Liquid delivery method and analytical device

Abstract

The present application provides a liquid delivery method and an analysis apparatus. A sample is extruded by a sheath liquid to one wall surface of a flow cell to make the sample flow so that the sample reliably contacts the wall surface and flows at a shooting position. The liquid delivery method is a liquid delivery method for delivering a sample to a flow cell having a wedge portion with a wedge surface that is an inner wall inclined so as to approach an opposite inner wall toward a downstream, and a measurement flow path provided downstream of the wedge portion, the sample and the sheath liquid both flowing in the wedge portion, the liquid delivery method having a sample introduction step of delivering the sample to the wedge portion along the inner wall opposite to the wedge surface until the sample reaches the measurement flow path, and a sample extrusion step of delivering the sheath liquid to the wedge portion along the wedge surface after the sample reaches the measurement flow path.

Description

TECHNICAL FIELD

[0001] The present application relates to a liquid feeding method for feeding a sample to a flow cell, and an analysis apparatus using the same. BACKGROUND

[0002] Patent Literature 1 and Patent Literature 2 disclose a flow cell having a sheath liquid flow path through which a sheath liquid flows, a sample flow path through which a sample of a liquid flows, and a merging path at which the sheath liquid flow path and the sample flow path merge and imaging of a formed component contained in the sample is performed.

[0003] Patent Literature 1: Japanese Patent Application Publication No. 2018-112516

[0004] Patent Literature 2: Japanese Patent Application Publication No. 2019-7893

[0005] In the technology described in Patent Literature 2, in the merging path, the sample flowing from the sample flow path is flattened and pressed against the lower surface of the flow cell by the sheath liquid flowing from the sheath liquid flow path, with the aim of imaging the formed component of the sample by a photographing device opposite the lower surface of the flow cell. However, there are cases in which the sample becomes a state in which it is not pressed against the bottom surface, and the sheath liquid intervenes between the sample and the photographing device, so that there are cases in which clear imaging of the formed component is difficult. SUMMARY

[0006] Therefore, the object of the embodiments of the present application is to enable the sample to reliably contact the one wall surface of the flow cell and flow at the imaging position in a flow cell in which the sample is pressed against the one wall surface of the flow cell by the sheath liquid and flows.

[0007] The liquid feeding method of the present disclosure is a liquid feeding method for feeding a sample to a flow cell, the flow cell having a wedge-shaped portion having a wedge surface that is an inner wall inclined so as to approach an opposite inner wall as it goes downstream, and a measurement flow path provided downstream of the wedge-shaped portion, the sample and a sheath liquid both flowing in the wedge-shaped portion, the liquid feeding method having the steps of:

[0008] a sample introduction step of feeding the sample to the wedge-shaped portion along the inner wall opposite the wedge surface until the sample reaches the measurement flow path; and

[0009] a sample pressing step of feeding the sheath liquid to the wedge-shaped portion along the wedge surface after the sample reaches the measurement flow path.

[0010] The analysis apparatus of the present disclosure has:

[0011] a flow cell having a wedge portion and a measurement flow path 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 toward the downstream, both a sample and a sheath liquid flowing in the wedge portion;

[0012] a sheath liquid delivery unit that delivers the sheath liquid along the wedge surface;

[0013] a sample delivery unit that delivers the sample along the inner wall opposite to the wedge surface;

[0014] a measurement unit that measures the sample flowing in the measurement flow path; and

[0015] a control unit that controls the sample delivery unit to deliver the sample along the inner wall opposite to the wedge surface until the sample reaches the measurement flow path, and controls the sheath liquid delivery unit to deliver the sheath liquid along the wedge surface after the sample reaches the measurement flow path.

[0016] In an embodiment of the present application, in a flow cell in which a sample is caused to flow by being pressed against a wall surface of the flow cell with a sheath liquid, the sample is caused to reliably contact the wall surface and flow at a photographing position. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 is a schematic view of an analysis device of an embodiment of the present disclosure.

[0018] Figure 2 is a perspective view schematically showing a positional relationship between a flow cell and a measurement unit in an analysis device of the embodiment.

[0019] Figure 3 is a perspective view of a flow cell of the embodiment.

[0020] Figure 4 is a plan view of the flow cell of the embodiment.

[0021] Figure 5 is an exploded perspective view of the flow cell of the embodiment.

[0022] Figure 6 is an enlarged perspective view of a vicinity of a junction of a sample and a sheath fluid of the flow cell of the embodiment.

[0023] Figure 7 is a sectional view of the flow cell of the embodiment.

[0024] Figure 8 is a functional block diagram of the analysis device of the embodiment.

[0025] Figure 9 a hardware structure of the control unit is shown in a block diagram.

[0026] Figure 10 is a flowchart showing the operation of the analysis device of the present embodiment.

[0027] Figure 11 is a flowchart showing the operation of the analysis device of the present embodiment.

[0028] Figure 12 is a cross-sectional view of the vicinity of the confluence portion of the flow cell.

[0029] Figure 13 is a cross-sectional view of the vicinity of the confluence portion of the flow cell.

[0030] Figure 14 is a schematic diagram showing the operation of the analysis device of the present embodiment.

[0031] Figure 15 is a cross-sectional view of the vicinity of the confluence portion of the flow cell.

[0032] Explanation of Reference Signs

[0033] 10: analysis device; 11: measurement unit; 12: suction portion; 13: sheath liquid supply portion; 14: housing; 14A: recess; 15: light source; 20: flow cell; 20A: upper plate-like member; 20B: lower plate-like member; 20C: lower surface (of the upper plate-like member); 20D: upper surface (of the lower plate-like member); 21: sheath liquid flow path; 21A: sheath liquid opening; 21B: curved portion; 21C: curved portion; 21D: sheath liquid inflow hole; 21X: top surface (of the sheath liquid flow path); 21Y: bottom surface (of the sheath liquid flow path); 22: sample flow path; 22A: sample opening; 22B: sample inflow port; 22X: top surface (of the sample flow path); 22Y: bottom surface (of the sample flow path); 23: confluence path; 23A: waste liquid opening; 23B: confluence portion; 23C: wedge-shaped portion; 23D: flat portion (measurement flow path); 23E: wedge surface; 23X: top surface (of the confluence path); 23Y: bottom surface (of the confluence path); 24: end surface. DETAILED DESCRIPTION

[0034] Embodiments of the present disclosure are described below. Note that the reference signs given to each structure in the following description correspond to those described in the drawings, but the present disclosure is of course not limited to this. Furthermore, in the present disclosure, in each flow path, the side close to the inflow source of the liquid is referred to as "upstream", and the side close to the outflow destination of the liquid is referred to as "downstream".

[0035] <Method of feeding sample 70>

[0036] [1st Mode]

[0037] The first aspect of the present disclosure is a liquid delivery method for delivering a sample 70 to a flow cell 20, the flow cell 20 having: a merging path 23 through which the sample 70 and a sheath liquid 80 flow; a sample flow path 22 that introduces the sample 70 to the merging path 23; and at least one sheath liquid flow path 21 that introduces the sheath liquid 80 to the merging path 23, the merging path 23 having: a merging portion 23B at which the sample flow path 22 and the sheath liquid flow path 21 merge; a flat portion 23D disposed on a downstream side of the merging portion 23B, formed along one of opposite wall surfaces of the merging portion 23B, the distance between the opposite wall surfaces being shorter than the merging portion 23B; and a wedge-shaped portion 23C that connects the merging portion 23B and the flat portion 23D, the distance between the opposite wall surfaces gradually shortening toward the downstream, and the sheath liquid flow path 21 introducing the sheath liquid 80 to the merging portion 23B along a wall surface in which a wedge surface (first inner wall) 23E is provided in the wedge-shaped portion 23C, the sample flow path 22 introducing the sample 70 to the merging portion 23B along a wall surface (second inner wall 23F) opposite to the wall surface in which the wedge surface 23E is provided.

