Measurement device

Abstract

This measurement device comprises: a nozzle for suctioning a specimen liquid; a flow cell provided with a specimen flow passage; a specimen suction unit that is connected to the nozzle, and that suctions a specimen; a specimen extrusion unit that extrudes and supplies the specimen; a specimen storage unit that stores the specimen suctioned by the nozzle; and a flow passage switching mechanism capable of switching between a specimen suction mode, in which the nozzle and the specimen suction unit are connected via the specimen storage unit and the specimen extrusion unit and the flow cell are not connected to the specimen storage unit, and a specimen supply mode, in which the nozzle and the specimen suction unit are connected without using the specimen storage unit and the specimen extrusion unit and the flow cell are connected via the specimen storage unit.

Description

Measuring equipment

[0001] The present invention relates to a measuring device for analyzing a sample.

[0002] Japanese Patent Application Laid-Open No. 2020-173106 discloses a measuring device that analyzes a sample using a flow cell.

[0003] Furthermore, Japanese Patent No. 5442627 discloses a liquid chromatography device that supplies a sample using an injection valve.

[0004] The devices disclosed in JP 2020-173106 A and JP 5442627 A were unable to simultaneously perform sample aspirating, sample delivery, and cleaning of the nozzle that aspirates the sample liquid in preparation for the next sample.

[0005] An object of the present disclosure is to provide a measuring device that can perform cleaning in preparation for the next sample in parallel with the transfer of the sample.

[0006] The measuring device of the present disclosure includes a nozzle for aspirating specimen liquid, a flow cell having flow paths for the specimen and sheath liquid, a sheath liquid container for storing sheath liquid, a specimen aspirating unit connected to the nozzle and capable of switching between a specimen aspirating operation for aspirating the specimen from the nozzle and an extrusion operation for supplying sheath liquid from the sheath liquid container to the nozzle to clean the nozzle, a specimen pushing unit for pushing and supplying the specimen, and a specimen storage unit for storing the specimen aspirated by the nozzle, the nozzle and the specimen aspirating unit being connected via the specimen storage unit, and the specimen pushing unit and the pre-extrusion unit being connected to each other. The flow path switching mechanism is capable of switching between a sample aspiration mode in which the flow cell is not connected to the sample storage section and a sample supply mode in which the nozzle and the sample aspiration section are connected without the sample storage section and the sample extrusion section and the flow cell are connected via the sample storage section, and a control section that controls the flow path switching mechanism to switch between the sample aspiration mode and the sample supply mode and causes the sample aspiration section to perform the sample aspiration operation in the sample aspiration mode and the extrusion operation in the sample supply mode.

[0007] The measurement device of the present disclosure can be configured such that the flow path switching mechanism has a first port connected to the sample extrusion section, a second port connected to the sample flow path of the flow cell, a third port connected to the nozzle, and a fourth port connected to the sample suction section, and in the sample suction mode, the sample storage section is connected to the third port and the fourth port, and in the sample supply mode, the sample storage section is switched to be connected to the first port and the second port.

[0008] The measurement device of the present disclosure can include a sheath extrusion unit that extrudes and supplies sheath liquid.

[0009] In the measuring device of the present disclosure, the flow path switching mechanism may be configured to include a rotary valve.

[0010] According to the measuring device of the present disclosure, the speed of sample measurement processing can be significantly improved by performing cleaning in preparation for the next sample in parallel with sample delivery.

[0011] 1 is a schematic diagram of the measuring device of this embodiment (specimen aspiration mode). FIG. 2 is a schematic diagram of the measuring device of this embodiment (specimen supply mode). FIG. 3 is an explanation of the operation of the specimen agitation process. FIG. 4 is an explanation of the operation of the specimen agitation process. FIG. 5 is an explanation of the operation of the specimen agitation process. FIG. 6 is a block diagram of a part of the control system of the measuring device of this embodiment. FIG. 7 is a flowchart of the liquid delivery process. FIG. 8 is a flowchart of the specimen agitation process. FIG. 9 is a diagram showing the state after a specimen has been aspirated in specimen aspiration mode. FIG. 10 is a diagram showing the state of the specimen immediately after switching to specimen supply mode. FIG. 11 is a diagram showing the state in which a specimen is being supplied to a flow cell in specimen supply mode. FIG. 12 is a diagram showing a switching mechanism part (specimen aspiration mode) according to a modified example of this embodiment. FIG. 13 is a diagram showing a switching mechanism part (specimen supply mode) according to a modified example of this embodiment.

