component of the captured image. In the present embodiment, the examination of a solid component in urine was performed using a urine sample as a body fluid as an example of the sample 70, but a liquid sample such as a body fluid typified by blood may be used.

As shown in fig. 3 to 5, the flow cell 20 is formed as a substantially rectangular plate-like member. In the present embodiment, the flow cell 20 is configured by bonding the upper plate-like member 20A and the lower plate-like member 20B in a surface contact state. The flow cell 20 has: a merging path 23 through which the specimen 70 and the sheath liquid 80 flow together; and a sample channel 22 that is provided on an extension line in the longitudinal direction of the merged channel 23 on the upstream side (the opposite side to the L direction) of the merged channel 23 in the flow direction indicated by the arrow a, and through which the sample 70 flows (see fig. 5). The flow cell 20 also has 2 sheath fluid channels 21, which are arranged on the upstream side of the junction channel 23 in the flow direction (the direction of arrow a) so as to intersect the longitudinal direction of the junction channel 23, and through which the sheath fluid 80 flows.

The upper plate-like member 20A is provided with a merging channel 23, a sample channel 22, and 2 sheath fluid channels 21 (see fig. 5). In fig. 5, as described above, the vertical direction of the flow cell 20 is shown in a state reverse to that of fig. 1 and 2, and therefore the positional relationship of the 2 sheath fluid channels 21 is reverse to that of fig. 1 and 2. In the present embodiment, the lower surface 20C (the surface facing upward in the drawing) of the upper plate-like member 20A is grooved to form the merged channel 23, the sample channel 22, and 2 sheath fluid channels 21 (see fig. 5). In fig. 5, the bottom of the groove forming the sheath fluid channel 21 is the top surface 21X of the sheath fluid channel 21. The bottom of the groove forming the sample channel 22 is the top surface 22X of the sample channel 22. The bottom of the groove forming the merged path 23 is the top surface 23X of the merged path 23. The lower plate-like member 20B is a plate material having a plane substantially parallel to the upper and lower sides, and has no flow path or the like (see fig. 5). However, the bottom surface 21Y of the sheath fluid channel 21, the bottom surface 22Y of the sample channel 22, and the bottom surface 23Y of the junction channel 23 are formed by the upper surface 20D (the surface facing downward in the drawing).

The sample flow path 22 is arranged substantially linearly along the longitudinal direction of the flow cell 20, and the sample 70 flows in the direction of the arrow B. In the present embodiment, the cross-sectional shape in the direction perpendicular to the longitudinal direction of the sample channel 22 is substantially rectangular. A sample opening 22A for supplying the sample 70 is formed at an upstream end of the sample channel 22 in the flow direction (the direction of arrow B). The 2 nd channel 32 (see fig. 1) for supplying the sample 70 is connected to the sample opening 22A of the sample channel 22. In the sample flow path 22, the sample 70 supplied from the sample opening 22A flows in the direction of the merged path 23.

Each of the 2 sheath fluid channels 21 is a substantially U-shaped channel disposed laterally long in the longitudinal direction of the flow cell 20 in plan view, and the opening side of the substantially U-shape faces the width direction (W direction) of the flow cell 20. The 2 sheath liquid channels 21 face each other across the merging channel 23 in the width direction (W direction) of the flow cell 20. In the present embodiment, the cross-sectional shape in the direction perpendicular to the longitudinal direction of the sheath fluid channel 21 is substantially rectangular.

The 2 sheath liquid channels 21 are configured to allow the sheath liquid 80 to flow in the direction of arrow C and the direction of arrow D, respectively. A sheath liquid opening 21A for supplying the sheath liquid 80 is formed at an upstream end portion of the 2 sheath liquid channels 21 in the flow direction (the direction of arrow C and the direction of arrow D). In other words, in the sheath liquid channel 21, the sheath liquid 80 supplied from the sheath liquid opening 21A flows in the direction of the upstream side of the merged channel 23. 2 bent portions 21B and 21C are formed in the 2 sheath fluid channels 21 in the middle of the flow direction. The bent portion 21B on the upstream side in the flow direction of the sheath fluid channel 21 is bent in a substantially vertical direction, and the corner of the bent portion is formed by bending in a curved shape. The curved portion 21C on the downstream side of the curved portion 21B (the front side of the merging portion 23B) is curved in an acute angle direction, and the corner of the curved portion is curved.