[0038] In other words, the liquid delivery method for the sample 70 of the present aspect uses the flow cell 20 having the sheath liquid flow path 21, the sample flow path 22, and the merging path 23. The merging path 23 of the flow cell 20 has the merging portion 23B, the wedge-shaped portion 23C, and the flat portion 23D from the upstream side. The wedge-shaped portion 23C has the wedge surface 23E that is inclined toward a direction in which the opposite wall surfaces approach each other as it progresses from the upstream to the downstream. Also, in the merging portion 23B of the merging path 23 of the flow cell 20, the sheath liquid 80 is introduced to the merging portion 23B from the side of the wall surface in which the wedge surface 23E is provided. Then, the sheath liquid 80 flows from the upstream to the downstream along the wedge surface 23E, thereby generating a force that presses the sample 70 to be described later against the wall surface opposite to the wedge surface 23E. Thus, the sample 70 introduced to the merging portion 23B is pressed against the wall surface on the side opposite to the wall surface in which the wedge surface 23E is provided, that is, the side to which the sample 70 is to be pressed by the flow of the sheath liquid 80 along the wedge surface 23E, by the sheath liquid 80.

[0039] Here, the liquid delivery method for the sample 70 of the present aspect includes the following steps: a sample introduction step of delivering the sample 70 to the wedge-shaped portion 23C along the inner wall opposite to the wedge surface 23E at a higher liquid delivery pressure of the sample 70 in the merging path 23 than a liquid delivery pressure of the sheath liquid 80 in the merging path 23 until the sample 70 reaches the flat portion 23D as a measurement flow path; and a sample pressing step of delivering the sheath liquid 80 to the wedge-shaped portion 23C along the wedge surface 23E after the sample 70 reaches the flat portion 23D as the measurement flow path.

[0040] That is, until the sample 70 reaches the flat portion 23D as the measurement flow path, as the sample introduction step, the sample 70 is delivered to the sample flow path 22 and the sheath liquid 80 is delivered to the sheath liquid flow path 21 in such a manner that the liquid delivery pressure of the sample 70 in the merging path 23 is higher than the liquid delivery pressure of the sheath liquid 80 in the merging path 23. Assuming that the liquid delivery pressure of the sample 70 in the merging path 23, that is, in the merging path 23 in which both the sample 70 and the sheath liquid 80 flow, is lower than the liquid delivery pressure of the sheath liquid 80 until the sample 70 reaches the flat portion 23D, the sample 70 flows in the center portion of the laminar flow of the sheath liquid 80 in which the liquid delivery pressure is lower. Also, the sample 70 flows apart from the wall surface opposite to the wall surface provided with the wedge surface 23E, that is, the wall surface on the side to which the sample 70 is to be pressed by the sheath liquid 80 flowing along the wedge surface 23E. Therefore, until the sample 70 reaches the flat portion 23D, by making the liquid delivery pressure of the sample 70 in the merging path 23 higher than the liquid delivery pressure of the sheath liquid 80, it is possible to make the sample 70 reach the flat portion 23D along the wall surface opposite to the wall surface provided with the wedge surface 23E without being affected by the delivery of the sheath liquid 80.

[0041] Also, after the sample 70 reaches the flat portion 23D, as the sample pressing step, the sample 70 is delivered to the sample flow path 22 and the sheath liquid 80 is delivered to the sheath liquid flow path 21 in such a manner that the liquid delivery pressure of the sample 70 in the merging path 23 is lower than the liquid delivery pressure of the sheath liquid 80 in the merging path 23. That is, the liquid delivery pressure of the sample 70 in the merging path 23 in which both the sample 70 and the sheath liquid 80 flow is lower than the liquid delivery pressure of the sheath liquid 80 flowing in the merging path 23. Therefore, the sample 70 is pressed by the sheath liquid 80 having a higher liquid delivery pressure to the wall surface 23Y opposite to the wall surface 23X provided with the wedge surface 23E and is delivered to the flat portion 23D along the wall surface. At this time, the liquid delivery pressure of the sample 70 in the merging path 23 is lower than the liquid delivery pressure of the sheath liquid 80 in the merging path 23, so although the sample 70 is to flow apart from the wall surface 23Y opposite to the wall surface 23X provided with the wedge surface 23E, the sample 70 flows along one of the opposite wall surfaces because it is pressed by the sheath liquid 80 having a higher liquid delivery pressure in the merging path 23. Further, the sample 70 extends in a flattened manner in which the thickness thereof is reduced along the wall surface opposite to the wall surface provided with the wedge surface 23E. Thus, in the flat portion 23D, it is possible to easily perform the measurement and observation of the sample 70. As long as it is after the above-described sample introduction step, it is possible to shift to the above-described sample pressing step at any time point.

[0042] In the above-described sample introduction step, the sample 70 and the sheath liquid 80 can flow in the flattened portion 23D in a state where the liquid delivery pressure of the sample 70 in the merging path 23 is higher than the liquid delivery pressure of the sheath liquid 80 in the merging path 23. For example, in the flattened portion 23D, in a case where the sample 70 has reached the flattened portion 23D, but the liquid delivery pressure of the sample 70 flowing in the merging path 23 is lower than the liquid delivery pressure of the sheath liquid 80, the liquid delivery pressure of the sample 70 can be increased to flow the sample 70 in the flattened portion 23D, and after the sample 70 delivered by the increased liquid delivery pressure has reached the flattened portion 23D, the liquid delivery pressure of the sample 70 can be made lower than the liquid delivery pressure of the sheath liquid 80.

[0043] Here, the liquid delivery pressure of the sample 70 in the merging path 23 and the liquid delivery pressure of the sheath liquid 80 can be controlled by any unit. For example, a pressure sensor or the like can be provided in the merging path 23 to measure the liquid delivery pressure in the merging path 23, and based on the measurement result, the output of a device (e.g., a pump) that causes the sheath liquid 80 or the sample 70 to flow into the sheath liquid flow path 21 or the sample flow path 22 can be adjusted. Further, the actual liquid delivery pressures in the sheath liquid flow path 21 and the sample flow path 22 can be measured by a pressure sensor or the like, and based on the ratio of the cross-sectional area of the flow paths of the sheath liquid flow path 21 and the sample flow path 22 to the cross-sectional area of the merging path 23, the liquid delivery pressure of the merging path 23 can be calculated and controlled. Further, the control of the liquid delivery pressure is performed as follows: a control unit provided in the device measures the liquid delivery pressures of the merging path 23, the sheath liquid flow path 21, the sample flow path 22, and the like, and based on the result, the output of a pump or the like that flows into the device is controlled.

[0044] As described above, by the sample extrusion step, the sample 70 extends in a flattened manner in which the thickness is reduced along the wall surface opposite to the wall surface provided with the wedge-shaped surface 23E. Therefore, after the sample extrusion step, a measurement step of measuring the sample 70 flowing in the flattened portion 23D can be performed. The measurement unit 11 used for the measurement of the sample 70 is not limited, and a unit corresponding to the measurement item can be used. For example, a spectrophotometer, an optical unit using a camera, or the like, or an electrical unit such as a sensor can be used. The measurement of the sample also includes observation and imaging of an image captured by a camera or the like.

[0045] The measurement unit 11 is preferably provided at a position adapted to measure the sample 70 extending in a flattened manner. Specifically, the sample 70 extends in a flattened manner as it flows from the wedge surface 23E to the flat portion 23D. Therefore, the measurement unit 11 can be provided at a position opposite to the flat portion 23D or the wedge portion 23C, or at a position opposite to the position of the wedge portion 23C to the flat portion 23D. The sample 70 extends in the most flattened manner at the position from the wedge portion 23C to the flat portion 23D. Therefore, it is preferable to provide the measurement unit 11 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, the sample 70 flows along a wall surface 23Y opposite to a wall surface 23X provided with the wedge surface 23E, and therefore it is preferable to provide the measurement unit 11 at a position opposite to the sample 70 across the wall surface. This is because the measurement unit 11 is able to measure the sample 70 without being affected by the sheath liquid 80, with no sheath liquid 80 interposed between the measurement unit 11 and the sample 70. In addition, the flow path connected to the downstream of the wedge portion 23C, and in which the sample to be measured by the measurement unit 11 flows, corresponds to a measurement flow path. For example, in the case where the measurement unit 11 is provided at a position opposite to the upstream portion of the flat portion 23D, the flat portion 23D becomes the measurement flow path. Also, for example, in the case where the measurement unit 11 is provided at a position opposite to an intermediate portion between the upstream portion and the downstream portion of the wedge portion 23C, the intermediate portion is the measurement flow path.