[0012]

[0023] Hereinafter, an embodiment of the present disclosure will be described with reference to the drawings. A measurement device 10 of this embodiment will be described as an example of an apparatus for analyzing formed elements in urine using urine as a sample. As shown in Figure 1, the measurement device 10 includes a nozzle 16, a flow cell 20, a rotary valve 30, a sample aspirator 40, a sample extruder 42, and a sheath fluid extruder 44.

[0013] Flow cell 20 is a rectangular plate-like structure, and is formed with a specimen inlet 20A, a sheath inlet 20B, a confluence channel 22, and an outlet 20C. In confluence channel 22, the introduced specimen and sheath fluid are merged, and the specimen is measured by acquiring an image at a predetermined measurement position. After measurement, the specimen and sheath fluid are discharged from outlet 20C and collected, for example, in a waste liquid tank (not shown).

[0014] The nozzle 16 is connected to the pipe L1. The tip of the nozzle 16 can be inserted into the spitz tube 13, and the nozzle 16 aspirates the specimen inside the spitz tube 13. The nozzle 16 can move up and down and horizontally so that specimens inside different spitz tubes 13 can be collected sequentially.

[0015] The rotary valve 30 has six ports, 30A, 30B, 30C, 30D, 30E, and 30F, spaced at equal intervals of 60°. A first flow path 32, a second flow path 34, and a third flow path 36 are formed on a flow path member that can rotate relative to the ports, with one end corresponding to each of the ports. A pipe L1 is connected to the third port, port 30A, and a pipe L2 is connected to the fourth port, port 30B, and a pipe L3 is connected to the first port, port 30D, and a pipe L4 is connected to the second port, port 30E, respectively. The other end of pipe L4 is connected to the specimen inlet 20A of the flow cell 20. A specimen storage flow path 38, serving as a specimen storage section, is connected to ports 30C and 30F, connecting the two. The rotary valve 30 functions as a flow path switching mechanism that switches the connection positions of each port with the first flow path 32, the second flow path 34, and the third flow path 36 between a sample aspiration mode M1 and a sample supply mode M2. Details of the sample aspiration mode M1 and the sample supply mode M2 ​​will be described later.

[0016] The specimen aspirating unit 40 is connected to a pipe L2 and is connected to the port 30B via the pipe L2. The specimen aspirating unit 40 is capable of aspirating a fluid from the port 30B toward the specimen aspirating unit 40, or of pushing out the sheath fluid stored in the sheath fluid container A from the specimen aspirating unit 40 toward the port 30B. The specimen aspirating unit 40 can be formed by a plunger pump.

[0017] The specimen pushing section 42 is connected to the pipe L3, and is connected to the port 30D via the pipe L3. The specimen pushing section 42 is capable of pushing out a fluid in a direction from the specimen pushing section 42 toward the port 30D, and can be formed by a pump.

[0018] The sheath fluid pushing unit 44 is connected to a pipe L5, and the other end of the pipe L5 is connected to the sheath inlet 20B of the flow cell 20. The sheath fluid pushing unit 44 is capable of pushing out fluid in the direction from the sheath fluid pushing unit 44 toward the sheath inlet 20B, and can be formed by a pump.

[0019] The specimen aspirating section 40, specimen pushing section 42, and sheath fluid pushing section 44 are each connected to a pipe L6, which is in turn connected to a sheath fluid container A. Sheath fluid is stored in the sheath fluid container A. A pump 46 is provided in the pipe L6 upstream of the connection between the specimen aspirating section 40, specimen pushing section 42, and sheath fluid pushing section 44. The sheath fluid stored in the sheath fluid container A is sent out to the downstream side of the pipe L6 by the pump 46.

[0020] Next, the sample suction mode M1 and the sample supply mode M2 ​​will be described.

[0021] In specimen aspiration mode M1, one end of the first flow path 32 of the rotary valve 30 is connected to port 30F, and the other end is connected to port 30A, with ports 30F and 30A connected via the first flow path 32. Furthermore, one end of the second flow path 34 is connected to port 30B, and the other end is connected to port 30C, with ports 30B and 30C connected via the second flow path 34. Furthermore, one end of the third flow path 36 is connected to port 30D, and the other end is connected to port 30E, with ports 30D and 30E connected via the third flow path 36. This forms a specimen aspiration path R1, which communicates with the nozzle 16, piping L1, first flow path 32, specimen storage flow path 38, second flow path 34, piping L2, and specimen aspiration unit 40. The specimen aspiration unit 40 can be operated to aspirate a specimen from the spitz tube 13 into the specimen aspiration path R1 (see also FIG. 7 ).