A junction 23B is provided at an upstream end of the junction path 23 in the flow direction (the direction of arrow a), and the specimen 70 flowing from the specimen flow path 22 and the sheath liquid 80 flowing from the 2 sheath liquid flow paths 21 are joined at the junction 23B (see fig. 6). That is, the merging portion 23B is a part of the merging path 23.

As shown in fig. 7, a sample inlet 22B (see fig. 1 to 3) that opens at an end surface 24 on the upstream side in the flow direction (the direction of arrow a) of the junction channel 23 is provided at the downstream end in the flow direction (the direction of arrow B) of the sample channel 22. The specimen inflow port 22B is formed on one side in the depth direction of the end surface 24 of the junction channel 23 (in the present embodiment, the lower portion in the direction opposite to the H direction). More specifically, the merged path 23 has a bottom surface 23Y and a top surface 23X as wall surfaces opposed in the depth direction. The sample channel 22 is provided along the bottom surface 23Y which is a wall surface of the junction 23B of the junction path 23 and which faces the wall surface of the wedge 23E in the wedge 23C. The bottom surface 22Y of the sample channel 22 and the bottom surface 23Y of the junction channel 23 are connected to each other in the same horizontal plane. The sample 70 in the sample channel 22 flows from the sample inlet 22B into the junction 23B. In other words, the sample channel 22 causes the sample 70 to flow into the junction 23B along the bottom surface 23Y of the junction 23B. That is, in the present embodiment, the 2 nd pump 42 is a sample liquid feeding unit 42 (see fig. 1) that feeds the sample 70 along the inner wall facing the wedge surface 23E.

At the downstream end of the sheath fluid channel 21 in the flow direction (the direction of arrow C and the direction of arrow D), sheath fluid inlets 21D (see fig. 1 to 3) that are open at both sides on the upstream side of the junction channel 23 in the flow direction (the direction of arrow a) are provided. The sheath fluid inlet 21D of the sheath fluid channel 21 is formed at a position intersecting the end face 24 of the junction channel 23 in a plan view. In the present embodiment, the downstream portion of the sheath fluid channel 21 is connected to the junction 23B at an obtuse angle with respect to the longitudinal direction of the junction channel 23. The sheath liquid channel 21 is provided along the top surface 23X, which is a wall surface of the wedge-shaped portion 23C provided with the wedge surface 23E, out of the opposing wall surfaces of the merged channel 23. In the present embodiment, in a cross-sectional view in the depth direction of the junction path 23, the sheath fluid inlet 21D of the sheath fluid channel 21 is provided in a range from the bottom surface 23Y to the top surface 23X of the junction portion 23B, and a lower portion of the sheath fluid inlet 21D overlaps with a range in which the specimen inlet 22B is provided (see fig. 5). The sheath liquid 80 in the sheath liquid channel 21 flows from the sheath liquid inlet 21D into the junction portion 23B of the junction path 23. In other words, the sheath fluid channel 21 causes the sheath fluid 80 to flow into the junction 23B from the direction in which the sheath fluid 80 flows by pressing the specimen 70 against the bottom surface 23Y. That is, in the present embodiment, the 1 st pump 41 is a sheath liquid feeding unit 41 (see fig. 1) that feeds the sheath liquid along the wedge surface.