[0046] Before the above measurement step, a step of measuring the liquid feeding pressure of the sample in the flow path and determining whether the liquid feeding pressure indicates a certain range can also be implemented. In a case where the liquid feeding pressure when the sample 70 is introduced into the merging path 23 in the sample introduction step is different from the liquid feeding pressure when the sample 70 is introduced into the merging path 23 in the sample extrusion step, the liquid feeding pressure immediately after the transition to the sample extrusion step is unstable. For example, in the sample introduction step, in order to rapidly introduce the sample 70 into the sample flow path 22, 23 of the flow cell 20, the sample is sometimes transported at a higher liquid feeding pressure than the liquid feeding pressure when the sample 70 is introduced in the sample extrusion step. That is, the liquid feeding pressure of the sample 70 in the merging path 23 in the sample introduction step is sometimes greater than the liquid feeding pressure of the sample 70 in the merging path 23 in the sample extrusion step. In this case, after the transition from the sample introduction step to the sample extrusion step, the liquid feeding pressure of the sample 70 in the merging path 23 is sometimes unstable and higher than the liquid feeding pressure when the sample 70 is introduced in the sample extrusion step. When the measurement of the sample 70 is implemented in this state, the measurement accuracy deteriorates. Therefore, in a case where the liquid feeding pressure of the sample 70 in the merging path 23 for a certain period is measured and is within a certain liquid feeding pressure range, the transition to the measurement step is made. On the other hand, in a case where it is not within the certain pressure range, the transport of the sheath liquid 80 and the sample 70 for a certain period is continued, and the liquid feeding pressure of the sample 70 in the merging path 23 for a certain period is measured again, and then it is determined whether to transition to the measurement step. Thus, even if the liquid feeding pressure of the sample 70 in the merging path 23 in the sample introduction step is greater than the liquid feeding pressure of the sample 70 in the merging path 23 in the sample extrusion step, the deterioration of the measurement accuracy can be avoided. Also, in the sample introduction step, the sample 70 can be rapidly introduced into the sample flow path 22, 23 of the flow cell 20.

[0047] Further, it can be determined whether the sample 70 has reached the flat portion 23D based on whether the measurement unit 11 provided at the flat portion 23D detects a certain attribute (e.g., the color of a liquid, a certain component) of the sample 70. Alternatively, a sensor capable of detecting the sample 70 can be provided at the flat portion 23D, and the determination can be made based on the reaction of the sensor.

[0048] [2nd Mode]

[0049] In the 2nd mode of the sample 70 liquid feeding method of the present disclosure, a flow cell 20 having the same structure as the 1st mode is also adopted.

[0050] Here, the sample 70 delivery method of the present embodiment, after the merging path 23 is filled with the sheath liquid 80, includes the sample introduction step and the sample extrusion step of the above-described first embodiment, and the delivery of the sheath liquid 80 to the sheath liquid flow path 21 is stopped in the sample introduction step. That is, the delivery of the sheath liquid 80 to the sheath liquid flow path 21 is stopped in a state where the sheath liquid 80 is delivered to the sheath liquid flow path 21 and the merging path 23 (the merging portion 23B, the flat portion 23D, and the wedge portion 23C) is filled with the sheath liquid 80. In this state where the delivery of the sheath liquid 80 to the sheath liquid flow path 21 is stopped, the sample 70 is delivered to the sample flow path 22 until the sample 70 reaches the flat portion 23D as the sample introduction step. Further, after the sample 70 reaches the flat portion 23D, that is, in the sample extrusion step, the sample 70 is delivered to the sample flow path 22 and the sheath liquid 80 is delivered to the sheath liquid flow path 21 in a manner that the delivery pressure of the sample 70 in the merging path 23 is lower than the delivery pressure of the sheath liquid 80 in the merging path 23.

[0051] That is, in the sample introduction step, the delivery pressure of the sheath liquid 80 in the merging path 23 is substantially zero or extremely low.

[0052] Further, in this state, the sample 70 flows into the sample flow path 22 until the sample 70 reaches the flat portion 23D. At this time, as described above, the delivery pressure of the sheath liquid 80 in the merging path 23 is substantially zero or extremely low, and thus the delivery pressure of the sample 70 in the merging path 23 is necessarily higher than the delivery pressure of the sheath liquid 80 in the merging path 23.

[0053] Further, after the sample 70 reaches the flat portion 23D, the sample 70 and the sheath liquid 80 are delivered in the same manner as the sample extrusion step of the above-described first embodiment, so that the observation of the sample 70 can be easily performed.

[0054] The other is the same as the first embodiment.

[0055] <Analysis device 10 of sample 70>

[0056] The analysis device 10 of the specimen 70 of the second aspect of the present disclosure employs a flow cell 20 having: a merging path 23 through which the specimen 70 and a sheath liquid 80 flow; a specimen flow path 22 that introduces the specimen 70 to the merging path 23; and at least one sheath liquid flow path 21 that introduces the sheath liquid 80 to the merging path 23, the merging path 23 having: a merging portion 23B at which the specimen flow path 22 and the sheath liquid flow path 21 merge; a flat portion 23D disposed on a downstream side of the merging portion 23B, formed along one of opposite wall surfaces of the merging portion 23B, the distance between the opposite wall surfaces being shorter than the merging portion 23B; and a wedge portion 23C that connects the merging portion 23B and the flat portion 23D, the distance between the opposite wall surfaces gradually shortening toward the downstream, the sheath liquid flow path 21 introducing the sheath liquid 80 to the merging portion 23B from the other of the opposite wall surfaces of the merging portion 23B.

[0057] That is, the significance and structure of the flow cell 20 in the present aspect are the same as those in the above-described liquid delivery method of the specimen 70.

[0058] Further, the analysis device 10 of the specimen 70 of the present aspect has: a measurement unit 11 disposed at a position opposite the flat portion 23D, a first flow path 31 connected to an upstream of the sheath liquid flow path 21, a first pump 41 that supplies the sheath liquid 80 to the flow cell 20 through the first flow path 31, a second flow path 32 connected to an upstream of the specimen flow path 22, a second pump 42 that supplies the specimen 70 to the flow cell 20 through the second flow path 32, and a control unit 100 that controls the first pump 41 and the second pump 42.

[0059] Further, in the analysis device 10 of the specimen 70 of the present aspect, the control unit 100 controls the first pump 41 and the second pump 42 so that the liquid delivery pressure of the specimen 70 in the merging path 23 is higher than the liquid delivery pressure of the sheath liquid 80 in the merging path 23 before the specimen 70 reaches the flat portion 23D.

[0060] For example, before the specimen 70 reaches the flat portion 23D, the control unit 100 controls the first pump 41 and the second pump 42 so that the liquid delivery pressure of the specimen 70 in the merging path 23 is higher than the liquid delivery pressure of the sheath liquid 80 in the merging path 23, and the specimen 70 is transported to the specimen flow path 22 and the sheath liquid 80 is transported to the sheath liquid flow path 21. That is, the pressure with which the second pump 42 transports the specimen 70 to the merging path 23 is higher than the pressure with which the first pump 41 transports the sheath liquid 80 to the merging path 23. The technical significance of such control to introduce the specimen 70 and the sheath liquid 80 to the flow cell 20 is the same as that described in the above-described first aspect, and thus the description is omitted.