[0022] In specimen supply mode M2, as shown in FIG. 2 , the rotary valve 30 is rotated 60° clockwise from specimen aspiration mode M1. One end of the first flow path 32 of the rotary valve 30 is connected to port 30A, and the other end is connected to port 30B, with ports 30A and 30B connected via the first flow path 32. Furthermore, one end of the second flow path 34 is connected to port 30C, and the other end is connected to port 30D, with ports 30C and 30D connected via the second flow path 34. Furthermore, one end of the third flow path 36 is connected to port 30E, and the other end is connected to port 30F, with ports 30E and 30F connected via the third flow path 36. This forms a specimen supply channel R2, which communicates with the specimen extrusion section 42, piping L3, second flow path 34, specimen storage flow path 38, third flow path 36, and piping L4. The specimen pushing section 42 can be operated to push the specimen from the specimen storage channel 38 into the flow cell 20 .

[0023] In the specimen supply mode M2, a cleaning path R3 is formed, which communicates from the nozzle 16 to the pipe L1, the first flow path 32, the pipe L2, and the specimen aspirating unit 40. This cleaning path R3 is separated from the specimen supply path R2 (see FIG. 8 ), and the specimen aspirating unit 40 is pushed out to push the sheath fluid into the cleaning path R3, thereby cleaning the cleaning path R3. By also operating the pump 46 when the specimen aspirating unit 40 is pushed out, the amount of sheath fluid required for cleaning can be supplied to the nozzle in a short time.

[0024] The sample in the spitz tube 13 is subjected to a sample agitation process before being supplied to the measurement device 10. In the sample agitation process, as shown in Fig. 3A, air is aspirated from the tip of the nozzle 16, and then, as shown in Fig. 3B, the nozzle 16 is inserted into the spitz tube 13 to slightly aspirate the sample. Then, as shown in Fig. 3C, the aspirated air is discharged into the sample in the spitz tube 13 to agitate the sample. The sample agitation process is performed immediately before the sample is aspirated by the nozzle 16.

[0025] 4, the control device 50 includes a CPU 50A, a ROM 50B, a RAM 50C, a storage 50D, and an I / O 50E, all of which are connected via a bus 50F. The I / O 50E is connected to the nozzle 16, the rotary valve 30, the specimen aspirating unit 40, the specimen pushing unit 42, and the sheath liquid pushing unit 44. The storage 50D stores various programs and data, such as a liquid delivery processing program and data necessary for measurements by the measurement device 10.

[0026] In FIG. 4, only the connection relationships of the parts related to the liquid transfer are shown, and the control device 50 is also connected to parts (not shown) necessary for other measurements.

[0027] Next, the liquid transfer process in the measurement device 10 will be described.

[0028] In the initial state, each pipe and flow path of the measuring device 10 is filled with sheath liquid. Also, the rotary valve 30 is set to the sample supply mode M2. When an instruction to start measurement is given, the measuring device 10 executes the liquid delivery process shown in Fig. 5. First, in step S12, a sample agitation process is executed.

[0029] As shown in Figure 5, the sample agitation process involves operating the sample aspiration unit 40 in step S12-1 to aspirate a predetermined amount of air from the tip of the nozzle 16 (see Figure 3A). Next, in step S12-2, the nozzle 16 is inserted into the spitz tube 13, and in step S12-3, a small amount of sample is aspirated (see Figure 3B). In step S12-4, the sample aspiration unit 40 is operated for a predetermined time to eject the aspirated air into the spitz tube 13 (see Figure 3C). This agitates the sample in the spitz tube 13. Furthermore, a predetermined amount of air remains in the nozzle 16, forming an air layer "Air."

[0030] After the sample agitation process, in step S14, the sample aspirator 40 is operated for a predetermined time to aspirate the sample from the spitz tube 13. As a result, the sample is aspirated into the nozzle 16 via the air layer Air.