In the flow cell 20 of the present embodiment, the longitudinal direction of the sample channel 22 is arranged on an extension line of the longitudinal direction of the junction channel 23. In the present embodiment, the cross-sectional shape in the direction perpendicular to the longitudinal direction of the merged channel 23 is substantially rectangular. The width and depth of the merged path 23 are larger than those of the sample flow path 22. The sample channel 22 is connected to the central portion in the width direction of the junction 23B of the junction path 23, and is connected to the lower portion in the depth direction of the junction 23B of the junction path 23 (see fig. 7). In the present embodiment, the sheath liquid 80 is first caused to flow from the sheath liquid channel 21 into the junction portion 23B of the junction channel 23 (see fig. 12) so as not to waste the specimen 70. Then, the sample 70 flows into the sample channel 22 (see fig. 14).

On the downstream side of the merged part 23B of the merged path 23 in the flow direction (the direction of the arrow a), a wedge-shaped part 23C (see fig. 6 and 7) is provided in which the top surface 23X gradually approaches the bottom surface 23Y toward the downstream side in the upper wall part of the merged path 23. The wedge portion 23C includes a1 st inner wall 23E and a2 nd inner wall 23F opposite to the 1 st inner wall 23E. In the present embodiment, the 1 st inner wall 23E is disposed above the 2 nd inner wall. In other words, in the present embodiment, the wedge portion 23C has a shape in which the distance between the bottom surface 23Y and the top surface 23X, which are opposite wall surfaces, gradually decreases. That is, the portion of the top surface 23X of the wedge portion 23C becomes a wedge surface 23E inclined in a direction approaching the opposing wall surface as it goes from upstream to downstream. In the present embodiment, a wedge portion 23C is provided at a position adjacent to the merging portion 23B of the merging path 23. The wedge-shaped portion 23C is inclined at an angle of 2 to 8 °, for example, with respect to the plane direction of the flow cell 20 (the plane direction of the bottom surface 23Y in the present embodiment).

On the downstream side of the wedge portion 23C of the merged path 23 in the flow direction (the direction of arrow a), a flat portion 23D is formed that maintains the height of the downstream end of the wedge portion 23C. In other words, the distance between the top surface 23X and the bottom surface 23Y as the opposing wall surfaces in the flat portion 23D is shorter than the distance between the top surface 23X and the bottom surface 23Y as the opposing wall surfaces in the confluent portion 23B. The wedge portion 23C is configured to connect the merging portion 23B and the flat portion 23D.

In the flow cell 20, the sample 70 flows along the bottom surface 23Y of the sample channel 22 by arranging the bottom surface 23Y of the junction channel 23 and the bottom surface 22Y of the sample channel continuously on the same horizontal plane. The sheath liquid 80 merged from the sheath liquid channel 21 to the merging portion 23B flows while pressing the specimen 70 against the bottom surface 23Y (see fig. 15). The sample channel 22 may be provided so that the sample 70 flows along the bottom surface 23Y of each of the junction 23B, the wedge 23C, and the flat 23D, and the bottom surfaces 22Y and 23Y of the sample channel 22, the junction 23B, the wedge 23C, and the flat 23D may not be on the same horizontal plane. For example, the bottom surfaces 22Y and 23Y may be curved, or may have an angle therebetween.

A camera (see fig. 7) as the measurement unit 11 for imaging the specimen 70 is disposed at a position facing the flat portion 23D in the outer portion of the flow cell 20. That is, the flat portion 23D corresponds to the measurement flow path. The measurement unit 11 is disposed at a position where the specimen 70 flows in contact with the bottom surface 23Y. The cross-sectional area of the sheath fluid channel 21 is larger than that of the sample channel 22.

As shown in fig. 3 to 5, a waste liquid opening 23A through which a waste liquid 75 obtained by mixing the specimen 70 and the sheath liquid 80 is discharged is formed at the downstream end of the junction channel 23 in the flow direction (the direction of arrow a). The waste liquid opening 23A is connected to the waste liquid passage 36, and the waste liquid 75 is discharged from the waste liquid opening 23A to the outside through the waste liquid passage.