[0061] Also, after the sample 70 reaches the flat portion 23D, that is, in a state where the sample 70 has reached the flat portion 23D, the control section 100 controls the first pump 41 and the second pump 42 so that the liquid delivery pressure of the sample 70 in the merging path 23 is lower than the liquid delivery pressure of the sheath liquid 80 in the merging path 23, and the sample 70 is delivered to the sample flow path 22 and the sheath liquid 80 is delivered to the sheath liquid flow path 21. That is, the pressure at which the second pump 42 delivers the sample 70 to the merging path 23 is lower than the pressure at which the first pump 41 delivers the sheath liquid 80 to the merging path 23. The technical significance of conducting such control to introduce the sample 70 and the sheath liquid 80 to the flow cell 20 is the same as that described in the first mode, and thus the description is omitted.

[0062] Here, the liquid delivery pressure of the sample 70 in the merging path 23 and the liquid delivery pressure of the sheath liquid 80 can be controlled by any means. The control means is the same as that described in the first mode, and thus the description is omitted.

[0063] Further, the technical significance of making the liquid delivery pressure of the sample 70 in the merging path 23 in the sample introduction step greater than the liquid delivery pressure of the sample 70 in the merging path 23 in the sample extrusion step is the same as that described in the first mode, and thus the description is omitted.

[0064] Further, the means for determining whether the sample 70 has reached the flat portion 23D is the same as that described in the first mode, and thus the description is omitted.

[0065] In addition, in the present mode, the "opposite wall surface" is the top surface 23X and the bottom surface 23Y of the merging path 23, and the sample 70 is extruded by the sheath liquid 80 from the upper side to the "wall surface opposite to the wall surface provided with the wedge-shaped surface 23E", that is, the bottom surface 23Y, but the sample liquid delivery method of the present disclosure and the analysis device 10 of the sample 70 are not limited to this mode. For example, it can also be that the "wall surface opposite to the wall surface provided with the wedge-shaped surface 23E" is provided as the upper side surface of the merging path 23, and the sample 70 is extruded by the sheath liquid 80 from the lower side to the upper side surface. Or, it can also be that the "opposite wall surface" is set as the left and right opposite wall surfaces, and any one of the left and right, for example, the left side surface is set as the "wall surface opposite to the wall surface provided with the wedge-shaped surface 23E", and the sample is extruded by the sheath liquid 80 from the right side to the left side surface.

[0066] <EMBODIMENT>

[0067] Hereinafter, an embodiment of the present disclosure will be described with reference to the drawings.

[0068] Figure 1An embodiment of the analysis device 10 that schematically shows the specimen 70 is shown. In this embodiment, a first flow path 31 and a second flow path 32 are connected as flow paths that flow into the flow cell 20. Further, a waste liquid path 36 is connected as a flow path that flows out from the flow cell 20.

[0069] [Structure of analysis device 10]

[0070] The sheath liquid 80 is supplied from the first pump 41 to the first flow path 31 (refer to FIG. 1). Figure 13 Further, at the end of the most upstream end of the second flow path 32, a suction portion 12 that is formed as a nozzle is installed. As described later, the suction portion 12 is a portion that sucks the specimen 70 from the specimen housing portion 60 that houses the specimen 70 by the first pump 41. A first valve 51 that is a three-way valve is provided midway through the second flow path 32. A third flow path 33 is connected to the second flow path 32 via the first valve 51. The sheath liquid 80 is supplied from the second pump 42 to the third flow path 33. In this embodiment, both the first pump 41 and the second pump 42 are plunger pumps, and it is also possible to suck the sheath liquid 80 from the first flow path 31 and the third flow path 33, respectively. Alternatively, a pump that does not have a suction function but only has a liquid delivery function, such as a tube pump, can be used as the second pump 42.

[0071] The sheath liquid supply portion 13 is a tank that stores the sheath liquid 80 to be supplied to the flow cell 20 by the first pump 41 and the second pump 42. A tube that is connected to the first pump 41 and the second pump 42, that is, a sheath liquid supply path 35 is provided so as to extend from the sheath liquid supply portion 13. In the sheath liquid supply path 35, a first sheath liquid valve 54 is provided between the sheath liquid supply portion 13 and the first pump 41, and a second sheath liquid valve 55 is provided between the sheath liquid supply portion 13 and the second pump 42. Both the first sheath liquid valve 54 and the second sheath liquid valve 55 are one-way opening and closing valves.

[0072] Further, in this embodiment, in the first flow path 31, the second flow path 32, and the third flow path 33, the side toward the flow cell 20 is defined as the downstream side, and the opposite side is defined as the upstream side.

[0073] Further, in this embodiment, in the first flow path 31, the second flow path 32, and the third flow path 33, the side toward the flow cell 20 is defined as the downstream side, and the opposite side is defined as the upstream side.

[0074] The first flow path 31, the second flow path 32, the third flow path 33, the fourth flow path 34, the sheath liquid supply path 35, and the waste liquid path 36 are each composed of a tube (for example, a Teflon (registered trademark) tube) that has flexibility and softness.

[0075] Here, in the three-way flow path that merges with the first valve 51, the side of the third flow path 33 is referred to as branch 1A, the downstream side of the second flow path 32 is referred to as branch 1B, and the upstream side of the second flow path 32 is referred to as branch 1C. Furthermore, in the three-way flow path that merges with the second valve 52, the upstream side of the second flow path 32 is referred to as branch 2A, the downstream side of the second flow path 32 is referred to as branch 2B, and the fourth flow path 34 is referred to as branch 2C. Also, in the three-way flow path that merges with the third valve 53, the upstream side of the first flow path 31 is referred to as branch 3A, the downstream side of the first flow path 31 is referred to as branch 3B, and the fourth flow path 34 is referred to as branch 3C.

[0076] <Circulation Pool 20>

[0077] like Figure 2 As shown, the flow cell 20 is mounted in a suitable recess 14A of the housing 14 within the analytical apparatus 10. The light source 15 and the measuring unit 11 are positioned across the flow cell 20 along the confluence path 23, specifically from the wedge-shaped portion 23C to the flat portion 23D (see reference). Figure 7 At the opposite position, the wedge-shaped portion 23C has a wedge-shaped surface 23E as an inclined surface. The light source 15 illuminates the sample 70 flowing in the confluence path 23. The measuring unit 11 measures the sample 70 flowing in the confluence path 23 together with the sheath fluid 80. That is, the measuring unit 11 measures the sample 70 flowing in the flow path opposite to the measuring unit 11 in the portion of the flow path opposite to the measuring unit 11 across the bottom surface 23Y in the confluence path 23. The sample 70, squeezed by the sheath fluid 80 flowing along the wedge-shaped surface 23E, flows in the flow path of this portion. Therefore, in this manner, the flow path of this portion corresponds to the measuring flow path provided downstream of the wedge-shaped portion 23C. In addition, the measurement described herein also includes quantitatively or qualitatively detecting specific components of the sample 70 by means of an optical measuring unit (e.g., a spectrophotometer) serving as the measuring unit 11, and observing or photographing the specific components of the sample 70 as an image using another measuring unit 11, such as a camera. Furthermore, the measuring unit 11 is positioned close to the bottom surface 23Y, which is the wall surface opposite to the top surface 23X, which has a wedge-shaped surface 23E.