[0031] Next, in step S16, the nozzle 16 is removed from the spitz tube 13, and in step S18, the rotary valve 30 is switched to the specimen aspiration mode M1. This forms a specimen aspiration path R1 that connects the nozzle 16, piping L1, first flow path 32, specimen storage path 38, second flow path 34, piping L2, and specimen aspiration unit 40. Then, in step S20, the specimen aspiration unit 40 is operated for a predetermined time to aspirate the specimen through the air layer Air formed during stirring. This causes the specimen to be aspirated through the air layer Air into piping L1, first flow path 32, specimen storage path 38, second flow path 34, and piping L2 (specimen aspiration path R1). Therefore, the specimen is introduced into the specimen storage path 38 (see FIG. 7 ).

[0032] Next, in step S22, the rotary valve 30 is switched to the specimen supply mode M2. This forms a specimen supply path R2 that connects the specimen pushing unit 42, pipe L3, second flow path 34, specimen storage path 38, third flow path 36, and pipe L4, and also forms a cleaning path R3 that connects from the nozzle 16 to pipe L1, first flow path 32, pipe L2, and specimen aspirating unit 40 (see FIG. 8). Then, the processes of steps S30, S31, S32, S34, and S35 and the processes of steps S24, S26, and S28 are executed in parallel.

[0033] In step S30, the sample aspirator 40 and pump 46 are activated to push sheath fluid into the cleaning channel R3. This causes the cleaning channel R3, including the nozzle 16, to be cleaned with sheath fluid. In step S31, it is determined whether all of the planned series of measurements have been completed. If the determination is affirmative, the process proceeds to step S28. If the determination is negative, steps S32, S34, and S36 are executed in sequence. Steps S32, S34, and S36 are similar to steps S12, S14, and S16.

[0034] Meanwhile, in step S24, the specimen pushing unit 42 is operated to push the fluid in the specimen supply channel R2 toward the flow cell 20. As a result, the specimen introduced into the specimen storage channel 38 is supplied from the specimen inlet 20A to the flow cell 20. At the same time, the sheath fluid pushing unit 44 is operated to supply sheath fluid from the sheath inlet 20B of the flow cell 20. As a result, the sheath fluid and the specimen are supplied to the flow cell 20, and the sheath fluid and the specimen merge in the junction channel 22, allowing the specimen to be measured. The specimen is measured by acquiring an image at a predetermined measurement position, and the sheath fluid and the specimen are discharged from the outlet 20C downstream of the junction channel 22 (see FIG. 9 ).

[0035] Then, in step S26, the pump 46 is operated to clean the flow path of the flow cell 20, and in step S28, it is determined whether or not all of the scheduled measurements have been completed (including the positive determination of measurement completion in step S31), and if the determination is positive, this process is terminated.

[0036] If the determination in step S28 is negative, or after the processing of step S36, the process returns to step S18, and the above processing is repeated to measure the sample in the next spitz tube 13.

[0037] In the measuring device 10 of this embodiment, after aspirating a sample into the sample storage flow path 38 in sample aspiration mode M1, switching to sample supply mode M2 ​​forms a sample supply path R2 connecting the sample storage flow path 38 to the flow cell 20, and forms a washing path R3 connecting the nozzle 16 and the sample aspiration unit 40 without passing through the sample storage flow path 38. This makes it possible to supply a sample to the flow cell 20 for measurement while washing the washing path R3 that connects to the nozzle 16. This therefore shortens the time until the sample is supplied for the next measurement.

[0038] Although the rotary valve 30 is used as the switching mechanism in this embodiment, the switching mechanism may be configured using other switching valves.

[0039] As an example, a measuring device 11 can be configured as shown in Figures 10 and 11. The measuring device 11 includes a first specimen storage section 38A and a second specimen storage section 38B, as well as switching valves V1 and V2.

[0040] Switching valve V1 is provided with ports 30A and 30B, with piping L1 connected to port 30A and piping L4 connected to port 30E. Switching valve V1 is also connected to one end of first specimen storage section 38A and one end of second specimen storage section 38B. Switching valve V1 is capable of switching between a first flow path pattern P1 (see FIG. 10 ) in which port 30A is connected to first specimen storage section 38A and port 30E is connected to second specimen storage section 38B, and a second flow path pattern P2 (see FIG. 11 ) in which port 30A is connected to second specimen storage section 38B and port 30E is connected to first specimen storage section 38A.

[0041] Switching valve V2 is provided with ports 30B and 30D, with piping L2 connected to port 30B and piping L3 connected to port 30D. The other ends of first specimen storage section 38A and second specimen storage section 38B are also connected to switching valve V2. Switching valve V2 is capable of switching between a first flow path pattern P1 (see FIG. 10 ) in which port 30B is connected to first specimen storage section 38A and port 30D is connected to second specimen storage section 38B, and a second flow path pattern P2 (see FIG. 11 ) in which port 30B is connected to second specimen storage section 38B and port 30D is connected to first specimen storage section 38A.