The flow cell 20 is preferably formed of a material having light transmittance (for example, a material having 90% or more visible light transmittance such as synthetic resin such as polymethyl methacrylate resin, cycloolefin polymer resin, polydimethylsiloxane resin, and polypropylene resin, or glass). The upper plate-like member 20A is formed with a merging channel 23, a sample channel 22, 2 sheath fluid channels 21, and the like by laser processing or the like. The flow cell 20 is formed by bonding the upper plate-like member 20A and the lower plate-like member 20B. In the present embodiment, the upper plate-like member 20A and the lower plate-like member 20B are bonded by thermocompression bonding, for example.

[ function frame ]

Fig. 8 shows a functional block diagram of the analysis device 10. The control unit 100 controls each part of the analyzer 10. The control unit 100 functions as a measurement control unit 111 that controls the measurement unit 11, a light source control unit 115 that controls the light source 15, a1 st pump control unit 141 that controls supply and suction of the liquid by the 1 st pump 41, a2 nd pump control unit 142 that controls supply and suction of the liquid by the 2 nd pump 42, a1 st valve control unit 151 that controls switching of the flow path of the 1 st valve 51, a2 nd valve control unit 152 that controls switching of the flow path of the 2 nd valve 52, and a 3 rd valve control unit 153 that controls switching of the flow path of the 3 rd valve 53, by a hardware configuration described later.

As shown in the hardware configuration of fig. 9, the control Unit 100 includes a CPU (Central Processing Unit) 101, a ROM (Read Only Memory) 102, a RAM (Random Access Memory) 103, and a Memory 104. The respective structures are connected to be able to communicate with each other via a bus 109.

The CPU101 is a central processing unit and can execute various programs and control each part. That is, the CPU101 reads out a program from the ROM102 or the storage 104, and executes the program with the RAM 103 as a work area. The CPU101 performs control of the above-described configurations and various arithmetic processes in accordance with programs recorded in the ROM102 or the memory 104.

The ROM102 stores various programs and various data. The RAM 103 temporarily stores programs or data as a work area. The storage 104 is formed of an HDD (Hard Disk Drive), an SSD (Solid State Drive), or a flash memory, and stores various programs including an operating system and various data. In the present embodiment, a program and various data related to measurement and determination are stored in the ROM102 or the memory 104. In addition, measurement data can also be stored in the memory 104.

By executing the program by the CPU101 in the hardware configuration, the control section 100 functions as the measurement control unit 111, the light source control unit 115, the 1 st pump control unit 141, the 2 nd pump control unit 142, the 1 st valve control unit 151, the 2 nd valve control unit 152, and the 3 rd valve control unit 153 shown in fig. 8 in the analysis device 10. The details of these functions will be described later.

[ operation of the analysis device 10 ]

The operation of the analyzer 10 according to the present embodiment will be described below with reference to fig. 10 to 15. Fig. 10 and 11 are flowcharts showing the operation of the analysis device according to the present embodiment. The respective parts of the analysis apparatus are shown in FIG. 1. In fig. 13, the flow direction of the liquid (or gas) is indicated by arrows marked near the respective pipes, and the direction colored black in the respective valves indicates the flow path.

Before the start of use, in the sheath liquid filling step S100 of fig. 10, each channel of the analyzer 10 is filled with the sheath liquid 80. First, the 1 st sheath fluid valve 54 is opened. Then, the 1 st valve control unit 151 conducts the flow path to the branch 1B and the branch 1C at the 1 st valve 51, the 2 nd valve control unit 152 conducts the flow path to the branch 2A and the branch 2C at the 2 nd valve 52, and the 3 rd valve control unit 153 conducts the flow path to the branch 3A and the branch 3C at the 3 rd valve 53.