[0078] Figure 3 The flow cell 20 of this embodiment is shown in a three-dimensional view. Figure 4 The flow cell 20 is shown in a top view. Furthermore... Figure 5 The flow cell 20 is shown in an exploded perspective view. Furthermore, in... Figure 6In the middle, the vicinity of the merging portion 23B of the flow cell 20 is shown in an enlarged state by a perspective view. In addition, the arrow H shown in the drawing appropriately indicates the height direction of the flow cell 20, and the arrow W indicates the width direction of the flow cell 20. Further, in the drawing, the arrow L indicates the length direction of the flow cell 20 which is perpendicular to the height direction and the width direction, respectively (the arrow L points to the downstream side of the flow direction of the flow path after the merging of the sheath liquid 80 and the specimen 70). In Figure 5 and Figure 6 In the middle, the vicinity of the merging portion 23B of the flow cell 20 is shown in an enlarged state by a perspective view. In addition, the arrow H shown in the drawing appropriately indicates the height direction of the flow cell 20, and the arrow W indicates the width direction of the flow cell 20. Further, in the drawing, the arrow L indicates the length direction of the flow cell 20 which is perpendicular to the height direction and the width direction, respectively (the arrow L points to the downstream side of the flow direction of the flow path after the merging of the sheath liquid 80 and the specimen 70). In Figure 1 and Figure 2 In the middle, the vicinity of the merging portion 23B of the flow cell 20 is shown in an enlarged state by a perspective view. In addition, the arrow H shown in the drawing appropriately indicates the height direction of the flow cell 20, and the arrow W indicates the width direction of the flow cell 20. Further, in the drawing, the arrow L indicates the length direction of the flow cell 20 which is perpendicular to the height direction and the width direction, respectively (the arrow L points to the downstream side of the flow direction of the flow path after the merging of the sheath liquid 80 and the specimen 70). In

[0079] The flow cell 20 of the present embodiment can be used for urine formed element examination which photographs a urine specimen by the measurement unit 11 by causing a urine specimen which is an example of the specimen 70 to flow in together with the sheath liquid 80, and performs analysis based on the shape of the formed element of the photographed image, for example. In the present embodiment, the urine formed element examination was performed using a urine specimen which is a body fluid as an example of the specimen 70, but a liquid specimen such as a body fluid represented by blood can also be used.

[0080] As shown in Figures 3-5 , the flow cell 20 is formed as a substantially rectangular plate-shaped member. In the present embodiment, the flow cell 20 is constituted by joining the upper plate-shaped member 20A and the lower plate-shaped member 20B in a surface contact state. The flow cell 20 has a merging path 23 in which the specimen 70 and the sheath liquid 80 merge and flow, and a specimen flow path 22 which is provided on the extension line of the length direction of the merging path 23 on the upstream side (the opposite side of the L direction) of the flow direction indicated by the arrow A of the merging path 23, and in which the specimen 70 flows (refer to Figure 5 ). Further, the flow cell 20 has two sheath liquid flow paths 21 which are arranged so as to cross the length direction of the merging path 23 on the upstream side of the flow direction (the A direction) of the merging path 23, and in which the sheath liquid 80 flows.

[0081] The merging path 23, the specimen flow path 22, and the two sheath liquid flow paths 21 are provided in the upper plate-shaped member 20A (refer to Figure 5 ). In addition, in Figure 5 , as described above, the upper and lower directions of the flow cell 20 are shown in the opposite state to Figure 1 and Figure 2 , so the positional relationship of the two sheath liquid flow paths 21 is opposite to Figure 1 and Figure 2 . In the present embodiment, the merging path 23, the specimen flow path 22, and the two sheath liquid flow paths 21 are formed by groove processing the lower surface 20C (the upward-facing surface in the drawing) of the upper plate-shaped member 20A (refer toFigure 5 ). In addition, Figure 5 The bottom of the groove forming the sheath liquid flow path 21 is the top surface 21X of the sheath liquid flow path 21. Further, the bottom of the groove forming the sample flow path 22 is the top surface 22X of the sample flow path 22. Also, the bottom of the groove forming the merging path 23 is the top surface 23X of the merging path 23. The lower plate-like member 20B is a plate material having a plane that is substantially parallel in the up-down direction, and no flow path or the like is formed therein (see FIG. 2). Figure 5 ). However, the bottom surface 21Y of the sheath liquid flow path 21, the bottom surface 22Y of the sample flow path 22, and the bottom surface 23Y of the merging path 23 are formed by the upper surface 20D (the face facing downward in the drawing) thereof.

[0082] The sample flow path 22 is configured in a substantially straight line along the length direction of the flow cell 20, and is a structure for flowing the sample 70 in the direction of the arrow B. In the present embodiment, the cross-sectional shape in the direction perpendicular to the length direction of the sample flow path 22 is substantially rectangular. At the upstream side end in the flow direction (the direction of the arrow B) of the sample flow path 22, a sample opening 22A for supplying the sample 70 is formed. At the sample opening 22A of the sample flow path 22, the 2nd flow path 32 for supplying the sample 70 is connected (see FIG. 2). Figure 1 ). In the sample flow path 22, the sample 70 supplied from the sample opening 22A flows in the direction of the merging path 23.

[0083] The two sheath liquid flow paths 21 each become a substantially U-shaped path that is horizontally long in plan view along the length direction of the flow cell 20, and the opening side of the substantially U-shaped form faces in the width direction (W direction) of the flow cell 20. The two sheath liquid flow paths 21 face each other across the merging path 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 length direction of the sheath liquid flow path 21 is substantially rectangular.

[0084] The two sheath liquid flow paths 21 are configured to flow the sheath liquid 80 in the direction of the arrow C and the direction of the arrow D, respectively. At the upstream side end in the flow direction (the direction of the arrow C and the direction of the arrow D) of the two sheath liquid flow paths 21, a sheath liquid opening 21A for supplying the sheath liquid 80 is formed. In other words, in the sheath liquid flow path 21, the sheath liquid 80 supplied from the sheath liquid opening 21A flows in the direction of the upstream side of the merging path 23. The two sheath liquid flow paths 21 each have two bend portions 21B, 21C formed midway in the flow direction. The bend portion 21B on the upstream side in the flow direction of the sheath liquid flow path 21 is bent in a substantially perpendicular direction, and the corner portion of the bent portion is curved in a curved line shape. The bend portion 21C on the downstream side (the side near the merging portion 23B) of this bend portion 21B is bent in a direction of an acute angle, and the corner portion of the bent portion is curved in a curved line shape.

[0085] At the upstream side end portion in the flow direction of the merging path 23 (arrow A direction), a merging portion 23B is provided, and the specimen 70 flowing from the specimen flow path 22 and the sheath liquid 80 flowing from the two sheath liquid flow paths 21 merge at the merging portion 23B (refer to Figure 6 ). That is, the merging portion 23B is a part of the merging path 23.

[0086] As shown in Figure 7 , at the downstream side end portion in the flow direction of the specimen flow path 22 (arrow B direction), a specimen flow inlet 22B is provided which opens at the end face 24 of the merging path 23 on the upstream side in the flow direction (arrow A direction) (refer to Figures 1-3 ). The specimen flow inlet 22B is formed at one side in the depth direction of the end face 24 of the merging path 23 (in this embodiment, the lower portion in the opposite direction of the H direction). More specifically, the merging path 23 has a bottom face 23Y and a top face 23X as wall faces opposing in the depth direction. The specimen flow path 22 is provided along the bottom face 23Y of the merging portion 23B of the merging path 23 which opposes the wall face on the side where the wedge face 23E is provided in the wedge portion 23C. The bottom face 22Y of the specimen flow path 22 is connected to the bottom face 23Y of the merging path 23 in such a manner as to be on the same level. The specimen 70 of the specimen flow path 22 flows from the specimen flow inlet 22B into the merging portion 23B. In other words, the specimen flow path 22 causes the specimen 70 to flow into the merging portion 23B along the bottom face 23Y of the merging portion 23B. That is, in this embodiment, the second pump 42 is a specimen liquid delivery unit 42 which delivers the specimen 70 along the inner wall opposing the wedge face 23E (refer to Figure 1 ).