[0042] When the switching valves V1 and V2 are switched to the first flow path pattern P1, a specimen aspiration path R1A is formed, which communicates with the nozzle 16, the pipe L1, the first specimen storage section 38A, the pipe L2, and the specimen aspiration section 40. In addition, a specimen supply path R2B is formed, which communicates with the specimen extrusion section 42, the pipe L3, the second specimen storage path 38B, the pipe L4, and the flow cell 20.

[0043] Furthermore, when the switching valves V1 and V2 are switched to the second flow path pattern P2, a specimen aspiration path R1B is formed, which communicates with the nozzle 16, the pipe L1, the second specimen storage section 38B, the pipe L2, and the specimen aspiration section 40. Furthermore, a specimen supply path R2A is formed, which communicates with the specimen extrusion section 42, the pipe L3, the first specimen storage path 38A, the pipe L4, and the flow cell 20.

[0044] When the switching valves V1 and V2 are switched to the first flow path pattern P1, the specimen aspirating unit 40 can be pushed out to push sheath fluid into the specimen aspirating path R1A, thereby cleaning the specimen aspirating path R1A. Then, the specimen aspirating unit 40 can be operated to aspirate the specimen from the spitz tube 13 into the specimen aspirating path R1A. At the same time, the specimen pushing unit 42 can be operated to push out the specimen from the second specimen storage path 38B into the flow cell 20.

[0045] When the switching valves V1 and V2 are switched to the second flow path pattern P2, the specimen aspirating unit 40 is operated to push out sheath fluid into the specimen aspirating path R1B, thereby cleaning the specimen aspirating path R1B. The specimen aspirating unit 40 is then operated to aspirate the specimen from the spitz tube 13 into the specimen aspirating path R1B. At the same time, the specimen pushing unit 42 is operated to push out the specimen from the first specimen storage path 38A into the flow cell 20.

[0046] In the measuring device 11, the sample aspirating path R1A and the sample supply path R2B in the first flow path pattern P1 are also separated, and the sample aspirating path R1B and the sample supply path R2A in the second flow path pattern P2 are also separated. Therefore, the sample aspirating paths R1A and R1B that communicate with the nozzle 16 can be washed while the sample is being supplied to the flow cell 20 and a measurement is being performed. This reduces the time required to supply the sample for the next measurement.

[0047] The disclosure of Japanese Patent Application No. 2024-134454, filed on August 9, 2024, is incorporated herein by reference in its entirety. All documents, patent applications, and technical standards mentioned herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference.

Claims

a sheath fluid container for storing sheath fluid; a specimen aspirating unit connected to the nozzle and capable of switching between a specimen aspirating operation for aspirating the specimen from the nozzle and an extrusion operation for supplying sheath fluid from the sheath fluid container to the nozzle and cleaning the nozzle; a specimen pushing unit for pushing and supplying the specimen; a specimen storage unit for storing the specimen aspirated by the nozzle; a flow path switching mechanism capable of switching between a specimen aspirating mode in which the nozzle and the specimen aspirating unit are connected via the specimen storage unit and the specimen pushing unit and the flow cell are not connected to the specimen storage unit, and a specimen supply mode in which the nozzle and the specimen aspirating unit are connected without the specimen storage unit and the specimen pushing unit and the flow cell are connected via the specimen storage unit; a control unit that controls the flow path switching mechanism to switch between the sample aspiration mode and the sample supply mode, and causes the sample aspiration unit to perform the sample aspiration operation in the sample aspiration mode and the extrusion operation in the sample supply mode.

2. The measuring device of claim 1, wherein the flow path switching mechanism has a first port connected to the sample extrusion section, a second port connected to the sample flow path of the flow cell, a third port connected to the nozzle, and a fourth port connected to the sample suction section, and in the sample suction mode, the sample storage section is connected to the third port and the fourth port, and in the sample supply mode, the sample storage section is switched to be connected to the first port and the second port.

3. The measuring device according to claim 1, further comprising a sheath extrusion section for extruding and supplying sheath liquid.

4. The measuring device according to any one of claims 1 to 3, wherein the flow path switching mechanism includes a rotary valve.

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