In this state, the 1 st pump control unit 141 operates the 1 st pump 41 to supply the sheath liquid 80 to the 1 st channel 31. Thus, the sheath liquid 80 supplied from the sheath liquid supply portion 13 to the 1 st pump 41 via the 1 st sheath liquid valve 54 reaches the suction portion 12 from the 1 st pump 41 through the 3 rd valve 53, the 2 nd valve 52, and the 1 st valve 51, and is discharged from the tip thereof. That is, the branch 3A from the 1 st pump 41 to the 1 st channel 31, the branch 2A, the branch 1B, and the branch 1C from the 4 th channel 34 and the 2 nd channel 32 are filled with the sheath liquid 80.

Subsequently, the 1 st sheath liquid valve 54 and the 2 nd sheath liquid valve 55 are also opened. Then, the 1 st valve control unit 151 conducts the flow path to the branch 1A and the branch 1B at the 1 st valve 51, the 2 nd valve control unit 152 conducts the flow path to the branch 2A and the branch 2B at the 2 nd valve 52, and the 3 rd valve control unit 153 conducts the flow path to the branch 3A and the branch 3B at the 3 rd valve 53.

In this state, the 1 st pump control unit 141 operates the 1 st pump 41 to supply the sheath liquid 80 to the 1 st channel 31. Thus, the sheath liquid 80 supplied from the sheath liquid supply unit 13 to the 1 st pump 41 via the 1 st sheath liquid valve 54 passes from the 1 st pump 41 to the flow cell 20 via the 3 rd valve 53. That is, the 1 st channel 31 extending from the 1 st pump 41 to the flow cell 20 through the 3 rd valve 53 is entirely filled with the sheath liquid 80.

At the same time, the 2 nd pump control unit 142 operates the 2 nd pump 42 to supply the sheath liquid 80 to the 3 rd flow path 33. Thus, the sheath liquid 80 supplied from the sheath liquid supply unit 13 to the 2 nd pump 42 via the 2 nd sheath liquid valve 55 reaches the flow cell 20 from the 2 nd pump 42 through the 1 st valve 51 and the 2 nd valve 52. That is, the branches 1B, 2A, and 2B of the 2 nd pump 42 to the 3 rd channel 33 and the 2 nd channel 32 are also all filled with the sheath liquid 80.

In the flow cell 20, the sheath liquid 80 from the 1 st channel 31 passes through the sheath liquid opening 21A and fills the sheath liquid channel 21 branched into two. On the other hand, the sheath liquid 80 from the 2 nd channel 32 passes through the sample opening 22A to fill the sample channel 22. Then, the sheath liquids 80 on both sides are merged at the merging channel 23 to fill the merging channel 23, and pass through the waste liquid opening 23A to fill the waste liquid channel 36, and are discharged to the outside, not shown.

Through the above steps, each channel of the analyzer 10 is filled with the sheath liquid 80. Then, in the flow cell 20, as shown in the cross-sectional view of fig. 12, the 1 st pump control unit 141 stops the operation of the 1 st pump 41 in a state where the sample channel 22, the junction 23B, the wedge 23C, and the flat 23D are filled with the sheath liquid 80. Meanwhile, the 2 nd pump control unit 142 controls to stop the operation of the 2 nd pump 42. In this state, the feeding pressure of the sheath liquid 80 in the merged path 23 is substantially zero or extremely low.

Then, in the flow path switching step S110 of fig. 10, the 1 st valve control unit 151 leads the flow path to the branch 1B and the branch 1C at the 1 st valve 51, the 2 nd valve control unit 152 leads the flow path to the branch 2A and the branch 2C at the 2 nd valve 52, and the 3 rd valve control unit 153 leads the flow path to the branch 3A and the branch 3C at the 3 rd valve 53.

In this state, in the air suction step S120 of fig. 10, the 1 st pump control unit 141 operates the 1 st pump 41 to apply a negative pressure to the 1 st channel 31, and sucks the sheath liquid 80 from the branch 3A of the 1 st channel 31. Thereby, the air 90 is sucked from the suction portion 12. The sucked air 90 reaches the branch 1B from the branch 1C of the 2 nd flow path 32.