[0087] At the downstream side end portion in the flow direction of the sheath liquid flow path 21 (arrow C direction and arrow D direction), a sheath liquid flow inlet 21D is provided which opens at both sides on the upstream side in the flow direction (arrow A direction) of the merging path 23 (refer to Figures 1-3 ). When viewed from above, the sheath liquid flow inlet 21D of the sheath liquid flow path 21 is formed at a position intersecting the end face 24 of the merging path 23. In this embodiment, the downstream portion of the sheath liquid flow path 21 is connected to the merging portion 23B in such a manner as to make an obtuse angle with the length direction of the merging path 23. Further, the sheath liquid flow path 21 is provided along the top face 23X of the opposing wall faces of the merging path 23, on the side where the wedge face 23E is provided in the wedge portion 23C. In this embodiment, when viewed in cross section in the depth direction of the merging path 23, the sheath liquid flow inlet 21D of the sheath liquid flow path 21 is provided within the range from the bottom face 23Y to the top face 23X of the merging portion 23B, and the lower portion of the sheath liquid flow inlet 21D overlaps the range where the specimen flow inlet 22B is provided (refer to Figure 5The sheath liquid 80 in the sheath liquid flow path 21 flows from the sheath liquid inflow port 21D into the merging portion 23B of the merging path 23. In other words, the sheath liquid flow path 21 causes the sheath liquid 80 to flow into the merging portion 23B from a direction in which the sheath liquid 80 flows while pressing the sample 70 against the bottom surface 23Y. That is, in the present embodiment, the first pump 41 is a sheath liquid delivery unit 41 that delivers the sheath liquid along the wedge surface (see FIG. 2). The sheath liquid 80 is delivered from the sheath liquid flow path 21 to the merging portion 23B of the merging path 23 by the sheath liquid delivery unit 41. Figure 1

[0088] In the flow cell 20 of the present embodiment, the length direction of the sample flow path 22 is disposed on an extension line of the length direction of the merging path 23. In the present embodiment, the cross-sectional shape in the direction perpendicular to the length direction of the merging path 23 is substantially rectangular. The width and the depth of the merging path 23 are larger than the width and the depth of the sample flow path 22. The sample flow path 22 is connected to the central portion in the width direction of the merging portion 23B of the merging path 23, and is connected to the lower portion in the depth direction of the merging portion 23B of the merging path 23 (see FIG. 2). Figure 7 Figure 12 In the present embodiment, the sheath liquid 80 is caused to flow first from the sheath liquid flow path 21 into the merging portion 23B of the merging path 23 in order not to waste the sample 70 (see FIG. 2). Figure 14

[0089] On the upper wall portion of the merging path 23 on the downstream side in the flow direction (arrow A direction) of the merging portion 23B of the merging path 23, a wedge portion 23C is provided in which the ceiling surface 23X gradually approaches the bottom surface 23Y toward the downstream (see FIG. 2). Figure 6 Figure 7 In the present embodiment, the first inner wall 23E is disposed above the second inner wall. In other words, in the present embodiment, the wedge portion 23C is a shape in which the distance between the bottom surface 23Y and the ceiling surface 23X as the opposing wall surfaces gradually shortens. That is, this portion of the ceiling surface 23X in the wedge portion 23C becomes a wedge surface 23E that is inclined in a direction approaching the opposing wall surface as it progresses from the upstream to the downstream. In the present embodiment, the wedge portion 23C is provided at a position of the merging path 23 adjacent to the merging portion 23B. The inclination angle of the wedge portion 23C with respect to the face direction of the flow cell 20 (in the present embodiment, the face direction of the bottom surface 23Y) is, for example, 2 to 8°.

[0090] ​​​​On the downstream side of the flow direction (arrow A direction) of the wedge portion 23C of the merging path 23, a flat portion 23D is formed which 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, which are the opposing wall surfaces, in the flat portion 23D is shorter than the distance between the top surface 23X and the bottom surface 23Y, which are the opposing wall surfaces, in the merging portion 23B. The wedge portion 23C is configured to connect the merging portion 23B and the flat portion 23D.

[0091] In the flow cell 20, by continuously configuring the bottom surface 23Y of the merging path 23 and the bottom surface 22Y of the sample flow path 22 on the same horizontal plane, the sample 70 flows along the bottom surface 23Y. Also, the sheath liquid 80 that merges from the sheath liquid flow path 21 to the merging portion 23B flows while pressing the sample 70 against the bottom surface 23Y (refer to Figure 15 ). In addition, the sample flow path 22 can be provided so that the sample 70 flows along the bottom surface 23Y of each of the merging portion 23B, the wedge portion 23C, and the flat portion 23D, and the bottom surfaces 22Y, 23Y of the sample flow path 22, the merging portion 23B, the wedge portion 23C, and the flat portion 23D can not be on the same horizontal plane. For example, it can be a curved surface, and there can be an angle between the respective bottom surfaces 22Y, 23Y.

[0092] At a position outside the flow cell 20 that is opposite the flat portion 23D, a camera that photographs the sample 70 is provided as the measurement unit 11 (refer to Figure 7 ). That is, the flat portion 23D corresponds to a measurement flow path. Also, the measurement unit 11 is provided at a position at which the sample 70 flows in contact with the bottom surface 23Y. The cross-sectional area of the sheath liquid flow path 21 is larger than the cross-sectional area of the sample flow path 22.

[0093] As shown in Figures 3-5 , at the downstream end of the flow direction (arrow A direction) of the merging path 23, a waste liquid opening 23A is formed through which the waste liquid 75, which is a mixture of the sample 70 and the sheath liquid 80, is discharged. The waste liquid opening 23A is connected to the waste liquid path 36, and the waste liquid 75 is discharged from the waste liquid opening 23A through the waste liquid path to the outside, which is not shown.

[0094] The flow cell 20 is preferably formed of a material having light transmittance, such as a synthetic resin such as polymethyl methacrylate resin, cyclic olefin polymer resin, polydimethylsiloxane resin, and polypropylene resin, or a material having a visible light transmittance of 90% or more such as glass. The merging path 23, the sample flow path 22, the two sheath liquid flow paths 21, and the like are formed in the upper plate-shaped member 20A by laser processing or the like. The flow cell 20 is formed by joining the upper plate-shaped member 20A and the lower plate-shaped member 20B. In the present embodiment, as an example, the upper plate-shaped member 20A and the lower plate-shaped member 20B are joined by heat pressure bonding.

[0095] [Functional Block]

[0096] Figure 8 A functional block diagram of the analysis device 10 is shown. The control section 100 controls each part of the analysis device 10. The control section 100 functions as a measurement control section 111 that controls the measurement section 11, a light source control section 115 that controls the light source 15, a first pump control section 141 that controls the supply and suction of the liquid by the first pump 41, a second pump control section 142 that controls the supply and suction of the liquid by the second pump 42, a first valve control section 151 that controls the switching of the flow path of the first valve 51, a second valve control section 152 that controls the switching of the flow path of the second valve 52, and a third valve control section 153 that controls the switching of the flow path of the third valve 53, by the hardware structure described later.

[0097] As shown in the hardware structure of the control section 100, Figure 9 The control section 100 has a CPU (Central Processing Unit) 101, a ROM (Read Only Memory) 102, a RAM (Random Access Memory) 103, and a storage 104. Each structure is connected in a manner capable of communicating with each other via a bus 109.

[0098] The CPU 101 is a central arithmetic processing unit, and can execute various programs and control each part. That is, the CPU 101 reads out 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 the control of each structure and various arithmetic processing according to the program recorded in the ROM 102 or the storage 104.

[0099] The ROM 102 stores various programs and various data. The RAM 103 temporarily stores a program or data as a work area. The storage 104 is constituted by a HDD (Hard Disk Drive), a SSD (Solid State Drive), or a flash memory, and stores various programs including an operating system, and various data. In the present mode, a program and various data related to measurement and determination are stored in the ROM 102 or the storage 104. Further, measurement data can be saved in the storage 104.

[0100] By executing the program by the CPU 101 in the hardware structure described above, the control section 100 functions as the measurement control section 111, the light source control section 115, the first pump control section 141, the second pump control section 142, the first valve control section 151, the second valve control section 152, and the third valve control section 153 in the analysis device 10. Figure 8The measurement control unit 111, light source control unit 115, first pump control unit 141, second pump control unit 142, first valve control unit 151, second valve control unit 152, and third valve control unit 153 shown herein perform their functions. Details of these functions will be described later.

[0101] [Operation of Analysis Device 10]

[0102] The following is for reference Figures 10-15 This explains the operation of the analysis device 10 in this embodiment. Additionally, Figure 10 and Figure 11 This is a flowchart illustrating the operation of the analysis apparatus according to this embodiment. The various parts of the analysis apparatus are as follows: Figure 1 As shown. Furthermore, in Figure 13 In this system, arrows marked near each pipe are used to indicate the direction of liquid (or gas) flow, and in each valve, the direction colored black indicates the flow path.