When the negative pressure is continuously applied to the 1 st channel 31 while maintaining this operation state and the suction unit 12 is immersed in the specimen 70 stored in the specimen storage unit 60, in the specimen suction step S130 in fig. 10, the specimen 70 is sucked by the suction unit 12 from the branch 1C of the 2 nd channel 32 to the branch 2C reaching the 4 th channel 34 through the branch 1B and the branch 2A. On the other hand, the entire amount of the air 90 sucked reaches the 4 th flow path 34 through the 2 nd valve 52. In this state, the 1 st pump control unit 141 stops the operation of the 1 st pump 41 and stops the application of the negative pressure to the 1 st flow path 31. Thereby, the entire amount of the air 90 sucked is sealed in the 4 th flow path 34.

Then, in the flow path switching step S140 of fig. 11, the 1 st valve control unit 151 leads the flow path to the branch 1A and the branch 1B at the 1 st valve 51, the 2 nd valve control unit 152 leads the flow path to the branch 2A and the branch 2B at the 2 nd valve 52, and the 3 rd valve control unit 153 leads the flow path to the branch 3A and the branch 3B at the 3 rd valve 53.

In this state, in the sample introduction step S150 in fig. 11, the 1 st pump 41 is kept stopped, and the 2 nd pump control unit 142 operates the 2 nd pump 42 to apply a positive pressure to the 3 rd channel 33 and supply the sheath liquid 80 to the 3 rd channel 33 again. Thereby, the sheath liquid 80 is caused to flow from the 2 nd pump 42 through the 1 st valve 51 and the 2 nd valve 52, and the sample 70 in the 2 nd channel 32 is pushed out to the flow cell 20. At this time, since the 1 st pump is not operated, the flow of the sheath liquid 80 from the 1 st channel 31 into the flow cell 20 is stopped.

In this state, in the junction 23B of the flow cell 20, as shown in the cross-sectional view of fig. 13, the specimen 70 flowing in from the specimen flow path 22 pushes out the sheath liquid 80 to the downstream, fills the junction 23B, and reaches the flat portion 23D. The liquid feeding pressure of the specimen 70 in the merged channel 23 at this time is naturally higher than the liquid feeding pressure of the sheath liquid 80 in the merged channel 23. That is, the control unit 100 controls the liquid feeding pressure of the specimen 70 fed by the 2 nd pump 42 in the merged channel 23 by the 2 nd pump control unit 142 so as to be higher than the liquid feeding pressure of the sheath liquid 80 fed by the stopped 1 st pump 41 in the merged channel 23. In the present embodiment, the 1 st pump 41 is stopped until the specimen 70 reaches the flat portion 23D, and the sheath liquid 80 is not fed to the merged channel 23, but the present invention is not limited to this. That is, the control unit 100 may operate the 1 st pump 41 by the 1 st pump control unit 141 to feed the sheath liquid 80 so that the feeding pressure of the sheath liquid 80 fed by the 1 st pump 41 in the merged channel 23 is lower than the feeding pressure of the specimen 70 fed by the 2 nd pump 42 by the 2 nd pump control unit 142 in the merged channel 23.

Then, in the sample pressing step S160 in fig. 11, as shown in fig. 14, the 2 nd pump control unit 142 operates the 2 nd pump 42, and the 1 st pump control unit 141 restarts the operation of the 1 st pump 41, so that the sheath liquid 80 restarts to flow from the 1 st channel 31 into the flow cell 20. That is, the sheath liquid 80 in the 1 st channel 31 is once branched into 2 sheath liquid channels 21 after flowing into the flow cell 20 from the sheath liquid opening 21A, and then merged with the specimen 70 at the merging channel 23.