[0103] Before starting use, Figure 10 In the sheath fluid filling step S100, the various pipes of the analysis device 10 are filled with sheath fluid 80. First, the first sheath fluid valve 54 is opened. Then, the first valve control unit 151 opens the flow path to branches 1B and 1C at the first valve 51, the second valve control unit 152 opens the flow path to branches 2A and 2C at the second valve 52, and the third valve control unit 153 opens the flow path to branches 3A and 3C at the third valve 53.

[0104] In this state, the first pump control unit 141 operates the first pump 41 to supply sheath fluid 80 to the first flow path 31. Thus, the sheath fluid 80 supplied from the sheath fluid supply unit 13 via the first sheath fluid valve 54 passes from the first pump 41 through the third valve 53, the second valve 52, and the first valve 51 to the suction unit 12 and is discharged from its end. That is, the branch 3A of the first pump 41 to the first flow path 31, the fourth flow path 34, and the branches 2A, 1B, and 1C of the second flow path 32 are filled with sheath fluid 80.

[0105] Next, along with the first sheath fluid valve 54, the second sheath fluid valve 55 also opens. Then, the first valve control unit 151 opens the flow path to branches 1A and 1B at the first valve 51, the second valve control unit 152 opens the flow path to branches 2A and 2B at the second valve 52, and the third valve control unit 153 opens the flow path to branches 3A and 3B at the third valve 53.

[0106] In this state, the first pump control unit 141 operates the first pump 41 to supply the sheath liquid 80 to the first flow path 31. Thereby, the sheath liquid 80 supplied from the sheath liquid supply section 13 to the first pump 41 via the first sheath liquid valve 54 reaches the flow cell 20 from the first pump 41 through the third valve 53. That is, the first flow path 31 from the first pump 41 through the third valve 53 to the flow cell 20 is entirely filled with the sheath liquid 80.

[0107] Meanwhile, the second pump control unit 142 operates the second pump 42 to supply the sheath liquid 80 to the third flow path 33. Thereby, the sheath liquid 80 supplied from the sheath liquid supply section 13 to the second pump 42 via the second sheath liquid valve 55 reaches the flow cell 20 from the second pump 42 through the first valve 51 and the second valve 52. That is, the third flow path 33 from the second pump 42, and the branch 1B, the branch 2A, and the branch 2B of the second flow path 32 are also entirely filled with the sheath liquid 80.

[0108] Also, in the flow cell 20, the sheath liquid 80 from the first flow path 31 fills the sheath liquid flow path 21 having two branches through the sheath liquid opening 21A. On the other hand, the sheath liquid 80 from the second flow path 32 fills the sample flow path 22 through the sample opening 22A. Then, the two sheath liquids 80 merge at the merging path 23 to fill the merging path 23, and are discharged to the outside not shown through the waste liquid opening 23A after filling the waste liquid path 36.

[0109] Through the above steps, each of the conduits of the analysis device 10 is filled with the sheath liquid 80. Then, in the flow cell 20, as shown in the cross-sectional view of Figure 12 , in a state where the sample flow path 22, the merging section 23B, the wedge section 23C, and the flat section 23D are filled with the sheath liquid 80, the first pump control unit 141 controls to stop the operation of the first pump 41. Meanwhile, the second pump control unit 142 controls to stop the operation of the second pump 42. In this state, the liquid delivery pressure of the sheath liquid 80 in the merging path 23 is substantially zero, or extremely low.

[0110] Then, in the flow path switching step S110 of Figure 10 , the first valve control unit 151 makes the flow path conductive to the branch 1B and the branch 1C at the first valve 51, the second valve control unit 152 makes the flow path conductive to the branch 2A and the branch 2C at the second valve 52, and the third valve control unit 153 makes the flow path conductive to the branch 3A and the branch 3C at the third valve 53.

[0111] In this state, in the air suction step S120 of Figure 10 , the first pump control unit 141 operates the first pump 41 to apply a negative pressure to the first flow path 31, and sucks the sheath liquid 80 from the branch 3A of the first flow path 31. Thereby, the air 90 is sucked from the suction section 12. The sucked air 90 reaches the branch 1B from the branch 1C of the second flow path 32.

[0112] When the working state is maintained and negative pressure is continued to be applied to the first flow path 31, and the suction portion 12 is dipped into the specimen 70 housed in the specimen housing portion 60, in the specimen suction step S130, Figure 10 the specimen 70 is sucked from the branch 1C of the second flow path 32 through the branch IB and the branch 2A to the branch 2C of the fourth flow path 34 by the suction portion 12. On the other hand, the entire amount of the air 90 sucked is guided to the fourth flow path 34 by the second valve 52. In this state, the first pump control unit 141 stops the operation of the first pump 41, and stops the application of negative pressure to the first flow path 31. Thus, the entire amount of the air 90 sucked is enclosed to the fourth flow path 34.

[0113] Then, in the flow path switching step S140, Figure 11 the first valve control unit 151 makes the flow path conductive to the branch IA and the branch IB at the first valve 51, the second valve control unit 152 makes the flow path conductive to the branch 2A and the branch 2B at the second valve 52, and the third valve control unit 153 makes the flow path conductive to the branch 3A and the branch 3B at the third valve 53.

[0114] In this state, in the specimen introduction step S150, Figure 11 the first pump 41 is kept stopped, and the second pump control unit 142 operates the second pump 42 to apply positive pressure to the third flow path 33, and the sheath liquid 80 is supplied again to the third flow path 33. Thus, the sheath liquid 80 flows from the second pump 42 through the first valve 51 and the second valve 52 to flow into the flow cell 20 to press the specimen 70 of the second flow path 32 out to the flow cell 20. At this time, since the first pump is not operated, the inflow of the sheath liquid 80 from the first flow path 31 to the flow cell 20 is stopped.

[0115] In this state, in the flow cell 20, at the merging portion 23B, Figure 13As shown in the cross-sectional view, the specimen 70 flowing in from the specimen flow path 22 pushes the sheath fluid 80 downstream to fill the confluence portion 23B and reach the flattened portion 23D. At this time, the delivery pressure of the specimen 70 in the confluence path 23 is naturally greater than the delivery pressure of the sheath fluid 80 in the confluence path 23. That is, the control unit 100 controls the delivery pressure of the specimen 70 delivered by the second pump 42 in the confluence path 23 through the second pump control unit 142 to be greater than the delivery pressure of the sheath fluid 80 delivered by the stopped first pump 41 in the confluence path 23. In addition, in this embodiment, the first pump 41 stops until the specimen 70 reaches the flattened portion 23D and does not deliver sheath fluid 80 to the confluence path 23, but the present invention is not limited to this. That is, the control unit 100 may operate the first pump 41 through the first pump control unit 141, and deliver the sheath fluid 80 in a manner in which the delivery pressure of the sheath fluid 80 delivered by the first pump 41 in the confluence path 23 is lower than the delivery pressure of the specimen 70 delivered by the second pump 42 in the confluence path 23 caused by the second pump control unit 142.

[0116] Then, in Figure 11 In the sample compression step S160, such as Figure 14 As shown, the second pump control unit 142 activates the second pump 42, and the first pump control unit 141 restarts the first pump 41, thereby allowing the sheath fluid 80 to resume flowing from the first flow path 31 into the flow cell 20. That is, after the sheath fluid 80 in the first flow path 31 flows into the flow cell 20 from the sheath fluid opening 21A, it temporarily branches into two sheath fluid flow paths 21, and then merges with the specimen 70 at the confluence path 23.

[0117] In this state, in the confluence section 23B of the flow pool 20, such as Figure 15 As shown in the cross-sectional view, the sample 70 and sheath fluid 80 merge. However, above the sample 70 flowing in along the bottom surfaces 22Y and 23Y, the sheath fluid 80 in the sheath fluid flow path 21 flows in along the top surface 23X and merges, thus suppressing the mixing of the sample 70 and sheath fluid 80. At this time, the control unit 100 controls the delivery pressure of the first pump 41 through the first pump control unit 141, and simultaneously controls the delivery pressure of the second pump 42 through the second pump control unit 142, so that the delivery pressure of the sheath fluid 80 in the merging path 23 is greater than the delivery pressure of the sample 70 in the merging path 23. That is, the control unit 100 controls the pressure of the first pump 41 delivering sheath fluid to the merging path 23 to be greater than the pressure of the second pump 42 delivering the sample to the merging path 23.

[0118] Here, the sample flow path 22 is provided along the bottom surface 23Y of the merging portion 23B, whereby the sample 70 flowing from the sample flow path 22 flows along the bottom surface 23Y of the merging path 23 toward the arrow Al direction. Further, the sheath flow path 21 is provided along the wall surface provided with the wedge surface 23E, that is, the top surface 23X, whereby the sheath liquid 80 introduced from the sheath flow path 21 flows into the merging portion 23B along the top surface 23X of the merging path 23. Further, in the top surface 23X of the merging path 23, the wedge portion 23C that gradually approaches the bottom surface 23Y toward the downstream is provided. Thus, as shown in FIG. 6, in the merging path 23, the sheath liquid 80 flowing into the merging portion 23B from the sheath flow path 21 flows along the wedge surface 23E of the wedge portion 23C and flows in the arrow A2 direction to press the sample 70 against the bottom surface 23Y of the merging path 23. Thus, as shown in FIG. 7, in the wedge portion 23C of the merging path 23, the sheath liquid 80 presses the sample 70 from above, whereby the sample 70 extends in a flat shape along the bottom surface 23Y, the thickness gradually thins, and the width gradually increases. At this time, the sample 70 flows in contact with the bottom surface 23Y. Thus, in the upstream portion of the flat portion 23D of the merging path 23, the sample 70 flows along the bottom surface, whereby the state in which the thickness of the sample 70 thins and the width increases. The thickness of the sample 70 at this time is, for example, about 5 to 30 μm. That is, when the thickness of the sample 70 thus becomes the thinnest, the measurement unit 11 is arranged as shown in FIG. 8 at the position of the wedge portion 23C to the flat portion 23D. Further, the light source 15 is arranged at the position opposite to the measurement unit 11 with the flow cell 20 interposed therebetween. Figure 15 Figure 15 Figure 7

[0119] Figure 11

[0120] As described above, the sample 70 flows in contact with the bottom surface 23Y, and thus the sheath liquid 80 is not interposed between the measurement unit 11 and the sample 70, and it is possible to measure the sample 70 without being affected by the sheath liquid 80. Further, the sample 70 extends in a flat shape along the bottom surface 23Y and the thickness gradually thins, and thus it is useful in the case where the shape and size of the formed component contained in the sample 70 are observed using a camera as the measurement unit 11.

[0121] Further, in the waste liquid step S180, the waste liquid 75 obtained by mixing the sample 70 and the sheath liquid 80 in the merging path 23 is discharged from the waste liquid path 36 to the outside not shown through the waste liquid opening 23A. Figure 11

[0122] ​​​​​​In the flow cell 20 of the present embodiment, the flow rates of the sample 70 and the sheath liquid 80 in the sheath liquid flow path 21 are controlled. The flow rate ratio of the sample 70 and the sheath liquid 80 is set to 1:20 to 40. By controlling the flow rate ratio of the sample 70 and the sheath liquid 80, the width and thickness of the sample 70 flowing in the merging path 23 are controlled.

[0123] Industrial Applicability

[0124] The present application can be used for a liquid delivery method for delivering a sample to a flow cell and an analysis device using the method.

Claims

1. A liquid delivery method for conveying a liquid sample to a flow cell having a wedge-shaped portion comprising a first inner wall and a second inner wall opposite to the first inner wall, wherein both the liquid sample and sheath fluid flow within the wedge-shaped portion, the first inner wall being inclined relative to the second inner wall in such a manner that the distance between the first inner wall and the second inner wall on the downstream side of the wedge-shaped portion is shorter than the distance between the first inner wall and the second inner wall on the upstream side of the wedge-shaped portion. The flow pool also includes: The specimen flow path is disposed upstream of the wedge and has a first bottom surface, the first bottom surface being connected to the second inner wall and being in the same plane as the second inner wall; A sheath fluid flow path, which is disposed upstream of the wedge-shaped portion and has a top surface connected to the first inner wall; and A measuring flow path is provided downstream of the wedge-shaped portion and has a second bottom surface connected to the second inner wall. The liquid delivery method includes the following steps: The sample introduction step involves introducing the sample by conveying the liquid sample along the first bottom surface into the sample flow path until the liquid sample reaches the measurement flow path; and In the sample compression step, after the liquid sample reaches the measuring flow path, the sheath fluid is delivered into the sheath fluid flow path, whereby the liquid sample and the sheath fluid flow on the second bottom surface, such that the second bottom surface, the liquid sample, and the sheath fluid are sequentially arranged. In the sample compression step, the delivery pressure of the liquid sample in the confluence path of the liquid sample and the sheath fluid is lower than the delivery pressure of the sheath fluid in the confluence path. If the delivery pressure of the liquid sample in the confluence path is measured for a certain period of time and is within a specific delivery pressure range, the process is transferred to the measurement step of measuring the liquid sample flowing in the measurement flow path.

2. The liquid delivery method according to claim 1, wherein, During the specimen introduction step, the delivery of the sheath fluid to the wedge-shaped portion is stopped.

3. The liquid delivery method according to claim 1 or 2, wherein, After the sheath fluid is used to fill the measurement flow path, the sample introduction step is performed.

4. The liquid delivery method according to claim 1, wherein, The liquid is a bodily fluid.

5. The liquid delivery method according to claim 4, wherein, The fluid in question is urine.

6. An analytical apparatus comprising: A flow cell having a wedge-shaped portion comprising a first inner wall and a second inner wall opposite to the first inner wall, in which both a liquid sample and sheath fluid flow, the first inner wall being inclined relative to the second inner wall in such a way that the distance between the first inner wall and the second inner wall on the downstream side of the wedge is shorter than the distance between the first inner wall and the second inner wall on the upstream side of the wedge; The flow pool also includes: The specimen flow path is disposed upstream of the wedge and has a first bottom surface, the first bottom surface being connected to the second inner wall and being in the same plane as the second inner wall; A sheath fluid flow path, which is disposed upstream of the wedge-shaped portion and has a top surface connected to the first inner wall; and A measuring flow path is provided downstream of the wedge-shaped portion and has a second bottom surface connected to the second inner wall. The analytical device has: A sheath fluid delivery unit that delivers the sheath fluid into the sheath fluid flow path; A sample delivery unit that delivers the liquid sample into the sample flow path; A measuring unit that measures the liquid sample flowing in the measuring flow path; and The control unit controls the sample delivery unit to transport the liquid sample along the first bottom surface to the sample flow path until the liquid sample reaches the measurement flow path. After the liquid sample reaches the measurement flow path, the control unit controls the sheath fluid delivery unit to deliver the sheath fluid into the sheath fluid flow path, thereby allowing the liquid sample and the sheath fluid to flow on the second bottom surface, so that the second bottom surface, the liquid sample, and the sheath fluid are arranged sequentially. When the liquid sample and the sheath fluid flow on the second bottom surface, the delivery pressure of the liquid sample in the confluence path of the liquid sample and the sheath fluid is lower than the delivery pressure of the sheath fluid in the confluence path. When the delivery pressure of the liquid sample in the confluence path is measured for a certain period of time and is within a specific delivery pressure range, the liquid sample flowing in the measurement flow path is measured.

7. The analytical apparatus according to claim 6, wherein, The control unit controls the sample delivery unit to deliver the liquid sample to the wedge-shaped portion until the measuring unit detects the liquid sample. After the measuring unit detects the liquid sample, it controls the sheath fluid delivery unit to deliver the sheath fluid to the wedge-shaped portion.

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