In this state, in the junction 23B of the flow cell 20, as shown in the cross-sectional view of fig. 15, the specimen 70 and the sheath liquid 80 are merged, but the sheath liquid 80 in the sheath liquid channel 21 flows in and merges along the top surface 23X on the upper side of the specimen 70 flowing in along the bottom surfaces 22Y, 23Y, and therefore mixing of the specimen 70 and the sheath liquid 80 is suppressed. At this time, the control unit 100 controls the liquid feeding pressure of the 1 st pump 41 by the 1 st pump control unit 141 and controls the liquid feeding pressure of the 2 nd pump 42 by the 2 nd pump control unit 142 such that the liquid feeding pressure of the sheath liquid 80 in the merged channel 23 becomes larger than the liquid feeding pressure of the specimen 70 in the merged channel 23. That is, the control unit 100 controls the pressure at which the 1 st pump 41 feeds the sheath liquid to the junction channel 23 to be higher than the pressure at which the 2 nd pump 42 feeds the specimen to the junction channel 23.

Here, the sample channel 22 is provided along the bottom surface 23Y of the junction 23B, and thus the sample 70 flowing in from the sample channel 22 flows along the bottom surface 23Y of the junction channel 23 in the direction of the arrow a 1. Further, the sheath liquid channel 21 is provided along the wall surface provided with the wedge surface 23E, that is, the ceiling surface 23X, and thus the sheath liquid 80 introduced from the sheath liquid channel 21 flows into the junction portion 23B along the ceiling surface 23X of the junction channel 23. The top surface 23X of the merged channel 23 is provided with a wedge portion 23C gradually approaching the bottom surface 23Y toward the downstream. Thus, as shown in fig. 15, in the merged channel 23, the sheath liquid 80 flowing from the sheath liquid channel 21 into the merged part 23B flows along the wedge surface 23E of the wedge part 23C, and flows in the direction of the arrow a2 to press the specimen 70 against the bottom surface 23Y of the merged channel 23. Therefore, as shown in fig. 15, in the wedge-shaped portion 23C of the merging path 23, the sheath liquid 80 presses the specimen 70 from above, whereby the specimen 70 extends flatly along the bottom surface 23Y, and the thickness gradually decreases and the width gradually increases. At this time, the specimen 70 flows in contact with the bottom surface 23Y. Thus, the specimen 70 flows along the bottom surface at the upstream portion of the flat portion 23D of the merging path 23, and the thickness of the specimen 70 is reduced and the width thereof is increased. The thickness of the specimen 70 at this time is, for example, about 5 to 30 μm. That is, when the thickness of the specimen 70 is minimized, the measurement unit 11 is disposed at a position from the wedge portion 23C to the flat portion 23D as shown in fig. 7. Further, a light source 15 is disposed at a position facing the measurement unit 11 via the flow cell 20.

Then, in the specimen measurement step S170 in fig. 11, the specimen 70 pressed by the sheath liquid 80 is measured by the measurement unit 11 controlled by the measurement control unit 111 by the illumination of the light source 15 whose light amount is adjusted by the light source control unit 115.

As described above, since the specimen 70 flows in contact with the bottom surface 23Y, the sheath liquid 80 is not interposed between the measurement unit 11 and the specimen 70, and the specimen 70 can be measured without being affected by the sheath liquid 80. The specimen 70 extends along the bottom surface 23Y in a flat shape and has a gradually reduced thickness, and therefore, is useful when the shape and size of the visible component contained in the specimen 70 are observed using an imaging device as the measurement unit 11.

In the liquid discharge step S180 in fig. 11, the waste liquid 75 obtained by mixing the body 70 and the sheath liquid 80 in the merged channel 23 passes through the waste liquid opening 23A and is discharged from the waste liquid channel 36 to the outside, not shown.

In the flow cell 20 of the present embodiment, the flow rate of the sheath liquid 80 in the sample 70 and the sheath liquid channel 21 is controlled. The flow ratio between the sample 70 and the sheath liquid 80 is set to 1: 20 to 40. By controlling the flow rate ratio between the specimen 70 and the sheath liquid 80, the width and thickness of the specimen 70 flowing through the merged channel 23 are controlled.

Industrial applicability

The present invention can be used for a liquid feeding method for feeding a sample to a flow cell and a sample analyzer using the method.